Porth's Essentials of Pathophysiology, 4e

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Endocrine System

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In addition, changes in fat distribution (peripheral lipoatrophy and visceral obesity), sometimes referred to as lipodystrophy, often occur (see Chapter 16). These people should be aggressively treated to prevent cardiovascular complications resulting from the abnor- mal risk factors. Gestational Diabetes Gestational diabetes mellitus (GDM) is defined as glu- cose intolerance that develops during pregnancy and is not clearly overt diabetes (either type 1 or type 2). 11 It occurs in 3% to 7% of pregnancies in the United States and is growing in prevalence. 26,27 The hyperglyce- mia varies in severity from glucose concentrations that would be diagnostic of diabetes apart from pregnancy to concentrations that are asymptomatic and only slightly above normal. 27 Factors that indicate a high risk for GDM include glycosuria, strong family history of type 2 diabetes, severe obesity, polycystic ovary disease, and prior history of GDM or delivery of a previous large- for-gestational-age infant. All pregnant women should undergo risk assessment for diabetes during their first prenatal visit to determine the need for additional screening tests. Women who are younger than 25 years of age; were of normal body weight before pregnancy; have no family history of dia- betes, prior history of GDM or large-for-gestational age infant, or presence of glycosuria; and are not members of a high-risk ethnic/racial group (e.g., Hispanic, Native American, Asian, African American) may not need to be screened. 11,26,27 Women at high risk for GDM should undergo glucose testing as soon as possible. An FPG greater than or equal to 126 mg/dL; or a casual plasma glucose greater than or equal to 200 mg/dL; or a A1C greater or equal to 6.5% meets the threshold for diag- nosis of diabetes mellitus and should be confirmed on a subsequent day as soon as possible. 11 Women of average or low risk, including those not found to have diabetes early in pregnancy, should undergo GDM testing at 24 to 28 weeks of gestation using a 50-g OGTT. This screen- ing test consists of 50 g of glucose given without regard to the last meal, followed in 1 hour by a venous blood sample for glucose concentration. If the plasma glucose level is greater than 140 mg/dL (7.8 mmol/L), a 100-g 3-hour OGTT is indicated to establish the diagnosis of GDM. 27 If the plasma glucose measured 3 hours after the test is greater or equal to 140 mg/dL (7.8 mmol/L), a diagnosis of GDM is made. 27 Diagnosis and careful medical management are essen- tial because women with GDM are at higher risk for complications of pregnancy, mortality, and fetal abnor- malities. 3 Fetal abnormalities include macrosomia (i.e., large body size), hypoglycemia, hypocalcemia, polycy- themia, and hyperbilirubinemia. Treatment of GDM includes close observation of mother and fetus because even mild hyperglycemia has been shown to be detrimental to the fetus. 26,27 Maternal fasting and postprandial blood glucose levels should be measured regularly. The mother’s diet should provide the necessary nutrients for maternal and fetal health,

CHART 33-1   NCEP ATP III Criteria for a Diagnosis of Metabolic Syndrome Three or more of the following: ■■ Abdominal obesity: waist circumference >35 inches (88 cm) in women or >40 inches (102 cm) in men ■■ Triglycerides: ≥ 150 mg/dL (1.7 mmol/L) ■■ High-density lipoproteins (HDL): <50 mg/dL (1.3 mmol/L) in women or <40 mg/dL (1.0 mmol/L) in men

■■ Blood pressure: >130/85 mm Hg

■■ Fasting plasma glucose: >100 mg/dL (5.6 mmol/L)

Developed from Grundy SM. Panel Chair.Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, andTreatment of High Blood Cholesterol in Adults (AdultTreatment Panel III). NIH Publication No. 01–3670. Bethesda, MD: National Institutes of Health; 2001.

or removal of pancreatic tissue and with other endocrine diseases, such as acromegaly, Cushing syndrome, or pheochromocytoma. Endocrine disorders that produce hyperglycemia do so by increasing the hepatic produc- tion of glucose or decreasing the cellular use of glucose. Several specific types of diabetes are associated with single gene defects in beta cell function. These specific types of diabetes, which resemble type 2 diabetes but occur at an earlier age (usually before 25 years of age), were formerly referred to as maturity-onset diabetes of the young (MODY). 3 Cystic fibrosis–related diabetes (CFRD) is now recognized as the most common com- plication of cystic fibrosis. Glucose abnormalities are especially common in children younger than 10 years old. The pathophysiology of CFRD is poorly under- stood, but insulin deficiency is the major factor (possibly related to pancreatic scarring). 11 Several diuretics—thiazide and loop diuretics—can elevate blood glucose. These diuretics increase potas- sium loss, which is thought to impair beta cell release of insulin. Other drugs and therapies known to cause hyperglycemia include diazoxide, glucocorticoids, oral contraceptives, antipsychotic agents, and total paren- teral nutrition (i.e., hyperalimentation). Drug-related increases in blood glucose usually are reversed after the drug has been discontinued. A newly recognized form of diabetes, new-onset diabetes after transplant (NODAT), is a common complication after tissue or organ transplant and occurs in 15% to 30% of recipi- ents. Several drugs are thought to be important in the pathophysiology of this condition including glucocor- ticoids (which can increase insulin resistance) and cer- tain immunosuppressants such as cyclosporine (which are beta-cell toxic). 11 The advent of potent antiretro- viral therapy (especially protease inhibitors) for the treatment of human immunodeficiency virus (HIV) infection has significantly improved survival in these conditions. However, these people are now developing metabolic derangements with features similar to those seen in the metabolic syndrome (see Chart 33-1). 25