Diabetes mellitus is a metabolic syndrome characterized by hyperglycemia and sometimes ketoacidosis; it results from a lack of or markedly diminished insulin secretion or from ineffective insulin action associated with moderately diminished insulin secretion. Secondary vascular changes include abnormalities in the small vessels (microangiopathy) and large vessels (macroangiopathy). Microangiopathy appears as diabetic retinopathy and nephropathy. Macroangiopathy leads to stroke, myocardial infarction, and peripheral vascular disease. Many peripheral nervous system abnormalities also contribute to the clinical picture of diabetes. Most are due to metabolic changes, although a few may be secondary to vascular changes.
PHYSIOLOGY
The liver produces glucose through two processes: glycogenolysis, the breakdown of glycogen that provides about 75% of the glucose after an overnight fast, and gluconeogenesis, the synthesis of new glucose from noncarbohydrate precursors delivered to the liver. As the fasting period lengthens, glycogenolysis decreases considerably, and gluconeogenesis becomes the dominant process.
Glucose production is regulated by insulin levels, glucagon levels, and autoregulation. Insulin decreases glucose production; glucagon increases it. Autoregulation is the process by which the glucose level mediates hepatic glucose production independently of external hormonal stimuli. During fasting, insulin levels fall as glucagon levels rise.
But after a meal, the increased plasma glucose level stimulates pancreatic beta cells to release insulin, while glucagon production by the alpha-islet cells is suppressed. The insulin first passes through the liver, where about 50% is degraded. The rest enters the general circulation, where its half-life is about 5 min. Insulin then binds to specific receptors on the cell surfaces of the liver, muscle, and fat tissue, where it may exert an effect for several hours.
Thus, after a meal, hepatic glucose production is markedly suppressed, and glucose enters the tissues. About 25% of the meal’s carbohydrate content is stored in the liver, and the rest goes to peripheral tissues–mostly muscle.
In younger persons without diabetes, plasma glucose levels rise 20 to 50 mg/dL immediately after a meal and return to baseline 2 h later. With age, resistance to insulin gradually increases, so that postprandial plasma glucose levels rise an additional 5 mg/dL with each decade after the fifth. Fasting plasma glucose levels rise only 1 to 2 mg/dL in a decade.
Five mechanisms have been proposed to explain aging’s effect on carbohydrate metabolism: poor diet, physical inactivity, decreased lean body mass in which to store carbohydrate, impaired insulin secretion, and insulin resistance. Low carbohydrate intake explains only a small part of the problem. Recent studies indicate that older persons who routinely exercise vigorously do not show glucose intolerance–a finding that suggests inactivity plays a large role in age-related glucose intolerance. Although lean body mass diminishes with age, tissue redistribution cannot explain age-related changes in carbohydrate metabolism. Also, insulin secretion in response to glucose does not diminish with age. Almost all studies of the insulin response to various stimuli (oral or IV glucose, amino acids, or tolbutamide) show normal or even increased insulin levels in older people. Although many older people do have a delayed response to oral glucose, the significance of this delay is uncertain.
In contrast, insulin resistance is associated with aging, especially in those >= 60 yr who do not exercise regularly. Anti aging hormones like hgh can be helpful here. The mechanism, however, remains unclear. The site of insulin resistance probably lies in intracellular pathways of insulin sensitive tissues; ie, defects in insulin binding and receptor function do not explain the resistance.
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