Aims: Therapy with either angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB) or thiazolidinediones (TZD) is associated with dose-dependent decrements in hematocrit and hemoglobin levels. We aimed to investigate the impact of the coadministration of TZD and ACEI/ARB on hematocrit and hemoglobin values in uncomplicated patients with type 2 diabetes mellitus and normal serum creatinine. Methods: Data from patients with type 2 diabetes currently followed, were reviewed and patients treated with ACEI/ARB and/or TZD were identified. For the purpose of this study the following 4 groups of 30 stable non-anemic diabetic patients each matched for age, gender, and BMI were formed. Group ACEI/ARB included patients on ACEI/ARB without TZD, group TZD included patients on TZD and antihypertensive agents other than ACEI/ARB, group ACEI/ARB/TZD consisted of patients on combined therapy with ACEI/ARB and TZD and the control group C included patients never exposed to ACEI/ARB or TZD. Clinical and laboratory data were collected prior to initiation of treatment and after 6 months. Results: Neither hematocrit nor hemoglobin showed any significant change from baseline at the end of the study in group C. In both group ACEI/ARB and group TZD a small, but statistically significant reduction in hematocrit (~?1% point) and hemoglobin levels (~?0.3 g/dl) was seen. A greater statistically and clinically important reduction in hematocrit (~?3% points) and hemoglobin (~?1?g/dl) levels was observed in group ACEI/ARB/TZD. Furthermore, incident anemia at the end reached 7% in group TZD and 23% in group ACEI/ARB/TZD. Conclusions: Coadministration of RAS inhibitors and PPAR-? agonists should be considered in the differential diagnosis of hematocrit lowering and anemia in uncomplicated type 2 diabetic patients with normal serum creatinine. Further studies are required to clarify the mechanism(s), the cardiovascular consequences and the cost utility of anemia workup in such patients.
The combination of a sulfonylurea with a biguanide improves the pancreatic beta-cell insulin secretion and the insulin utilization in peripheral tissues in NIDDM. This open, crossover, randomised and prospective study was designed to compare the effects of the fixed combination glibenclamide-metformin (GL-METF)-2.5 and 400 mg respectively, with the fixed combination glibenclamide-phenformin (GL-PHEN)-2.5 and 25 mg respectively, on NIDDM diabetes control. Thirty NIDDM patients, in ideal metabolic control, who were being treated with GL-PHEN were divided in two groups. One group received GL-PHEN for 12 weeks followed by 12 weeks treatment with GL-METF and the reverse treatment was given to the second group. A statistically significant decrease of post-prandial blood glucose (p = 0.034) and glycosylated haemo-globin (p < 0.02) values was observed under GL-METF treatment compared to those with GL-PHEN. The values of lactic acid were within normal limits during both treatments. The insulin secretion after breakfast was similar with both drug compounds. The BMI of the patients remained the same during a follow-up study of 24 weeks. Lipid metabolism did not change significantly during the trial and the safety parameters (renal and liver function, full blood count) remained unchanged. In conclusion, the administration of GL-METF leads to better diabetes control in NIDDM patients compared to that of GL-PHEN.
In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS)
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