Porth's Essentials of Pathophysiology, 4e

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Endocrine System

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there often is a short period of improved beta cell func- tion, during which symptoms of diabetes disappear and insulin injections are reduced or not needed. This is sometimes called the honeymoon period. Immune interventions (immunomodulation) designed to inter- rupt the destruction of beta cells before development of type 1 diabetes are being investigated in various trials. Unfortunately, none of the interventions studied to date has shown real clinical utility. IdiopathicType 1B Diabetes. The term idiopathic type 1B diabetes is used to describe those cases of beta cell destruction in which no evidence of autoimmunity is present. Only a small number of people with type 1 dia- betes fall into this category; most are of African or Asian descent. Type 1B diabetes is strongly inherited. People with the disorder have episodic DKA due to varying degrees of insulin deficiency with periods of absolute insulin deficiency that may come and go. Type 2 diabetes mellitus, previously described as non– insulin-dependent diabetes , is a condition of hyperglyce- mia that accompanies a relative rather than an absolute insulin deficiency (although insulin therapy may be still be required for glycemic control). 3,10,11 It currently accounts for about 90% to 95% of the cases of diabetes. Most people with type 2 diabetes are overweight and older. Recently, however, type 2 diabetes has become a more common occurrence in obese children and ado- lescents. 12,13 Although type 1 diabetes remains the main form of diabetes in children worldwide, it seems likely Type 2 Diabetes Mellitus and the Metabolic Syndrome

that type 2 diabetes will become the predominant form within 10 years in some ethnic groups. 13 Metabolic Abnormalities Involved in Type 2 Diabetes. The metabolic abnormalities involved in type 2 diabetes include (1) insulin resistance, (2) increased glucose production by the liver, and (3) impaired secre- tion of insulin by the pancreatic beta cells 14–16 (Fig. 33-7). Insulin resistance, which can be defined as the fail- ure of target tissues to respond to insulin, predates the development of hyperglycemia. That is, in the early stages of the evolution of type 2 diabetes, insulin resis- tance is usually accompanied by compensatory beta cell hyperfunction and hyperinsulinemia. In skeletal muscle, insulin resistance prompts decreased uptake of glucose. Although muscle glucose uptake is slightly increased after a meal, the efficiency with which it is taken up (glucose clearance) is dimin- ished, resulting in an increase in postprandial (following a meal) blood glucose levels. 16 In contrast, in the liver, insulin resistance leads to impaired suppression of glucose production with an overproduction of glucose despite a fasting hyperinsu- linemia. In fact, the excessive rate of hepatic glucose production is the primary determinant of elevated FPG in persons with type 2 diabetes. 15,16 Several mechanisms can lead to impaired secretion of insulin by the pancreatic beta cells. These include an initial decrease in beta cell mass related to genetic or epigenetic factors, increased apoptosis or decreased regeneration of beta cells, or beta cell exhaustion due to long-standing insulin resistance. 15 According to one study, beta cell function was reduced by an average of 50% at the time of diagnosis in type 2 diabetes, and

Genetic predisposition

Environmental factors

Insulin resistance

Obesity

Deranged insulin release

Decreased glucose uptake

Hyperglycemia

Increased hepatic glucose output

Type 2 diabetes

FIGURE 33-7. Pathogenesis of type 2 diabetes mellitus.