Plasma proinsulin in first-degree relatives of type 2 diabetic subjects.
Glucose intolerant relatives of Type 2 diabetic subjects have impaired insulin secretory responses to glucose but their proinsulin secretion has not been assessed. Plasma intact proinsulin was measured in 101 normoglycaemic and glucose intolerant first-degree relatives of Type 2 diabetic subjects both fasting and one hour after an infusion of glucose of 5 mg glucose.kg ideal weight.min-1. Geometric mean (+/- SD) plasma proinsulin increased from 2.4 (+2.5-1.2) and increased to 4.5 (+4.2-2.1) pmol/l at 1 hour (p less than 0.001). Linear regression revealed no relationship of fasting or achieved proinsulin with sex or obesity and a non-significant trend towards increasing fasting and achieved proinsulin with age and fasting plasma glucose. Proinsulin was assessed as a ratio to the simultaneous plasma C-peptide to estimate the relative amounts of insulin and proinsulin secreted by the beta-cells. Analysis of partial correlation coefficients, controlling for age and obesity, showed that the Achieved Proinsulin/Achieved C-peptide ratio was related to both fasting (r = 0.27, p = 0.004) and achieved plasma glucose (r = 0.25, p = 0.008). Glucose intolerant relatives (n = 37) had a small but significant increase in relative proinsulin secretion compared with normoglycaemic relatives (n = 64) (Achieved Proinsulin/Achieved C-peptide 0.07 +/- 0.05 vs 0.04 +/- 0.02 p less than 0.01). This is in accord with abnormal beta cell function being an early feature of Type 2 diabetes but does not distinguish between a primary beta-cell abnormality and a secondary effect of mild hyperglycaemia.
Beer
S F
SF
University Department of Clinical Biochemistry, Addenbrookes Hospital, Cambridge, UK.
O'Rahilly
S
S
Spivey
R S
RS
Hales
C N
CN
Turner
R C
RC
D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005190:Family; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood; D011236:Prediabetic State / Q000097:blood / Q000235:genetics; D011384:Proinsulin / Q000097:blood*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin