ABSTRACT
The purpose of the study was the comparison of the effect of the oral therapy of non-insulin-dependent diabetes mellitus (NIDDM) with either a sulphonylurea or biguanide derivative on plasma amylin level. In 10 healthy individuals the fasting plasma amylin level was 1.56 +/- 0.27 pmol/l (mean +/- SEM) and 6 min after i.v. injection of 1 mg glucagon a fourfold increase was observed. In 10 patients with NIDDM receiving glibenclamide (CAS 10238-21-8) the fasting plasma amylin level was twofold higher than in healthy control (2.72 +/- 0.38 pmol/l; p < 0.025) but following glucagon administration it increased only twofold. In 15 patients treated with metformin (CAS 657-24-9) the fasting plasma amylin level was similar to that in healthy individuals (1.64 +/- 0.25 pmol/l), but after glucagon stimulation the increment of plasma amylin was minimal and the relevant mean value was significantly lower when compared with those in healthy individuals and with NIDDM patients treated with glibenclamide. In 10 untreated obese patients with newly diagnosed NIDDM the administration of glibenclamide (14 days) resulted in the increase of basal (2.47 +/- 0.23 and 3.16 +/- 0.29 pmol/l; p < 0.1), and glucagon stimulated (3.34 +/- 0.39 and 4.56 +/- 0.38; p < 0.05) plasma amylin concentrations, whereas other 10 patients receiving metformin showed a decrease in fasting plasma level of this peptide before (2.64 +/- 0.59 and 1.28 +/- 0.38 pmol/l; p < 0.1), and after glucagon injection (5.02 +/- 0.55 and 2.83 +/- 0.65 pmol/l; p < 0.02). With the respect to the trophic effect of amyloid deposits in the pancreatic islets and to a hypothetic effect of amylin increasing insulin resistance, the present results emphasize the particular usefulness of metformin in the pharmacological treatment of NIDDM. All contraindications and side effects of metformin should be taken into account before drug administration.
Subject(s)
Amyloid/blood , Diabetes Mellitus, Type 2/blood , Glyburide/adverse effects , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Adult , Blood Glucose/metabolism , C-Peptide/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/drug therapy , Female , Glyburide/therapeutic use , Humans , Hypoglycemic Agents/therapeutic use , Insulin/blood , Islet Amyloid Polypeptide , Male , Metformin/therapeutic useABSTRACT
The study was carried out on 20 patients, aged 20-60 years, with non-insulin-dependent (type 2) diabetes of 3-17 years duration and with secondary failure of sulphonylurea derivatives. In the initial run-in-period (8 weeks) the patients were treated only with insulin in a dose decreasing glycaemia in fasting state to 160 mg% (8.9 mmol/l), then during 16 weeks they received insulin and gliclazide 160-320 mg per day, and finally during the final period (8 weeks) they were transferred again to exclusive insulin therapy. The association of gliclazide with insulin resulted in better metabolic control expressed by significant decrease of basal and postprandial glycaemia and small (non-significant) decrease of serum triglycerides level--with simultaneous reduction of daily insulin requirement by 34% on the average. In this period an increase of basal and stimulated (test meal) C-peptide secretion was observed. The improvement of the metabolic state and the increased C-peptide secretion persisted also after gliclazide withdrawal (during the second period of exclusive insulin therapy), although the determined parameters were less favourable than when combined treatment was applied. The mechanism of metabolic improvement of patients with type 2 diabetes and secondary failure of sulphonylurea derivatives, which follows the addition of gliclazide to insulin, is not fully clarified. Probably it is the consequence of both, the increased secretion of endogenous insulin and the enhanced activity of this hormone in insulin-sensitive tissues.
