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Chapter: Modern Pharmacology with Clinical Applications: Insulin and Oral Drugs for Diabetes Mellitus

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Metabolic Disturbances and Complications of the Diabetic State

There are only two major sources of blood glucose: ex-ogenous, or the ingestion of dietary carbohydrate, and endogenous, which is contributed by hepatic and renal gluconeogenesis and hepatic glycogenolysis.

METABOLIC DISTURBANCES AND COMPLICATIONS OF THE DIABETIC STATE

 

There are only two major sources of blood glucose: ex-ogenous, or the ingestion of dietary carbohydrate, and endogenous, which is contributed by hepatic and renal gluconeogenesis and hepatic glycogenolysis. Diabetes mellitus is a metabolic disorder in which carbohydrate metabolism is reduced while that of proteins and lipids is increased. In diabetics, exogenous and endogenous glu-cose is not used effectively, and it accumulates in the blood (hyperglycemia). As blood glucose levels in-crease, the amount of glucose filtered by the glomeruli eventually exceeds the reabsorption capacity (Tm, trans-port maximum) of the proximal tubule cells, and glu-cose appears in the urine (glucosuria). Protein catabo-lism and the rate of nitrogen excretion are increased when blood insulin falls to low levels; stimulation of he-patic gluconeogenesis converts amino acids to glucose. The catabolism of lipids and fatty acids is also acceler-ated in the absence of insulin, leading to the formation of ketone bodies, such as acetoacetic acid, -hydroxybu-tyric acid, and acetone. Renal losses of glucose, nitroge-nous substances, and ketone bodies promote osmotic diuresis that can result in dehydration, electrolyte ab-normalities, and acid–base disturbances. Diabetic ke-toacidosis is the end result of insulin deficiency in un-controlled type I diabetes.

 

Type II diabetics are less prone to develop ketone bodies or diabetic ketoacidosis but may develop hyper-osmolar coma, a condition characterized by severe hy-perglycemia and dehydration. Both diabetic ketoacido-sis and hyperosmolar coma are medical emergencies that require prompt insulin administration and intra-venous fluids.

 

Diabetes mellitus is associated with many complica-tions that are increased in the setting of poor glycemic control. Diabetes mellitus can cause microvascular complications (e.g., retinopathy, nephropathy, and neu-ropathy) and macrovascular complications (e.g., athero-sclerotic cardiovascular disease), associated with dia-betic dyslipidemia (usually elevated triglycerides and low-density lipoprotein cholesterol). Recent clinical tri-als have demonstrated that the risk of developing chronic complications of diabetes is reduced by achiev-ing good glycemic control. This can be accomplished by a combination of diet, exercise, and rational pharmaco-logical therapy directly targeted to optimize diabetes management.

 

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