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AIMS/HYPOTHESIS: First-degree relatives of Type II (non-insulin-dependent) diabetic patients in cross-sectional studies have increased insulin resistance, associated cardiovascular risk factors and abnormalities of fibrinolysis and coagulation. To minimise between-family genetic and environmental confounders, we investigated within-family relationships between early hyperglycaemia and risk factors. METHODS: Thirteen age and gender matched sibling pairs of Type II (non-insulin-dependent) diabetic patients, one hyperglycaemic, one normoglycaemic (fasting plasma glucose at screening 6.0-7.7 mmol.l(-1) and < 6.0 mmol.l(-1), respectively) were assessed for plasminogen activator inhibitor antigen (PAI-1), tissue plasminogen activator antigen (t-PA), fibrinogen, Factor VII and Factor VIII/von Willebrand factor antigen. Fasting lipid profiles, blood pressure and HOMA insulin sensitivity (%S) were also measured in siblings and in matched subjects without family history of diabetes. RESULTS: Hyperglycaemic and normoglycaemic siblings (7 female, 6 male) were aged, mean (SD) 56.8 (8.7) and 55.8 (8.4) years. Hyperglycaemic siblings had increased PAI-1 antigen, geometric mean (i.q.r.): 26.3 (15.1-45.6) vs 11.1 (2.1-23.3) ng/ml, p=0.0002, similar t-PA antigen, mean (SD) 9.5 (4.3) vs 7.4 (2.5) ng/ml, p=0.2 and fibrinogen 2.2 (0.3) vs 2.3 (0.6) g/l, p=0.5, and reduced %S 66.3 (30.5) vs 82.9 (25), p=0.04. PAI-1 correlated negatively with %S ( r=-0.55, p=0.005). No significant differences were found in blood pressure or fasting lipids. CONCLUSION/INTERPRETATION: A minor increase in plasma glucose in non-diabetic sibling pairs of Type II (non-insulin-dependent) diabetic patients was associated with reduced insulin sensitivity, increased central adiposity and a doubling of PAI-1 antigen concentration, suggesting impaired fibrinolysis. It is possible that this could contribute to increased cardiovascular risk in these subjects.

Original publication

DOI

10.1007/s00125-002-0795-8

Type

Journal article

Journal

Diabetologia

Publication Date

05/2002

Volume

45

Pages

635 - 641

Keywords

Blood Glucose, C-Peptide, Cross-Sectional Studies, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Insulin, Insulin Resistance, Islets of Langerhans, Male, Middle Aged, Obesity, Plasminogen Activator Inhibitor 1, Proinsulin, Reference Values, Siblings, Smoking