A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients: association of impaired or diabetic glucose tolerance with other components of the metabolic syndrome

Abstract.   A follow-up study of first-degree relatives of type 2diabetic patients presented the opportunity to study theassociation of components of the metabolic syndrome with oralglucose tolerance in these subjects. In 1992, 25 years after thefirst analysis of the cohort, we performed 75-g oral glucosetolerance tests and measured anthropometric data (body massindex, waist-hip ratio), insulin and C-peptide concentrations,and parameters of lipoprotein metabolism (free fatty acids,triglycerides, cholesterol, HDL cholesterol). Of 135participants, 71 had normal glucose tolerance (GT), 22 hadimpaired GT, and 42 had diabetic GT (WHO 1985 criteria).Impaired glucose tolerance and diabetes were significantly(Kruskal- Wallis test) associated with advanced age (p=0.001), higher body mass index(p=0.005) and waist-hip ratio(p=0.027), systolichypertension (p=0.031),elevated basal insulin concentrations (p<0.001), higher free fatty acids(p<0.001) andtriglycerides (p=0.017), andlower HDL cholesterol (p=0.003); no associations were foundwith total and LDL cholesterol levels (Friedewalds formula,p=0.25). Abnormalities(obesity, hypertriglyceridemia, low HDL cholesterol,hypertension, pathological oral glucose tolerance) wereassociated with significant deterioriations in all othercomponents of the metabolic syndrome, if their number exceededthree. Disturbances of oral glucose tolerance are present in ahigh percentage of first-degree relatives after 25 years offollow-up (51% of those tested). Impaired or diabetic glucosetolerance in such a cohort was associated with overweight,hypertension and disturbances of lipoprotein metabolismcharacteristic of the metabolic syndrome. Hypercholesterolemia(LDL-cholesterol) is not a component of the metabolic syndromein a German population with a high hereditary burden regardingtype 2 diabetes. A metabolic syndrome should certainly bediagnosed if three components are present, although even in thepresence of only two components, an elevated risk isevident.