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emedicinemedscape Type 2 diabetes mellitus comprises an array of dysfunctions resulting from the combination of resistance to insulin action and

inadequate insulin secretion. It is disorders are characterized by hyperglycemia and associated with microvascular (ie, retinal, renal, possibly neuropathic), macrovascular (ie, coronary, peripheral vascular), and neuropathic (ie, autonomic, peripheral) complications. (See Pathophysiology and Clinical Presentation.) Unlike patients with type 1 diabetes mellitus, patients with type 2 are not absolutely dependent upon insulin for life. This distinction was the basis for the older terms for types 1 and 2, insulin dependent and noninsulin dependent diabetes. However, many patients with type 2 diabetes are ultimately treated with insulin. Because they retain the ability to secrete some endogenous insulin, they are considered to require insulin but not to depend on insulin. Nevertheless, given the potential for confusion due to classification based on treatment rather than etiology, these terms have been abandoned. [1] (See Treatment and Management and Medication.) Another older term for type 2 diabetes mellitus was adult-onset diabetes. Currently, because of the epidemic of obesity and inactivity in children, type 2 diabetes mellitus is occurring at younger and younger ages. Although type 2 diabetes mellitus typically affects individuals older than 40 years, it has been diagnosed in children as young as 2 years of age who have a family history of diabetes. (See Epidemiology.) Diabetes mellitus is a chronic disease that requires long-term medical attention both to limit the development of its devastating complications and to manage them when they do occur. It is a disproportionately expensive disease; in the United States in 2002, the per-capita cost of health care was $13,243 for people with diabetes, while it was $2560 for those without diabetes. The emergency department utilization rate by people with diabetes is twice that of the unaffected population. [2] This article focuses on the diagnosis and treatment of type 2 diabetes and its acute and chronic complications, other than those directly associated with hypoglycemia and severe metabolic disturbances, such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).

Type 2 diabetes is characterized by the combination of peripheral insulin resistance and inadequate insulin secretion by pancreatic beta cells. Insulin resistance, which has been attributed to elevated levels of free fatty acids in plasma,[3] leads to decreased glucose transport into muscle cells, elevated hepatic glucose production, and increased breakdown of fat. For type 2 diabetes mellitus to occur, both defects must exist. For example, all overweight individuals have insulin resistance, but diabetes develops only in those who cannot increase insulin secretion sufficiently to compensate for their insulin resistance. Their insulin concentrations may be high, yet inappropriately low for the level of glycemia. Beta cell dysfunction is a major factor across the spectrum of pre-diabetes to diabetes. A study of obese adolescents by Bacha et al confirms what is increasingly being stressed in adults as well: Beta cell function happens early in the pathological process and does not necessarily follow stage of insulin resistance.[4] Singular focus on insulin resistance as the "be all and end all" is gradually shifting, and hopefully better treatment options that focus on the beta cell pathology will emerge to treat the disorder early. In the progression from normal glucose tolerance to abnormal glucose tolerance, postprandial blood glucose levels increase first; eventually, fasting hyperglycemia develops as suppression of hepatic gluconeogenesis fails.

A simplified scheme for the pathophysiology of abnormal glucose metabolism in type 2 diabetes mellitus is depicted in the image below.

etiology Presumably, type 2 diabetes mellitus develops when a diabetogenic lifestyle (ie, excessive caloric intake, inadequate caloric expenditure, obesity) is superimposed upon a susceptible genotype. The body mass index at which excess weight increases risk for diabetes varies with different racial groups. For example, compared with persons of European ancestry, persons of Asian ancestry are at increased risk for diabetes at lower levels of overweight.[10]Hypertension and prehypertension are associated with greater risk of developing diabetes in whites compared with African Americans. [11] In addition, an in utero environment resulting in low birth weight may predispose some individuals to develop type 2 diabetes mellitus.[12, 13] About 90% of patients who develop type 2 diabetes mellitus are obese. However, a large, populationbased, prospective study has shown that an energy-dense diet may be a risk factor for the development of diabetes that is independent of baseline obesity.[14] Diabetes mellitus may be caused by other conditions. Secondary diabetes may occur in patients taking glucocorticoids or when patients have conditions that antagonize the actions of insulin (eg, Cushing syndrome, acromegaly, pheochromocytoma). The major risk factors for type 2 diabetes mellitus are the following: Age greater than 45 years (though, as noted above, type 2 diabetes mellitus is occurring with increasing frequency in young individuals) Weight greater than 120% of desirable body weight Family history of type 2 diabetes in a first-degree relative (eg, parent or sibling) Hispanic, Native American, African American, Asian American, or Pacific Islander descent History of previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) Hypertension (>140/90 mm Hg) or dyslipidemia (high-density lipoprotein [HDL] cholesterol level < 40 mg/dL or triglyceride level >150 mg/dL) History of gestational diabetes mellitus or of delivering a baby with a birth weight of >9 lb Polycystic ovarian syndrome (which results in insulin resistance) The genetics of type 2 diabetes are complex and not completely understood. Evidence supports the involvement of multiple genes in pancreatic beta-cell failure and insulin resistance. Some forms of diabetes, however, have a clear association with genetic defects. The syndrome previously known as maturity onset diabetes of youth (MODY) has now been reclassified as a variety of defects in beta-cell function. These defects account for 2-5% of individuals with type 2 diabetes who present at a young age and have mild disease. The trait is autosomal dominant and can be screened for through commercial laboratories. To date, 6 mutations have been identified: HNF-4-alpha Glucokinase gene HNF-1-alpha IPF-1 HNF-1-beta NEUROD1 In addition, the SURI-1 gene causes hyperglycemia in infancy, which is often misdiagnosed as type 1 diabetes. Variants in mitochondrial DNA have been proposed as an etiologic factor. A specific mitochondrial point mutation has been identified as a rare cause of maternally inherited type 2 diabetes and sensorineural hearing loss.

Diabetes is caused by a problem in the way your body makes or uses insulin. Insulin is needed to move blood sugar (glucose) into cells, where it is stored and later used for energy. When you have type 2 diabetes, the body does not respond correctly to insulin. This is called insulin resistance. Insulin resistance means that fat, liver, and muscle cells do not respond normally to insulin. As a result blood sugar does not get into cells to be stored for energy. When sugar cannot enter cells, abnormally high levels of sugar build up in the blood. This is called hyperglycemia. High levels of blood sugar often trigger the pancreas to produce more and more insulin, but it is not enough to keep up with the body's demand. People who are overweight are more likely to have insulin resistance, because fat interferes with the body's ability to use insulin. Type 2 diabetes usually occurs gradually. Most people with the disease are overweight at the time of diagnosis. However, type 2 diabetes can also develop in those who are thin, especially the elderly. Family history and genetics play a large role in type 2 diabetes. Low activity level, poor diet, and excess body weight (especially around the waist) significantly increase your risk for type 2 diabetes. Other risk factors include: Age greater than 45 years HDL cholesterol of less than 35 mg/dL or triglyceride level of greater than 250 mg/dL High blood pressure History of gestational diabetes Polycystic ovarian syndrome Previously identified impaired glucose tolerance by your doctor Race/ethnicity (African Americans, Hispanic Americans, and Native Americans all have high rates of diabetes)

Symptoms Often, people with type 2 diabetes have no symptoms at all. If you do have symptoms, they may include: Blurred vision Erectile dysfunction Fatigue Frequent or slow-healing infections Increased appetite Increased thirst Increased urination

Exams and Tests Type 2 diabetes is diagnosed with the following blood tests:

Fasting blood glucose level -- diabetes is diagnosed if higher than 126 mg/dL on two occasions. Hemoglobin A1c test -- this test has been used in the past to help patients monitor how well they are controlling their blood glucose levels. In 2010, the American Diabetes Association recommended that the test be used as another option for diagnosing diabetes and identifying prediabetes. Levels indicate: o Normal: Less than 5.7% o Pre-diabetes: Between 5.7% - 6.4% o Diabetes: 6.5% or higher Oral glucose tolerance test -- diabetes is diagnosed if glucose level is higher than 200 mg/dL after 2 hours. Random (non-fasting) blood glucose level -- diabetes is suspected if higher than 200 mg/dL and accompanied by the classic symptoms of increased thirst, urination, and fatigue (this test must be confirmed with a fasting blood glucose test).

You should see your health care provider every 3 months. At these visits, you can expect your health care provider to: Check your blood pressure Check the skin and bones on your feet and legs Check the sensation in your feet Examine the back part of the eye with a special lighted instrument called an ophthalmoscope

The following tests will help you and your doctor monitor your diabetes and prevent complications: Have your blood pressure checked at least every year (blood pressure goals should be 130/80 mm/Hg or lower). Have your glycosulated hemoglobin (HbA1c) checked every 6 months if your diabetes is well controlled; otherwise every 3 months. Have your cholesterol and triglyceride levels checked yearly (aim for LDL levels below 70-100 mg/dL). Get yearly tests to make sure your kidneys are working well (microalbuminuria and serum creatinine). Visit your ophthalmologist at least once a year, or more often if you have signs of diabetic retinopathy. See the dentist every 6 months for a thorough dental cleaning and exam. Make sure your dentist and hygienist know that you have diabetes.

Treatment The immediate goal of treatment is to lower high blood glucose levels. The long-term goals of treatment are to prevent diabetes-related complications. The primary treatment for type 2 diabetes is exercise and diet. LEARN THESE SKILLS

You should learn basic diabetes management skills. They will help prevent complications and the need for medical care. These skills include: How to test and record your blood glucose (See: Blood glucose monitoring) What to eat and when How to take medications, if needed How to recognize and treat low and high blood sugar How to handle sick days Where to buy diabetes supplies and how to store them

It may take several months to learn the basic skills. Always continue to educate yourself about the disease and its complications. Learn how to control and live with diabetes. Over time, stay current on new research and treatments. SELF-TESTING Self testing refers to being able to check your blood sugar at home yourself. It is also called selfmonitoring of blood glucose (SMBG). Regular self-testing of your blood sugar tells you and your health care provider how well your diet, exercise, and diabetes medications are working. A device called a glucometer can provide an exact blood sugar reading. There are different types of devices. Usually, you prick your finger with a small needle called a lancet. This gives you a tiny drop of blood. You place the blood on a test strip and put the strip into the device. Results are available in 30 - 45 seconds. A health care provider or diabetes educator will help set up an at-home testing schedule for you. Your doctor will help you set your blood sugar goals. Most people with type 2 diabetes only need to check their blood sugar once or twice a day. If your blood sugar levels are under control, you may only need to check them a few times a week. Tests may be done when you wake up, before meals, and at bedtime. More frequent testing may be needed when you are sick or under stress.

The results of the test can be used to adjust meals, activity, or medications to keep your blood sugar levels in an appropriate range. Testing can identify high and low blood sugar levels before serious problems develop. Keep a record for yourself and your health care provider. This will be a big help if you are having trouble managing your diabetes. DIET AND WEIGHT CONTROL People with type 2 diabetes should eat at about the same times each day and try to be consistent with the types of food they choose. This helps to prevent blood sugar from becoming extremely high or low. Meal planning includes choosing healthy foods, eating the right amount of food, and eating meals at the right

time. You should work closely with your doctor, nurse, and registered dietitian to learn how much fat, protein, and carbohydrates you need in your diet. Your meal plans should fit your daily lifestyle and habits, and should try to include foods that you like. Managing your weight and eating a well-balanced diet are important. Some people with type 2 diabetes can stop taking medications after losing weight (although they still have diabetes).