Annexure

Type 2 diabetes Mellitus- The Disease

Overview

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic non communicable disease (NCD) which
has attained epidemic proportions worldwide. T2DM is growing alarmingly in India. Today, India
is home to more than 65.1 million people with the disease, compared to 50.8 million in 2010.
Studies conducted in the past few years have reported that the incidence of T2DM in Asian Indian
people is among the highest in the world.

[Note: There are 2 types of Diabetes- Diabetes Mellitus and Diabetes Insipidus. Diabetes Insipidus is
a rare condition and is out of scope of current discussion. Diabetes mellitus can be classified into 2
types- Type 1 and Type 2. In this entire discussion, the term diabetes will refer to Type 2 Diabetes
Mellitus (T2DM)]

Pathology

Patients suffering from T2DM suffer from an abnormality because of which they are not able to
utilize glucose for energy generation. In healthy individuals glucose derived from food is
transferred into cells for energy generation via chemical called insulin. In case of T2DM, insulin
fails to do this function- either because of inefficiency (known as insulin resistance) or because of
insufficiency. This leads to increasing levels of glucose in blood. A persistent high level of glucose
in blood is harmful; it ultimately ends up damaging most of the body systems and an early death.

Symptoms

Increased thirst and frequent urination: Excess sugar building up in bloodstream causes
fluid to be pulled from the tissues. This leads to thirst. As a result, patient may drink water
more often and urinate more than usual.
Increased hunger: Without enough insulin to move sugar into cells, muscles and organs
become depleted of energy. This triggers intense hunger.
Weight loss: Despite eating more than usual to relieve hunger, patient may lose weight.
Without the ability to metabolize glucose, the body uses alternative fuels stored in muscle
and fat. Calories are lost as excess glucose is released in the urine.
Fatigue: If cells are deprived of sugar, patient becomes tired and irritable.
Blurred vision: If blood sugar is too high, fluid may be pulled from the lenses of eyes. This
may affect patients ability to focus.
Slow-healing sores or frequent infections: Type 2 diabetes affects bodys ability to heal and
resist infections.

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 Areas of darkened skin: Some patients with T2DM have patches of dark, velvety skin in
the folds and creases of their bodies usually in the armpits and neck. This condition,
called acanthosis nigricans, may be a sign of insulin resistance.

Risk Factors

Certain factors increase the risk of contracting T2DM, including:

Weight: Being overweight is a primary risk factor for type 2 diabetes. The more fatty tissue
one has, the more resistant the cells become to insulin. However, one doesnt has to be
overweight to develop type 2 diabetes.
Fat distribution: If body stores fat primarily in abdomen, risk of type 2 diabetes is greater
than if body stores fat elsewhere, such as hips and thighs.
Inactivity: The less active one is, the greater is the risk of type 2 diabetes. Physical activity
helps control your weight, uses up glucose as energy and makes cells more sensitive to
insulin.
Family history: The risk of type 2 diabetes increases if ones parent or sibling has type 2
diabetes.
Race: Although it's unclear why, people of certain races including blacks, Hispanics,
American Indians and Asian-Americans are more likely to develop type 2 diabetes than
whites are.
Age: The risk of type 2 diabetes increases as one gets older, especially after age 45. That's
probably because people tend to exercise less, lose muscle mass and gain weight as they
age. But type 2 diabetes is also increasing dramatically among children, adolescents and
younger adults.
Prediabetes: Prediabetes is a condition in which patints blood sugar level is higher than
normal, but not high enough to be classified as diabetes. Left untreated, prediabetes often
progresses to type 2 diabetes.
Gestational diabetes: If a female had developed gestational diabetes when she was
pregnant, her risk of developing type 2 diabetes increases. If a female gives birth to a baby
weighing more than 9 pounds (4 kilograms), she is also at risk of type 2 diabetes.
Polycystic ovarian syndrome: For females, having polycystic ovarian syndrome a
common condition characterized by irregular menstrual periods, excess hair growth and
obesity increases the risk of diabetes.

Complications

Type 2 diabetes can be easy to ignore, especially in the early stages when patient is feeling fine.
But diabetes affects many major organs, including heart, blood vessels, nerves, eyes and kidneys.
Controlling blood sugar levels can help prevent these complications.

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Although long-term complications of diabetes develop gradually, they can eventually be disabling
or even life-threatening. Some of the potential complications of diabetes include:

Heart and blood vessel disease: Diabetes significantly increases the risk of various
cardiovascular problems, including coronary artery disease with chest pain (angina), heart
attack, stroke, narrowing of arteries (atherosclerosis) and high blood pressure.
Nerve damage (neuropathy): Excess sugar can injure the walls of the tiny blood vessels
(capillaries) that nourish nerves, especially in the legs. This may cause tingling, numbness,
burning or pain that usually begins at the tips of the toes or fingers and gradually spreads
upward. Poorly controlled blood sugar can eventually lead to loss of all sense of feeling in
the affected limbs. Damage to the nerves that control digestion can cause problems such
as nausea, vomiting, diarrhea or constipation. For men, erectile dysfunction may result.
Kidney damage (nephropathy): The kidneys filter waste from blood. Diabetes can damage
this delicate filtering system. Severe damage can lead to kidney failure or irreversible end-
stage kidney disease, which eventually requires dialysis or a kidney transplant.
Eye damage: Diabetes can damage the blood vessels of the retina (diabetic retinopathy),
eventually leading to blindness. Diabetes also accentuates the risk of other serious vision
conditions, such as cataracts and glaucoma.
Foot damage: Nerve damage in the feet or poor blood flow to the feet increases the risk of
various foot related complications. Left untreated, cuts and blisters become serious
infections; this may heal poorly. Severe damage might need toe, foot or leg amputation.
Hearing impairment: Hearing problems are increasingly common in people with diabetes.
Skin conditions: Diabetes leaves patients more susceptible to skin problems, including
bacterial and fungal infections.
Alzheimer's disease: The poorer blood sugar control, the greater the risk of Alzheimer's
disease appears to be, although exact connection between these two conditions still
remains unclear.

Diagnosis

Glycated hemoglobin (A1C) test: This blood test indicates average blood sugar level for the
past two to three months. It measures the percentage of blood sugar attached to
hemoglobin, the oxygen-carrying protein in red blood cells. The higher the blood sugar
levels are, the more the hemoglobin gets attached with sugar. An A1C level of 6.5 percent
or higher on two separate tests indicates diabetes. A result between 5.7 and 6.4 percent is
considered prediabetes, which indicates a high risk of developing diabetes. Normal levels
are below 5.7 percent.
Random blood sugar test: A blood sample will be taken at a random time. Blood sugar
values are expressed in milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L).
Regardless of when patient last ate, a random blood sugar level of 200 mg/dL (11.1 mmol/L)

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 or higher suggests diabetes, especially when coupled with any of the signs and symptoms
of diabetes, such as frequent urination and extreme thirst.
Fasting blood sugar test: A blood sample will be taken after an overnight fast. A fasting
blood sugar level less than 100 mg/dL (5.6 mmol/L) is normal. A fasting blood sugar level
from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) is considered prediabetes. If it's 126 mg/dL (7
mmol/L) or higher on two separate tests, its diabetes.
Oral glucose tolerance test: For this test, one fasts overnight, and the fasting blood sugar
level is measured. Then patient drinks a sugary liquid, and blood sugar levels are tested
periodically for the next two hours. A blood sugar level less than 140 mg/dL (7.8 mmol/L)
is normal. A reading between 140 and 199 mg/dL (7.8 mmol/L and 11.0 mmol/L) indicates
prediabetes. A reading of 200 mg/dL (11.1 mmol/L) or higher after two hours may indicate
diabetes.

The American Diabetes Association recommends routine screening for type 2 diabetes beginning
at age 45, especially if you're overweight. If the results are normal, repeat the test every three
years. If the results are borderline, one must doctor when to come back for another test.

Screening is also recommended for people who are under 45 and overweight if there are other
heart disease or diabetes risk factors present, such as a sedentary lifestyle, a family history of type
2 diabetes, a personal history of gestational diabetes or blood pressure above 140/90 millimeters
of mercury (mm Hg).

If one is diagnosed with diabetes, the doctor may do other tests to distinguish between type 1 and
type 2 diabetes since the two conditions often require different treatments.

HbA1C levels need to be checked between two and four times a year. The target A1C goal may vary
depending on age and other factors. However, for most people, the American Diabetes
Association recommends an A1C level below 7 percent.

Compared with repeated daily blood sugar tests, the A1C test is a better indicator of how well the
diabetes treatment plan is working. An elevated A1C level may signal the need for a change in
medication, meal plan or activity level. In addition to the A1C test, doctor will take blood and
urine samples periodically to check cholesterol levels, thyroid function, liver function and kidney
function. The doctor will also assess blood pressure. Regular eye and foot exams also are
important.

Management of Type 2 Diabetes Mellitus

Management of T2DM consists of following elements:

Healthy eating, Regular exercise and blood glucose monitoring:

Contrary to popular perception, there's no specific diabetes diet. However, it's important to
center diet on high-fiber, low-fat foods. Low glycemic index foods also may be helpful. The

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 glycemic index is a measure of how quickly a food causes a rise in your blood sugar. Foods
with a high glycemic index raise your blood sugar quickly. Low glycemic index foods may help
you achieve a more stable blood sugar. Foods with a low glycemic index typically are foods
that are higher in fiber.

Everyone needs regular aerobic exercise, and people who have type 2 diabetes are no
exception. Aim should be for at least 30 minutes of aerobic exercise five days of the week.
Stretching and strength training exercises are important, too. A combination of exercises
aerobic exercises, such as walking or dancing on most days, combined with resistance
training, such as weightlifting or yoga twice a week often helps control blood sugar more
effectively than either type of exercise alone.

Depending on your treatment plan, a diabetic may need to check and record blood sugar level
every now and then or, if on insulin, multiple times a day.

Drugs

Early initiation of pharmacologic therapy is associated with improved glycemic control and
reduced long-term complications in type 2 diabetes. Drug classes used for the treatment of
type 2 diabetes include the following:

o Biguanides
o Sulfonylureas (SU)
o Meglitinide derivatives
o Alpha-glucosidase inhibitors
o Thiazolidinediones (TZDs)
o Glucagonlike peptide1 (GLP-1) agonists
o Dipeptidyl peptidase IV (DPP-4) inhibitors
o Selective sodium-glucose transporter-2 (SGLT-2) inhibitors
o Insulins
o Amylinomimetics
o Bile acid sequestrants
o Dopamine agonists

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