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Acta Clin Belg. 2002 Jun-Jul;57(3):134-41.
Clinical, biophysical and biochemical variables from African-heritage subjects with type 2 diabetes.
Hermans MP, Dumont C, Buysschaert M.
Service d'Endocrinologie et Nutrition, Cliniques Universitaires St Luc, UCL-DIAB 54.74, Avenue Hippocrate 54, B-1200 Brussels, Belgium.
We compared the metabolic profile of two ethnic populations with type 2 diabetes, one from Bantu (n = 23; Ban) and the other from Belgian (n = 314) extraction followed at St Luc Hospital. Further comparison with a Belgian sub-cohort (n = 64; Be) matched for age (52 yrs) and sex distribution (M/F: 61/39%) showed no significant difference between Belgian and Bantu subjects with regards to diabetes duration (9 and 11 yrs; Ban and Be respectively), age at diabetes diagnosis (43 and 42 yrs), HbA1c (8.1 +/- 1.9 vs. 8.5 +/- 1.9%; NS), and achieved education level. BMI was lower in Ban (29 +/- 4 vs. 32 +/- 7 in Be; p < 0.02), as were body fat (33 +/- 12 vs. 37 +/- 11 kg; NS) and waist diameter (99 +/- 9 vs. 106 +/- 16 cm; p < 0.02). Forty-eight and 72% of Ban and Be were on metformin (p < 0.05), while insulin was given to 39 and 34%. Daily insulin dose was lower in Ban (0.31 +/- 0.20 vs. 0.47 +/- 0.18 IU.kg-1.24 h-1; p < 0.001). There was no difference in beta-cell function (% beta; normal: 100%) or insulin sensitivity (%S; normal: 100%) as determined with HOMA between groups. % beta (median [perc 25-75]) was 51 [23-119] and 67 [45-84] in Ban and Be, while %S was 32 [29-37] and 37 [27-45]. Smoking (past & current) prevalence was 5 and 47% in Ban and Be (p < 0.0001). Prevalence of micro- and macroangiopathy did not differ between groups, although Ban had more macroalbuminuria (29 vs. 9%; p < 0.05), and were more often treated with Ca(2+)-channel- and beta-blockers than Be subjects (36 and 39% vs. 16 and 8%; p = 0.07 and < 0.05, respectively). Fasting (F) and interprandial (IP) triglycerides (TG) were lower in Ban: 115 [81-149] vs. 189 [155-325] mg.dL-1 for F-TG and 127 [81-160] vs. 170 [128-305] mg.dL-1 for IP-TG (p < 0.0001), as was total cholesterol (201 +/- 53 vs. 223 +/- 40 mg.dL-1 (p < 0.05), despite lower use of hypolipidaemic drug (13 vs. 44%; p < 0.01). African-heritage subjects with type 2 diabetes have similar degree of diabetes control and complications, in the presence of leaner biophysical status, minimal tobacco exposure and lower fasting and interprandial triglycerides.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12212354&dopt=Abstract
Curr Med Res Opin. 1989;11(5):273-8.
Metformin efficacy and tolerance in obese non-insulin dependent diabetics: a comparison of two dosage schedules.
Menzies DG, Campbell IW, McBain A, Brown IR.
Diabetic Department, Victoria Hospital, Kirkcaldy, Scotland.
A comparative open study of metformin unit doses of 500 mg and 850 mg was carried out in 64 obese, non-insulin dependent diabetics on 1.5 to 3 g metformin daily. Glycaemic response, blood lactate, plasma metformin concentrations and tolerance for metformin were assessed. On changing from a 500 mg unit dose to an equivalent total dose of metformin using the 850 mg preparation, there were no significant changes in the random blood glucose, glycated haemoglobin, or blood lactate concentrations. Metformin plasma concentrations remained unchanged except for patients transferred from 1.5 to 2.0 g daily to 850 mg twice daily; in these patients plasma concentrations increased from 1.83 +/- 0.87 to 2.50 +/- 0.89 micrograms/l (p less than 0.01). Seven patients (3 asymptomatic and 4 with background symptoms) became intolerant of the 850 mg regimen and required to return to the 500 mg dose regimen. After exclusion of patients intolerant of the 850 mg dose regimen (11%), the remaining patients noted no significant change in symptoms and 28% of all patients transferred to the 850 mg dose unit indicated an overall preference for this regimen.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2702849&dopt=Abstract
Midwestern.edu
The ability of metformin (MF) to acutely relax phenylephrine (PE)-induced contraction in the isolated rat tail artery is reported to be accompanied by repolarization of the arterial smooth muscle cell (SMC) membranes. These membranes contain potassium (K) channels which if opened could mediate such repolarization and resultant relaxation. We have shown that the acute relaxation of rat tail arterial tissue rings by graded levels of MF > or = 0.24 mmol/L is markedly antagonized by a high concentration of tetraethylammonium (TEA; 10 mmol/L) which nonselectively inhibits nearly all K channels. Thus, we tested effects of more selective inhibitors of K channels in the same tissue. We also tested MF for relaxation of contractions induced by high levels of extracellular K. To avoid confounding variables, we also conducted these tests in arterial rings in which endothelium and sympathetic nerve endings had been removed. In the absence of K channel inhibition, half-maximal PE-induced contractions were rapidly relaxed by all levels of MF with an EC50 of 1.7+/-0.2 mmol/L (n=8 rings). 1 mmol/L 4-aminopyridine (4AP) which only inhibits voltage-operated and ATP-sensitive K channels markedly antagonized this relaxation, shifting the EC50 for MF to 7.5+/-0.7 mmol/L (n=8; p < 0.05). TEA at 1 mmol/L (which only inhibits calcium-activated K channels), barium at 20 micromol/L (which only inhibits inward rectifier K channels) and glyburide at 5 micromol/L (which only inhibits ATP-sensitive K channels) did not alter this relaxation. Finally, MF failed to relax contractions produced by elevations of extracellular K to levels high enough to abolish the K gradient across arterial SMC membranes. Thus, acute relaxation of rat tail arterial smooth muscle by MF may be dependent on the transmembrane K gradient and mediated at least in part by specific activation of K efflux through 4AP-sensitive voltage-dependent K channels in arterial SMC membranes.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10622240&dopt=Abstract
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