Diabetes Mellitus: April 2014
Diabetes Mellitus: April 2014
Diabetes Mellitus: April 2014
April 2014
Definition
Epidemiology
• The most common endocrine metabolic disorder in
children & adolescents
• Bimodal peak age of presentation
– 5-7 years – Time for exposure to infections
– Puberty – ↑ in growth hormone secretion + ↑ gonadal
steroids
• ↑ed incidence in individuals with
HLA – DR3 or HLA – DR4 gene
• Polygenic ( multifactorial) inheritance
Natural history includes
1. Initiation of autoimmunity
2. Preclinical β-cell autoimmunity with
progressive defect of insulin secretion
3. Onset of clinical diabetes
4. Transient remission “honeymoon period”
5. Established DM
6. Development of complications
Etiology
Immunologic damage to the insulin-producing B-cells of the pancreas
Genetic predisposition – polygenic
The most important genes are located within the MHC HLA class II
Genes -HLA- DR3 and HLA-DR4 account for about 60% genetic
susceptibility
Environmental factors – Trigger autoimmunity
Viral infections
– Coxsackie B virus
– Mumps
– CMV
– Rubella virus
Environmental factors
• Pathogens can precipitate the self-reactive
process by 3 mechanisms.
1. Molecular mimicry b/n viral proteins & self-
proteins
2. Antigen presenting cells present the self-
peptides to T cells
3. Cytokines secreted during viral infection up-
regulate the expression of co-stimulatory
molecules
Cont,
• Prenatal infection with rubella is associated
with β-cell autoimmunity in up to 70%, with
development of T1DM in up to 40% of
infected children
• Pubertal changes may contribute to
accelerated onset of type 1 DM in genetically
susceptible individuals
Pathogenesis
Autoimmune Injury
• T cell–mediated autoimmune destruction of the
pancreatic islets
• Genetic predisposition & environmental factors lead to
initiation of the autoimmune process
• Anti–islet cell antibodies (GADA, ICA,IA, and IAA)
before the onset of diabetes
• Gradual and progressive destruction of β cells ,and at
the onset of clinical diabetes 80–90% of the pancreatic
islets are destroyed
The autoimmune response against pancreatic
β cells consist of 4 phases:
Proposed model of the pathogenesis & natural
history of T1DM
IAA- insulin auto ab
GADA- glutamic acid decarboxylase ab
ICA- islet cell ab
IVGTT- IV glucose tolerance test
Pathophysiology
• Hyperglycemia – Osmotic diuresis (glycosuria)
→ polyuria & Polydipsia
• Lack of glucose utilization by the body
→ Polyphagia
• Mobilization of fat from adipose tissues and excess
free fatty acid production that are converted to
ketone bodies
– Ketonemia
– Ketonuria
Cont,
• Impaired Protein synthesis resulting in
Weight loss
Muscle wasting
Growth retardation
• Loss of calories, electrolyte & persistent DHN due to polyuria
physiologic stress
hyper secretion of counter– regulatory hormones
impair insulin secretion (Epinephrine)
antagonizing its action (epinephrine, cortisol, GH)
Cont,
Insulin deficiency + Counter- regulatory hormones result in
• Hyperglycemia causes
• Movement of water out of cells
→ Intracellular DHN
→ Extracellular fluid expansion and hyponatremia
Effect of changes
Clinical Manifestation
Symptoms of hyperglycemia
– Polyuria/nocturia , polydipsia, polyphagia
– Weight loss
– Recurrent infections /Candidiasis/
– May present initially with DKA up to 20% of the
cases
Laboratory
• RBS ≥ 200mg/dl
• FBS ≥126 mg/dl or
• U/A
– Glucosuria
– Ketonuria
Cont,
CBC (Hgb A1C)
Serum electrolyte
– Hypokalemia
– Hypophosphatemia
– Serum Bicarbonate – low
– PH – low in DKA
– Antithyroid peroxidase and antithyroglobulin
antibodies
Criteria for Impaired Glucose Tolerance &
DM
Complications
Acute
– DKA
– Hypoglycemia
– Infection
– Cerebral edema
Chronic complications
1. Microvascular complications
-Due to glycation of tissue proteins resulting in vessel wall
thickening
-Retinopathy
-Nephropathy
2. Macrovascular complications
– Coronary artery disease
– Cerebrovascular disease
– Peripheral vascular disease
Diabetic Ketoacidosis(DKA)
• End result of metabolic abnormalities from severe
deficiency or effectiveness of insulin
• Leading cause of morbidity & mortality in Type I-DM
• Occurs in 20–40% of children with new-onset DM
Risk factors
• Initial presentation
• Infection & other medical illnesses
• Insulin omission/poor control
• Previous DKA
Clinical
• Poly Symptoms
• Profound dehydration
Hypotension
Sunken eyes
Dry mucosa
Lethargy – coma
• Kusmaul respiration
Diagnosis
Biochemical data
• Hyperglycemia
• Venus PH < 7.3 and / or
• Venous bicarbonate < 15 mmol/L
• Urinary ketone ≥ 3+
• Glycosuria
• Ketonemia
• Hyponatremia
• Hypophosphatemia
DKA Classification
Parameter Normal Mild Moderate Severe
Monitoring
Frequent blood glucose monitoring
Insulin dose adjustment
How insulin works
• Electrolyte imbalance
• Brain edema
• Fluid over load
• Hyponatremia
Other related events
Somogyi phenomenon
Hypoglycemia induced morning hyperglycemia
Due to larger doses of evening insulin and an
exaggerated counter-regulatory response
Dawn phenomenon
Morning hyperglycemia with out preceding
hypoglycemia
Is due to overnight growth hormone secretion and
increased insulin clearance
Cont,
Brittle diabetes
- Marked fluctuation of blood glucose often with
recurrent DKA despite frequent insulin dose
adjustment
Hypoglycemia
Hyperglycemia and ketosis
Diet Managment