FIGURE 19-1 ■. This figure shows the hyperbolic relationship of insulin resistance and beta cell function. On the y-axis is beta cell function as reflected in the first-phase insulin response during intravenous (IV) glucose infusion; on the x-axis is insulin sensitivity and its mirror image resistance. In a subject with normal glucose tolerance (NGT) and beta-cell reserve, an increase in insulin resistance results in increased insulin release and normal glucose tolerance. In an individual for whom the capacity to increase insulin release is compromised, increasing insulin resistance with partial or no beta-cell compensation results in progression from normal glucose tolerance, to impaired glucose tolerance (IGT), and finally to diabetes (T2D). Differences between these categories are small at high insulin sensitivity, which may be maintained by weight reduction, exercise, and certain drugs. At a critical degree of insulin resistance, due to obesity or other listed factors, only a further small increment in resistance requires a large increase in insulin output. Those that can increase insulin secretion to this extent retain normal glucose tolerance; those who cannot achieve this degree of insulin secretion (e.g., due to a mild defect in genes regulating insulin synthesis, insulin secretion, insulin action, or an ongoing immune destruction of beta cells) now unmask varying degrees of carbohydrate intolerance. The product of insulin sensitivity (the reciprocal of insulin resistance) and acute insulin response (a measurement beta-cell function) has been called the “disposition index.” This index remains constant in an individual with normal beta cell compensation in response to changes in insulin resistance. IGT, impaired glucose tolerance; NGT, normal glucose tolerance; T2D, type 2 diabetes.
Constant advances are being made in development of new oral medications for persons with diabetes. In 2003, a drug called Metaglip combining glipizide and metformin was approved in a dingle tablet. Along with diet and exercise, the drug was used as initial therapy for Type 2 diabetes. Another drug approved by the U.S. Food and Drug Administration (FDA) combines metformin and rosiglitazone (Avandia), a medication that increases muscle cells' sensitivity to insulin. It is marketed under the name Avandamet. So many new drugs are under development that it is best to stay in touch with a physician for the latest information; physicians can find the best drug, diet and exercise program to fit an individual patient's need.
Another area of pathologic changes associated with diabetes mellitus is the nervous system (diabetic neuropathy), particularly in the peripheral nerves of the lower extremities. The patient typically experiences a “stocking-type” anesthesia beginning about 10 years after the onset of the disease. There may eventually be almost total anesthesia of the affected part with the potential for serious injury to the part without the patient being aware of it. In contrast, some patients experience debilitating pain and hyperesthesia, with loss of deep tendon reflexes.
Type 2 diabetes is most common is those who are genetically predisposed and who are overweight, lead a sedentary lifestyle, have high blood pressure, and/or have insulin resistance due to excess weight. People of certain ethnicities are more likely to develop diabetes, too. These include: African Americans, Mexican Americans, American Indians, Native Hawaiians, Pacific Islanders, and Asian Americans. These populations are more likely to be overweight and have high blood pressure, which increases the risk of developing diabetes.
Recently, battery-operated insulin pumps have been developed that can be programmed to mimic normal insulin secretion more closely. A person wearing an insulin pump still must monitor blood sugar several times a day and adjust the dosage, and not all diabetic patients are motivated or suited to such vigilance. It is hoped that in the future an implantable or external pump system may be perfected, containing a glucose sensor. In response to data from the sensor the pump will automatically deliver insulin according to changing levels of blood glucose.
Weight fluctuations also fall under the umbrella of possible diabetes signs and symptoms. When you lose sugar through frequent urination, you also lose calories. At the same time, diabetes may keep the sugar from your food from reaching your cells — leading to constant hunger. The combined effect is potentially rapid weight loss, especially if you have type 1 diabetes.
Diabetic foot disease, due to changes in blood vessels and nerves, often leads to ulceration and subsequent limb amputation. It is one of the most costly complications of diabetes, especially in communities with inadequate footwear. It results from both vascular and neurological disease processes. Diabetes is the most common cause of non-traumatic amputation of the lower limb, which may be prevented by regular inspection and good care of the foot.
A random blood sugar of greater than 11.1 mmol/l (200 mg/dl) in association with typical symptoms[23] or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes.[10] In 2009 an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes.[48] This recommendation was adopted by the American Diabetes Association in 2010.[49] Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/l (>200 mg/dl).[48]
High blood sugar levels (hyperglycemia) can lead to a condition called glucose toxicity. This leads to further damage to the pancreas, and the body is less able to produce insulin. Without insulin, glucose levels continue to rise to levels that can cause damage to organs such as the eyes, nerves, and kidneys. These problems are similar to the complications associated with type 1 diabetes.
According to the Mayo Clinic, doctors may use other tests to diagnose diabetes. For example, they may conduct a fasting blood glucose test, which is a blood glucose test done after a night of fasting. While a fasting blood sugar level of less than 100 milligrams per deciliter (mg/dL) is normal, one that is between 100 to 125 mg/dL signals prediabetes, and a reading that reaches 126 mg/dL on two separate occasions means you have diabetes.
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