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Effects of antihyperglycaemic therapies on proinsulin and relation between proinsulin and cardiovascular risk factors in type 2 diabetes
Author(s) -
Hermann L. S.,
Ranstam J.,
Vaaler S.,
Melander A.
Publication year - 1999
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.1999.00034.x
Subject(s) - proinsulin , medicine , metformin , endocrinology , type 2 diabetes , insulin , diabetes mellitus , glibenclamide , insulin resistance , body mass index
Summary Aim: To assess the effect of oral antihyperglycaemic therapy on fasting proinsulin and the relation between proinsulin levels and cardiovascular risk factors in type 2 diabetes. Methods: One hundred and sixty‐five patients with type 2 diabetes, fasting blood glucose concentration (FBG) ≥ 6.7 mmol/l, were recruited from five diabetes outpatient clinics in primary health care. Diet and antihyperglycaemic medication, aiming at FBG <6.7 mmol/l, was maintained for 6 months after completed dose titration in a randomized, double‐blind, double‐dummy trial with metformin (M), glibenclamide (G) and primary combination of both drugs (MG). The study compared M, G and MG in low dose (MGL) and also different high‐dose regimens, i.e. G added to M (M/G), M added to G (G/M) and primary combination (MGH). Outcome measures were fasting proinsulin, glycaemia, body mass index, blood pressure, lipids, insulin and C‐peptide. Results: Lower proinsulin levels were found when therapy was initiated with metformin (M vs. G, p = 0.013 and M/G vs. G/M, p = 0.033). M and G were equally effective on glucose levels. In the group as a whole FBG decreased from (mean ± s.d.) 10.2 ± 2.7 to 7.0 ± 1.2 mmol/l with no change in proinsulin. Proinsulin was associated with cardiovascular risk factors, linking high proinsulin to an atherogenic risk marker profile. Mean proinsulin change from baseline was inconsistently associated with markers of insulin resistance. Meal‐stimulated glucose (net AUC) decreased after treatment only in those with low baseline proinsulin levels. Conclusion: It may be advantageous to initiate oral antihyperglycaemic therapy with metformin rather than with sulphonylurea. High proinsulin levels are associated with an atherogenic‐risk marker profile and an impaired therapeutic postprandial glucose response after treatment in patients with type 2 diabetes. Proinsulin change after therapy is inconsistently associated with markers of insulin resistance and unrelated to fasting blood glucose reduction.