Hyperproinsulinemia is not a characteristic feature in the offspring of patients with different phenotypes of type II diabetes.
OBJECTIVE
The purpose of this work was to study whether there are differences in plasma proinsulin levels and proinsulin-to-specific insulin ratio in the offspring of patients with different phenotypes of type II diabetes.


METHODS
Eleven glucose-tolerant offspring of type II diabetic patients with deficient insulin secretion phenotype (IS group), nine glucose-tolerant offspring of patients with insulin-resistant phenotype (IR group), and fourteen healthy control subjects without a family history of diabetes were studied.


METHODS
Plasma specific insulin, plasma proinsulin, and plasma C-peptide levels were measured during a 2-h oral glucose tolerance test and during hyperglycemic clamp.


RESULTS
Plasma proinsulin levels during the oral glucose tolerance test and the hyperglycemic clamp did not differ among the study groups. The IR group had a lower fasting plasma proinsulin-to-specific insulin ratio (10.3+/-1.7%) than the control group (15.4+/-1.4%; P<0.05) and the IS group (18.6+/-2.7%; P<0.05). Furthermore, the IR group had lower plasma proinsulin-to-specific insulin ratio at 30, 60 and 90 min after the oral glucose load than the IS group. However, there were no significant differences in proinsulin-to-C-peptide ratio during the oral glucose tolerance test among the study groups. In stepwise multiple regression analysis, hepatic specific insulin extraction in the fasting state (beta =0.65; P<0.001) and fasting blood glucose (beta =0.32; P<0.05) together explained 52% of the variation in fasting plasma proinsulin-to-specific insulin ratio.


CONCLUSIONS
Hyperproinsulinemia is not a characteristic finding in glucose-tolerant offspring of type II diabetic probands with deficient insulin secretion or insulin-resistant phenotype. The differences in proinsulin-to-specific insulin ratios were most likely explained by different hepatic extraction among the study groups.
Department of Medicine, Kuopio University Hospital and University of Kuopio, Kuopio, Finland.
I K
IK
Vauhkonen
L K
LK
Niskanen
L
L
Mykkänen
S M
SM
Haffner
M I
MI
Uusitupa
M
M
Laakso
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005215:Fasting; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D016014:Linear Models; D008875:Middle Aged; D010641:Phenotype; D011384:Proinsulin / Q000097:blood*; D012044:Regression Analysis
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin