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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.
BACKGROUND: The cross-sectional IRIS-II study tried to assess the prevalence of insulin resistance and macrovascular disease in orally treated patients with Type 2 diabetes. METHODS: In total, 4,270 patients were enrolled into the study (2,146 male, 2,124 female; mean +/- SD age 63.9 +/- 11.1 years; body mass index 30.1 +/- 5.5 kg/m2; duration of disease 5.4 +/- 5.6 years; hemoglobin A1c 6.8 +/- 1.3%). The study consisted of a single morning visit with completion of a standardized questionnaire and collection of a fasting blood sample. RESULTS: The mean intact proinsulin value was 11.4 +/- 12.4 pmol/L (normal range < 10 pmol/L). Homeostasis model assessment resulted in 1,147 insulin-sensitive patients (26.9%) and 3,123 patients (73.1%) with insulin resistance. Of the latter patients 1,465 (34.3% of all patients) had also elevated intact proinsulin values, while 1,658 (38.8%) had no proinsulin elevation. In contrast, 1,042 (24.4%) of the insulin-sensitive patients had normal intact proinsulin, and only 105 (2.4%) had elevated intact proinsulin concentrations (chi2 test P < 0.0001). A specificity of 93.2% (sensitivity 46.9%) was calculated for elevated intact proinsulin as an indirect marker for insulin resistance. Of the 1,451 patients treated with sulfonylurea 52% had elevated intact proinsulin values and increased prevalence of cardiovascular complications (odds ratio 1.45). CONCLUSION: Type 2 patients with elevated fasting intact proinsulin values can be regarded as being insulin resistant. The results confirm that fasting intact proinsulin is a suitable measure for beta-cell dysfunction and insulin resistance in type 2 diabetes and may be used to support therapeutic decisions.
Background:The aim of our study was to examine the efficacy of short-term intravenous insulin intervention followed by oral pioglitazone/metformin therapy to prevent patients from continuous insulin application.Methods:This prospective, open-label, 4-month pilot study comprised of 14 diabetes patients (5 female, 9 male; age 60 ± 2 years; body mass index 29 ± 3.2 kg/m2; hemoglobin A1c [HbAlc] 7.6 ± 1.1%) with (1) insufficient glycemic control under a dose of metformin >1700 mg/day and/or metformin plus additional oral antidiabetes drugs (OADs) and (2) appropriate residual ?-cell function. Initially, an inpatient 34 h continuous intravenous insulin infusion was performed, and metformin was given (2? 850 mg/day). Insulin was stopped, and pioglitazone 30 mg/day was added at the second inpatient day. Patients were followed for four months. Efficacy parameters [change of HbA1c, fasting blood glucose [FBG], intact proinsulin, adiponectin, and high-sensitivity C-reactive protein (hsCRP)] were assessed after initial normalization of blood glucose values by intravenous insulin and at the study end point.Results:During the acute insulin intervention, FBG levels were stabilized in all study subjects. In the following OAD treatment period, five patients showed an improvement of HbA1c > 0.5% [35.7%; seven patients remained stable (50.0%), two patients were nonresponders (14.3%)].Fasting glucose values dropped after insulin infusion (?17.7%; p < .001). This effect was maintained during the consecutive OAD treatment period (glucose +0.3%, not significant (NS); HbA1c ?6.0%; p < .05). The initial decrease in fasting intact proinsulin levels was also maintained during the study (end value ?41%, p < .05).Improvements in hsCRP values (postinsulin value, ?15%, NS; end value ?37%; p < .05) and adiponectin values (postinsulin value +15%, NS; end value +128%; p < .001) were demonstrated at end point only after continued glitazone intake.Conclusions:Our pilot study demonstrated that a beneficial effect of a short-term intravenous insulin application on glycemic control was effectively maintained by pioglitazone/metformin treatment for at least 4 months. In addition, the oral therapy significantly improved cardiovascular risk parameters.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin.
METHODS
The study was designed as a multicenter, randomized, double-blinded two-arm trial. Patients with T2DM and dyslipidemia under metformin monotherapy with hemoglobin A1c value between 6.5% and 9.0% were eligible for trial participation. Blood was drawn at baseline and after 24 weeks of treatment from patients of five centers. Markers of inflammation and thrombocyte function (soluble CD40 ligand, thromboxane, vWillebrand factor, adhesion molecules, clotting reaction) were evaluated subsequently in a central laboratory.
RESULTS
A total of 46 patients were included in the final analyses. Mean (± standard deviation) age was 58.5 ± 9.0 years (13 women, 33 men; disease duration 6.3 ± 5.0 years; body mass index 32.0 ± 4.8 kg/m(2)). A total of 25 patients were treated with pioglitazone plus metformin, and 21 patients were in the glimepiride arm. There was a significant decline of E-selectin (-3.7 ± 4.8 ng/ml, p < .001 versus baseline), vWillebrand factor (-19.5 ± 32.0%, p < .05), and high-sensitivity C-reactive protein concentrations (-1.08 ± 0.91 mg/liter, p < .05) in the metformin + pioglitazone arm only (metformin + glimepiride, -0.5 ± 3.4 ng/ml, +1.4 ± 33.2%, + 0.08 ± 0.72 mg/liter, respectively, all not significant). Also, all other surrogate markers for platelet function and inflammation showed slight improvements in the metformin + pioglitazone arm but not in the metformin + glimepiride arm.
CONCLUSIONS
The fixed metformin + pioglitazone combination treatment showed an overall improvement of laboratory surrogate markers, indicating improvement of platelet function and of chronic systemic inflammation, which was not seen with metformin + glimepiride.
