Serum Lipoprotein Levels and Plasma Concentrations of Insulin,Intact and 32, 33 Split Proinsulin in Normoglycaemic Relatives of Patients with Type 2 Diabetes

Type 2 diabetes is associated with abnormal lipoprotein levels and altered plasma concentrations of insulin, intact and 32, 33 split proinsulin. To investigate whether these are early features of the disease, we studied 36 normoglycaemic first-degree relatives of patients with Type 2 diabetes (13 European, 15 of Asian (Indian-subcontinent), and 8 of Afro-Caribbean origin) and 36 control subjects with no family history of diabetes. Relatives and controls were matched for age (mean ± S.E. 33 ± 2 vs 34 ± 2 years), body mass index (23.7 ± 0.5 vs 23.7 ± 0.6 kg m^?2), sex (17 M, 19 F) and ethnic origin. After an overnight fast, blood was sampled for measurement of serum lipids, plasma glucose and insulin, intact and 32, 33 split proinsulin by specific immunoradiometric assays. Relatives and controls had similar fasting concentrations of glucose (5.0 ± 0.1 vs 4.9 ± 0.1 mmol l^?1), total cholesterol (4.51 ±0.13 vs 4.54 ± 0.17 mmol l^?1), HDL-cholesterol (1.21 ± 0.06 vs 1.10 ± 0.05 mmol l^?1), LDL-cholesterol (2.84 ± 0.14 vs 2.96 ± 0.14 mmol l^?1) and triglyceride (median (range) 0.78 (0.44–2.45) vs 0.83 (0.41–4.03) mmol l^?1). Fasting levels of insulin (50.4 (18.9–174.0) vs 51.6 (10.0–118.0) pmol l^?1 intact proinsulin (2.8 (0.1–15.0) vs 2.1 (0.6–6.4) pmol l^?1 and 32, 33 split proinsulin (2.0(0–23.7) vs 1.6 (0.3–6.0) pmol l^?1) were not significantly different between relatives and controls. Analysis of results for each ethnic group separately did not alter the findings. It is concluded that glucose-tolerant subjects at risk of future diabetes have normal fasting lipid concentrations and plasma levels of insulin and its precursors. This suggests that the dyslipidaemia and altered insulin concentrations found in overt Type 2 diabetes are not present before the onset of glucose intolerance.