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Diabetes Res Clin Pract. 2004 Jan;63(1):19-26.
Decrease in serum C-reactive protein levels by troglitazone is associated with pretreatment insulin resistance, but independent of its effect on glycemia, in type 2 diabetic subjects.

Yatagai T, Nakamura T, Nagasaka S, Kusaka I, Ishikawa SE, Yoshitaka A, Ishibashi S.

Division of Endocrinology and Metabolism, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, 329-0498, Tochigi, Japan.

Insulin-sensitizing thiazolidinediones (TZDs) decrease inflammatory markers such as high-sensitive C-reactive protein (hsCRP) in sera in addition to their hypoglycemic effects. However, factors associated with the decrease in serum hsCRP concentrations are unclear. In the present study, an effect of troglitazone on serum hsCRP levels was investigated and compared with its effect on glycemia. A total of 34 subjects with type 2 diabetes (17 men and 17 women, aged 54+/-2 years and body mass index (BMI) 26.7+/-0.6 kg/m(2), mean+/-S.E.) were studied. Nineteen out of the 34 subjects was treated with troglitazone 400mg daily for 12 weeks. The remaining 15 subjects were treated with metformin 750 mg daily as a control group. Baseline hsCRP levels were comparable between the two groups, and those were positively associated with fasting insulin levels. After treatment, glycemic control assessed by HbA1c and fasting glucose levels improved in both groups, whereas insulin sensitivity index estimated by homeostasis model assessment (HOMA-R) decreased only in the troglitazone-treated group. Serum levels of hsCRP significantly decreased from 916+/-210 ng/ml to 569+/-123 ng/ml (P<0.05) in the troglitazone-treated group, whereas the levels remained unchanged in the metformin-treated group (from 1087+/-248 ng/ml to 1152+/-301 ng/ml). In the troglitazone-treated group, there was no difference in the absolute and percent change in serum hsCRP levels between responders, who displayed the decrease in HbA1c greater than 0.6% (n=12), and the remaining non-responders (n=7). The decrease in serum hsCRP concentrations was negatively related to baseline levels of serum hsCRP and insulin and HOMA-R. In conclusion, troglitazone, but not metformin, reduced serum hsCRP levels in type 2 diabetic patients. The decrease in serum hsCRP concentrations by troglitazone was associated with the pretreatment levels of hsCRP and insulin resistance, but independent of the changes in glycemia.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14693409&dopt=Abstract [PubMed - in process]

bath.ac.uk

OBJECTIVE: To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes. RESEARCH DESIGN AND METHODS: Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL(1), LDL(2), and LDL(3)) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL(3). RESULTS: HbA(1c), triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL(3) mass and the LDL(3)-to-LDL ratio fell with pioglitazone (LDL(3) mass 36.2 to 28.0 mg/dl, P < 0.01; LDL(3)-to-LDL 19.2:13.3%, P < 0.01) and metformin (42.7 to 31.5 mg/dl, P < 0.01; 21.3:16.2%, P < 0.01, respectively) with no change on gliclazide. LDL(3) reductions were associated with reciprocal LDL(1) increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P = 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P = NS) or metformin (1.26 to 1.18 mmol/l, P = NS), largely due to an HDL(2) increase (0.3 to 0.4 mmol/l, P < 0.05). HDL(3) cholesterol fell on metformin (0.9 to 0.85 mmol/l, P < 0.01). On pioglitazone and metformin, the HDL(2)-to-HDL(3) ratio increased compared with no change on gliclazide. CONCLUSIONS: For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14693964&dopt=Abstract [PubMed - in process]

gwt-tud.de

OBJECTIVE: The goal was to assess the 1-year efficacy and safety of the addition of pioglitazone or metformin to existing sulfonylurea (SU) therapy in patients with inadequately controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: In this multicenter, double-blind study, patients were randomized to receive either pioglitazone 15 mg (n = 319) or metformin 850 mg (n = 320) and up to 45 mg/day and 2,550 mg/day, respectively. The primary efficacy endpoint was HbA(1c) at week 52. Fasting plasma glucose, insulin, and lipid profiles were also measured. RESULTS: HbA(1c) was reduced by 1.20% in the SU plus pioglitazone group and 1.36% in the SU plus metformin group, and fasting plasma glucose was reduced by 2.2 and 2.3 mmol/l in the respective groups. Fasting insulin levels were also reduced (pioglitazone arm -1.3 micro IU/ml; metformin arm -0.8 micro IU/ml). There were no significant between-treatment differences in these three parameters. Pioglitazone addition to SU significantly reduced triglycerides (-16 vs. -9%; P = 0.008) and increased HDL cholesterol (14 vs. 8%; P < 0.001) compared with metformin addition. LDL cholesterol was increased 2% by the addition of pioglitazone and decreased 5% by the addition of metformin to SU (P < 0.001). Urinary albumin-to-creatinine ratio was reduced by 15% in the SU plus pioglitazone group and increased 2% in the SU plus metformin group (P = 0.017). Both combinations were well tolerated with no evidence of hepatic or cardiac toxicity in either group. CONCLUSIONS: Clinically equivalent improvements in glycemic control were observed for both combinations. Compared with metformin plus SU, addition of pioglitazone to SU resulted in a reduction of the urinary albumin-to-creatinine ratio, a small but significant rise in LDL cholesterol, and significantly greater improvements in triglyceride levels and HDL cholesterol levels. Metformin plus SU was associated with a significant reduction in LDL cholesterol. SU plus pioglitazone is an effective and well-tolerated combination regimen that may provide additional beneficial effects for patients with type 2 diabetes.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14693980&dopt=Abstract [PubMed - in process]





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