Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder characterized by insulin resistance, insulin deficiency, and hyperglycemia. Nearly 21 million Americans have diabetes, and at least 54 million people over age 20 reported to have prediabetes. About 151,000 people below the age of 20 have been diagnosed with diabetes. The World Health Organization (WHO) estimates that more than 180 million people worldwide have diabetes and this number will double by 2030. In 2005, it was reported that an estimated 1.1 million people died from diabetes and 80 percent of diabetes deaths occur in low- and middle-income countries. Most of the deaths occur in people under the age of 70; 55 percent of diabetes deaths are in women.
The metabolic changes in T2DM may lead to organ damage, impairment of organ functions, and mortality due to cardiovascular disease. T2DM is often associated with obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, proinlammatory cytokines, and coagulation factors, and cluster of all these risk factors may lead to cardiometabolic syndrome. The common symptoms of T2DM are increased thirst, increased hunger, fatigue, increased urination especially at night, weight loss, blurred vision, and sores that do not heal.
DIAGNOSIS OF T2DM
The diagnosis criteria of T2DM is based on fasting blood glucose, postprandial blood glucose, and glycosylated hemoglobin (HbA1c). The normal fasting plasma glucose levels is considered normal if it is less than 100 milligrams per deciliter (mg/dl). If the fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes of an individual. A random blood glucose test can also be used to diagnose diabetes. A blood glucose level of 200 mg/dl or higher indicates diabetes. When fasting blood glucose stays above 100mg/dl but in the range of 100-126mg/dl, this is known as impaired fasting glucose (IFG). A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl. A person is said to have impaired glucose tolerance when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high. A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl. Glycosylated hemoglobin test (HbA1c) measures blood sugar control over an extended period in people with diabetes.
In general, the higher the HbA1c value, the higher the risk that develop complications such as eye disease, kidney disease, nerve damage, heart disease, and stroke. The American Diabetes Association (ADA) currently recommends an A1c goal of less than 7.0 percent. The HbA1c is linearly related to the average blood sugar over the past 1 to 3 months.
Elevated blood sugar levels due to lack of insulin or a relative deficiency of insulin or abnormally low levels of insulin causes acute complications in diabetic individuals. This leads to increased urine glucose, which in turn leads to excessive loss of fluid and electrolytes in urine. Lack of insulin also causes the inability to store fat and protein along with breakdown of existing fat and protein stores. This dysregulation results in the process of ketosis and the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis. Ketoacidosis can rapidly go into shock, coma, and death. A hyperosmolar coma usually occurs in elderly patients with T2DM.
In cohort studies, direct relationships were observed between higher systolic blood pressure levels and death, coronary artery disease, nephropathy, and proliferative retinopathy. Diabetes and hypertension are interrelated and they strongly predispose to end-stage renal disease, coronary artery disease, and peripheral vascular and cerebrovascular disease.
The chronic diabetes complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys, and nerves (microvascular disease), and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart disease, strokes, and pain in the lower extremities because of lack of blood supply (claudication), which in turn lead to peripheral arterial disease. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina. Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood.
Diabetic nerve damage includes numbness, burning, and aching of the feet and lower extremities. Minor foot injuries can lead to serious infection, ulcers, and even gangrene necessitating surgical amputation of toes, feet, and other infected parts. In men, diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction and impotence.
The most common lipid pattern in T2DM consists of hypertriglyceridemia (hyper-TG), low high-density lipoprotein cholesterol (HDL-C), and normal plasma concentrations of low-density lipoprotein cholesterol (LDL-C). However, in the presence of even mild hyper-TG, LDL-C particles are typically small and dense and may be more susceptible to oxidation. Chronic hyperglycemia promotes the glycation of LDL-C and both these processes are believed to increase the atherogenicity of LDL-C.
Excessive upper body fat, or abdominal obesity, is a strong independent predictor of metabolic comorbidities. Waist circumference values 102 centimeters or more (40 inches) in men and 88 centimeters or more (35 inches) in women are associated with substantially increased abdominal fat accumulation and health risks. People at high risk for T2DM can prevent or delay the onset of the disease by losing 5 to 7 percent of their body weight.
DM is associated with increased prevalence of endothelial cell dysfunction and vascular diseases. Mechanisms leading to alterations in endothelial cell function are poorly understood. High glucose concentration activates endothelial cells leading to monocytes adhesion providing further evidence that hyperglycemia might be implicated in vessel wall lesions contributing to diabetic vascular disease. Diabetes-associated pathophysiological conditions in the endothelium are modifications of lipoproteins, formation of advanced glycation end-products and circulating lipoprotein immune complexes, alteration of the nitric oxide pathway, and elevated levels of homocysteine. The main goals in restoration of endothelial function are optimal glycemic control, lipid lowering, cessation of smoking, normalization of elevated blood pressure, supplementation of antioxidants for scavenging free radicals, and normalization of homocysteine and insulin levels. There is abundant evidence that some pharmacological agents exert direct beneficial effects on endothelium, suggesting that at least part of their therapeutic action is associated with improvement in endothelial dysfunction.
Depression is twice as common in people with diabetes as in the general population. Depression may develop because of stress but may also result from the metabolic effects of diabetes on the brain. Depression and T2DM increases the risk of death for heart patients.
T2DM is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered. In prevention trials, it was clearly observed that aggressive and intensive control of elevated levels of blood sugar in patients with T1DM and T2DM decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 160 mg/dl after meals; and a near-normal hemoglobin A1C levels. Studies have shown that there is a 10 percent decrease in relative risk for every 1 percent reduction in A1C.
American Diabetes Association, http://www.diabetes.org/diabetes-basics/type-2/;
Center for Disease Control and Prevention, www.cdc.gov/diabetes/index.htm;
National Diabetes Education Program, http://ndep.nih.gov/.
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