Type 1 diabetes is characterized by an absolute loss of beta cells such that there is almost a total absence of insulin secretion (1). The majority of patients who develop type 1 diabetes have an autoimmune process that destroys the beta cells. There is another group of individuals who have type 1 diabetes in which beta-cell function is severely reduced in the absence of autoimmune destruction and in which the etiology of the beta-cell dysfunction is unknown. In type 1 diabetes, -g there is no significant obesity, the plasma lipid profile is normal, blood pressure is usually not elevated, and there is no evidence of a specific procoagulant state during the first few years of the disease (Table 4) (11). These metabolic abnormal- J
ities do not appear to be part of the primary disease process, but they are acquired a
Hyperglycemia Hyperinsulinemia Central obesity Diabetic dyslipidemia T plasma triglycerides ■ plasma HDL cholesterol small, dense LDL pattern Procoagulant state T plasma fibrinogen T plasma PAI-1 Hypertension yes no no no no no no no not Î (?)
yes yes yes yes yes yes yes yes Tin normal weight but not in obese
Source: The table reflects the results of studies cited in Refs. 6, 7, 26, 29, 30, 41, and 45.
as a consequence of the development of obesity, which appears to be a result of intensive insulin treatment (12) or poorly controlled glycemia that leads to hypertriglyceridemia, excessive activation of vascular cell protein kinase C, increased production of advanced glycosylation end products (AGEs), endothelial dysfunction, and oxidative stress (13). Type 1 diabetic patients have increased cardiovascular risk factors as a consequence of their hyperglycemia and its treatment and not as an intrinsic part of the disease itself. The development of cardiovascular disease is thus a very late complication of type 1 diabetes and manifests itself after age 35 in those with onset of type 1 diabetes prior to age 20 (as shown in Figs. 1 and 2) (14). In cross-sectional studies, the prevalence of cardiovascular disease in type 1 diabetic patients has been between 8 and 10% and did not differ significantly between men and women. The prevalence increases with age (from 6% in patients 15 to 29 years old to 25% in patients 45 to 59 years old) and with duration of diabetes (15,16). In a comparison of 16 European countries, the prevalence of cardiovascular disease in cross-sectional studies in type 1 diabetic populations varied from 3 to 19% (16).
The factors responsible for the increase in cardiovascular disease in type 1 diabetic patients have been investigated recently in several large cohorts. The <j results vary somewhat depending on the specific cohort, gender, and the age of onset of the diabetes. Patients with type 1 diabetes may develop nephropathy as a consequence of poor glycemic control and extensive data document that
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