Dka Hhs Ada Guideline

Diabetes Care 1
Hyperglycemic Crises in Adults Guillermo E. Umpierrez,1

Georgia M. Davis,1 Nuha A. ElSayed,2,3
With Diabetes: A Consensus Gian Paolo Fadini,4,5 Rodolfo J. Galindo,6
Irl B. Hirsch,7 David C. Klonoff,8
Report Rozalina G. McCoy,9,10 Shivani Misra,11,12
CONSENSUS REPORT
Robert A. Gabbay,2,3
Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

https://doi.org/10.2337/dci24-0032 Raveendhara R. Bannuru,2 and
Ketan K. Dhatariya 13,14
The American Diabetes Association (ADA), European Association for the Study of
Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), Ameri-
can Association of Clinical Endocrinology (AACE), and Diabetes Technology Soci-
ety (DTS) convened a panel of internists and diabetologists to update the ADA
consensus statement on hyperglycemic crises in adults with diabetes, published
in 2001 and last updated in 2009. The objective of this consensus report is to pro-
vide up-to-date knowledge about the epidemiology, pathophysiology, clinical
presentation, and recommendations for the diagnosis, treatment, and preven-
tion of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS)
in adults. A systematic examination of publications since 2009 informed new rec-
ommendations. The target audience is the full spectrum of diabetes health care
professionals and individuals with diabetes.
1
Division of Endocrinology, Metabolism, and
Lipids, Department of Medicine, Emory University
Diabetic ketoacidosis (DKA) and the hyperglycemic hyperosmolar state (HHS) are the School of Medicine, Atlanta, GA
2
two most serious, acute, and life-threatening hyperglycemic emergencies in individu- American Diabetes Association, Arlington, VA
3
Department of Medicine, Harvard Medical
als with type 1 diabetes (T1D) and type 2 diabetes (T2D) (1–3). Global reports clearly School, Boston, MA
show an increase in the number of DKA and HHS admissions during the past decade, 4
Department of Medicine, University of Padua,
with recent data reporting a 55% increase in the rate of DKA hospitalizations, espe- Padua, Italy
5
cially in adults aged <45 years (4–6). DKA is characterized by the triad of hyperglyce- Veneto Institute of Molecular Medicine, Padua,
Italy
mia, increased ketone concentration in the blood and/or urine, and metabolic 6
Division of Endocrinology, Diabetes and Meta-
acidosis, while HHS is characterized by severe hyperglycemia, hyperosmolality, and bolism, Department of Medicine, University of
dehydration in the absence of significant ketosis or acidosis. The metabolic derange- Miami Miller School of Medicine, Miami, FL
7
ments in DKA result from the combination of absolute or relative insulin deficiency Division of Metabolism, Endocrinology, and
Nutrition, Department of Medicine, University
(levels insufficient to suppress gluconeogenesis and ketone production) and elevation of Washington, Seattle, WA
of counterregulatory hormones (glucagon, epinephrine, norepinephrine, cortisol, and 8
Diabetes Research Institute, Mills-Peninsula
growth hormone) (1,3,7). In HHS, there is a residual amount of insulin secretion that Medical Center, San Mateo, CA
9
minimizes ketosis but does not control hyperglycemia (1,3). Division of Endocrinology, Diabetes and Nutrition,
Department of Medicine, University of Maryland
Both DKA and HHS can occur at any age in people with T1D, T2D, or any other School of Medicine, Baltimore, MD
type of diabetes. DKA is more common in young people with T1D, and HHS is 10
University of Maryland Institute for Health
more frequently reported in older adults with T2D. Although any acute illness or Computing, Bethesda, MD
11
physiological stress can precipitate DKA and HHS, the most frequent causes are in- Division of Metabolism, Digestion & Re-
production, Imperial College London, U.K.
fection, particularly urinary tract infections and pneumonia, and the omission of in- 12
Department of Diabetes & Endocrinology,
sulin therapy. In recent years, sodium–glucose cotransporter 2 (SGLT2) inhibitors Imperial College Healthcare NHS Trust, London,
have been found to increase the risk of DKA, most often when used in T1D but U.K.
13
also in T2D (2). The incidence of both DKA and HHS was reported to have increased Elsie Bertram Diabetes Centre, Norfolk and
Norwich University Hospitals NHS Foundation
during the COVID-19 pandemic (8,9). Early diagnosis and management of DKA and Trust, Norwich, U.K.
HHS are essential to improve outcomes. The mainstays of treatment of DKA and 14
Department of Medicine, Norwich Medical
HHS are fluid replacement, insulin therapy, electrolyte repletion, and treatment of School, University of East Anglia, Norwich, U.K.
2 Consensus Report Diabetes Care
underlying precipitating events. Appropri- Monthly calls were held between Octo- 45–64 years (47.5%) with T2D (88.1%) (13).
ate treatment has reduced mortality ber 2022 and September 2023, with addi- Additionally, several studies have revealed
owing to DKA to <1%; however, mortal- tional email and web-based collaboration. that over half of Black/African American
ity has remained 5- to 10-fold higher in in- One in-person meeting was conducted to and Hispanic/Latino adults with newly diag-
dividuals with HHS (1,10). provide organization to the process, estab- nosed diabetes presenting with unpro-
The objective of this consensus report is lish the review process, reach consensus on voked DKA have T2D (14–16). The clinical
to provide up-to-date knowledge about the the content and key definitions, and dis- presentation in such cases is acute, as in
epidemiology, pathophysiology, clinical pre- cuss the recommendations. Once the draft classical DKA observed in people with T1D;
sentation, and recommendations for the di- was completed, the structured peer re- however, after immediate stabilization and
agnosis, treatment, and prevention of DKA view process was implemented, and the a short course of insulin therapy, prolonged

and HHS in adults. The target audience is report was sent to external peer reviewers near-euglycemia is often possible because
the full spectrum of diabetes health care and respective committees of all the con- of restoration of pancreatic b-cell function
professionals and individuals with diabetes. tributing organizations. A final draft was and insulin sensitivity, with gradual cessa-
completed and submitted to all five organ- tion of insulin treatment and maintenance
RESEARCH DESIGN AND METHODS izations for final review and approval. The of glycemic goals with medical nutrition
This consensus report is an update of the guidance represents the panel’s collective therapy and non-insulin agents (4). Such in-
American Diabetes Association (ADA) con- analysis, evaluation, and expert opinion. dividuals often have clinical and metabolic
sensus statement on hyperglycemic crises Questions related to clinical practice features of T2D, including high rates of obe-
in adults with diabetes, published in 2001 provide the framework for this update on sity, a strong family history of diabetes, a
and last updated in 2009 (11,12). The ADA hyperglycemic crises in adults. This update measurable pancreatic insulin reserve, the
convened a panel of internists and diabe- includes eight sections that cover new evi- absence of autoimmune markers of b-cell
tologists representing the ADA, European dence about epidemiology, pathogenesis, destruction, and the ability to discontinue
Association for the Study of Diabetes diagnostic criteria, recommended treat- insulin therapy during follow-up (14,17).
(EASD), Joint British Diabetes Societies for ment, complications during treatment, This presentation of diabetes has been re-
Inpatient Care (JBDS), American Association management in special populations, preferred to in the literature as atypical diabe-
of Clinical Endocrinology (AACE), and Dia- vention, and priority areas for future tes or ketosis-prone T2D (14,17).
betes Technology Society (DTS). research. Epidemiologic studies conducted in
At the beginning of the writing pro- the U.S. and Europe over the past de-
cess, all members of the expert panel Section 1. What Are Recent Global cade have revealed a concerning rise in
participated in a day-long virtual meet- Trends in Epidemiology and the rate of hyperglycemic emergencies
ing and agreed on the direction for this Outcomes? in adults with both T1D and T2D (4–6,
consensus report, the methodology and Nearly 1% of all hospitalizations in people 13,18–21). This represents a marked de-
rigor to be followed for this report, and with diabetes are for hyperglycemic parture from the previously observed
the established writing teams to author crises. However, estimates vary widely improvements seen between 2000 and
the various sections of the report. The among studies because of different popu- 2009 (6). During the first decade of the
writing group, with the help of a method- lations, settings, types of events captured, 21st century, reported incidence rates
ologist, conducted comprehensive litera- and methods of event ascertainment. In of DKA in adults with T1D in Europe,
ture searches in PubMed using medical a U.S.-based study, 38% of hospital admis- U.S., and Israel have varied between 0
subject headings to identify human studies sions for hyperglycemic crises were for and 56 events per 1,000 person-years,
published in English between 1 January DKA, 35% for HHS, and 27% for mixed although one study conducted in China
2009 and 1 June 2023. To identify contem- DKA/HHS (10). Most DKA events occur in between 2010 and 2012 reported an
porary evidence, they included information young adults aged 18–44 years (61.7%) outlying rate of 263 per 1,000 person-
from observational studies, randomized with T1D (70.6%), while HHS events are years (22). No population-level data are
controlled trials, and systematic reviews. more common among middle-aged adults available for HHS or mixed DKA/HHS ep-
Corresponding author: Guillermo E. Umpierrez, This article is being simultaneously published in research. Consensus reports undergo a formal
[email protected] Diabetes Care (https://doi.org/10.2337/dci24-0032) review process, including external peer review and
Received 28 March 2024 and accepted 29 and Diabetologia (https://doi.org/10.1007/s00125- review by the ADA Professional Practice Committee
March 2024 024-06183-8) by the ADA and the EASD. and ADA scientific team for publication.
This consensus report is fully endorsed by the A consensus report is a document on a particular © 2024 by the American Diabetes Association
American Diabetes Association (ADA), European topic that is authored by a technical expert panel and the European Association for the Study of
Association for the Study of Diabetes (EASD), under the auspices of ADA. The document does not Diabetes. Readers may use this article as long
American Association of Clinical Endocrinology reflect the official ADA position but rather as the work is properly cited, the use is
(AACE), Joint British Diabetes Societies for Inpatient represents the panel’s collective analysis, evaluation, educational and not for profit, and the work
Care (JBDS), and Diabetes Technology Society (DTS). and expert opinion. The primary objective of a is not altered. More information is available
consensus report is to provide clarity and insight on at https://www.diabetesjournals.org/journals/
This consensus report was reviewed and endorsed a medical or scientific matter related to diabetes for pages/license.
by the ADA Professional Practice Committee and which the evidence is contradictory, emerging, or
the EASD Committee on Clinical Affairs and incomplete. The report also aims to highlight
approved by the EASD Executive Board, AACE, evidence gaps and to propose avenues for future
JBDS Group, and DTS.
diabetesjournals.org/care Umpierrez and Associates 3
isodes, but some studies grouped all hy- to 1.04% in T2D (6,32). Inpatient mortal- is the most common precipitating factor for
perglycemic crises together, as it can be ity among people with T2D hospitalized DKA, occurring in 14–58% of cases (3,24).
challenging to reliably classify events us- for HHS decreased from 1.44% in 2008 Other acute conditions that may precipitate
ing administrative data such as hospital- to 0.77% in 2018 (20). Patients with DKA include stroke, alcohol and substance
ization databases that many studies rely mixed DKA/HHS have higher hospital use, pancreatitis, pulmonary embolism, myo-
on. Among people with T1D, most recent mortality than those with HHS (adjusted cardial infarction, and trauma (1,53–56).
data suggest hyperglycemic crisis rates of odds ratio [OR] 2.7; 95% CI 1.5–4.9) or The omission of insulin therapy, often
up to 44.5–82.6 per 1,000 person-years with DKA (adjusted OR 1.8; 95% CI in the setting of psychological and socio-
(5,21) and among people with T2D up to 0.9–3.6), with inpatient mortality rates of economic factors, is a major cause of
3.2 per 1,000 person-years (5). 8% for mixed DKA/HHS, 5% for HHS, and DKA, particularly among adults with T1D

A substantial proportion of individuals 3% for DKA (10). In Japan, inpatient mor- living in socioeconomically deprived areas
hospitalized with DKA experience recurrent tality has been reported as 3.3–5.7% in (1,24,48,54,57). A study assessing the clinical,
episodes (23), underscoring the importance DKA admissions, 13.2% in HHS, and 5.3% socioeconomic, and psychological factors
of engaging patients experiencing these in mixed DKA/HHS admissions (35,36). associated with DKA recurrence in urban pa-
events to identify triggers and prevent re- Mortality rates reported in low- and mid- tients from racial and ethnic minority back-
currence. In a U.S.-based study conducted dle-income countries are much higher, po- grounds found discontinuation of insulin
between 2006 and 2012 in Chicago, Illinois, tentially because of delayed diagnosis and therapy to account for more than two-thirds
21.6% of people hospitalized for DKA had treatment. Inpatient mortality in DKA ad- of all DKA admissions (48).
more than one episode over 6 years, with missions has ranged from 26% to 41.3% Factors associated with a higher risk
5.8% of individuals accounting for 26.3% of in sub-Saharan Africa (37), 30% in India of hyperglycemic crisis in people with
DKA hospitalizations (23). Similarly, analysis (37), and 23.6% in Pakistan (38). In Ja- T1D include younger age, prior history
of inpatient data from the U.K. in 2014 maica, inpatient mortality has been re- of hyperglycemic and hypoglycemic cri-
revealed that 33.7% of people admitted ported as 6.7% in DKA admissions, 20.3% ses, presence of kidney disease, neurop-
with DKA had at least one episode of DKA in HHS, and 25% in mixed DKA/HHS ad- athy, depression, smoking, alcohol and
in the prior year (24). In general, the all- missions (39). In Nigeria, inpatient mortal- substance abuse, high hemoglobin A1c
cause readmission rate after episodes of ity has been reported as 2.7% in DKA, (HbA1c), and social determinants of health
DKA or hyperglycemic crises in general 0.9% in HHS, and 3.6% in mixed DKA/HHS (SDOH) (1,6,7,16,55,58). In people with
ranges between 10% and 20%, with (40). T2D, risk factors include younger age, prior
40–65% of these readmissions being for People discharged after an episode of history of hyperglycemic or hypoglycemic
recurrent hyperglycemic crises (the remain- DKA have a 1-year age-corrected mortality crises, presence of comorbidities (both
der are for other causes, including occa- rate that is 13 times higher than the gen- diabetes-related and unrelated), and ele-
sionally for severe hypoglycemia), mostly eral population (41). This is more pro- vated HbA1c and SDOH (7,16,42,48). Mul-
occurring within 2 weeks of discharge from nounced among younger individuals (aged tiple studies have suggested that low
the prior DKA episode (25–27). 15–39 years), in whom the mortality rate is income, area-level deprivation, housing in-
49 times higher than the general popula- security, and lack of insurance or presence
Morbidity and Mortality tion (41). In the U.S., all-cause mortality of underinsurance (e.g., having a high de-
Hyperglycemic crises are associated with within 30 days of a hyperglycemic crisis is ductible health plan or Medicaid coverage
substantial morbidity, mortality, and costs 0.1% among patients with T1D and 2.0% in the U.S.) lead to increased risk of DKA
(28–31). In the U.S., the mean length of among patients with T2D (34). The 1-year and HHS (7,10,16,31,33,59,60), with ap-
stay for patients hospitalized with DKA is mortality rates were 0.9% and 9.5% in pa- proximately 40% of hyperglycemic crises
3.0 days among people with T1D and tients with T1D and T2D, respectively (34). occurring in lower-income and under-
3.7 days among people with T2D (32) Compared with patients with a single DKA served populations (13,61). Food inse-
and has been shortening over time (29). admission, those with 2–5 admissions have curity is also associated with triple the
In the U.K, the mean length of stay is a threefold higher risk of death, while those rate of DKA in youth and young adults
generally higher, at 5.6 days (28). In U.S.- with six or more admissions have a sixfold with T2D (62). In addition, SDOH and
based studies, hospital charges for DKA higher risk of death (42). Post-hospital mor- mental health conditions are the stron-
admissions have ranged from $21,215 to tality data for HHS are scarce, with one Ital- gest factors associated with recurrent
$36,600 per admission, are higher for in- ian study reporting a 30-day mortality rate DKA (23,25,31,42).
dividuals with T2D than for those with after HHS of 16% (43). People with diabetes who have a his-
T1D, and have been rising over time tory of DKA (compared with those with-
(25,29,31–33). In the U.K, costs of DKA Risk Factors out such a history) have been reported
admission were estimated at £2,064 per Between 6% and 21% of adults present to have a significantly higher prevalence
hospitalization (28). with DKA as their initial diagnosis of of mental health disorders such as de-
While DKA mortality appeared to be T1D (21,24,44). In adults with a known pression, diabetes distress, substance
decreasing in studies conducted between history of diabetes, the most common pre- abuse, psychoses, and bipolar disorder
2007 and 2014 (6,19,29), these improve- cipitating factors for DKA include infec- (63). Psychological comorbidities, includ-
ments have plateaued in the past decade tions, intercurrent illnesses, psychological ing eating disorders, have been reported
(4,21,34). Recent estimates reported an stress, and omission or insufficient use of in recurrent episodes of DKA in young
inpatient mortality during hospital admis- insulin therapy, as described in Table 1 women (64,65). Depression and psycho-
sion for DKA ranging from 0.20% in T1D (24,27,28,30,38,44–52). Worldwide, infection logical comorbidities have a correlation
Some drug classes can affect carbohy-

Table 1—Precipitating causes of DKA in adults by region
drate metabolism and precipitate the
Region New-onset diabetes Infection Insulin omission Other Unknown
development of DKA and HHS (82). Glu-
Australia 5.7 28.6 40 25.7 NR cocorticoids may precipitate acute and
Brazil 12.2 25 39 15 8.8 sustained hyperglycemia by countering
China NR 39.2 24 10.9 25.9
insulin action (83,84). Antipsychotic med-
ications may also raise DKA risk, although
Indonesia 3.3 58.3 13.3 17.1 8 the precise mechanism is uncertain (85).
South Korea NR 25.3 32.7 11.2 30.8 Approximately 1–2% of patients receiving
Nigeria NR 32.5 27.5 4.8 34.6 checkpoint inhibitors develop new-onset

autoimmune diabetes (86), characterized
Spain 12.8 33.2 30.7 23.3 NR
by rapid onset of hyperglycemia, swift
Syria NR 47.8 23.5 7.8 20.9 progression of endogenous insulin defi-
Taiwan 18.2 31.7 27.7 6.2 16.2 ciency, and a high risk of DKA or severe hy-
perglycemia if not detected and treated
U.K. 6.1 44.6 19.7 10.9 18.7
promptly with insulin therapy (87,88). A
U.S. 17.2–23.8 14.0–16.0 41.0–59.6 9.7–18.0 3.0–4.2 recent systematic review of 278 patients
Data are %. Adapted from Dhatariya et al. (3). NR, not reported. with checkpoint inhibitor–associated au-
toimmune diabetes reported that DKA
was present at diagnosis in 69.7%, while
with decreased blood glucose monitoring other studies have shown higher rates of hyperglycemia without acidosis was pre-
sent in the remainder (89).
and treatment engagement, which are as- DKA with insulin pumps in T1D (73,74). In
DKA risk is also increased with SGLT2
sociated with an increased risk of hospi- pump users presenting with DKA, the
inhibitors in adults with T1D (90,91) and
talization for hyperglycemic crises (66). In most common precipitating factors are
insulin-deficient T2D (92). SGLT2 inhibitor–
addition, observational studies have re- management error and underlying in-
associated DKA occurs in approximately
ported that people with T1D and a his- fection; these are more common precip-
4% of people with T1D; the risk can be
tory of DKA have an increased prevalence itating causes than device malfunction
5–17 times higher than in people with
of depression and risk of hospitalization (74). As insulin pumps increasingly be-
T1D not treated with SGLT2 inhibitors
for a suicide attempt, with the highest risk come integrated with continuous glu-
(90). In contrast, observational studies
of suicide attempt in the 12 months fol- cose monitoring (CGM) in automated
and randomized controlled trials have
lowing the DKA episode (67,68). Impor- insulin delivery systems, these systems shown that DKA is uncommon in people
tantly, the relationship between mental may be associated with less DKA and with T2D treated with SGLT2 inhibitors,
health conditions and hyperglycemic crises higher rates of attaining glycemic man- with an estimated incidence of 0.6–4.9
may be bidirectional, and all individuals agement goals (75–77); however, larger events per 1,000 patient-years (93). A
experiencing hyperglycemic crises should studies and real-world data are still meta-analysis of four randomized con-
be screened for mental health concerns. needed. trolled trials found the relative risk (RR) of
The Patient Health Questionnaire (PHQ-9) Several studies have reported DKA at DKA in participants with T2D treated
is the most used and validated screening the presentation of newly diagnosed T1D with SGLT2 inhibitors versus placebo or
test for depression in people with diabe- during or after a COVID-19 infection (9,78). active comparator arm to be 2.46 (95%
tes, with a high sensitivity and specificity The precise mechanisms for new-onset di- CI 1.16–5.21), while a meta-analysis of
(69). Importantly, symptoms associated abetes in people with COVID-19 are not five observational studies found the RR
with hyperglycemia may complicate known, but several complex interrelated to be 1.74 (95% CI 1.07–2.83) (94). Risk
screening because they may be mistaken processes may be involved, including de- factors for DKA in individuals with T2D
for symptoms of depression (e.g., fatigue, tection of previously undiagnosed diabe- treated with SGLT2 inhibitors include very-
hypersomnia, psychomotor slowing). In tes, stress hyperglycemia, steroid-induced low-carbohydrate diets and prolonged fast-
addition, screening for diabetes dis- ing, dehydration, excessive alcohol intake,
hyperglycemia, and direct or indirect ef-
tress is indicated using the T1-Diabetes and the presence of autoimmunity, in addi-
fects of severe acute respiratory syndrome
Distress Assessment System (T1-DDAS) tion to typical precipitating factors (94,95).
coronavirus 2 on the b-cell (8,9). Rates of
to assess the degree of emotional bur- Notably, in one series, 35% of people
DKA during the COVID-19 pandemic in-
den related to diagnosis and manage- treated with SGLT2 inhibitors presenting
creased primarily among individuals with
ment of diabetes, particularly T1D, that with DKA had glucose levels <200 mg/dL
can influence management behaviors newly diagnosed diabetes and preexisting
(11.1 mmol/L) (96), and in another series,
and clinical outcomes (70). T2D (79,80). While rates of DKA decreased 71% of people treated with SGLT2 inhibi-
Recent studies have shown mixed re- among people with preexisting T1D in tors presenting with DKA had glucose lev-
sults regarding the risk of DKA with insulin the U.K., they increased among people els #250 mg/dL (13.9 mmol/L) (97).
pump therapy. Some studies have shown with T1D in the U.S. (79,81). Older adults Volume depletion is a primary driver
improved glycemic goals and a reduced from racial and ethnic minority back- of HHS, which commonly occurs in
risk of both DKA and severe hypoglycemia grounds experienced the greatest rise in older adults with above-target glucose
in insulin pump users (71,72). However, DKA events (79,81). levels who are at particularly high risk
Infection/insufficient insulin administration/stress/medication
Absolute insulin deficiency Counterregulatory hormones Relative insulin deficiency
Glucose utilization Peripheral tissues Glucose utilization
Amino acids
A Lactate
Gluconeogenesis

Lipolysis FFA Glycerol Glycogenolysis
Ketone body
production
Glycosuria + osmotic diuresis

+ electrolyte loss
Hyperglycemia
Hyperketonemia
Impaired renal function
Volume depletion
Hyperosmolarity
Ketoacidosis
Additional contributors: Oxidative stress Inflammation
DKA HHS
Figure 1—Pathogenesis of DKA and HHS. FFA, free fatty acids.
for developing dehydration because of severe insulin deficiency and a rise in con- If fluid intake is not maintained, then this can
polyuria, age-related impairment of thirst centrations of counterregulatory hormones lead to a hyperosmolar state, renal impair-
mechanisms, and limited access to fluids (glucagon, cortisol, epinephrine, and growth ment, and, ultimately, a decline in cognitive
(7,98). Infection is the major precipitat- hormones) (1,3,7). The resulting changes in function. (Fig. 1)
ing factor in 30–60% of patients with the insulin/glucagon ratio lead to increased Hyperglycemia in people with hyper-
HHS, with urinary tract infections and gluconeogenesis, accelerated glycogenolysis, glycemic crises is associated with a se-
pneumonia being the most common and impaired glucose utilization by peripheral vere inflammatory state characterized by
(99). Other common precipitating causes tissues. The combination of insulin deficiency an elevation of proinflammatory cyto-
of HHS include acute cerebrovascular and increased counterregulatory hormones kines (tumor necrosis factor-a and inter-
events, acute myocardial infarction, sur- results in the release of free fatty acids from leukin-1, -6, and -8), C-reactive protein,
gery, acute pancreatitis, and the use of adipose tissues (lipolysis), leading to unre- reactive oxygen species, and lipid peroxi-
drugs that affect carbohydrate metabo- strained hepatic fatty acid oxidation and the dation biomarkers even in the absence
lism by decreasing insulin release or production of excess ketone bodies with re- of obvious infection or cardiovascular pa-
activity. These include corticosteroids, sulting ketonemia and metabolic acidosis (3). thology (100). All these measurements
sympathomimetic agents, and antipsy- In HHS, compared with DKA, there is return to near-normal values within 24 h
chotic drugs (1,99). less severe insulin deficiency and, there- following correction of hyperglycemia
fore, sufficient insulin to prevent keto- with insulin therapy and hydration.
Section 2. What Is the Pathogenesis genesis but not enough to prevent hy-
of Hyperglycemic Crises? perglycemia, due to increased hepatic glu- Section 3. What Are the Diagnostic
The key difference between DKA and cose production and decreased glucose Criteria of DKA and HHS?
HHS is the degree of insulin insufficiency. utilization by peripheral tissues. Hypergly- Diagnostic Criteria for DKA
The pathogenesis of these two diseases is cemia leads to an osmotic diuresis, leading The diagnosis of DKA should be based on
presented in Fig. 1. DKA is characterized by to volume depletion and hemoconcentration. the three criteria described in Fig. 2A. All
A. DKA Diagnostic Criteria

Diabetes/hyperglycemia Glucose ≥200 mg/dL (11.1 mmol/L) OR prior history of diabetes
DKA
Ketosis β-Hydroxybutyrate concentration ≥3.0 mmol/L OR urine ketone strip 2+ or greater
Metabolic Acidosis pH <7.3 and/or bicarbonate concentration <18 mmol/L

B. HHS Diagnostic Criteria
Hyperglycemia Plasma glucose ≥600 mg/dL (33.3 mmol/L)
Calculated effective serum osmolality >300 mOsm/kg (calculated as [2xNa+

HHS
Hyperosmolarity (mmol/L) + glucose (mmol/L)]), OR total serum osmolality >320 mOsm/kg [(2xNa+
(mmol/L) + glucose (mmol/L) + urea (mmol/L)]
AbSence of significant ketonemia β-Hydroxybutyrate concentration <3.0 mmol/L OR urine ketone strip less than 2+
Absence of acidosis pH ≥7.3 and bicarbonate concentration ≥15 mmol/L

Figure 2—The diagnosis criteria of DKA (A) and HHS (B).
three components must be present to by the nitroprusside reaction in urine or reduce the time for assessment, duration
make this diagnosis. In this consensus re- serum, which measures acetoacetic acid of admission, and time to recovery from
port, we have defined hyperglycemia as a (but not b-hydroxybutyrate, the main ke- DKA (2,12,110). A systematic review of
diagnostic criterion for DKA from >250 toacid produced in DKA), or quantitatively nine studies on the accuracy of capillary b-
mg/dL (13.9 mmol/L) to either a glucose by direct measurement of b-hydroxybuty- hydroxybutyrate measurement for identi-
value of $200 mg/dL (11.1 mmol/L) or a rate in blood from capillary point-of-care fying DKA, compared with multiple other
prior history of diabetes irrespective of the testing (POCT) or in the hospital labora- analytical and clinical tests, reported high
presenting glucose value. Hyperglycemia tory (3). Both types of ketones have simi- sensitivity, specificity, and positive and
and/or diabetes must be accompanied by lar diagnostic sensitivity, but measuring negative predictive values (111). However,
two additional criteria—elevated ketones b-hydroxybutyrate in blood is more spe- there is concern about how accurate POCT
and metabolic acidosis—for the diagnosis cific for detecting DKA than measuring instruments are compared with laboratory
of DKA to be established. Although hyper- acetoacetate in urine (108). instruments for measuring b-hydroxybuty-
glycemia remains a key diagnostic criterion Reliance on urine ketone testing can rate levels $5 mmol/L (108,112).
of DKA, a wide range of plasma glucose underestimate the severity of ketone- Most people with DKA present with a
concentrations can be present on admis- mia early in the course of DKA because high anion gap metabolic acidosis. The
sion. Approximately 10% of patients with of a lag in the formation of acetoace- anion gap is calculated by subtracting
DKA present with euglycemic DKA, which tate, and conversely overestimate its se- the major measured anions (chloride
is defined as plasma glucose levels <200 verity later in the course of DKA when and bicarbonate) from the major mea-
mg/dL [11.1 mmol/L] in the presence of b-hydroxybutyrate is being cleared and sured cation (sodium). An anion gap
ketosis and metabolic acidosis criteria of converted into acetoacetate (3). In addi- >12 mmol/L indicates the presence of
DKA described in Fig. 2 (91,101,102). Eu- tion, several sulfhydryl drugs (e.g., capto- a high anion gap metabolic acidosis consis-
glycemic DKA can be caused by a variety pril) and medications such as valproate tent with DKA. However, mixed acid-base
of factors, including exogenous insulin in- can give false-positive nitroprusside urine disorders are present in about one-third of
jection, reduced food intake, pregnancy, tests (109). Thus, for diagnosis and moni- those presenting with DKA because of hy-
or impaired gluconeogenesis due to alco- toring of the response to therapy, we rec- perglycemia-induced osmotic diuresis and
hol use, liver failure, and/or SGLT2 inhibi- ommend direct measurement of venous natriuresis, nausea and vomiting leading to
tor therapy (103,104). In recent years, the or capillary b-hydroxybutyrate, which is volume contraction and metabolic alkalosis,
use of SGLT2 inhibitors in those with T1D the main ketoacid in DKA (3,108). Blood and a compensatory respiratory alkalosis
and T2D has accounted for the majority of concentrations of b-hydroxybutyrate $3.0 caused by hyperventilation due to rapid
cases of euglycemic DKA (105–107). In recog- mmol/L correlate well with acid-base and/or deep breathing (Kussmaul breathing)
nition of the wider range of glucose levels at changes, with >90% sensitivity and specif- (113,114). In addition, hyperchloremic nor-
presentation with DKA, the criteria for diag- icity for the diagnosis of DKA (1,2,12). mal anion gap acidosis is commonly seen
nosis of DKA have been changed to encom- b-Hydroxybutyrate measurement can be following successful treatment of DKA and
pass a lower glucose value of >200 mg/dL performed on serum samples using labora- may delay transition back to subcutaneous
(11.1 mmol/L) and a prior history of diabetes tory analysis or capillary blood samples us- insulin if mistaken for persistent DKA
(irrespective of the glucose level) (2). ing handheld POCT meters with similar (7,115). Although the anion gap is not rec-
The key diagnostic feature in DKA is precision in quantifying b-hydroxybutyrate ommended as a first-line diagnostic or res-
the elevation of the circulating total ketone (3,108). Compared with a laboratory mea- olution criterion for these reasons, it may
body concentration. Assessment of ketone- surement, the convenience of testing still have some utility in resource settings
mia can be performed semiquantitatively and rapidity of results from POCT can where ketone measurement is unavailable.
Table 2—DKA classification and suggested level of care by severity: mild, moderate, or severe
Mild DKA Moderate DKA Severe DKA
“D”: history of diabetes or Glucose $200 mg/dL (11.1 mmol/L) Glucose $200 mg/dL (11.1 mmol/L) Glucose $200 mg/dL (11.1 mmol/L)
elevated glucose level
“K”: ketonemia b-Hydroxybutyrate 3.0–6.0 mmol/L b-Hydroxybutyrate 3.0–6.0 mmol/L b-Hydroxybutyrate >6.0 mmol/L
“A”: acidosis pH >7.25 to <7.30 or pH 7.0–7.25 pH <7.0
bicarbonate 15–18 mmol/L Bicarbonate 10 to <15 mmol/L Bicarbonate <10 mmol/L
Mental status Alert Alert/drowsy Stupor/coma
Suggested level of care Regular or observation nursing unit Step-down unit or Intensive care unit

intermediate care unit
Not all variables need to be fulfilled to be defined as either mild, moderate, or severe, and the admission site and level of care are ultimately
a clinical decision.
The severity of DKA is classified as Clinical overlap between DKA and pain are common in DKA (>50%) but are
mild, moderate, or severe based on the HHS has been reported in more than uncommon in HHS (118). Caution is needed
magnitude of metabolic acidosis (blood one-third of people with hyperglycemic with patients who present with abdominal
pH, serum bicarbonate, and ketone lev- crises (50). Although most people with pain because the symptoms could be either
els) and the presence of altered mental HHS have an admission pH $7.30 and a a result of the DKA or an indication of a
status, as presented in Table 2 (12). This bicarbonate level $18 mmol/L, mild ke- precipitating cause of DKA, particularly in
categorization may be clinically useful for tonemia may be present. the absence of severe metabolic acidosis.
guiding the location where an individual is Further clinical evaluation is necessary if
Clinical Presentation of DKA and HHS this complaint is not resolved with the
assigned to receive care (e.g., emergency
Figure 3 illustrates common clinical fea- resolution of dehydration and metabolic
department, intensive care unit [ICU], or
tures in individuals admitted with DKA acidosis.
step-down unit) and for identifying patients
and HHS. In DKA, the time between ini- If DKA or HHS is suspected, initial
with mild DKA who are candidates for sub- tial symptoms and acute presentation samples should be taken for glucose, se-
cutaneous insulin dosing rather than intra- may be hours to a few days, whereas rum electrolytes, venous blood gases,
venous insulin infusion (116). However, not with HHS, it may take days or weeks to complete blood count, and blood or
all variables need to be fulfilled to be de- develop. Both conditions may present urine ketone levels. Volume status can
fined as either mild, moderate, or severe, with polyuria, polydipsia, weight loss, be assessed with vital sign parameters.
and the admission site and level of care vomiting, dehydration, and change in Tachycardia and hypotension correlate
are ultimately a clinical decision. cognitive state. The respiratory compen- with severe hypovolemia. However, some
sation for metabolic acidosis found in patients can maintain hemodynamic sta-
Diagnostic Criteria for HHS DKA is manifest by Kussmaul breathing, bility and intravascular volume because of
HHS is a state of significant hyperglyce- which consists of deep breaths with a the hypertonicity associated with hypergly-
mia and hyperosmolality in the absence fruity odor smell because of the presence cemia and the subsequent movement of
of severe ketonemia and metabolic aci- of acetone (a breakdown product of the intracellular water into the extracellu-
dosis. The diagnosis of HHS should be ketone acetoacetic acid) in the breath. lar space. Patients should be examined
based on the four criteria presented in Changes in cognitive state are usually pre- for signs of infection, ischemia, and other
Fig. 2B. All four components must be sent in patients with severe DKA and potential precipitants of a hyperglycemic
present to make the diagnosis (12,117). HHS. Nausea, vomiting, and abdominal crisis. In addition, an electrocardiogram
DKA HHS
Develops over hours to days Develops over days to a week
Usually alert Change in cognitive state common
Polyuria, polydipsia, weight loss, and dehydration
Nausea, vomiting, and abdominal pain Often co-presenting with other acute illness
Kussmaul respiration
1/3 of hyperglycemic emergencies have a hybrid DKA/HHS presentation
Figure 3—Clinical presentation in patients with DKA and HHS.

should be performed to assess for evi- increased counterregulatory hormones, and nursing units have not demonstrated clear
dence of biochemically induced repolariza- loss of fluid and electrolytes. The manage- differences in mortality rate, length of hos-
tion abnormalities, such as peaked T waves ment of DKA and HHS includes the admin- pital stay, or time to resolution of ketoacido-
from hyperkalemia and ischemia. istration of intravenous fluids, insulin, and sis. ICU admission in people with mild DKA
It is important to consider the differen- electrolytes as well as identification and has also been associated with more labora-
tial diagnosis of elevated ketones, including treatment of the precipitating cause. Capil- tory testing and higher hospitalization costs
starvation ketosis, alcoholic ketoacidosis, lary blood glucose testing should be per- (122,123). In contrast, individuals with se-
and ketosis of pregnancy and hyperemesis formed during treatment every 1–2 h using vere DKA or HHS, or those with critical ill-
(3). The diagnosis of starvation ketosis is a hospital-calibrated glucose meter, and ness as the precipitating cause (e.g.,
suggested by a history of dietary intake blood should be drawn every 4 h for deter- myocardial infarction, gastrointestinal

of <2,090 kJ/day (500 kcal/day), which mination of electrolytes, phosphate, creati- bleeding, sepsis) or with altered mental
is associated with low insulin concentra- nine, b-hydroxybutyrate, and venous pH status (1,3,12,124) should be treated in
tions, leading to ketone production. Peo- until resolution of DKA. In patients with the ICU, as outlined in Table 2.
ple with chronic ethanol use with a HHS, in addition to measuring glucose, cre-
recent binge culminating in vomiting and atinine, and electrolytes, serum osmolarity Fluid Therapy
acute starvation may develop ketoacidosis should be measured every 4 h. Treatment Initial intravenous fluid resuscitation re-
with or without hyperglycemia (119,120). pathways for DKA and HHS emphasizing in- stores the effective circulating intravascular
The vomiting of hyperemesis gravidarum travenous fluids, short-acting insulin, and volume, increases tissue/organ perfusion
leads to excess counterregulatory hor- potassium are illustrated in Fig. 4. (which decreases lactate formation), im-
mone concentrations, also predisposing to Most people with uncomplicated mild proves renal perfusion (which promotes re-
ketone formation. or moderate DKA can be treated in the nal excretion of glucose and ketone bodies),
emergency department or a step-down corrects electrolyte deficits, and decreases
Section 4. What Is the Recommended unit if close nursing supervision and mon- plasma osmolarity. In addition, correction
Treatment of DKA and HHS? itoring are available (121). In such pa- of a fluid deficit improves insulin sensitivity
DKA and HHS have a similar underlying tients, several comparisons of treating DKA by reducing counterregulatory hormone
pathogenesis consisting of insulin deficiency, in the ICU versus step-down and general concentrations (7,12). Mean plasma glucose
I.V. Fluids Insulin Potassium
Moderate or Establish adequate renal function

Mild DKA HHS
severe DKA (urine output ~ 0.5 mL/kg/h)
Determine hydration status
s.c. insulin i.v. insulin i.v. insulin K+ <3.5 mmol/L
Severe Consider 10–20 mmol/L/h

Cardiac Start
Mild hypovolemia 0.1 units/kg short-acting until K+ >3.5
hypovolemia compromise 0.1 units/kg 0.05 units/kg/h
insulin as i.v. bolus mmol/L (faster K+
rapid-acting insulin short-acting insulin
if there is a delay replacement will
analog as s.c. bolus as fixed-rate i.v.
in setting up the require central
insulin infusion†
infusion venous access)
0.9% NaCl or Hemodynamic
other crystalloid monitoring/
K+ = 3.5–5.0 mmol/L
(1.0 L/h) pressors 0.1 units/kg 0.1 units/kg/h
rapid-acting insulin short-acting insulin
analog every 1 h or i.v. fixed-rate i.v. Give 10–20 mmol/L
0.2 units/kg every 2 h insulin infusion K+ in each
liter of i.v. fluid as
needed to keep
When glucose reaches <250 mg/dL, reduce short-acting insulin dose serum K+ between
0.9% NaCl or other crystalloid at a clinically appropriate rate aiming to 0.05 units/kg/h i.v. (or 0.05 units/kg/h or 0.1 units/kg every 4 and 5 mmol/L
to replace 50% of the estimated fluid deficit in the first 8–12 h 2 h s.c. in "mild" DKA)
K+ >5.0 mmol/L
When glucose reaches <250 mg/dL, add 5% or 10% dextrose to the
DKA HHS
0.9% NaCI/crystalloid Start insulin, but
Keep glucose between 150 and Target glucose to between 200
In euglycemic DKA (glucose <200 mg/dL and positive BOHB), 5% or do not give K+;
200 mg/dL until resolution* and 250 mg/dL until resolution*
10% dextrose needs to be started alongside 0.9% NaCl/crystalloid check serum
at the start of the insulin treatment K+ every 2 h
Check electrolytes, renal function, venous pH, osmolality, and glucose every 2–4 h until stable. After resolution of DKA or HHS and when patient is able to eat and drink, initiate s.c. multidose insulin
regimen. To transfer from i.v. to maintenance s.c. insulin, continue i.v. insulin infusion for 1–2 h after s.c. insulin. See Fig. 5 for guidance.
†
Some have recommended that insulin be withheld until glucose has stopped dropping with fluid
administration alone; see text. 150 mg/dL = 8.3 mmol/L Bicarbonate should only be considered if pH is <7.0
* Definitions of resolution (use clinical judgment and do not delay discharge or level of care if these are
not met): 200 mg/dL = 11.0 mmol/L Phosphate should not be given unless
› DKA: Venous pH >7.3 or bicarbonate >18 mmol/L and plasma/capillary ketones <0.6 mmol/L 250 mg/dL = 13.9 mmol/L there is muscle weakness, respiratory
› HHS: Calculated serum osmolality falls to <300 mOsm/kg and urine output is >0.5 mL/kg/h and
glucose is <250 mg/dL 300 mg/dL = 16.6 mmol/L compromise, and a phosphate <1.0 mmol/L
Figure 4—Treatment pathways for DKA and HHS. BOHB, b-hydroxybutyrate.

concentrations have been reported to drop In patients with HHS, the usual time to intravenous insulin infusion (12). Once
by approximately 50–70 mg/dL/h resolve hyperglycemia is between 8 and the blood glucose falls below 250 mg/dL
(2.8–3.9 mmol/L/h) solely in response to in- 10 h and the decline should not exceed (13.9 mmol/L), 5–10% dextrose should
travenous fluid administration in the ab- 90–120 mg/dL/h (5–6.7 mmol/L/h) to be added to the 0.9% saline infusion
sence of insulin (2). This rate of decrease prevent cerebral edema. Similarly, the and the insulin infusion rate should be
may be even more pronounced in HHS. rate of decline of serum sodium should reduced to 0.05 units/kg/h. Thereafter,
The fluid choice for initial resuscitation not exceed 10 mmol/L in 24 h and the intravenous insulin infusion should be
should be determined by local availabil- rate of fall in osmolality should be no adjusted to maintain glucose levels at
ity, cost, and resources. Most clinical greater than 3.0–8.0 mOsm/kg/h to min- approximately 200 mg/dL (11.1 mmol/L)
guidelines recommend the administra- imize the risk of neurological complica- and continued until the ketoacidosis is
tions (117). Initial fluid replacement will

tion of isotonic saline (0.9% sodium chlo- resolved (1–3).
ride solution) as the initial resuscitation lower the glucose concentration and os- In people on basal or basal-bolus insu-
fluid because of its widespread availability, molality, causing a shift of water into the lin therapy before admission, this regi-
lower cost, and efficacy in restoring circu- intracellular space, which may result in a men can be continued at the usual dose
lating volume in clinical studies (2,12). rise in serum sodium (a reduction of 100 and adjusted as needed. In those newly
While effective, its use in large volumes mg/dL [5.6 mmol/L] of glucose will result diagnosed, multidose insulin regimens with
may be associated with hyperchloremic in a 1.6 mmol/L rise in sodium concen- basal and prandial rapid-acting insulin ana-
normal anion gap metabolic acidosis and tration). The initial rise in serum sodium logs should be started after the resolution
prolonged length of ICU and hospital stay is not an indication to give hypotonic of DKA (1,12). Long-acting basal insu-
(125). Recent prospective and observa- fluids, and the administration of 0.45% lin should be initiated subcutaneously
tional studies and meta-analyses have re- sodium chloride is indicated only if osmo- at 0.15–0.3 units/kg. This medication
ported that the administration of balanced lality is not declining despite adequate posi- may be administered once daily or di-
crystalloid solutions (e.g., Ringer’s lactate tive fluid balance and appropriate insulin vided equally and administered twice
or plasmalyte-148), compared with the ad- administration. Some have recommended daily. Rapid-acting insulin is added as
ministration of the isotonic saline solution, that insulin be withheld until glucose has needed, depending on nutritional intake
results in faster DKA resolution (125–129), stopped dropping, with initial fluid adminis- and glucose levels.
shorter hospital length of stay, and less tration alone to prevent a rapid fall in os- The administration of basal insulin
frequent development of hyperchlore- molality (117). while on fixed-rate intravenous insulin
mic metabolic acidosis. Older adults with DKA or HHS, as infusion is advocated by many clinicians
In adults with DKA or HHS without re- well as individuals with heart failure or but avoided by others because of the
nal or cardiac compromise, we recom- end-stage kidney disease on dialysis, should risk of hypoglycemia (134) or hypokale-
mend starting the administration of be treated cautiously with smaller boluses mia (135). Several studies have reported
isotonic saline or balanced crystalloid of isotonic or crystalloid solutions (e.g., that the coadministration of a low dose
solutions at an initial rate of 500–1,000 250 mL boluses) and should undergo fre- (0.15–0.3 units/kg) of basal insulin dur-
mL/h during the first 2–4 h. After resto- quent assessment of hemodynamic status ing insulin infusion reduces time to DKA
ration of intravascular volume, the sub- (131). In such patients, the use of a stan- resolution, duration of insulin infusion
dard fluid replacement protocol may be (136,137), and length of hospital stay
sequent choice for fluid replacement
associated with treatment-related compli- (136) and prevents rebound hyperglyce-
depends on the state of hydration as-
cations, including volume overload, need mia, all without increased risk of hypo-
sessed by blood pressure, heart rate,
for mechanical ventilation, and longer glycemia (136,138,139).
fluid input-output balance, and sodium
length of stay (131). Patients with uncomplicated mild or
concentration. Fluid replacement should moderate DKA may be treated with sub-
correct estimated deficits within the Insulin cutaneous rapid-acting insulin analogs
first 24–48 h. However, caution should Insulin therapy is the cornerstone of DKA (130,138,140). Several randomized studies
be used when rapidly replacing fluids in management and should be started as and a meta-analysis have reported that
those at high risk of fluid overload, in- soon as possible after diagnosis. Short- the administration of subcutaneous rapid-
cluding older adults, pregnant individu- acting insulin administered intravenously acting insulin analogs every 1–2 h is an ef-
als, and people with heart or kidney by continuous infusion is the preferred fective alternative to intravenous infusion
disease or other serious comorbidities. choice. Depending on the severity of of short-acting insulin for people with mild
In patients with DKA, plasma glu- the condition and the available facilities, or moderate DKA (138,141,142). This treat-
cose concentrations usually decrease to this should be done using a fixed-rate ment can be delivered in emergency de-
<250 mg/dL (13.9 mmol/L) within 4– intravenous insulin infusion started at partments and step-down units without
8 h, which is before ketoacidosis resolves 0.1 units/kg/h (1–3,12,132) or by a nurse- the need for ICU care. A 2016 Cochrane
(130). Thus, once the plasma glucose con- driven insulin infusion protocol with a review suggested that there were neither
centration is <250 mg/dL (13.9 mmol/L), variable rate for DKA (133). In adults, advantages nor disadvantages to using
replacement fluids should be modified to treatment protocols recommend the subcutaneous insulin over intravenous in-
contain 5–10% dextrose in addition to the initial administration of an insulin bolus sulin when treating mild or moderate DKA
0.9% sodium chloride to prevent hypoglyce- (0.1 units/kg) (intravenously or intramuscu- (138). Intramuscular rapid-acting insulin is
mia and allow continued insulin administra- larly) if a delay in obtaining venous access also effective for treating DKA, but this
tion until the ketonemia is corrected (7,12). is anticipated to be followed by fixed-rate route is more painful than subcutaneous
injection and might increase the risk of using 0.5–0.6 units/kg/day in insulin-naive Insulin therapy, correction of acidosis,
bleeding for patients receiving anticoagu- patients, with the understanding that volume expansion, and increased kaliu-
lation therapy (1,143). The use of rapid- body composition and/or insulin resis- resis decrease serum potassium. Within
acting subcutaneous insulin analogs is tance may impact this estimate (7,12). 48 h of admission, potassium levels typi-
not recommended for the treatment of Similarly, for people with risk factors for cally decline by 1–2 mmol/L during treat-
severe and complicated DKA or with hypoglycemia, including kidney failure or ment of DKA, HHS, and mixed DKA/HHS
HHS. frailty, a calculation using approximately (24). To prevent hypokalemia, potassium
Few studies have assessed the optimal 0.3 units/kg/day may be more appropri- replacement should be started after serum
insulin regimen in HHS. If the individual ate. Second, consideration of the pread- levels fall below 5.0 mmol/L to maintain
is already being treated with basal insu- mission outpatient insulin regimen and a potassium level of 4–5 mmol/L (2,12).

lin, it should be continued at the usual HbA1c levels may help guide transition For most patients with DKA, 20–30 mmol
dose and adjusted as needed. If HHS is dosing needs. However, it is necessary to of potassium per liter of intravenous fluid
present with no ketosis or with mild or understand how medication-taking behav- is sufficient to maintain a serum potas-
moderate ketonemia (blood b-hydroxy- iors and dietary factors may have influ- sium concentration within the target range.
butyrate $1.0 to <3.0 mmol/L or urine enced outpatient insulin dosing re- Low-normal or low potassium levels (<3.5
ketones <21) and without acidosis commendations. Finally, TDD may be mmol/L) are present on admission in
(pH $7.3 and bicarbonate $18 mmol/L), calculated by considering the hourly intra- 5–10% of patients with DKA (147); in such
then a fixed-rate intravenous insulin infu- venous insulin infusion rate requirements, cases, potassium replacement should begin
sion should be started at 0.05 units/kg/h. but with caution given the potential varia- at a rate of 10 mmol/h, and insulin therapy
If significant ketonemia is present (i.e., tion in insulin needs based on factors should be delayed until the potassium level
b-hydroxybutyrate $3.0 mmol/L, keto- such as glucotoxicity, duration of treat- increases to >3.5 mmol/L to avoid life-
nuria $21, pH <7.30, or bicarbonate ment with intravenous insulin, concurrent threatening arrhythmias and respiratory
<18 mmol/L), which represents mixed dextrose infusion, medications associated muscle weakness (147). Severe hypokale-
DKA/HHS, then a fixed-rate intravenous with hyperglycemia, and nutritional intake mia #2.5 mmol/L during treatment of DKA
insulin infusion should be started at (144). Once a TDD estimate has been de- and HHS has been reported to be associ-
0.1 units/kg/h (117). termined, a multidose insulin regimen ated with a threefold increase in mortality
should be started, with basal insulin initi- (10). To avoid hypokalemia, we recom-
Transition to Maintenance Insulin Therapy ated at least 1–2 h before cessation of mend measuring serum potassium 2 h after
In the hospital, patients with DKA will intravenous insulin infusion. Although first- starting insulin administration and every
eventually transition from intravenous generation basal analogs and NPH insulin 4 h thereafter until the resolution of DKA.
to subcutaneous insulin, as illustrated in are frequently administered once a day, Use of too low or too high doses of potas-
Fig. 5. To prevent the recurrence of hy- greater flexibility and better coverage of sium compared with the recommended
perglycemia or ketoacidosis during the basal insulin needs may be obtained if potassium replacement protocols in the
transition period to subcutaneous insu- they are administered twice daily. The use management of DKA has been associated
lin, it is important to allow an overlap of a basal-bolus insulin regimen with basal with longer hospital stays (148).
of 1–2 h between the administration of and rapid-acting insulin analogs has
subcutaneous insulin and the discontin- been proposed as a more physiologic Bicarbonate
uation of intravenous insulin. Patients regimen and has been reported to re- Routine bicarbonate administration is not
with known diabetes may be given insu- duce the rate of hypoglycemia after recommended. Intravenous fluid resusci-
lin at the dosage they were receiving transition from intravenous to subcuta- tation and insulin administration are usu-
before the admission. If there is concern neous insulin after resolution of DKA ally sufficient to resolve the metabolic
for inadequate baseline insulin therapy compared with human (i.e., short-acting acidosis of DKA (24,149). Several obser-
(i.e., high HbA1c) or any potentially pre- and NPH) insulins (130). Human insulin vational and randomized studies have re-
cipitating drug as a contributing factor regimens may also be used, but proper ported that bicarbonate administration in
to the DKA or HHS event, then the dosing should ensure 24-h insulin cover- DKA offers no advantage in improving
treatment regimen should be changed age. There are no current studies on cardiac or neurologic outcomes or in the
at discharge and not deferred to outpa- transitioning to ultra-long-acting insulin rate of recovery of hyperglycemia and ke-
tient follow-up (1,3,12). (e.g., degludec, glargine U300). toacidosis (3,12). In addition, potential
To transition from intravenous to sub- detrimental effects of bicarbonate ther-
cutaneous insulin therapy, an estimation Potassium apy have been reported, such as an in-
of the total daily insulin requirement is Despite experiencing a total-body potas- creased risk of hypokalemia, decreased
needed. This estimated total daily dose sium depletion of 3–6 mmol/kg due to tissue oxygen uptake, cerebral edema,
(TDD) of insulin may be calculated using long-standing osmotic diuresis, emesis, and development of paradoxical central
several methods based on weight, pre- and hyperaldosteronism (7), most pa- nervous system acidosis (3). However,
admission insulin regimen, or intravenous tients with DKA present with normal or because severe metabolic acidosis may
insulin requirements. However, each of high serum potassium levels (10,145). lead to adverse vascular effects, bicar-
these methods has limitations that must This is because metabolic acidosis and bonate administration should be considered
be considered when assessing overall in- insulin deficiency cause the movement if the acidosis is severe (i.e., pH <7.0)
sulin needs. First, a weight-based formula of potassium from the intracellular to (146,150). If indicated, then 100 mmol of so-
may be considered for TDD calculation the extracellular compartment (146). dium bicarbonate (8.4% solution) in 400 mL
GENERAL POINTS › Is there an excess risk of hypoglycemia that may warrant insulin dose reductions? (e.g., reduced renal function, frailty, older age)
› What is the current and anticipated nutritional intake?
› What is the amount of intravenous dextrose infusion?
› Is there concurrent use of subcutaneous basal insulin during intravenous insulin infusion?
OPTIONS FOR Conversion from intravenous to subcutaneous insulin dosing may be guided by any of the following methods*:
CALCULATING
SUBCUTANEOUS
Weight-based Estimates: Preadmission Insulin Requirements: Hourly Intravenous Insulin Requirements:
INSULIN TDD
› 0.5–0.6 units/kg/day for TDD › Consider TDD of insulin regimen prescribed › Summation of stable hourly intravenous
› 0.3 units/kg/day for those with risk for outpatient use prior to admission insulin requirements may help estimate
factors for hypoglycemia (e.g., frailty, › Consider potential impact of outpatient TDD (e.g., the prior 6 h)

chronic kidney disease) glycemic management, medication- › Caution as TDD may be overestimated
taking behavior, and nutritional habits because of glucotoxicity
*Each of these approaches has limitations. The evidence base for some of these approaches is weak, but these recommendations are based on clinical experience.
GENERAL PRINCIPLES › Start subcutaneous insulin 1-2 h prior to discontinuing intavenous insulin infusion
› Ensure insulin regimen provides 24-h coverage
» Basal and rapid-acting insulin analogs preferred (once or twice daily basal insulin + mealtime rapid-acting insulin)
» Human NPH and short-acting insulin formulations may be used; ensure regimen provides 24-h coverage
» Begin with 40–60% of TDD given as basal insulin + remaining proportion divided into three mealtime doses of rapid-acting insulin
» If NPO, give basal insulin + corrective dosing of rapid-acting insulin every 4-6 h
NON-INSULIN AGENTS › Do not initiate or continue SGLT2 inhibitor treatment during hospitalization
› Non-insulin agents are not recommended in T1D
› Other non-insulin agents may be considered for use with insulin in T2D or ketosis-prone T2D during hospitalization or at discharge
DISCHARGE PLANS › Basal-bolus regimen is recommended; 24-h insulin coverage should be ensured
› Discharge dosing recommendations may differ from transition dosing due to anticipated dietary changes or hypoglycemia risk
› Discharge plans should include scheduling of timely follow-up for review of insulin requirements and potential addition of non-insulin agents when appropriate
Figure 5—Transition to maintenance insulin administration in DKA. Calculation of the transition subcutaneous dose should account for hypoglyce-
mia risk factors and anticipated nutritional intake. Estimates can be made using a weight-based calculation or in those already on insulin, the pre-
admission insulin dose. Basal-bolus insulin is the preferred regimen and should be started 1–2 h before cessation of intravenous insulin. At
discharge, dosing of basal-bolus insulin may change again considering hypoglycemia risk. Follow-up plans should be in place to provide necessary
support and training at discharge.
of sterile water (an isotonic solution) can be recommend a similar approach to phos- cognitive status has improved, and the
given every 2 h to achieve a pH >7.0 (12). phorus replacement. blood glucose is <250 mg/dL (13.9 mmol/L)
(12,117).
Phosphate Criteria for Resolution of DKA and HHS
In DKA, there is a shift of phosphate from Resolution of DKA is defined as achieving
intracellular to extracellular fluid, with plasma ketone <0.6 mmol/L and venous Section 5. What Are Complications
During Treatment?
an excess urinary phosphate loss leading pH $7.3 or bicarbonate $18 mmol/L (2).
Table 3 describes current evidence, risks,
to hypophosphatemia (151). Whole-body Ideally, the blood glucose concentration
and mitigation strategies of the most im-
losses can be up to 1.0 mmol/kg; however, should also be <200 mg/dL (11.1 mmol/L).
portant complications of treating acute
unless there is evidence of muscle weak- The anion gap should not be used as a cri-
hyperglycemic crises in adults, including
ness, such as respiratory or cardiac com- terion, as it may be misleading because
hypoglycemia, hypokalemia, normal an-
promise with the phosphate <1.0 mmol/L, of the presence of hyperchloremic meta-
ion gap metabolic acidosis, thrombosis,
routine administration of phosphate is not bolic acidosis caused by large volumes of
cerebral edema, osmotic demyelination
indicated. Several prospective randomized 0.9% sodium chloride solution. Because
syndrome, and acute kidney injury.
studies have failed to show any beneficial b-hydroxybutyrate is converted into ace-
effect of phosphate replacement on the toacetate as the acidosis improves, uri-
clinical outcome of DKA (3,152), and ex- nary ketone measurement should be Section 6. What Are the
cessively rapid phosphate replacement avoided as a criterion of DKA resolution. Recommended Management
may precipitate hypocalcemia (152). While there is no consensus on the def- Strategies for Special Populations?
When necessary, 20–30 mmol of potas- inition for resolution of HHS, we consider Table 4 highlights some important con-
sium phosphate can be added to re- HHS to be resolved when the measured siderations regarding DKA and HHS in
placement fluids. There is scarce data on or calculated serum osmolality falls to special populations. These conditions or
phosphate deficiency or the effects of <300 mOsm/kg, hyperglycemia has been scenarios include frail older adults, indi-
phosphate replacement in HHS, so we corrected, urine output is >0.5 mL/kg/h, viduals receiving SGLT2 inhibitor therapy,
Table 3—Complications during treatment of DKA and HHS

Complication Evidence Risk Mitigation
Hypoglycemia (10,24) Hypoglycemia is a common Hypoglycemia (<40 mg/dL Frequent blood glucose
complication encountered in the [2.2 mmol/L]) during treatment monitoring (every 1–2 h) is
treatment of DKA. was associated with a 4.8-fold mandatory to recognize
In studies of DKA treatment, the increase in mortality (adjusted hypoglycemia.
risk of hypoglycemia (<70 mg/dL OR 4; 95% CI 1.4–16.8). When glucose levels are
[3.9 mmol/L]) varied between reduced to <250 mg/dL
16% and 28%, with severe (13.9 mmol/L), it is advised to
hypoglycemia (<40 mg/dL reduce the insulin infusion

[2.2 mmol/L]) occurring in 2% of rate to 0.05 units/kg/h and
cases. replacement fluids should be
modified to contain 5–10%
dextrose to prevent
hypoglycemia.
Hypokalemia (24) Hypokalemia is a common Severe hypokalemia Potassium should be carefully
complication owing to #2.5 mmol/L was associated monitored every 4 h during
intracellular shift of potassium with increased inpatient treatment.
following insulin treatment. mortality (adjusted OR 4.9; 95% Potassium replacement should
Hypokalemia (<3.5 mmol/L) CI 1.3–18.8). be added to fluid resuscitation.
occurred in 55% of DKA and
51% of HHS patients.
Severe hypokalemia <2.5 mmol/L
occurs in 16% of people with
DKA and 9% of people with HHS.
Normal anion gap Hyperchloremic non–anion gap Observed during the recovery There is some evidence that
metabolic acidosis acidosis may be seen during the phase of DKA, it is self-limiting hyperchloremic acidosis occurs
(173,174) recovery phase of DKA, but the with few clinical consequences. less frequently with balanced
risk is unknown. It is likely to be electrolyte solutions and when
caused by loss of keto-anions, slower saline infusion is
which are metabolized to administered.
bicarbonate, and excess fluid
infusion of chloride-containing
fluids during treatment.
Thrombosis (43,175,176) Both DKA and HHS, but especially Although case series highlight Currently, unless thrombosis is
HHS, are thought to be the risk of venous and arterial suspected, prophylactic dose
prothrombotic states. thromboembolism in HHS, a low-molecular-weight heparin
There is evidence that clot nationwide Taiwanese study should be used to mitigate the
microstructure may be altered in examining the risk of venous risk of thrombosis.
people with acidosis and thromboembolism in people
dehydration, but this is reversible. with HHS versus those
hospitalized without HHS found
similar rates.
Cerebral edema (3,177) Cerebral edema is rare in adults. Cerebral edema is a serious Recognizing potential risk
The underlying cause is not fully complication with a reported factors and being alerted to
understood but may reflect mortality of 30% compared changes in mental status is
osmotic changes, hypoperfusion, with those without edema. advised, with a low threshold
and/or inflammatory responses. Cerebral edema may be for brain imaging.
In adult patients with HHS and subclinical and visible only on Mannitol infusion and
DKA, rapid shifts in osmolarity imaging studies. mechanical ventilation are
may also be associated with suggested for treatment of
cerebral edema thought to occur cerebral edema.
in <0.1% of events. In adults with HHS, a slow rate
for correction of
hyperosmolarity is indicated.
Osmotic demyelination Previously known as central The risk is specifically In patients with HHS, the fall in
syndrome (117,178) pontine myelinolysis, osmotic associated with rapid correction serum osmolarity should be
demyelination syndrome can of hyponatremia. corrected with 0.9% saline
occur with rapid correction of May complicate treatment of solution.
hyponatremia. The incidence is adults with HHS where The fall in serum osmolality
unclear. hyperosmolar patients may be should be between 3.0 and
relatively hyponatremic. 8.0 mOsm/kg/h.
Continued on p. 13
Table 3—Continued
Complication Evidence Risk Mitigation
Acute kidney injury Using RIFLE (risk, injury, failure, Acute kidney injury is more Acute kidney injury usually
(179,180) loss) criteria, 50% of adult common in older adults, those resolves with rehydration.
patients admitted with DKA and with higher osmolarity, and Monitoring renal function daily
HHS have acute kidney injury. those with higher admission is recommended.
glucose levels.

end-stage kidney disease requiring dialy- In a recent study, people from an area their family need to review the appro-
sis, pregnancy, and COVID-19 infection. with the lowest income quartile had a priate glucose and ketone monitoring
46% increase in the odds of four or more and when to call for assistance. Home
Section 7. How Can DKA and HHS Be DKA readmissions in a given calendar year, measurement of capillary blood and se-
Prevented? while a patient with Medicare insurance rum ketones helps to identify impend-
Key issues at the time of hospital discharge had over a threefold increased odds of this ing DKA (156). Unfortunately, the rate
include transitions of care, therapeutic in- outcome compared with those with pri- of appropriate ketone monitoring, espe-
ertia, the risk of hypoglycemia, and pre- vate insurance (59). In the U.S., policy solu- cially in adults, is low among people
vention of recurrent severe hyperglycemic tions such as increasing access to health with diabetes (158,161).
events. In U.S. nationwide studies, up to insurance, affordable insulin, medical care, The ADA-EASD consensus report on T1D
22% of people admitted with DKA had at nutritious food, and housing would be ex- recommends CGM as the monitoring
least one readmission within 30 days or pected to reduce the incidence of DKA method of choice for most people with
the same calendar year (25,153). Among (157). T1D (162). CGM is superior to capillary
those readmitted within 30 days, 40.8% Before discharge, all individuals ad- blood glucose monitoring for improving
represented recurrent DKA episodes, with mitted with DKA or HHS should be of- glycemic patterns among insulin-treated
approximately 50% being readmitted fered appropriate education focused on patients with T1D and T2D, especially those
within 2 weeks (25). Among those read- both the current event and overall dia- with out-of-range glucose levels. Results
mitted within the same calendar year, betes management. Patient education— from a nationwide study in France reported
86% and 14% had 1–3 and $4 readmis- especially structured education that in- that access to a CGM system was associ-
sions for DKA, respectively (153). Assess- ated with a subsequent decrease in the
cludes problem-solving—is effective at
ment of precipitating and contributing rate of DKA hospitalizations by 53% and by
reducing DKA admissions (158). Partici-
causes of DKA admission and close follow- 47% in T1D and T2D, respectively (163).
pation in a structured diabetes educa-
up within 2–4 weeks after discharge may These results were observed both in pa-
tion program leads to a substantial risk
reduce recurrent DKA (154). For exam- tients treated with multidose insulin and in
reduction for DKA and HHS (156). In pa-
ple, the Novel Interventions in Children’s those treated with continuous insulin infu-
tients with recurrent DKA, up to 75% of
Healthcare program supports families sion (pump) therapy (164) Although CGM
the admissions have been attributed to
with children who have had multiple ad- has not been approved for use in hospital-
insufficient use of insulin therapy (i.e.,
missions for recurrent DKA (154,155). ized patients with diabetes or with DKA,
missed insulin doses) as the immediate
Similarly, close observation, early detec- real-time or intermittently scanned CGM
tion of symptoms, and timely medical contributing factor (48). Omission or insuf-
should be offered to people admitted with
care help prevent HHS in older adults ficient use of insulin therapy is a major
DKA after hospital discharge (165).
(154). Presence of mental health disor- cause of DKA admissions and readmissions In individuals with multiple episodes
ders and SDOH need to be assessed on ad- (159). Thus, education on insulin admin- of DKA, intensified and multidisciplinary
mission and before discharge. Extensive istration and “sick day advice” must be approaches such as psychological interven-
evidence indicates that mental health provided or reinforced. Upon discharge, tions, peer support, individual coaching,
conditions—particularly eating disorders, patients should receive an adequate sup- and behavioral family systems therapy
depression, or schizophrenia—are inde- ply of insulin and diabetes-durable medi- have been reported to reduce DKA risk
pendent risk factors for poor glycemic cal equipment (i.e., glucose monitoring (156). In addition, the use of telemedicine
control and DKA (156). Thus, regular and insulin administration devices) as and digital communication methods, as
screening of people with diabetes for psy- well as contact information for health care well as the provision of a 24-h emergency
chological and behavioral disorders should professionals who can assist in managing call service that offers medical advice for
be implemented in clinical practice. future episodes of high blood glucose and symptoms of DKA or when blood glucose
Socioeconomic disadvantage is a major ketone concentrations. For individuals with or ketone concentrations are high, may re-
risk factor for DKA and HHS. Several indi- poor access to insulin, the social service de- duce the risk of DKA admissions (156).
cators of socioeconomic disadvantage partment should be consulted to address
have been associated with an increased these barriers to optimal self-management. Section 8. What Are the Priority
risk of hyperglycemic crises. These include Education should include reviewing Areas for Future Research?
low income, homelessness, lack of health injection techniques (including sites), To date, clinical recommendations for the
insurance or underinsurance, food insecu- glucose monitoring, and urine or blood management of DKA and HHS are largely
rity, and low educational attainment (59). ketone testing (160). Each patient and based on consensus and opinion rather
Table 4—Features of DKA and HHS occurring in special populations

Clinical characteristics and Specific management
Special population presentation Diagnostic considerations considerations Future care considerations
Frail or older adults High rate of preexisting Isolated HHS and mixed Fluid resuscitation and Assessment of cognitive
(181) comorbidities. DKA/HHS occur more rate of fluid and functional status,
High risk for hospital frequently than DKA. replacement need to including capacity for
mortality, prolonged Evaluate for specific account for self-management.
hospitalization, and DKA precipitating factors and comorbidities and acute Continued management
recurrences. concurrent diagnoses precipitating events. of comorbidities and
(cardiovascular events, Address polypharmacy. risk factors for DKA/HHS
infection, medications). recurrence.

SGLT2 inhibitor May be spontaneous or May present with near- Acute management as SGLT2 inhibitor therapy
(91,93,103,182) preceded by insulin dose normal glucose for “general” DKA. In is not recommended for
reduction or insulin concentrations or euglycemic DKA, 5–10% patients with T1D.
omission, prolonged euglycemic DKA dextrose should be In patients with T2D,
fasting, or acute illness. (glucose <200 mg/dL added to intravenous because of the lack of
May be prevented using [11.1 mmol/L]). fluid or started at the safety data, initiation or
specific “sick day rules.” same time as the 0.9% continuation of SGLT2
sodium chloride. inhibitor therapy after
SGLT2 inhibitors should DKA resolution is not
be stopped on routinely recommended.
admission.
End-stage kidney disease About 4% of patients Patients with end-stage Careful fluid Holistic multidisciplinary
(2,183) with diabetes and end- kidney disease usually administration and care and aggressive
stage kidney disease present with greater potassium replacement multiple risk factor
experienced DKA/HHS. hyperglycemia, more are needed. intervention is
May present with fluid frequent hyponatremia, Greater risk of cardiac necessary.
overload. High higher osmolality, co-complications. Closer glucose and
preexisting comorbidity hyperkalemia, and lower ketone monitoring is
burden with increased ketone concentrations of necessary.
risk of mortality. b-hydroxybutyrate
compared with patients
without end-stage kidney
disease.
Pregnancy (160,184) Up to 2% of pregnancies Euglycemic DKA (glucose The significant feto- Management guidelines
with pregestational <200 mg/dL [11.1 mmol/L]) maternal risk requires in the emergency
diabetes develop DKA. may occur. immediate expert senior department or obstetric
Most cases occur with Mixed acid-base medical and obstetric unit should include
preexisting T1D. disturbances may occur with intervention. sections on the
The incidence of DKA in hyperemesis, making the Ideally patients should management of DKA in
gestational diabetes is diagnosis challenging. be cared for in delivery pregnancy as well as
low (<0.1%). suites or high- sick day rules.
dependency units.
COVID-19 (79,185) Higher frequency of DKA Usual diagnostic criteria. Treatment with high- Discharge on insulin
during the COVID-19 Higher frequency of dose steroids requires treatment with careful
pandemic. mixed DKA/HHS especially higher-dose insulin to follow-up.
At-risk groups are adults in older adults. treat refractory
with preexisting T2D. ketonemia.
High risk for In newly diagnosed
complications, need for individuals presenting
ICU care, longer hospital with diabetes in DKA,
stays, and mortality. diabetes phenotyping
may be helpful.
than rigorous outcomes research. Thus, (0.9% sodium chloride vs. crystalloid solu- worse outcomes compared with isolated
large randomized controlled trials or ro- tions) as well as the optimal rates and DKA or HHS (2,10). However, no prospec-
bust observational studies conducted in techniques for insulin administration (2). tive studies have determined the best
generalizable settings and populations are Small case series and retrospective studies treatment for HHS and the combination of
needed to determine the best manage- suggest worse outcomes in patients with DKA and HHS. Dhatariya et al. reported
ment options, including optimizing the HHS compared with those with isolated that despite potassium replacement fol-
electrolyte content of intravenous fluids DKA and that mixed DKA and HHS have lowing protocol in the U.K., 67% of
patients had a potassium level <4 mmol/L the purchase of insulin to save money— MannKind and serves as consultant for Abbott
within 24 h of presentation (24). Similar has been reported in up to 20% of people Diabetes Care, Embecta, and Hagar. D.C.K. is a
consultant for Afon, Atropos Health, GlucoTrack,
findings were reported in Canada (166) treated with insulin (170). Cost-related in- Lifecare, Nevro, Novo Nordisk, Samsung, and
and the U.S. (10), where approximately sulin rationing is most commonly reported Thirdwayv. R.G.M. is supported by the NIDDK of
50% of patients developed hypokalemia in non-Hispanic Black, middle-income, and the NIH (R03DK127010 and R01DK135515),
(<3.5 mmol/L) despite 91% of them re- underinsured or uninsured populations the National Institute on Aging of the NIH
ceiving potassium replacement. Additional (48,171) and has been associated with in- (R01AG079113), the Patient-Centered Out-
studies are needed to determine the ideal comes Research Institute (DB-2020C2-20306),
creased risk of DKA. Insulin supply remains
and the American Diabetes Association. R.G.M.
potassium replacement regimen in this a challenge in low-income countries de- also serves as a consultant to EmmiEducation
clinical setting. spite insulin being included on the World (Wolters Kluwer) on developing patient educa-

A high ketone concentration is the Health Organization’s list of essential med- tion materials related to diabetes and to Yale
hallmark of DKA, with a consensus among ications. Additionally, further research is New Haven Health System’s Center for Out-
clinical guidelines that a concentration needed to understand better and ulti- comes Research and Evaluation on developing
$3 mmol/L correlates with acid-base pa- mately eliminate the disparities in DKA
quality measures related to diabetes. S.M.
holds a personal award from the Wellcome
rameters and severity of acidosis with and HHS rates experienced by racial and Trust Clinical Career Development Scheme
>90% sensitivity and specificity for a diag- ethnic minority communities (16,172). In (223024/Z/21/Z) and is supported by the Na-
nosis of DKA (117). b-Hydroxybutyrate the U.S., these disparities exist indepen- tional Institute for Health Research Imperial
measurement can be performed as a labo- dent of other confounding risk factors for Biomedical Research Centre. S.M. also reports an
ratory test or using hydroxybutyrate and investigator-initiated grant from Dexcom and has
hyperglycemic crises. Data on racial and
the nitroprusside methods. POCT of blood received speaker fees (donated to the institution)
ethnic disparities in DKA and HHS rates from Sanofi and Lilly. R.A.G. has served as a con-
b-hydroxybutyrate is easy to perform and outside the U.S. are scarce and need to sultant to Lark, Vida, and Sweetch. R.R.B. and
has advantages over laboratory mea- be examined. Ultimately, these disparities N.A.E. declare that there are no relationships or
surement, although safeguards about may call for comprehensive structural sol- activities that might bias, or be perceived to
staff training and instrument perfor- utions, including at the clinician, health bias, their work. K.K.D. has received honoraria
mance need to be in place (108). Three for travel, advisory boards, and speaker fees
system, payer, public health, and public pol-
areas of research interest include the from Abbott Diabetes, AstraZeneca, Boehringer
icy levels. Optimal management of DKA and Ingelheim, Novo Nordisk, Eli Lily, Menarini, and
use of real-time CGM at the time of hos- HHS will require greater knowledge of the Sanofi Diabetes. No other potential conflicts of
pital discharge (167), continuous intersti- pathophysiological, clinical, and social roots interest relevant to this article were reported.
tial ketone monitoring in the hospital and of these serious complications of diabetes. Prior Presentation. Parts of this work were
at home in high-risk individuals (168), presented at the 59th EASD Annual Meeting,
and transitioning to ultra-long-acting in- Hamburg, Germany, 2–6 October 2023; the
sulin after resolution of DKA and HHS. AACE Annual Meeting, New Orleans, LA, 9–11
Acknowledgments. The authors thank Rachel May 2024; and the ADA 84th Scientific Ses-
Because SDOH and structural barriers to Aaron and Tiffany Tian (Diabetes Technology So- sions, Orlando, FL, 21–24 June 2024.
accessing care are known drivers of sus- ciety, Burlingame, CA) for their editing assistance
ceptibility to hyperglycemic crises, it is and Michael Bonar (Leicester Diabetes Centre,
References
imperative to develop, implement, and rig- Leicester, U.K.) for figure design.
Funding and Duality of Interest. G.E.U. is
1. Umpierrez G, Korytkowski M. Diabetic
orously evaluate clinical, public health, and supported by research grants from the Na- emergencies — ketoacidosis, hyperglycaemic hyper-
policy interventions to prevent these tional Institutes of Health (NIH) (NATS UL osmolar state and hypoglycaemia. Nat Rev Endo-
events. Interventions by community health 3UL1TR002378-05S2) from the Clinical and crinol 2016;12:222–232
Translational Science Award program and from 2. Dhatariya KK; Joint British Diabetes Societies
workers and community paramedics and
the NIH and National Center for Research Re- for Inpatient Care. The management of diabetic
even peer support interventions have ketoacidosis in adults—an updated guideline
sources (NIH/National Institute of Diabetes
been implemented to improve diabetes and Digestive and Kidney Diseases [NIDDK] from the Joint British Diabetes Society for
management, but these programs have 2P30DK111024-06) and has served as a member Inpatient Care. Diabet Med 2022;39:e14788
not been examined for impact on DKA or of advisory boards for Dexcom and GlyCare. 3. Dhatariya KK, Glaser NS, Codner E, Umpierrez
HHS. While prescribing healthy food can G.M.D. is supported by a research grant from GE. Diabetic ketoacidosis. Nat Rev Dis Primers
NIH/NIDDK Career Development Award 2020;6:40
lead to substantial improvements in glu- 4. Zhong VW, Juhaeri J, Mayer-Davis EJ. Trends
K23DK122199, has received research support
cose levels, the impact of such interven- from Insulet, and has consulted for Medscape. in hospital admission for diabetic ketoacidosis in
tions on hyperglycemic crises is unknown. G.P.F. has received honoraria and consultancy adults with type 1 and type 2 diabetes in England,
More information is needed about how to and lecture fees from Abbott, AstraZeneca, 1998–2013: a retrospective cohort study. Diabetes
encourage behavior that will lead to avoid- Boehringer Ingelheim, Lilly, MSD, Novo Nor- Care 2018;41:1870–1877
disk, Mundipharma, Sanofi, Takeda, and Serv- 5. McCoy RG, Herrin J, Galindo RJ, et al. Rates of
ance of DKA, especially in people with a
ier. R.J.G. is supported by the NIDDK of the hypoglycemic and hyperglycemic emergencies
history of recurrent episodes. Prospective among U.S. adults with diabetes, 2011–2020.
NIH under award numbers P30DK111024-08,
studies focused on high-risk individuals 1K23DK123384, and 1R03DK138255. R.J.G. has Diabetes Care 2023;46:e69–e71
with mental health disorders, diabetes dis- also received research support (to Emory Uni- 6. Benoit SR, Zhang Y, Geiss LS, Gregg EW,
tress, and depression are needed (69,169). versity) for studies from Novo Nordisk, Dex- Albright A. Trends in diabetic ketoacidosis hospi-
Finally, it will be important to under- com, and Eli Lilly and consulting/advisory or talizations and in-hospital mortality – United
honoraria/lecture fees from Abbott Diabetes, States, 2000–2014. MMWR Morb Mortal Wkly
stand the impact of lowering insulin prices
Dexcom, Eli Lilly, Novo Nordisk, AstraZeneca, Rep 2018;67:362–365
in the U.S., where insulin rationing— Boehringer Ingelheim, Medtronic, and Bayer 7. Kitabchi AE, Umpierrez GE, Murphy MB, et al.
defined as skipping insulin doses, using outside of this work. I.B.H. has received re- Management of hyperglycemic crises in patients
less insulin than prescribed, or delaying search support from the NIH, Dexcom, and with diabetes. Diabetes Care 2001;24:131–153
8. Misra S. Rise in diabetic ketoacidosis during the fragmentation of care, and mortality across and outcome of diabetic ketoacidosis in patients
COVID-19 pandemic: several questions remain. Chicago, Illinois. Diabetes Care 2016;39:1671–1676 with type 1 diabetes. Cureus 2019;11:e4789
Lancet Diabetes Endocrinol 2022;10:763–765 24. Dhatariya KK, Nunney I, Higgins K, Sampson 39. Chung ST, Perue GG, Johnson A, et al.
9. Khunti K, Del Prato S, Mathieu C, Kahn SE, MJ, Iceton G. National survey of the man- Predictors of hyperglycaemic crises and their
Gabbay RA, Buse JB. COVID-19, hyperglycemia, agement of diabetic ketoacidosis (DKA) in the UK associated mortality in Jamaica. Diabetes Res Clin
and new-onset diabetes. Diabetes Care 2021;44: in 2014. Diabet Med 2016;33:252–260 Pract 2006;73:184–190
2645–2655 25. Hurtado CR, Lemor A, Vallejo F, et al. Causes 40. Nkpozi MO, Akhidue K, Unachukwu CN,
10. Pasquel FJ, Tsegka K, Wang H, et al. Clinical and predictors for 30-day re-admissions in adult Chinenye S, Chappjumbo AU. Hyperglycaemic
outcomes in patients with isolated or combined patients with diabetic ketoacidosis in the United emergencies in a tertiary health facility in south-
diabetic ketoacidosis and hyperosmolar hyper- States: a nationwide analysis, 2010–2014. Endocr eastern Nigeria. West Afr J Med 2018;35:
glycemic state: a retrospective, hospital-based Pract 2019;25:242–253 137–143
cohort study. Diabetes Care 2020;43:349–357 26. McCoy RG, Herrin J, Lipska KJ, Shah ND. 41. Shand JAD, Morrow P, Braatvedt G.

11. American Diabetes Association. Hyperglycemic Recurrent hospitalizations for severe hypoglycemia Mortality after discharge from hospital following
crises in patients with diabetes mellitus. Diabetes and hyperglycemia among U.S. adults with diabetes. an episode of diabetic ketoacidosis. Acta Diabetol
Care 2001;24:1988–1996 J Diabetes Complications 2018;32:693–701 2022;59:1485–1492
12. Kitabchi AE, Umpierrez GE, Miles JM, Fisher 27. Shaka H, Aguilera M, Aucar M, et al. Rate 42. Gibb FW, Teoh WL, Graham J, Lockman KA.
JN. Hyperglycemic crises in adult patients with and predictors of 30-day readmission following Risk of death following admission to a UK
diabetes. Diabetes Care 2009;32:1335–1343 diabetic ketoacidosis in type 1 diabetes mellitus: hospital with diabetic ketoacidosis. Diabetologia
13. Benoit SR, Hora I, Pasquel FJ, Gregg EW, a US analysis. J Clin Endocrinol Metab 2021; 2016;59:2082–2087
Albright AL, Imperatore G. Trends in emergency 106:2592–2599 43. Fadini GP, de Kreutzenberg SV, Rigato M,
department visits and inpatient admissions for 28. Dhatariya KK, Skedgel C, Fordham R. The et al. Characteristics and outcomes of the
hyperglycemic crises in adults with diabetes in cost of treating diabetic ketoacidosis in the UK: a hyperglycemic hyperosmolar non-ketotic syndrome
the U.S., 2006–2015. Diabetes Care 2020;43: national survey of hospital resource use. Diabet in a cohort of 51 consecutive cases at a single
1057–1064 Med 2017;34:1361–1366 center. Diabetes Res Clin Pract 2011;94:172–179
14. Vellanki P, Umpierrez GE. Diabetic ketoacidosis: 29. Desai D, Mehta D, Mathias P, Menon G, 44. Michaelis M, Shochat T, Shimon I, Akirov A.
a common debut of diabetes among african Schubart UK. Health care utilization and burden Features and long-term outcomes of patients
americans with type 2 diabetes. Endocr Pract of diabetic ketoacidosis in the U.S. over the past hospitalized for diabetic ketoacidosis. Diabetes
2017;23:971–978 decade: a nationwide analysis. Diabetes Care Metab Res Rev 2021;37:e3408
15. Lebovitz HE, Banerji MA. Ketosis-prone 2018;41:1631–1638 45. Otieno CF, Kayima JK, Omonge EO, Oyoo
diabetes (Flatbush diabetes): an emerging world- 30. Fernando SM, Bagshaw SM, Rochwerg B,
GO. Diabetic ketoacidosis: risk factors, mechanisms
wide clinically important entity. Curr Diab Rep et al. Comparison of outcomes and costs
and management strategies in sub-Saharan Africa:
between adult diabetic ketoacidosis patients
2018;18:120 a review. East Afr Med J 2005;82(Suppl.):S197–S203
admitted to the ICU and step-down unit. J Crit
16. McCoy RG, Galindo RJ, Swarna KS, et al. 46. Davis TME, Davis W. Incidence and associates
Care 2019;50:257–261
Sociodemographic, clinical, and treatment-related of diabetic ketoacidosis in a community-based
31. Lyerla R, Johnson-Rabbett B, Shakally A,
factors associated with hyperglycemic crises among cohort: the Fremantle Diabetes Study Phase II. BMJ
Magar R, Alameddine H, Fish L. Recurrent DKA
adults with type 1 or type 2 diabetes in the US from Open Diabetes Res Care 2020;8:e000983
results in high societal costs - a retrospective
2014 to 2020. JAMA Netw Open 2021;4:e2123471 47. Dhatariya KK. Defining and characterising
study identifying social predictors of recurrence
17. Kikani N, Balasubramanyam A. Remission in diabetic ketoacidosis in adults. Diabetes Res Clin
for potential future intervention. Clin Diabetes
ketosis-prone diabetes. Endocrinol Metab Clin Pract 2019;155:107797
Endocrinol 2021;7:13
North Am 2023;52:165–174 48. Randall L, Begovic J, Hudson M, et al.
32. Shaka H, Wani F, El-Amir Z, et al. Comparing
18. Di Giovanni P, Meo F, Cedrone F, et al. Recurrent diabetic ketoacidosis in inner-city
patient characteristics and outcomes in type 1
Predictors and trend of ketoacidosis hospitaliza- minority patients: behavioral, socioeconomic,
versus type 2 diabetes with diabetic ketoacidosis:
tion rate in type 2 diabetes mellitus patients from and psychosocial factors. Diabetes Care 2011;34:
a review and a propensity-matched nationwide
2006 to 2015 in Abruzzo region, Italy. Clin Ter analysis. J Investig Med 2021;69:1196–1200 1891–1896
2020;170:e53–e58 33. Gaffney A, Christopher A, Katz A, et al. The 49. Fayfman M, Pasquel FJ, Umpierrez GE.
19. Desai R, Singh S, Syed MH, et al. Temporal incidence of diabetic ketoacidosis during “emerg- Management of hyperglycemic crises: diabetic
trends in the prevalence of diabetes decompensation ing adulthood” in the USA and Canada: a ketoacidosis and hyperglycemic hyperosmolar
(diabetic ketoacidosis and hyperosmolar hyper- population-based study. J Gen Intern Med 2019; state. Med Clin North Am 2017;101:587–606
glycemic state) among adult patients hospitalized 34:1244–1250 50. Paulson WD, Gadallah MF. Diagnosis of
with diabetes mellitus: a nationwide analysis 34. McCoy RG, Herrin J, Galindo RJ, et al. All- mixed acid-base disorders in diabetic keto-
stratified by age, gender, and race. Cureus 2019; cause mortality after hypoglycemic and hyper- acidosis. Am J Med Sci 1993;306:295–300
11:e4353 glycemic emergencies among U.S. adults with 51. Del Degan S, Dube F, Gagnon C, Boulet G.
20. Shaka H, El-Amir Z, Wani F, et al. Hospitali- diabetes, 2011-2020. Diabetes Res Clin Pract Risk factors for recurrent diabetic ketoacidosis in
zations and inpatient mortality for hyperosmolar 2023;197:110263 adults with type 1 diabetes. Can J Diabetes 2019;
hyperglycemic state over a decade. Diabetes Res 35. Nishikawa T, Kinoshita H, Ono K, et al. 43:472–476.e1
Clin Pract 2022;185:109230 Clinical profiles of hyperglycemic crises: a single- 52. Morris AD, Boyle DI, McMahon AD, Greene
21. O’Reilly JE, Jeyam A, Caparrotta TM, et al.; center retrospective study from Japan. J Diabetes SA, MacDonald TM, Newton RW; DARTS/MEMO
Scottish Diabetes Research Network Epidemio- Investig 2021;12:1359–1366 Collaboration. Adherence to insulin treatment,
logy Group. Rising rates and widening socio- 36. Sato Y, Morita K, Okada A, Matsui H, Fushimi glycaemic control, and ketoacidosis in insulin-
economic disparities in diabetic ketoacidosis K, Yasunaga H. Factors affecting in-hospital dependent diabetes mellitus. Lancet 1997;350:
in type 1 diabetes in Scotland: a nationwide mortality of diabetic ketoacidosis patients: a 1505–1510
retrospective cohort observational study. Dia- retrospective cohort study. Diabetes Res Clin 53. Delaney MF, Zisman A, Kettyle WM. Diabetic
betes Care 2021;44:2010–2017 Pract 2021;171:108588 ketoacidosis and hyperglycemic hyperosmolar
22. Fazeli Farsani S, Brodovicz K, Soleymanlou N, 37. Ibrahim A, Bayramoglu B, Hokenek NM, nonketotic syndrome. Endocrinol Metab Clin
Marquard J, Wissinger E, Maiese BA. Incidence Tekyol D. Lactate clearance during the first 2 North Am 2000;29:683–705
and prevalence of diabetic ketoacidosis (DKA) hours after hospital admission: a useful bio- 54. Nyenwe EA, Loganathan RS, Blum S, et al.
among adults with type 1 diabetes mellitus marker for predicting 30-day mortality in patients Active use of cocaine: an independent risk factor
(T1D): a systematic literature review. BMJ Open with diabetic ketoacidosis. Int J Clin Pract 2021; for recurrent diabetic ketoacidosis in a city
2017;7:e016587 75:e14204 hospital. Endocr Pract 2007;13:22–29
23. Mays JA, Jackson KL, Derby TA, et al. An 38. Ahuja W, Kumar N, Kumar S, Rizwan A. 55. Davis SN, Umpierrez GE. Diabetic keto-
evaluation of recurrent diabetic ketoacidosis, Precipitating risk factors, clinical presentation, acidosis in type 2 diabetes mellitus–patho-
physiology and clinical presentation. Nat Clin 70. Fisher L, Polonsky W, Naranjo D, Strycker L, 84. Shah M, Adel MM, Tahsin B, Guerra Y,
Pract Endocrinol Metab 2007;3:730–731 Hessler D. A novel approach to understanding and Fogelfeld L. Effect of short-term prednisone on
56. Nyenwe EA, Kitabchi AE. Evidence-based assessing the emotional side of type 1 diabetes: beta-cell function in subjects with type 2
management of hyperglycemic emergencies in the Type 1-Diabetes Distress Assessment System. diabetes mellitus and healthy subjects. PLoS One
diabetes mellitus. Diabetes Res Clin Pract 2011; Diabet Med 2024:e15282 2020;19:e0231190
94:340–351 71. Jeyam A, Gibb FW, McKnight JA, et al.; 85. Guenette MD, Hahn M, Cohn TA, Teo C,
57. Umpierrez GE, Kelly JP, Navarrete JE, Casals Scottish Diabetes Research Network (SDRN) Remington GJ. Atypical antipsychotics and
MM, Kitabchi AE. Hyperglycemic crises in urban Epidemiology Group. Marked improvements in diabetic ketoacidosis: a review. Psychopharma-
blacks. Arch Intern Med 1997;157:669–675 glycaemic outcomes following insulin pump cology (Berl) 2013;226:1–12
58. Thomas M, Harjutsalo V, Feodoroff M, therapy initiation in people with type 1 diabetes: 86. Zhang Z, Sharma R, Hamad L, Riebandt G,
Forsblom C, Gordin D, Groop PH. The long-term a nationwide observational study in Scotland. Attwood K. Incidence of diabetes mellitus in
incidence of hospitalization for ketoacidosis in Diabetologia 2021;64:1320–1331 patients treated with immune checkpoint

adults with established T1D—a prospective 72. Biester T, Schwandt A, Heidtmann B, et al.; inhibitors (ICI) therapy - a comprehensive
cohort study. J Clin Endocrinol Metab 2020;105: DPV Initiative. Declining frequency of acute cancer center experience. Diabetes Res Clin
231–241 complications associated with tubeless insulin Pract 2023;202:110776
59. Kurani SS, Heien HC, Sangaralingham LR, pump use: data from 2,911 patients in the 87. Chang LS, Barroso-Sousa R, Tolaney SM,
et al. Association of area-level socioeconomic German/Austrian Diabetes Patienten Verlaufs- Hodi FS, Kaiser UB, Min L. Endocrine toxicity of
deprivation with hypoglycemic and hyperglycemic dokumentation Registry. Diabetes Technol Ther cancer immunotherapy targeting immune checkpoints.
crises in US adults with diabetes. JAMA Netw Open 2021;23:527–536 Endocr Rev 2019;40:17–65
2022;5:e2143597 73. Wers€all JH, Adolfsson P, Forsander G, Hanas 88. Tittel SR, Laubner K, Schmid SM, et al.;
60. Jiang DH, Herrin J, Van Houten HK, McCoy R. Insulin pump therapy is associated with higher DPV Initiative. Immune-checkpoint inhibitor-
RG. Evaluation of high-deductible health plans rates of mild diabetic ketoacidosis compared to associated diabetes compared to other diabetes
and acute glycemic complications among injection therapy: a 2-year Swedish national types - a prospective, matched control study. J
adults with diabetes. JAMA Netw Open 2023;6: survey of children and adolescents with type 1 Diabetes 2021;13:1007–1014
e2250602 diabetes. Pediatr Diabetes 2022;23:1038–1044 89. Wu L, Tsang V, Menzies AM, et al. Risk factors
61. Matthews S, Coates MM, Bukhman A, et al. 74. Giessmann LC, Kann PH. Risk and relevance and characteristics of checkpoint inhibitor-associated
Health system capacity to manage diabetic of insulin pump therapy in the aetiology of autoimmune diabetes mellitus (CIADM): a systematic
ketoacidosis in nine low-income and lower-middle ketoacidosis in people with type 1 diabetes. Exp review and delineation from type 1 diabetes.
income countries: a cross-sectional analysis of Clin Endocrinol Diabetes 2020;128:745–751 Diabetes Care 2023;46:1292–1299
nationally representative survey data. EClinical- 75. Forlenza GP, Lal RA. Current status and 90. Wolfsdorf JI, Ratner RE. SGLT inhibitors for
emerging options for automated insulin delivery type 1 diabetes: proceed with extreme caution.
Medicine 2022;55:101759
62. Reid LA, Mendoza JA, Merchant AT, et al. systems. Diabetes Technol Ther 2022;24:362–371 Diabetes Care 2019;42:991–993
76. McVean J, Miller J. MiniMedTM780G Insulin 91. Fadini GP, Bonora BM, Avogaro A. SGLT2
Household food insecurity is associated with
pump system with smartphone connectivity for inhibitors and diabetic ketoacidosis: data from
diabetic ketoacidosis but not severe hypo-
the treatment of type 1 diabetes: overview of its the FDA Adverse Event Reporting System.
glycemia or glycemic control in youth and young
safety and efficacy. Expert Rev Med Devices Diabetologia 2017;60:1385–1389
adults with youth-onset type 2 diabetes. Pediatr
2021;18:499–504 92. Marilly E, Cottin J, Cabrera N, et al. SGLT2
Diabetes 2022;23:982–990
77. Crabtree TSJ, Griffin TP, Yap YW, et al.; ABCD inhibitors in type 2 diabetes: a systematic review
63. Goueslard K, Petit JM, Cottenet J, Chauvet-
Closed-Loop Audit Contributors. Hybrid closed- and meta-analysis of cardiovascular outcome
Gelinier JC, Jollant F, Quantin C. Increased risk of
loop therapy in adults with type 1 diabetes and trials balancing their risks and benefits. Dia-
rehospitalization for acute diabetes complications
above-target HbA1c: a real-world observational betologia 2022;65:2000–2010
and suicide attempts in patients with type 1
study. Diabetes Care 2023;46:1831–1838 93. Colacci M, Fralick J, Odutayo A, Fralick M.
diabetes and comorbid schizophrenia. Diabetes 78. Khan F, Paladino L, Sinert R. The impact of Sodium-glucose cotransporter-2 inhibitors and
Care 2018;41:2316–2321 COVID-19 on diabetic ketoacidosis patients. risk of diabetic ketoacidosis among adults with
64. Price HC; Joint British Diabetes Societies Diabetes Metab Syndr 2022;16:102389 type 2 diabetes: a systematic review and meta-
(JBDS) for Inpatient Care. Royal College of 79. Misra S, Barron E, Vamos E, et al. Temporal analysis. Can J Diabetes 2022;46:10–15.e2
Psychiatrists Liaison Faculty & Joint British trends in emergency admissions for diabetic 94. Bamgboye AO, Oni IO, Collier A. Predisposing
Diabetes Societies (JBDS): guidelines for the ketoacidosis in people with diabetes in England factors for the development of diabetic ketoacidosis
management of diabetes in adults and children before and during the COVID-19 pandemic: a with lower than anticipated glucose levels in type 2
with psychiatric disorders in inpatient settings. population-based study. Lancet Diabetes Endo- diabetes patients on SGLT2-inhibitors: a review. Eur
Diabet Med 2018;35:997–1004 crinol 2021;9:671–680 J Clin Pharmacol 2021;77:651–657
65. Brandstaetter E, Bartal C, Sagy I, Jotkowitz A, 80. Bello-Chavolla OY, Antonio-Villa NE, Fermın- 95. Wu XY, She DM, Wang F, et al. Clinical
Barski L. Recurrent diabetic ketoacidosis. Arch Martınez CA, et al. Diabetes-related excess profiles, outcomes and risk factors among type 2
Endocrinol Metab 2019;63:531–535 mortality in Mexico: a comparative analysis of diabetic inpatients with diabetic ketoacidosis and
66. Trief PM, Xing D, Foster NC, et al.; T1D national death registries between 2017-2019 and hyperglycemic hyperosmolar state: a hospital-
Exchange Clinic Network. Depression in adults in 2020. Diabetes Care 2022;45:2957–2966 based analysis over a 6-year period. BMC Endocr
the T1D Exchange clinic registry. Diabetes Care 81. Lavik AR, Ebekozien O, Noor N, et al. Trends Disord 2020;20:182
2014;37:1563–1572 in type 1 diabetic ketoacidosis during COVID-19 96. Bonora BM, Avogaro A, Fadini GP. Sodium-
67. Petit JM, Goueslard K, Chauvet-Gelinier JC, surges at 7 US centers: highest burden on non- glucose co-transporter-2 inhibitors and diabetic
et al. Association between hospital admission for Hispanic Black patients. J Clin Endocrinol Metab ketoacidosis: an updated review of the literature.
ketoacidosis and subsequent suicide attempt in 2022;107:1948–1955 Diabetes Obes Metab 2018;20:25–33
young adults with type 1 diabetes. Diabetologia 82. Jin H, Meyer JM, Jeste DV. Atypical 97. Blau JE, Tella SH, Taylor SI, Rother KI.
2020;63:1745–1752 antipsychotics and glucose dysregulation: a Ketoacidosis associated with SGLT2 inhibitor
68. Roberts SE, Goldacre MJ, Neil HAW. systematic review. Schizophr Res 2004;71:195–212 treatment: analysis of FAERS data. Diabetes
Mortality in young people admitted to hospital 83. Yuen KCJ, McDaniel PA, Riddle MC. Twenty- Metab Res Rev 2017;33:10.1002/dmrr.2924
for diabetes: database study. BMJ 2004;328: four-hour profiles of plasma glucose, insulin, C- 98. Phillips PA, Rolls BJ, Ledingham JGG, et al.
741–742 peptide and free fatty acid in subjects with Reduced thirst after water deprivation in healthy
69. Hermanns N, Caputo S, Dzida G, Khunti K, varying degrees of glucose tolerance following elderly men. N Engl J Med 1984;311:753–759
Meneghini LF, Snoek F. Screening, evaluation and short-term, medium-dose prednisone (20 mg/ 99. Umpierrez GE, Murphy MB, Kitabchi AE.
management of depression in people with day) treatment: evidence for differing effects on Diabetic ketoacidosis and hyperglycemic hyper
diabetes in primary care. Prim Care Diabetes insulin secretion and action. Clin Endocrinol (Oxf) osmolar syndrome. Diabetes Spectr 2002;15:
2013;7:1–10 2012;77:224–232 28–36
100. Stentz FB, Umpierrez GE, Cuervo R, diabetic ketoacidosis. JAMA Netw Open 2022; 132. Goyal N, Miller JB, Sankey SS, Mossallam U.
Kitabchi AE. Proinflammatory cytokines, markers 5:e226417 Utility of initial bolus insulin in the treatment of
of cardiovascular risks, oxidative stress, and lipid 117. Mustafa OG, Haq M, Dashora U, Castro E; diabetic ketoacidosis. J Emerg Med 2010;38:
peroxidation in patients with hyperglycemic Joint British Diabetes Societies (JBDS) for 422–427
crises. Diabetes 2004;53:2079–2086 Inpatient Care Group. Management of hyperosmolar 133. Anis TR, Boudreau M, Thornton T.
101. Munro JF, Campbell IW, McCuish AC, hyperglycaemic state (HHS) in adults: an updated Comparing the efficacy of a nurse-driven and a
Duncan LJ. Euglycaemic diabetic ketoacidosis. guideline from the Joint British Diabetes Societies physician-driven diabetic ketoacidosis (DKA)
BMJ 1973;2:578–580 (JBDS) for Inpatient Care group. Diabet Med treatment protocol. Clin Pharmacol 2021;13:
102. Chow E, Clement S, Garg R. Euglycemic 2023;40:e15005 197–202
diabetic ketoacidosis in the era of SGLT-2 118. Umpierrez G, Freire AX. Abdominal pain in 134. Singh RK, Perros P, Frier BM. Hospital
inhibitors. BMJ Open Diabetes Res Care 2023;11: patients with hyperglycemic crises. J Crit Care management of diabetic ketoacidosis: are clinical
e003666 2002;17:63–67 guidelines implemented effectively? Diabet Med

103. Long B, Lentz S, Koyfman A, Gottlieb M. 119. Han HJ, Cole AE, Verma A. Euglycemic diabetic 1997;14:482–486
Euglycemic diabetic ketoacidosis: etiologies, ketoacidosis caused by alcoholic pancreatitis and 135. Harrison VS, Rustico S, Palladino AA,
evaluation, and management. Am J Emerg Med starvation ketosis. J Gen Intern Med 2023;38: Ferrara C, Hawkes CP. Glargine co-administration
2021;44:157–160 1299–1301 with intravenous insulin in pediatric diabetic
104. Nasa P, Chaudhary S, Shrivastava PK, Singh 120. Chandrasekara H, Fernando P, Danjuma M, ketoacidosis is safe and facilitates transition to a
A. Euglycemic diabetic ketoacidosis: a missed Jayawarna C. Ketoacidosis is not always due to subcutaneous regimen. Pediatr Diabetes 2017;
diagnosis. World J Diabetes 2021;12:514–523 diabetes. BMJ Case Rep 2014;2014:bcr2013203263 18:742–748
105. Macfarlane J, Dhatariya K. Incidence of 121. Umpierrez GE, Cuervo R, Karabell A, Latif K, 136. Thammakosol K, Sriphrapradang C.
euglycemic diabetic ketoacidosis in adults with Freire AX, Kitabchi AE. Treatment of diabetic Effectiveness and safety of early insulin glargine
type 1 diabetes in the United Kingdom before the ketoacidosis with subcutaneous insulin aspart. administration in combination with continuous
widespread use of sodium glucose cotransporter Diabetes Care 2004;27:1873–1878 intravenous insulin infusion in the management
2 inhibitors. Mayo Clin Proc 2019;94:1909–1910 122. May ME, Young C, King J. Resource of diabetic ketoacidosis: a randomized controlled
106. He Z, Lam K, Zhao W, et al. SGLT-2 utilization in treatment of diabetic ketoacidosis in trial. Diabetes Obes Metab 2023;25:815–822
inhibitors and euglycemic diabetic ketoacidosis/ adults. Am J Med Sci 1993;306:287–294 137. Mohamed A, Ploetz J, Hamarshi MS.
diabetic ketoacidosis in FAERS: a pharmacovigilance 123. Javor KA, Kotsanos JG, McDonald RC, Baron Evaluation of early administration of insulin glargine
assessment. Acta Diabetol 2023;60:401–411 AD, Kesterson JG, Tierney WM. Diabetic keto- in the acute management of diabetic ketoacidosis.
107. Palanca A, van Nes F, Pardo F, Ampudia acidosis charges relative to medical charges of Curr Diabetes Rev 2021;17:e030221191986
Blasco FJ, Mathieu C. Real-world evidence of adult patients with type I diabetes. Diabetes Care 138. Andrade-Castellanos CA, Colunga-Lozano
efficacy and safety of SGLT2 inhibitors as 1997;20:349–354 LE, Delgado-Figueroa N, Gonzalez-Padilla DA.
adjunctive therapy in adults with type 1 diabetes: 124. Glaser NS, Ghetti S, Casper TC, Dean JM; Subcutaneous rapid-acting insulin analogues for
a european two-center experience. Diabetes Pediatric Emergency Care Applied Research diabetic ketoacidosis. Cochrane Database Syst
Care 2022;45:650–658 Network (PECARN) DKA FLUID Study Group. Rev 2016:CD011281
108. Kilpatrick ES, Butler AE, Ostlundh L, Atkin SL, Pediatric diabetic ketoacidosis, fluid therapy, and 139. Hsia E, Seggelke S, Gibbs J, et al. Sub-
Sacks DB. Controversies around the measurement cerebral injury: the design of a factorial cutaneous administration of glargine to diabetic
of blood ketones to diagnose and manage diabetic randomized controlled trial. Pediatr Diabetes patients receiving insulin infusion prevents
ketoacidosis. Diabetes Care 2022;45:267–272 2013;14:435–446 rebound hyperglycemia. J Clin Endocrinol Metab
109. Laffel L. Ketone bodies: a review of 125. Alghamdi NA, Major P, Chaudhuri D, et al. 2012;97:3132–3137
physiology, pathophysiology and application Saline compared to balanced crystalloid in 140. Umpierrez GE, Latif K, Stoever J, et al.
of monitoring to diabetes. Diabetes Metab Res patients with diabetic ketoacidosis: a systematic Efficacy of subcutaneous insulin lispro versus
Rev 1999;15:412–426 review and meta-analysis of randomized continuous intravenous regular insulin for the
110. Wolfsdorf JI, Allgrove J, Craig ME, et al.; controlled trials. Crit Care Explor 2022;4:e0613 treatment of patients with diabetic ketoacidosis.
International Society for Pediatric and Adolescent 126. Self WH, Evans CS, Jenkins CA, et al.; Am J Med 2004;117:291–296
Diabetes. ISPAD Clinical Practice Consensus Pragmatic Critical Care Research Group. Clinical 141. Stuhr K, LeeMaster R, Hickman AW, Reachi
Guidelines 2014. Diabetic ketoacidosis and effects of balanced crystalloids vs saline in adults B, Pace W, Meek C. Subcutaneous insulin versus
hyperglycemic hyperosmolar state. Pediatr with diabetic ketoacidosis: a subgroup analysis of traditional intravenous insulin infusion in
Diabetes 2014;15(Suppl. 20):154–179 cluster randomized clinical trials. JAMA Netw treatment of mild to moderate diabetic keto-
111. Huang J, Yeung AM, Bergenstal RM, et al. Open 2020;3:e2024596 acidosis. J Emerg Med 2023;65:e221–e228
Update on measuring ketones. J Diabetes Sci 127. Catahay JA, Polintan ET, Casimiro M, et al. 142. Karoli R, Fatima J, Salman T, Sandhu S,
Technol 2024;18:714–726 Balanced electrolyte solutions versus isotonic Shankar R. Managing diabetic ketoacidosis in
112. Brooke J, Stiell M, Ojo O. Evaluation of the saline in adult patients with diabetic ketoacidosis: a non-intensive care unit setting: role of insulin
accuracy of capillary hydroxybutyrate measurement systematic review and meta-analysis. Heart Lung analogs. Indian J Pharmacol 2011;43:398–401
compared with other measurements in the 2022;54:74–79 143. Kitabchi AE, Ayyagari V, Guerra SM. The
diagnosis of diabetic ketoacidosis: a systematic 128. Jahangir A, Jahangir A, Siddiqui FS, et al. efficacy of low-dose versus conventional therapy
review. Int J Environ Res Public Health 2016;13:837 Normal saline versus low chloride solutions in of insulin for treatment of diabetic ketoacidosis.
113. Cao S, Cao S. Diabetic ketoalkalosis: a treatment of diabetic ketoacidosis: a systematic Ann Intern Med 1976;84:633–638
common yet easily overlooked alkalemic variant review of clinical trials. Cureus 2022;14:e21324 144. ElSayed NA, Aleppo G, Aroda VR, et al.;
of diabetic ketoacidosis associated with mixed 129. Bergmann KR, Abuzzahab MJ, Nowak J, American Diabetes Association. 16. Diabetes care
acid-base disorders. J Emerg Med 2023;64: et al. Resuscitation with Ringer’s lactate compared in the hospital: Standards of Care in Diabetes—
282–288 with normal saline for pediatric diabetic keto- 2024. Diabetes Care 2024;47(Suppl. 1):S295–S306
114. Kamel KS, Halperin ML. Acid-base problems acidosis. Pediatr Emerg Care 2021;37:e236–e242 145. Arora S, Cheng D, Wyler B, Menchine M.
in diabetic ketoacidosis. N Engl J Med 2015;372: 130. Umpierrez GE, Jones S, Smiley D, et al. Prevalence of hypokalemia in ED patients with
546–554 Insulin analogs versus human insulin in the diabetic ketoacidosis. Am J Emerg Med 2012;
115. Basnet S, Venepalli PK, Andoh J, Verhulst S, treatment of patients with diabetic ketoacidosis: 30:481–484
Koirala J. Effect of normal saline and half normal a randomized controlled trial. Diabetes Care 146. Harris AN, Grimm PR, Lee HW, et al.
saline on serum electrolytes during recovery 2009;32:1164–1169 Mechanism of hyperkalemia-induced metabolic
phase of diabetic ketoacidosis. J Intensive Care 131. Galindo RJ, Pasquel FJ, Fayfman M, et al. acidosis. J Am Soc Nephrol 2018;29:1411–1425
Med 2014;29:38–42 Clinical characteristics and outcomes of patients 147. Murthy K, Harrington JT, Siegel RD.
116. Rao P, Jiang SF, Kipnis P, et al. Evaluation of with end-stage renal disease hospitalized with Profound hypokalemia in diabetic ketoacidosis: a
outcomes following hospital-wide implemen- diabetes ketoacidosis. BMJ Open Diabetes Res therapeutic challenge. Endocr Pract 2005;11:
tation of a subcutaneous insulin protocol for Care 2020;8:e000763 331–334
148. Cieluch A, Uruska A, Falkowski B, et al. United Kingdom: investigating the incidence, electrolyte abnormalities in children with diabetic
Nonadherence to potassium replacement protocol aetiology, management and outcomes. Diabet ketoacidosis. Diabetes Care 2021;44:2061–2068
leads to prolonged management of diabetic Med 2022;39:e14743 174. Mahler SA, Conrad SA, Wang H, Arnold TC.
ketoacidosis. Pol Arch Intern Med 2018;128: 161. Albanese-O’Neill A, Wu M, Miller KM, Resuscitation with balanced electrolyte solution
416–420 Jacobsen L, Haller MJ; T1D Exchange Clinic prevents hyperchloremic metabolic acidosis in
149. Chua HR, Schneider A, Bellomo R. Bicarbonate Network. Poor adherence to ketone testing in patients with diabetic ketoacidosis. Am J Emerg
in diabetic ketoacidosis - a systematic review. Ann patients with type 1 diabetes. Diabetes Care Med 2011;29:670–674
Intensive Care 2011;1:23 2017;40:e38–e39 175. Wei WT, Lin SM, Hsu JY, et al. Association
150. Glaser N, Barnett P, McCaslin I, et al.; 162. Holt RIG, DeVries JH, Hess-Fischl A, et al. between hyperosmolar hyperglycemic state and
Pediatric Emergency Medicine Collaborative The management of type 1 diabetes in adults. A venous thromboembolism in diabetes patients:
Research Committee of the American Academy consensus report by the American Diabetes a nationwide analysis in Taiwan. J Pers Med 2022;
of Pediatrics. Risk factors for cerebral edema in Association (ADA) and the European Association 12:302

children with diabetic ketoacidosis. N Engl J Med for the Study of Diabetes (EASD). Diabetes Care 176. Pillai S, Davies G, Lawrence M, et al. The
2001;344:264–269 2021;44:2589–2625 effect of diabetic ketoacidosis (DKA) and its
151. Ditzel J, Lervang HH. Disturbance of 163. Riveline JP, Roussel R, Vicaut E, et al. treatment on clot microstructure: are they
inorganic phosphate metabolism in diabetes Reduced rate of acute diabetes events with flash thrombogenic? Clin Hemorheol Microcirc 2021;
mellitus: clinical manifestations of phosphorus- glucose monitoring is sustained for 2 years after 77:183–194
depletion syndrome during recovery from initiation: extended outcomes from the RELIEF 177. Siwakoti K, Giri S, Kadaria D. Cerebral
diabetic ketoacidosis. Diabetes Metab Syndr study. Diabetes Technol Ther 2022;24:611–618 edema among adults with diabetic ketoacidosis
Obes 2010;3:319–324 164. Roussel R, Riveline JP, Vicaut E, et al. and hyperglycemic hyperosmolar syndrome:
152. Fisher JN, Kitabchi AE. A randomized study Important drop in rate of acute diabetes incidence, characteristics, and outcomes. J Dia-
of phosphate therapy in the treatment of complications in people with type 1 or type 2 betes 2017;9:208–209
diabetic ketoacidosis. J Clin Endocrinol Metab diabetes after initiation of flash glucose monitoring 178. Kusumoto K, Koriyama N, Kojima N, Ikeda
1983;57:177–180 in france: the RELIEF study. Diabetes Care 2021; M, Nishio Y. Central pontine myelinolysis during
153. Everett E, Mathioudakis NN. Association of 44:1368–1376 treatment of hyperglycemic hyperosmolar syn-
socioeconomic status and DKA readmission in 165. Spanakis EK, Cook CB, Kulasa K, et al. A drome: a case report. Clin Diabetes Endocrinol
adults with type 1 diabetes: analysis of the US consensus statement for continuous glucose
2020;6:23
National Readmission Database. BMJ Open monitoring metrics for inpatient clinical trials. J
179. Orban JC, Maiziere EM, Ghaddab A, Van
Diabetes Res Care 2019;7:e000621 Diabetes Sci Technol 2023;17:1527–1552
Obberghen E, Ichai C. Incidence and chara-
154. Gosmanov AR, Gosmanova EO, Kitabchi 166. Galm BP, Bagshaw SM, Senior PA. Acute
cteristics of acute kidney injury in severe diabetic
AE. Hyperglycemic crises: diabetic ketoacidosis management of diabetic ketoacidosis in adults at
ketoacidosis. PLoS One 2014;9:e110925
and hyperglycemic hyperosmolar state. In 3 teaching hospitals in Canada: a multicentre,
180. Chen IW, Lin CW. Improvement in renal
Endotext. Feingold KR, Anawalt B, Blackman MR, retrospective cohort study. Can J Diabetes 2019;
prognosis with prompt hemodialysis in hyper-
et al., Eds. MDText.com, Inc., 2000. Accessed 28 43:309–315.e2
osmolar hyperglycemic state-related rhabdomyo-
September 2023. Available from https://www 167. Tian T, Aaron RE, Seley JJ, et al. Use of
lysis: a case report. Medicine (Baltimore) 2018;
.ncbi.nlm.nih.gov/books/NBK279052/ continuous glucose monitors upon hospital
155. Harris MA, Wagner DV, Heywood M, discharge of people with diabetes: promise, 97:e13647
Hoehn D, Bahia H, Spiro K. Youth repeatedly barriers, and opportunity. J Diabetes Sci Technol 181. Schwarzfuchs D, Rabaev E, Sagy I, et al.
hospitalized for DKA: proof of concept for novel 2024;18:207–214 Clinical and epidemiological characteristics of
interventions in children’s healthcare (NICH). 168. Nguyen KT, Xu NY, Zhang JY, et al. diabetic ketoacidosis in older adults. J Am Geriatr
Diabetes Care 2014;37:e125–e126 Continuous ketone monitoring consensus report Soc 2020;68:1256–1261
156. Ehrmann D, Kulzer B, Roos T, Haak T, Al- 2021. J Diabetes Sci Technol 2022;16:689–715 182. Dhatariya K. Initiation and continuation
Khatib M, Hermanns N. Risk factors and 169. Hamblin PS, Abdul-Wahab AL, Xu SFB, of sodium-glucose cotransporter 2 inhibitors in
prevention strategies for diabetic ketoacidosis in Steele CE, Vogrin S. Diabetic ketoacidosis: a hospital inpatients: ready for prime time?
people with established type 1 diabetes. Lancet canary in the mine for mental health disorders? Diabetes Care 2022;45:2806–2807
Diabetes Endocrinol 2020;8:436–446 Intern Med J 2022;52:1002–1008 183. Galindo RJ, Pasquel FJ, Vellanki P, et al.
157. Tekin Z, Saygili M. The association between 170. Gaffney A, Himmelstein DU, Woolhandler Biochemical parameters of diabetes ketoacidosis
Medicaid expansion and diabetic ketoacidosis S. Prevalence and correlates of patient rationing in patients with end-stage kidney disease and
hospitalizations. Cureus 2022;14:e30631 of insulin in the United States: a national survey. preserved renal function. J Clin Endocrinol Metab
158. Elliott J, Jacques RM, Kruger J, et al. Ann Intern Med 2022;175:1623–1626 2021;106:e2673–e2679
Substantial reductions in the number of diabetic 171. Fang M, Selvin E. Cost-related insulin 184. Dhanasekaran M, Mohan S, Erickson D,
ketoacidosis and severe hypoglycaemia episodes rationing in US adults younger than 65 years with et al. Diabetic ketoacidosis in pregnancy:
requiring emergency treatment lead to reduced diabetes. JAMA 2023;329:1700–1702 clinical risk factors, presentation, and outcomes.
costs after structured education in adults with 172. Nip ASY, Lodish M. Trend of diabetes- J Clin Endocrinol Metab 2022;107:3137–3143
type 1 diabetes. Diabet Med 2014;31:847–853 related hospital admissions during the transition 185. Birkebaek NH, Kamrath C, Grimsmann JM,
159. Lee JH, Orr-Walker BJ. Diabetic ketoacidosis period from adolescence to adulthood in the et al. Impact of the COVID-19 pandemic on long-
admissions at Middlemore Hospital: observational state of California. Diabetes Care 2021;44: term trends in the prevalence of diabetic
study of cause and patient demographics. N Z Med 2723–2728 ketoacidosis at diagnosis of paediatric type 1
J 2020;133:34–40 173. Rewers A, Kuppermann N, Stoner MJ, et al.; diabetes: an international multicentre study
160. Diguisto C, Strachan MWJ, Churchill D, Pediatric Emergency Care Applied Research Network based on data from 13 national diabetes
Ayman G, Knight M. A study of diabetic (PECARN) FLUID Study Group. Effects of fluid registries. Lancet Diabetes Endocrinol 2022;10:
ketoacidosis in the pregnant population in the rehydration strategy on correction of acidosis and 786–794

Dka Hhs Ada Guideline

Uploaded by

Copyright:

Available Formats

Dka Hhs Ada Guideline

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Dka Hhs Ada Guideline

Uploaded by

Copyright:

Available Formats

Diabetes Care 1

Hyperglycemic Crises in Adults Guillermo E. Umpierrez,1

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Some drug classes can affect carbohy-

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Infection/insufﬁcient insulin administration/stress/medication

Absolute insulin deﬁciency Counterregulatory hormones Relative insulin deﬁciency

Glucose utilization Peripheral tissues Glucose utilization

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Glycosuria + osmotic diuresis

Additional contributors: Oxidative stress Inﬂammation

Figure 1—Pathogenesis of DKA and HHS. FFA, free fatty acids.

A. DKA Diagnostic Criteria

Ketosis β-Hydroxybutyrate concentration ≥3.0 mmol/L OR urine ketone strip 2+ or greater

Metabolic Acidosis pH <7.3 and/or bicarbonate concentration <18 mmol/L

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Absence of acidosis pH ≥7.3 and bicarbonate concentration ≥15 mmol/L

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Develops over hours to days Develops over days to a week

Usually alert Change in cognitive state common

Polyuria, polydipsia, weight loss, and dehydration

1/3 of hyperglycemic emergencies have a hybrid DKA/HHS presentation

Figure 3—Clinical presentation in patients with DKA and HHS.

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

I.V. Fluids Insulin Potassium

Moderate or Establish adequate renal function

s.c. insulin i.v. insulin i.v. insulin K+ <3.5 mmol/L

Severe Consider 10–20 mmol/L/h

Figure 4—Treatment pathways for DKA and HHS. BOHB, b-hydroxybutyrate.

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Table 3—Complications during treatment of DKA and HHS

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Table 4—Features of DKA and HHS occurring in special populations

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dci24-0032/773312/dci240032.pdf by Bangladesh Institution user on 22 June 2024

You might also like