Physiologic Changes
The long-term hyperglycemia of chronic diabetes mellitus can result in damage to and failure of vital organs, including the heart, kidneys, blood vessels, eyes, and nerves. Brief descriptions of the most common complications of diabetes are given below; for treatment of these complications, see Chapter 4.

Cardiovascular Disease
Cardiovascular disease is a major cause of death for persons with diabetes, The term applies to several diseases that affect the heart and blood vessels; they include hypertension and peripheral vascular disease, as well as coronary artery, cerebrovascular, and congenital heart disease.

Diabetic Nephropathy
Disease of the kidneys occurs in up to 40% of diabetic patients. The earliest stage of nephropathy is persistent microalbuminuria (30 to 299 mg albumin in urine/24 hours). Without specific interventions, these patients eventually progress to macroalbuminuria (300 mg or greater/24 hours), also called overt nephropathy. About half of type 1 diabetic patients progress to end-stage renal disease within 10 years of developing overt nephropathy, and about one-fifth of type 2 diabetic patients progress to end-stage renal disease approximately 20 years after onset of overt nephropathy.

Neuropathies
The metabolic disturbances of diabetes lead to two forms of neuropathy characterized by progressive nerve fiber loss.

Diabetic autonomic neuropathy. This is manifested by dysfunction of the autonomic nervous system. The most clinically important form of diabetic autonomic neuropathy is cardiovascular autonomic neuropathy. This reduces cardiovascular function, which is associated with an increased risk of silent myocardial ischemia (see Definitions) and death. Diabetic autonomic neuropathy can also affect gastrointestinal and genitourinary organs, causing bladder and erectile dysfunction.

Diabetic peripheral (or somatic) neuropathy. Patients may suffer pain or have dulled sensitivity to touch in their feet or hands. In the later stages of this neuropathy, diabetic patients often develop foot ulcerations, which, in some cases, do not heal, become infected, and lead to toe or other amputations. In the United States, more than 50,000 diabetes-related, lower-extremity amputations are performed annually.

Diabetic Retinopathy
Among adults 20 to 74 years of age, diabetic retinopathy is estimated to be the most frequent cause of new cases of blindness. In the earliest stage of retinopathy, no vision loss occurs, but capillary walls balloon and lose their ability to control the passage of substances between the blood vessels and the retina. Subsequent formation of fatty deposits within the retina and swelling of the retina can lead to macular edema and vision loss. In addition, over the years, the damaged tiny blood vessels may close and be replaced by new capillaries that are weaker, leak blood, and block vision. These capillaries may cause growth of scar tissue, which, when it shrinks, can cause retinal detachment.

Vision-threatening retinopathy begins to affect most type 1 diabetic patients during the 2 decades after they have had diabetes for 5 years. Up to one-fifth of type 2 diabetic patients already have some stage of retinopathy at the time of diabetes diagnosis.

Oral Cavity Disease
Studies indicate that poorly controlled blood glucose and long-term diabetes are risk factors for periodontal disease. Studies also show that periodontal disease can, in turn, worsen blood glucose control. Diabetic patients are also prone to other oral diseases and often have special needs; these are discussed in Chapter 5.

Biochemical Imbalances
Uncontrolled hyperglycemia can lead to biochemical imbalances that cause acute life-threatening events, such as diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome (see Table 10, Chapter 4).

Complications of Pregnancy
Prepregnancy diabetes that is poorly controlled before conception and during the first trimester can cause major birth defects in up to 10% of pregnancies and spontaneous abortions in up to 20% of pregnancies. Gestational diabetes mellitus (see Table 3) usually does not cause birth defects, but can lead to birth of an abnormally large baby and infant hypoglycemia immediately after birth.

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