mune process and/or of symptomatic disease in genetically susceptible subjects have been proposed including viral infections.

Type II diabetes accounts for the majority (approximately 90 percent) of cases of primary diabetes. It is rare before age 30, but increases steadily with age thereafter. The age, sex, and ethnic prevalences are given in Table B-1 . The etiology of Type II is unclear, but three cardinal components have been proposed: (1) peripheral insulin resistance (thought by many to be primary) in target tissues (e.g., muscle, adipose and liver); (2) β-cell insulin secretory defect; and (3) hepatic glucose overproduction. Although the relative contributions of these features are controversial, it is generally accepted that the main factors for increased risk of Type II diabetes include age (with older individuals at higher risk), obesity, central fat deposition, a history of gestational diabetes (if female), physical inactivity, ethnicity (prevalence is greater in African Americans and Hispanic Americans, for example), and perhaps most importantly, a positive family history of Type II (for example, more than 90 percent of monozygotic twins are concordant for diabetes compared to less than 50 percent for dizygotic twins). Defects at many intracellular sites could account for the impaired insulin action and secretion seen in Type II diabetes (Kruszynska and Olefsky, 1996). The insulin receptor itself, insulin receptor tyrosine kinase activity, insulin receptor substrate proteins, insulin-regulated glucose transporters, enhanced protein kinase C (PKC) activity, tumor necrosis factor-α, rad (ras associated with diabetes), and PC1 have all been proposed as potential mediators of insulin resistance; impaired insulin secretion has been linked to hyperglycemia itself, to abnormalities of glucokinase and hexokinase activity, and to abnormal fatty acid metabolism.

Finally, an increasing number of “other” types of diabetes have been described that are linked to specific genetic mutations, for example, maturity-onset diabetes of youth, which results from a variety of mutations of the β-cell glucokinase gene.

The diagnosis of diabetes is problematic and a major concern for clinicians and investigators. Whereas Type I is often clearly diagnosed at onset (a blood sugar >200 mg/dl plus symptoms), up to half of the Type II population goes undiagnosed. This occurs because the degree of metabolic disturbance needed to meet both the old and the recently revised criteria does not necessarily produce symptoms, but nonetheless is likely to lead to the late complications of diabetes (cardiovascular disease, nephropathy, retinopathy, and neuropathy). It is partly because of this large population of undiagnosed cases and the impracticability of the standard diagnostic test (oral glucose tolerance test) in busy clinical practice that a more simplified diagnostic approach has been recommended by the ADA based on the fasting plasma glucose. Table B-2 shows the earlier NDDG (WHO, 1980) and the current ADA (ADA, 1997) criteria. It should be noted that the vast majority of undiagnosed cases of diabetes under the 1979 criteria were diagnosable only by the 2-hour postglucose criterion (>200 mg/dl) and had fasting plasma glucose levels below the diagnostic level (140 mg/dl). This was one of the main reasons that current ADA recommendations have lowered the fasting criterion to 126 mg/dl (i.e., to capture those cases with the simpler [and more reproducible] fasting glucose test, as 126 mg/dl fasting approximates the 2-hour postchallenge diagnostic level).

TABLE B-1 Three-Year Mean Prevalence of Diagnosed Diabetes (per 1,000 population) by Gender, Age, and Race, 1990–1992





White (men and women)

Black (men and women)

























SOURCE: Kenny et al., 1995, Appendix 4.5, Chapter 4 (1990-1992 NationalHealth Interview Surveys).

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement