Diabetes Mellitus Differential Diagnosis

Secondary hyperglycemia has been associated with various disorders of insulin target tissues (liver, muscle, and adipose tissue). Other secondary causes of carbohydrate intolerance include endocrine disorders - often specific endocrine tumors - associated with excess production of growth hormone, glucocorticoids, catecholamines, glucagon, or somatostatin. In the first four situations, peripheral responsiveness to insulin is impaired. With excess of glucocorticoids, catecholamines, or glucagon, increased hepatic output of glucose is a contributory factor; in the case of catecholamines, decreased insulin release is an additional factor in producing carbohydrate intolerance, and with excess somatostatin production it is the major factor.

A rare syndrome of extreme insulin resistance associated with acanthosis nigricans afflicts either young women with androgenic features as well as insulin receptor mutations or older people, mostly women, in whom a circulating immunoglobulin binds to insulin receptors and reduces their affinity to insulin.

Medications such as diuretics, phenytoin, niacin, and high-dose corticosteroids can produce hyperglycemia that is reversible once the drugs are discontinued or when diuretic-induced hypokalemia is corrected. Chronic pancreatitis or subtotal pancreatectomy reduces the number of functioning B cells and can result in a metabolic derangement very similar to that of genetic type 1 diabetes except that a concomitant reduction in pancreatic A cells may reduce glucagon secretion so that relatively lower doses of insulin replacement are needed. Insulin-dependent diabetes is occasionally associated with Addison’s disease and autoimmune thyroiditis (Schmidt’s syndrome, or polyglandular failure syndrome). This occurs more commonly in women and represents an autoimmune disorder in which there are circulating antibodies to adrenocortical and thyroid tissue, thyroglobulin, and gastric parietal cells.

Nondiabetic glycosuria (renal glycosuria) is a benign asymptomatic condition wherein glucose appears in the urine despite a normal amount of glucose in the blood, either basally or during a glucose tolerance test. Its cause may vary from an autosomally transmitted genetic disorder to one associated with dysfunction of the proximal renal tubule (Fanconi’s syndrome, chronic renal failure), or it may merely be a consequence of the increased load of glucose presented to the tubules by the elevated glomerular filtration rate during pregnancy. As many as 50% of pregnant women normally have demonstrable sugar in the urine, especially during the third and fourth months. This sugar is practically always glucose except during the late weeks of pregnancy, when lactose may be present.

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