Porth's Essentials of Pathophysiology, 4e

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Diabetes Mellitus and the Metabolic Syndrome

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be multifactorial. Diabetic diarrhea is typically intermit- tent, watery, painless, and nocturnal and may be associ- ated with fecal incontinence. In the male, disruption of sensory and autonomic ner- vous system function may cause sexual dysfunction (see Chapter 39). Diabetes is the leading pathophysiological cause of erectile dysfunction (ED), and it occurs in both type 1 and type 2 diabetes. Of the 13 million men with diabetes in the United States, 30% to 60% have ED. 54 Diabetic Nephropathies Diabetic nephropathy , a term used to describe the com- bination of lesions that occur concurrently in the diabetic kidney, is the leading cause of chronic kidney disease (CKD) in persons starting renal replacement therapy (see Chapter 26). 57 Not all people with diabetes develop clinically significant nephropathy; for this reason, atten- tion is focused on risk factors for the development of this complication. Among the suggested risk factors are genetic and familial predisposition, elevated blood pres- sure, poor glycemic control, smoking, hyperlipidemia, and increased albumin excretion. 11,58 Diabetic nephrop- athy occurs in family clusters, suggesting a familial predisposition, although this does not exclude the pos- sibility of environmental factors shared by siblings. The risk for development of kidney disease is greater among Native Americans, Hispanic Americans (espe- cially Mexican Americans), and African Americans. 11,58 The most common kidney lesions in people with dia- betes are those that affect the glomeruli. These include capillary basement membrane thickening, diffuse glo- merular sclerosis, and nodular glomerulosclerosis, in which the development of nodular lesions in the glomer- ular capillaries causes impaired blood flow with progres- sive loss of kidney function and, eventually, renal failure (see Chapter 25). Nodular glomerulosclerosis is thought to occur only in people with diabetes. Changes in the basement membrane in diffuse nodular glomeruloscle- rosis allow plasma proteins to escape in the urine, caus- ing albuminuria, hypoalbuminemia, edema, and other signs of impaired kidney function. Kidney enlargement, nephron hypertrophy, and hyperfiltration are early accompaniments of diabetes, reflecting the increased work performed by the kidneys in reabsorbing excessive amounts of glucose. One of the first manifestations of diabetic nephropathy is an increase in urinary albumin excretion, which is defined as a urine protein loss greater or equal to 30 mg/day or an albumin-to-creatinine ratio (A/C ratio) greater or equal to 30  μ g/mg (normal <30  μ g/mg) from a spot urine collection. 58 It is recommended that the A/C ratio be the preferred screen for increased urinary albumin excretion. Both systolic and diastolic forms of hyper- tension accelerate the progression of diabetic nephrop- athy. Even moderate lowering of blood pressure can decrease the risk of CKD. 11 The estimated glomerular filtration rate (eGFR) should also be monitored on a regular basis. Measures to prevent diabetic nephropathy or its pro- gression in persons with diabetes include achievement of

occasionally severe “burning pain,” particularly at night, can become physically and emotionally disabling. 53 Autonomic Neuropathy. The autonomic neuropa- thies involve disorders of sympathetic and parasympa- thetic nervous system function. There may be disorders of vasomotor function, decreased cardiac responses, inability to empty the bladder, gastrointestinal motility problems, and sexual dysfunction. 54 Defects in vaso- motor reflexes can lead to dizziness and syncope due to postural hypotension when the person moves from the supine to the standing position (see Chapter 18). Incomplete emptying of the bladder predisposes to uri- nary stasis and bladder infection and increases the risk of renal complications. Gastrointestinal motility disorders are common in persons with long-standing diabetes. The symptoms vary in severity and include gastroparesis, constipation, diarrhea, and fecal incontinence. Gastroparesis (delayed emptying of stomach) is commonly seen in persons with diabetes. 55 The disorder is characterized by complaints of epigastric discomfort, nausea, postprandial vomiting, bloating, and early satiety. Abnormal gastric empty- ing also jeopardizes the regulation of the blood glucose level. Diarrhea is another common symptom seen mostly in persons with poorly controlled type 1 diabetes and autonomic neuropathy. 56 The pathogenesis is thought to CHART 33-2   Classification of Diabetic Neuropathies Somatic Polyneuropathies (bilateral sensory) Paresthesias, including numbness and tingling Impaired pain, temperature, light touch, two-point discrimination, and vibratory sensation Decreased ankle and knee-jerk reflexes Mononeuropathies Involvement of a mixed nerve trunk that includes loss of sensation, pain, and motor weakness Amyotrophy Associated with muscle weakness, wasting, and severe pain of muscles in the pelvic girdle and thigh Autonomic Impaired vasomotor function Postural hypotension Impaired gastrointestinal function Gastric atony Diarrhea, often postprandial and nocturnal Impaired genitourinary function Paralytic bladder Incomplete voiding Erectile dysfunction Retrograde ejaculation Cranial nerve involvement Extraocular nerve paralysis Impaired pupillary responses Impaired special senses