TYPE 2 DIABETES MELLITUS (T2DM)

BACKGROUND

Type 2 diabetes, once known as adult-onset or non-insulin-dependent diabetes, is a chronic condition that affects the way your body metabolizes sugar (glucose), your body's important source of fuel.

All the cells in your body need sugar to work normally. Sugar gets into the cells with the help of a hormone called insulin. If there is not enough insulin, or if the body stops responding to insulin, sugar builds up in the blood. That is what happens to people with diabetes.

There are 2 different types of diabetes. In type 1 diabetes, the problem is that the body makes little or no insulin. In type 2 diabetes, the problem is:

• The body's cells do not respond to insulin
• The body does not make enough insulin
• Or both

DISEASE OCCURRENCE IN POPULATION:

According to WHO, the number of people with diabetes has risen from 108 million in 1980 to 422 million in 2014. The global prevalence of diabetes among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014. In 2012, an estimated 1.5 million deaths were directly caused by diabetes and another 2.2 million deaths were attributable to high blood glucose. WHO projects that diabetes will be the 7th leading cause of death in 2030.

Pakistan ranks at number six in terms of number of people with diabetes worldwide. It was estimated that in 2000 there were 5.2 million diabetic patients and this will rise to 13.9 million by 2020, leading Pakistan to 4th most populous country for patients with diabetes mellitus.

Type II diabetes is a worldwide health problem and affecting more than 415 million individual and expected to reach 642 million individuals by end of 2040.

It is reported that 120,000 people die in Pakistan every year as a result of type II diabetes and its related complications. Prevalence of Type 2 diabetes in Pakistan is high ranging from 7.6 % (5.2 million populations) to 11 % and for 2030 it will increase to around 15% (14 million populations).

RISK FACTORS:

FAMILY HISTORY: Compared with individuals without a family history of type 2 diabetes, individuals with a family history in any first degree relative have a two to three-fold increased risk of developing diabetes.

ETHNICITY: Data from the prospective Nurses' Health Study (NHS) collected over 20 years found that the risk for developing diabetes in women, corrected for BMI, was increased for Asians, Hispanics, and African Americans compared with whites.

OBESITY: The risk of type 2 diabetes rises with increasing body weight. The more fatty tissue you have, the more resistant your cells become to insulin.

FAT DISTRIBUTION: The distribution of excess fatty tissue is another important determinant of the risk of insulin resistance and type 2 diabetes. The degree of insulin resistance and the incidence of type 2 diabetes are highest in those subjects with central or abdominal obesity, as measured by waist circumference or waist-to-hip circumference ratio.

INACTIVITY: A sedentary lifestyle lowers energy expenditure, promotes weight gain, and increases the risk of type 2 diabetes. Among sedentary behaviors, prolonged television watching is consistently associated with the development of obesity and diabetes. Physical inactivity, even without weight gain, appears to increase the risk of type 2 diabetes.

AGE: The risk of type 2 diabetes increases as you get 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 your 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 you developed gestational diabetes when you were pregnant, your risk of developing type 2 diabetes increases. If you gave birth to a baby weighing more than 9 pounds (4 kilograms), you're also at risk of type 2 diabetes.

POLYCYSTIC OVARIAN SYNDROME: For women, having polycystic ovarian syndrome — a common condition characterized by irregular menstrual periods, excess hair growth and obesity — increases the risk of diabetes.

SMOKING: Several large studies have raised the possibility that cigarette smoking increases the risk of type 2 diabetes. While a definitive causal association has not been established, a relationship between cigarette smoking and diabetes mellitus is biologically possible based upon a number of observations:

• Smoking increases the blood glucose concentration after an oral glucose challenge.
• Smoking may impair insulin sensitivity.
• Cigarette smoking has been linked to increased abdominal fat distribution and greater waist-to-hip ratio and may have an impact upon glucose tolerance

SLEEP DURATION: Quantity and quality of sleep may predict the risk of development of type 2 diabetes mellitus. Compared with approximately eight hours / day of sleep, short (≤5 to 6 hours / day) and long (>8 to 9 hours / day) duration of sleep were significantly associated with an increased risk of type 2 diabetes

DIETARY PATTERNS: Dietary patterns affect the risk of type 2 diabetes mellitus. Consumption of red meat, processed meat, and sugar sweetened beverages is associated with an increased risk of diabetes, whereas consumption of a diet high in fruits, vegetables, nuts, whole grains, and olive oil is associated with a reduced risk.

SIGN AND SYMPOTOMS:

Signs and symptoms of type 2 diabetes often develop slowly. In fact, you can have type 2 diabetes for years and not know it. Look for:

• Increased thirst and frequent urination: Excess sugar building up in your bloodstream causes fluid to be pulled from the tissues. This may leave you thirsty. As a result, you may drink — and urinate — more than usual.
• Increased hunger: Without enough insulin to move sugar into your cells, your muscles and organs become depleted of energy. This triggers intense hunger.
• Weight loss: Despite eating more than usual to relieve hunger, you 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 your cells are deprived of sugar, you may become tired and irritable.
• Blurred vision: If your blood sugar is too high, fluid may be pulled from the lenses of your eyes. This may affect your ability to focus.
• Slow-healing sores or frequent infections: Type 2 diabetes affects your ability to heal and resist infections.
• Areas of darkened skin: Some people with type 2 diabetes 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.

COMPLICATIONS:

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

• Increases your risk of various cardiovascular problems, including coronary artery disease with chest pain (angina), heart attack, stroke, narrowing of the arteries (atherosclerosis) and high blood pressure.
• Increase risk of nerve damage (Neuropathy) especially in the legs. This can cause tingling, numbness, burning or pain that usually begins at the tips of the toes or fingers and gradually spreads upward.
• Diabetes can cause Kidney damage (Neuropathy), severe damage can lead to kidney failure or irreversible end-stage kidney disease, which requires dialysis or a kidney transplant.
• Diabetes can damage the blood vessels of the retina (diabetic retinopathy), potentially leading to blindness, cataracts and glaucoma.
• Diabetes can causenerve damage in the feet or poor blood flow to the feet increases the risk of various foot complications.
• Diabetes may leave you more susceptible to skin problems, including bacterial and fungal infections.
• High blood sugar levels can be dangerous for both the mother and the baby. The risk of miscarriage, stillbirth and birth defects are increased when diabetes isn't well-controlled. For the mother, diabetes increases the risk of diabetic ketoacidosis, diabetic eye problems (retinopathy), pregnancy-induced high blood pressure and preeclampsia.
• Hearing problems are more common in people with diabetes.
• Type 2 diabetes may increase the risk of Alzheimer's disease.

DIAGNOSTIC TEST:

To diagnose type 2 diabetes, you'll be given a:

• Glycated hemoglobin (A1C) test: This blood test indicates your 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 your blood sugar levels, the more hemoglobin you'll have with sugar attached. An A1C level of 6.5 percent or higher on two separate tests indicates you have 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.

If the A1C test isn't available, or if you have certain conditions — such as if you're pregnant or have an uncommon form of hemoglobin (known as a hemoglobin variant) — that can make the A1C test inaccurate, your doctor may use the following tests to diagnose diabetes:

• 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 you last ate, a random blood sugar level of 200 mg / dL (11.1 mmol / L) 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, you have diabetes.
• Oral glucose tolerance test: For this test, you fast overnight, and the fasting blood sugar level is measured. Then you drink 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, ask your 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 you're 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.

TREATMENT OPTIONS:

Management of type 2 diabetes includes:

• Healthy eating
• Regular exercise
• Possibly, diabetes medication or insulin therapy
• Blood sugar monitoring

HEALTHY EATING: It is important to center your diet on these high-fibers, low-fat foods:

• Fruits
• Vegetables
• Whole grains

You'll also need to eat fewer animal products, refined carbohydrates and sweets.

Low glycemic index foods also may be helpful. The 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.

PHYSICAL ACTIVITY: Everyone needs regular aerobic exercise, and people who have type 2 diabetes are no exception. Get your doctor's approval before you start an exercise program. Then choose activities you enjoy, such as walking, swimming and biking. Aim for at least 30 minutes of aerobic exercise five days of the week. Stretching and strength training exercises are important, too. If you haven't been active for a while, start slowly and build up gradually.

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.

Remember that physical activity lowers blood sugar. Check your blood sugar level before any activity. You might need to eat a snack before exercising to help prevent low blood sugar if you take diabetes medications that lower your blood sugar.

MONITORING YOUR BLOOD SUGAR: Depending on your treatment plan, you may need to check and record your blood sugar level every now and then or, if you're on insulin, multiple times a day. Ask your doctor how often he or she wants you to check your blood sugar. Careful monitoring is the only way to make sure that your blood sugar level remains within your target range.

MEDICINES: A number of oral medicines (pills) are available to treat type 2 diabetes.

METFORMIN: Most people who are newly diagnosed with type 2 diabetes will immediately begin a medicine called metformin. Metformin improves how your body responds to insulin to reduce high blood sugar levels.

Metformin is a pill that is usually started with the evening meal; a second dose is added one to two weeks later (with breakfast). The dose may be increased every one to two weeks thereafter.

SIDE EFFECTS: Common side effects of metformin include nausea, diarrhea, and gas. These are usually not severe, especially if you take metformin along with food.

WHEN TO ADD A SECOND MEDICINE? Your doctor or nurse might recommend a second medicine within the first two to three months if your blood sugar levels and glycated hemoglobin (A1C) are still higher than your goal.

WHICH SECOND MEDICINE IS BEST? If your blood sugar levels are still high after two to three months but your A1C is close to the goal (between 7 and 8.5 percent), a second oral medicine might be added. Insulin shots might be recommended as the second medicine if your A1C is higher than 8.5 percent. The "best" second medicine depends upon individual factors, including the person's weight, other medical problems, and preferences regarding use of injections. The following are general recommendations:

• The most commonly recommended second medicine is a short-acting sulfonylurea, such as glipizide.
• A thiazolidinedione, such as pioglitazone, is an alternative to sulfonylureas but only for people who are not at increased risk of heart failure or bone fracture.
• A glucagon-like peptide (GLP) agonist, which requires injections, is an option for patients who are overweight and who want to avoid developing low blood sugar.
• A meglitinide, such as repaglinide, is another option for people who cannot take a sulfonylurea because of kidney failure.

SULFONYLUREAS: Sulfonylureas have been used to treat type 2 diabetes for many years. They work by increasing the amount of insulin your body makes and can lower blood sugar levels by approximately 20 percent. However, they stop working over time.

Sulfonylureas are generally used if metformin does not adequately control blood sugar levels when taken alone. You should not take a sulfonylurea in the setting of kidney failure.

If you take a sulfonylurea, you can develop low blood sugar, known as hypoglycemia. Low blood sugar symptoms can include:

• Sweating
• Shaking
• Feeling hungry
• Feeling anxious
• Feeling confused

Low blood sugar must be treated quickly by eating 10 to 15 grams of fast-acting carbohydrate (e.g. fruit juice, hard candy, glucose tablets).

INSULIN: In the past, insulin treatment was reserved for patients with type 2 diabetes whose blood sugars were not controlled with oral medicines and lifestyle changes. However, there is increasing evidence that using insulin at earlier stages may improve overall diabetes control and help to preserve the pancreas' ability to make insulin.

Insulin injections may be used as a first-line treatment in some people with type 2 diabetes, or it can be added to or substituted for oral medicines. Insulin must be injected by the patient or a family member / friend.

THIAZOLIDINEDIONES: This class of medicines includes pioglitazone and rosiglitazone, which work to lower blood sugar levels by increasing the body's sensitivity to insulin. They are taken in pill form and usually in combination with other medicines such as metformin, a sulfonylurea, or insulin.

Common side effects of thiazolidinediones include:

• Weight gain and swelling of the feet and ankles.
• A small but serious increased risk of developing or worsening heart failure. An early sign of heart failure is swelling of the feet and ankles. People who take thiazolidinediones should monitor for swelling.
• A small but serious increased risk of developing fluid retention at the back of the eyes (macular edema).
• A small but serious increased risk of developing certain types of cancer (like bladder cancer).
• A small increased risk of bone fractures.

GLP AGONISTS: The glucagon-like peptide (GLP) agonists, exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide, are injectable medicines. They are not a first-line treatment but might be considered for people whose blood sugar is not controlled on the highest dose of one or two oral medicines. They may be especially helpful for overweight patients who are gaining weight on oral medicine.

GLP agonists do not usually cause low blood sugar. They promote weight loss but can also cause bothersome side effects, including nausea, vomiting, and diarrhea. Pancreatitis has been reported rarely in patients taking GLP agonists, but it is not known if the drugs caused the pancreatitis. You should stop taking these drugs if you develop severe abdominal pain. These drugs are more expensive than insulin. Because they are relatively new drugs, long-term risks and benefits are not known.

DPP-4 INHIBITORS: This class of medicines includes sitagliptin, saxagliptin, linagliptin, alogliptin, and vildagliptin. They lower blood sugar levels by increasing insulin release from the pancreas in response to a meal. They are not a first-line treatment, but they can be given alone in patients who can't tolerate the first-line medicines (metformin, sulfonylureas), or they can be given with other oral medicines if blood sugars are still higher than goal. These medicines do not cause hypoglycemia or changes in body weight. However, they may cause some nausea and diarrhea. Dipeptidyl peptidase-4 (DPP-4) inhibitors are expensive, and the long-term risks and benefits are unknown.

MEGLITINIDES: Meglitinides include repaglinide and nateglinide. They work to lower blood sugar levels, similar to the sulfonylureas, and might be recommended in people who are allergic to sulfa-based drugs. They are taken in pill form. Meglitinides are not generally used as a first-line treatment because they are more expensive than sulfonylureas and are short acting, so they must be taken with each meal. Repaglinide can be used safely in patients with kidney failure.

ALPHA-GLUCOSIDASE INHIBITORS: These medicines, which include acarbose and miglitol, work by interfering with the absorption of carbohydrates in the intestines. This helps to lower blood sugar levels but not as well as metformin or the sulfonylureas. They can be combined with other medicines if the first medicine does not lower blood sugar levels enough.

The main side effects of alpha-glucosidase inhibitors are gas (flatulence), diarrhea, and abdominal pain; starting with a low dose may minimize these side effects. The medicine is usually taken three times per day with the first bite of each meal.

SGLT2 INHIBITORS: The sodium-glucose co-transporter 2 (SGLT2) inhibitors, dapagliflozin, canagliflozin, and empagliflozin, lower blood sugar by increasing the excretion of sugar in the urine. They are relatively weak diabetes drugs, similar in potency to the DPP-4 inhibitors. They are not a first-line treatment. Although they can be combined with other medications, including metformin, sulfonylureas, pioglitazone, sitagliptin, and insulin, in patients with persistently elevated blood sugars, we do not routinely use them because of the absence of long-term efficacy and safety data. SGLT2 inhibitors do not cause low blood sugar. They promote modest weight loss but can also cause bothersome side effects, including vaginal yeast infections and urinary tract infections.

OTHER CONSIDERATION:

BARIATRIC SURGERY: If you have type 2 diabetes and your body mass index (BMI) is greater than 35, you may be a candidate for weight-loss surgery (bariatric surgery). Blood sugar levels return to normal in 55 to 95 percent of people with diabetes, depending on the procedure performed. Surgeries that bypass a portion of the small intestine have more of an effect on blood sugar levels than do other weight-loss surgeries.

Drawbacks to the surgery include its high cost, and there are risks involved, including a risk of death. Additionally, drastic lifestyle changes are required and long-term complications may include nutritional deficiencies and osteoporosis.

PREGNANCY: Women with type 2 diabetes may need to alter their treatment during pregnancy. Many women will require insulin therapy during pregnancy. Cholesterol-lowering medications and some blood pressure drugs can't be used during pregnancy.

If you have signs of diabetic retinopathy, it may worsen during pregnancy. Visit your ophthalmologist during the first trimester of your pregnancy and at one year postpartum.

LOW BLOOD SUGAR (HYPOGLYCEMIA): If your blood sugar level drops below your target range, it's known as low blood sugar (hypoglycemia). Your blood sugar level can drop for many reasons, including skipping a meal, inadvertently taking more medication than usual or getting more physical activity than normal. Low blood sugar is most likely if you take glucose-lowering medications that promote the secretion of insulin or if you're taking insulin.

If you have signs or symptoms of low blood sugar, drink or eat something that will quickly raise your blood sugar level — fruit juice, glucose tablets, hard candy, regular (not diet) soda or another source of sugar. Retest in 15 minutes to be sure your blood glucose levels have normalized. If they haven't, treat again and retest in another 15 minutes. If you lose consciousness, a family member or close contact may need to give you an emergency injection of glucagon, a hormone that stimulates the release of sugar into the blood.

PRECAUTIONS:

Careful management of type 2 diabetes can reduce your risk of serious — even life-threatening — complications. Consider these tips:

• Commit to managing your diabetes: Learn all you can about type 2 diabetes. Make healthy eating and physical activity part of your daily routine. Establish a relationship with a diabetes educator, and ask your diabetes treatment team for help when you need it.
• Schedule a yearly physical exam and regular eye exams: Your regular diabetes checkups aren't meant to replace regular physicals or routine eye exams. During the physical, your doctor will look for any diabetes-related complications, as well as screen for other medical problems. Your eye care specialist will check for signs of retinal damage, cataracts and glaucoma.
• Identify yourself:Wear a necklace or bracelet that says you have diabetes.
• Keep your immunizations up to date: High blood sugar can weaken your immune system. Get a flu shot every year, and your doctor will likely recommend the pneumonia vaccine, as well. The Centers for Disease Control and Prevention (CDC) also recommends the hepatitis B vaccination if you haven't previously received this vaccine and you're an adult age 19 to 59 with type 1 or type 2 diabetes. The CDC advises vaccination as soon as possible after diagnosis with type 1 or type 2 diabetes. If you are age 60 or older, have diabetes and haven't previously received the vaccine, talk to your doctor about whether it's right for you.
• Take care of your teeth: Diabetes may leave you prone to more-serious gum infections. Brush your teeth at least twice a day, floss your teeth once a day and schedule regular dental exams. Consult your dentist right away if your gums bleed or look red or swollen.
• Pay attention to your feet: Wash your feet daily in lukewarm water. Dry them gently, especially between the toes, and moisturize with lotion. Check your feet every day for blisters, cuts, sores, redness and swelling. Consult your doctor if you have a sore or other foot problem that isn't healing.
• Keep your blood pressure and cholesterol under control: Eating healthy foods and exercising regularly can go a long way toward controlling high blood pressure and cholesterol. Medication also may be needed.
• If you smoke or use other types of tobacco, ask your doctor to help you quit: Smoking increases your risk of various diabetes complications. Talk to your doctor about ways to stop smoking or to stop using other types of tobacco.
• If you drink alcohol, do so responsibly: Alcohol, as well as drink mixers, can cause either high or low blood sugar, depending on how much you drink and if you eat at the same time. If you choose to drink, do so in moderation and always with a meal.

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