Diabetes Mellitus

What is diabetes?
• Diabetes mellitus (DM) is a group of diseases
characterized by high levels of blood glucose
resulting from defects in insulin production, insulin
action, or both.

• The term diabetes mellitus describes a metabolic

disorder of multiple aetiology characterized by
chronic hyperglycaemia with disturbances of
carbohydrate, fat and protein metabolism resulting
from defects in insulin secretion, insulin action, or
both.

• The effects of diabetes mellitus include long–term

damage, dysfunction and failure of various organs.
 Diabetes
• Diabetes mellitus may present with characteristic
symptoms such as thirst, polyuria, blurring of vision,
and weight loss.

• In its most severe forms, ketoacidosis or a non–

ketotic hyperosmolar state may develop and lead to
stupor, coma and, in absence of effective treatment,
death.

• Often symptoms are not severe, or may be absent,

and consequently hyperglycaemia sufficient to cause
pathological and functional changes may be present
for a long time before the diagnosis is made.
 Diabetes Long-term Effects
• The long–term effects of diabetes mellitus
include progressive development of the specific
complications of retinopathy with potential
blindness, nephropathy that may lead to renal
failure, and/or neuropathy with risk of foot
ulcers, amputation, Charcot joints, and features
of autonomic dysfunction, including sexual
dysfunction.

• People with diabetes are at increased risk of

cardiovascular, peripheral vascular and
cerebrovascular disease.
 Burden of Diabetes
• The development of diabetes is projected to reach
pandemic proportions over the next10-20 years.

• International Diabetes Federation (IDF) data indicate

that by the year 2025, the number of people affected
will reach 333 million –90% of these people will have
Type 2 diabetes.

• In most Western societies, the overall prevalence has

reached 4-6%, and is as high as 10-12% among 60-
70-year-old people.

• The annual health costs caused by diabetes and its

complications account for around 6-12% of all
health-care expenditure.
 Types of Diabetes

• Type 1 Diabetes Mellitus

• Type 2 Diabetes Mellitus
• Gestational Diabetes
• Other types:
LADA (
MODY (maturity-onset diabetes of
youth)
Secondary Diabetes Mellitus
 Type 1 diabetes
• Was previously called insulin-dependent diabetes mellitus
(IDDM) or juvenile-onset diabetes.
• Type 1 diabetes develops when the body’s immune system
destroys pancreatic beta cells, the only cells in the body
that make the hormone insulin that regulates blood
glucose.
• This form of diabetes usually strikes children and young
adults, although disease onset can occur at any age.
• Type 1 diabetes may account for 5% to 10% of all
diagnosed cases of diabetes.
• Risk factors for type 1 diabetes may include autoimmune,
genetic, and environmental factors.
 Type 2 diabetes
Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or
adult-onset diabetes.
Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of
diabetes.
It usually begins as insulin resistance, a disorder in which the cells do not
use insulin properly. As the need for insulin rises, the pancreas gradually
loses its ability to produce insulin.
Type 2 diabetes is associated with older age, obesity, family history of
diabetes, history of gestational diabetes, impaired glucose metabolism,
physical inactivity, and race/ethnicity.
African Americans, Hispanic/Latino Americans, American Indians, and some
Asian Americans and Native Hawaiians or Other Pacific Islanders are at
particularly high risk for type 2 diabetes.
Type 2 diabetes is increasingly being diagnosed in children and adolescents.
 Gestational diabetes
A form of glucose intolerance that is diagnosed in some women
during pregnancy.
Gestational diabetes occurs more frequently among African
Americans, Hispanic/Latino Americans, and American Indians. It is
also more common among obese women and women with a family
history of diabetes.
During pregnancy, gestational diabetes requires treatment to
normalize maternal blood glucose levels to avoid complications in
the infant.
After pregnancy, 5% to 10% of women with gestational diabetes are
found to have type 2 diabetes.
Women who have had gestational diabetes have a 20% to 50%
chance of developing diabetes in the next 5-10 years.
 Other types of DM
• Other specific types of diabetes result
from specific genetic conditions (such
as maturity-onset diabetes of youth),
surgery, drugs, malnutrition, infections,
and other illnesses.

• Such types of diabetes may account for

1% to 5% of all diagnosed cases of
diabetes.
 LADA
• Latent Autoimmune Diabetes in Adults (LADA) is a
form of autoimmune (type 1 diabetes) which is
diagnosed in individuals who are older than the
usual age of onset of type 1 diabetes.
• Alternate terms that have been used for "LADA"
include Late-onset Autoimmune Diabetes of
Adulthood, "Slow Onset Type 1" diabetes, and
sometimes also "Type 1.5
• Often, patients with LADA are mistakenly thought
to have type 2 diabetes, based on their age at the
time of diagnosis.
LADA (cont.)
 LADA (cont.)
• About 80% of adults apparently with recently
diagnosed Type 2 diabetes but with GAD
auto-antibodies (i.e. LADA) progress to
insulin requirement within 6 years.

• The potential value of identifying this group

at high risk of progression to insulin
dependence includes:
– the avoidance of using metformin treatment
– the early introduction of insulin therapy
 MODY
• MODY – Maturity Onset Diabetes of the Young

• MODY is a monogenic form of diabetes with an autosomal

dominant mode of inheritance:
– Mutations in any one of several transcription factors or in the
enzyme glucokinase lead to insufficient insulin release from
pancreatic ß-cells, causing MODY.
– Different subtypes of MODY are identified based on the mutated
gene.

• Originally, diagnosis of MODY was based on presence of

non-ketotic hyperglycemia in adolescents or young adults
in conjunction with a family history of diabetes.

• However, genetic testing has shown that MODY can occur

at any age and that a family history of diabetes is not
always obvious.
MODY (cont.)
 MODY (cont.)
Within MODY, the different subtypes can essentially be
divided into 2 distinct groups: glucokinase MODY and
transcription factor MODY, distinguished by characteristic
phenotypic features and pattern on oral glucose tolerance
testing.

Glucokinase MODY requires no treatment, while

transcription factor MODY (i.e. Hepatocyte nuclear factor -
1alpha) requires low-dose sulfonylurea therapy and PNDM
(caused by Kir6.2 mutation) requires high-dose
sulfonylurea therapy.
 Secondary DM
Secondary causes of Diabetes mellitus include:

Acromegaly,
Cushing syndrome,
Thyrotoxicosis,
Pheochromocytoma
Chronic pancreatitis,
Cancer
Drug induced hyperglycemia:
◦ Atypical Antipsychotics - Alter receptor binding characteristics, leading to increased insulin resistance.
◦ Beta-blockers - Inhibit insulin secretion.
◦ Calcium Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic calcium release.
◦ Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.
◦ Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium channels.
◦ Naicin - They cause increased insulin resistance due to increased free fatty acid mobilization.
◦ Phenothiazines - Inhibit insulin secretion.
◦ Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
◦ Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause increased insulin
resistance due to increased free fatty acid mobilization.
 Prediabetes: Impaired glucose tolerance and impaired fasting
glucose

Prediabetes is a term used to distinguish people who are at

increased risk of developing diabetes. People with prediabetes
have impaired fasting glucose (IFG) or impaired glucose
tolerance (IGT). Some people may have both IFG and IGT.

IFG is a condition in which the fasting blood sugar level is

elevated (100 to 125 milligrams per decilitre or mg/dL) after an
overnight fast but is not high enough to be classified as diabetes.

IGT is a condition in which the blood sugar level is elevated (140

to 199 mg/dL after a 2-hour oral glucose tolerance test), but is
not high enough to be classified as diabetes.
Prediabetes: Impaired glucose tolerance and impaired
fasting glucose (cont.)

• Progression to diabetes among those with

prediabetes is not inevitable. Studies suggest that
weight loss and increased physical activity among
people with prediabetes prevent or delay diabetes
and may return blood glucose levels to normal.

• People with prediabetes are already at increased

risk for other adverse health outcomes such as
heart disease and stroke.
Diagnosis of Diabetes Mellitus
Values of Diagnosis of Diabetes Mellitus
 Prevention or delay of diabetes:
Life style modification
Research studies have found that lifestyle changes can prevent
or delay the onset of type 2 diabetes among high-risk adults.

These studies included people with IGT and other high-risk

characteristics for developing diabetes.

Lifestyle interventions included diet and moderate-intensity

physical activity (such as walking for 2 1/2 hours each week).

In the Diabetes Prevention Program, a large prevention study of

people at high risk for diabetes, the development of diabetes
was reduced 58% over 3 years.
 Prevention or delay of diabetes: Medications
Studies have shown that medications have been successful in preventing
diabetes in some population groups.
In the Diabetes Prevention Program, people treated with the drug
metformin reduced their risk of developing diabetes by 31% over 3 years.
Treatment with metformin was most effective among younger, heavier
people (those 25-40 years of age who were 50 to 80 pounds overweight)
and less effective among older people and people who were not as
overweight.
Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the
drug acarbose reduced the risk of developing diabetes by 25% over 3 years.
Other medication studies are ongoing. In addition to preventing progression
from IGT to diabetes, both lifestyle changes and medication have also been
shown to increase the probability of reverting from IGT to normal glucose
tolerance.
 Management of
Diabetes Mellitus
 Management of DM
• The major components of the
treatment of diabetes are:

A • Diet and Exercise

• Oral hypoglycaemic
B therapy

C • Insulin Therapy
 A. Diet
Diet is a basic part of management in every case.
Treatment cannot be effective unless adequate
attention is given to ensuring appropriate nutrition.

Dietary treatment should aim at:

◦ ensuring weight control
◦ providing nutritional requirements
◦ allowing good glycaemic control with blood glucose levels
as close to normal as possible
◦ correcting any associated blood lipid abnormalities
 A. Diet (cont.)
The following principles are recommended as dietary guidelines for people
with diabetes:

Dietary fat should provide 25-35% of total intake of calories but saturated fat
intake should not exceed 10% of total energy. Cholesterol consumption should
be restricted and limited to 300 mg or less daily.

Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable
body weight). Requirements increase for children and during pregnancy.
Protein should be derived from both animal and vegetable sources.

Carbohydrates provide 50-60% of total caloric content of the diet.

Carbohydrates should be complex and high in fibre.

Excessive salt intake is to be avoided. It should be particularly restricted in

people with hypertension and those with nephropathy.
 Exercise
• Physical activity promotes weight reduction and
improves insulin sensitivity, thus lowering blood
glucose levels.

• Together with dietary treatment, a programme of

regular physical activity and exercise should be
considered for each person. Such a programme
must be tailored to the individual’s health status
and fitness.

• People should, however, be educated about the

potential risk of hypoglycaemia and how to avoid
it.
 B. Oral Anti-Diabetic Agents

• There are currently four classes of oral

anti-diabetic agents:

i. Biguanides
ii. Insulin Secretagogues – Sulphonylureas
iii. Insulin Secretagogues – Non-
sulphonylureas
iv. α-glucosidase inhibitors
v. Thiazolidinediones (TZDs)
 B.1 Oral Agent Monotherapy

• If glycaemic control is not achieved (HbA1c >

6.5% and/or; FPG > 7.0 mmol/L or; RPG
>11.0mmol/L) with lifestyle modification within 1
–3 months, ORAL ANTI-DIABETIC AGENT should
be initiated.

• In the presence of marked hyperglycaemia in

newly diagnosed symptomatic type 2 diabetes
(HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14
mmol/L), oral anti-diabetic agents can be
considered at the outset together with lifestyle
modification.
 B.1 Oral Agent Monotherapy (cont.)

As first line therapy:

Obese type 2 patients, consider use of metformin, acarbose or TZD.

Non-obese type 2 patients, consider the use of metformin or insulin

secretagogues

Metformin is the drug of choice in overweight/obese patients. TZDs and

acarbose are acceptable alternatives in those who are intolerant to metformin.

If monotherapy fails, a combination of TZDs, acarbose and metformin is

recommended. If targets are still not achieved, insulin secretagogues may be
added
 B.2 Combination Oral Agents

Combination oral agents is indicated in:

• Newly diagnosed symptomatic

patients with HbA1c >10

• Patients who are not reaching targets

after 3 months on monotherapy
 B.3 Combination Oral Agents and Insulin

• If targets have not been reached after optimal dose of

combination therapy for 3 months, consider adding
intermediate-acting/long-acting insulin (BIDS).

• Combination of insulin+ oral anti-diabetic agents (BIDS) has been

shown to improve glycaemic control in those not achieving target
despite maximal combination oral anti-diabetic agents.

• Combining insulin and the following oral anti-diabetic agents has

been shown to be effective in people with type 2 diabetes:
– Biguanide (metformin)
– Insulin secretagogues (sulphonylureas)
– Insulin sensitizers (TZDs)(the combination of a TZD plus insulin is not an
approved indication)
– α-glucosidase inhibitor (acarbose)

• Insulin dose can be increased until target FPG is achieved.

 Diabetes
Management
Algorithm
Oral Hypoglycaemic Medications
General Guidelines for Use of Oral Anti-Diabetic Agent in Diabetes

• In elderly non-obese patients, short acting insulin secretagogues

can be started but long acting Sulphonylureas are to be avoided.
Renal function should be monitored.

• Oral anti-diabetic agent s are not recommended for diabetes in

pregnancy

• Oral anti-diabetic agents are usually not the first line therapy in
diabetes diagnosed during stress, such as infections. Insulin
therapy is recommended for both the above

• Targets for control are applicable for all age groups. However, in
patients with co-morbidities, targets are individualized

• When indicated, start with a minimal dose of oral anti-diabetic

agent, while reemphasizing diet and physical activity. An
appropriate duration of time (2-16 weeks depending on agents
used) between increments should be given to allow achievement
of steady state blood glucose control
 C. Insulin Therapy

Short-term use:
• Acute illness, surgery, stress and emergencies
• Pregnancy
• Breast-feeding
• Insulin may be used as initial therapy in type 2 diabetes
• in marked hyperglycaemia
• Severe metabolic decompensation (diabetic ketoacidosis,
hyperosmolar nonketotic coma, lactic acidosis, severe
hypertriglyceridaemia)

Long-term use:
• If targets have not been reached after optimal dose of
combination therapy or BIDS, consider change to multi-dose
insulin therapy. When initiating this,insulin secretagogues should
be stopped and insulin sensitisers e.g. Metformin or TZDs, can
be continued.
 Insulin regimens
The majority of patients will require more than one daily injection if good
glycaemic control is to be achieved. However, a once-daily injection of an
intermediate acting preparation may be effectively used in some patients.

Twice-daily mixtures of short- and intermediate-acting insulin is a commonly

used regimen.

 In some cases, a mixture of short- and intermediate-acting insulin may be

given in the morning. Further doses of short-acting insulin are given before
lunch and the evening meal and an evening dose of intermediate-acting insulin
is given at bedtime.

Other regimens based on the same principles may be used.

A regimen of multiple injections of short-acting insulin before the main meals,

with an appropriate dose of an intermediate-acting insulin given at bedtime,
may be used, particularly when strict glycaemic control is mandatory.
Overview of Insulin and Action
 Self-Care

 Patients should be educated to practice self-care. This allows

the patient to assume responsibility and control of his / her
own diabetes management. Self-care should include:

◦ Blood glucose monitoring

◦ Body weight monitoring
◦ Foot-care
◦ Personal hygiene
◦ Healthy lifestyle/diet or physical activity
◦ Identify targets for control
◦ Stopping smoking