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- pioglitazone (4)
- thiazolidinediones (4)
- insulin resistance (3)
- type 2 diabetes (3)
- cardiovascular disease (2)
- cardiovascular risk (2)
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- sulfonylurea (2)
- type 2 diabetes mellitus (2)
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Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers). Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD): 66 ± 7 yrs, disease duration: 6.6 ± 9.6 yrs, HbA1c: 6.7 ± 0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: -19%/placebo: +6%, RelA: -20%/+2%, MMP-9: -36%/+9%, TNFα: -10%/+14%, P < 0.05 between groups in all cases). Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control.
Background and Objectives: In advanced β-cell dysfunction, proinsulin is increasingly replacing insulin as major component of the secretion product. It has been speculated that proinsulin has at least the same adipogenic potency than insulin, leading to an increased tendency of lipid tissue formation in patients with late stage β-cell dysfunction. Methods and Results: Mesenchymal stem cells obtained from liposuction material were grown in differentiation media containing insulin (0.01 μmol), proinsulin (0.01 μmol) or insulin+proinsulin (each 0.005 μmol). Cell culture supernatants were taken from these experiments and an untreated control at weeks 1, 2, and 3, and were stored at -80°C until analysis. Cell differentiation was microscopically supervised and adiponectin concentrations were measured as marker for differentiation into mature lipid cells. This experiment was repeated three times. No growth of lipid cells and no change in adiponectin values was observed in the negative control group (after 7/14/12 days: 3.2±0.5/3.3±0.1/4.4±0.5 ng/ml/12 h). A continuous differentiation into mature adipocytes (also confirmed by Red-Oil-staining) and a corresponding increase in adiponectin values was observed in the experiments with insulin (3.6±1.9/5.1±1.4/13.3±1.5 ng/ml/12 h; p<0.05 week 1 vs. week 3) and proinsulin (3.3±1.2/3.5±0.3/12.2±1.2 ng/ml/12 h; p<0.05). Comparable effects were seen with the insulin/proinsulin combination. Conclusions: Proinsulin has the same adipogenic potential than insulin in vitro. Proinsulin has only 10∼20% of the glucose-lowering effect of insulin. It can be speculated that the adipogenic potential of proinsulin may be a large contributor to the increased body weight problems in patients with type 2 diabetes and advanced β-cell dysfunction.
Improvement of Cardiovascular Risk Markers by Pioglitazone Is Independent From Glycemic Control
(2005)
High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus
(2006)
Background: Type 2 diabetes mellitus is associated with increased cardiovascular risk. One laboratory marker for cardiovascular risk assessment is high-sensitivity C-reactive protein (hsCRP).
Methods: This cross-sectional study attempted to analyze the association of hsCRP levels with insulin resistance, β-cell dysfunction and macrovascular disease in 4270 non-insulin-treated patients with type 2 diabetes [2146 male, 2124 female; mean age ±SD, 63.9±11.1years; body mass index (BMI) 30.1±5.5kg/m2; disease duration 5.4±5.6years; hemoglobin A1c (HbA1c) 6.8±1.3%]. It consisted of a single morning visit with collection of a fasting blood sample. Observational parameters included several clinical scores and laboratory biomarkers.
Results: Stratification into cardiovascular risk groups according to hsCRP levels revealed that 934 patients had low risk (hsCRP <1mg/L), 1369 patients had intermediate risk (hsCRP 1–3mg/L), 1352 patients had high risk (hsCRP >3–10mg/L), and 610 patients had unspecific hsCRP elevation (>10mg/L). Increased hsCRP levels were associated with other indicators of diabetes-related cardiovascular risk (homeostatic model assessment, intact proinsulin, insulin, BMI, β-cell dysfunction, all p<0.001), but showed no correlation with disease duration or glucose control. The majority of the patients were treated with diet (34.1%; hsCRP levels 2.85±2.39mg/L) or metformin monotherapy (21.1%; 2.95±2.50mg/L hsCRP). The highest hsCRP levels were observed in patients treated with sulfonylurea (17.0%; 3.00±2.43mg/L).
Conclusions: Our results indicate that hsCRP may be used as a cardiovascular risk marker in patients with type 2 diabetes mellitus and should be evaluated in further prospective studies.
