RISK-FACTORS FOR MORTALITY IN TYPE-II (NON-INSULIN-DEPENDENT) DIABETES - EVIDENCE OF A ROLE FOR NEUROPATHY AND A PROTECTIVE EFFECT OF HLA-DR4

To test the hypothesis that interaction between genetic, immunological , clinical and metabolic risk factors influences the outcome of Type I I (noninsulin-dependent) diabetes mellitus, we examined which of the a bove factors present at baseline were associated with mortality in 134 Type IT diabetic patients followed for 9 years. Thirty-eight patients (29 %) died during the follow-up period; the majority of whom (68 %) died from cardiovascular disease. At baseline, the deceased patients h ad higher HbA(1c) values (p = 0.002), higher LDL-triglycerides (p = 0. 007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty a cid (NEFA) concentrations (p = 0.014), and higher albumin excretion ra te (p < 0.0001) than the patients who survived. In addition, the frequ ency of HLA-DR4 (21 vs 39 %, p = 0.048) and of parietal cell antibodie s (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23 %, p < 0.001) , microalbuminuria (45 vs 6 %, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0 .005) at baseline than patients who survived. In a multiple logistic r egression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007) , HbA(1c) (p = 0.018) and albumin excretion rate (p = 0.016) were inde pendent risk factors for death. In patients free of cardiovascular dis ease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent developm ent of cardiovascular disease. In conclusion, in addition to coexistin g macroangiopathy, increased albumin excretion rate, poor glycaemic co ntrol and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of a utoimmunity may be associated with decreased risk of cardiovascular di sease.