Metabolism: clinical and experimental
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Randomized Controlled Trial Multicenter Study
Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients.
The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. ⋯ A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-alpha decrease in pioglitazone plus metformin group after the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA(1c), FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of beta-cell function.
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Pioglitazone is prescribed to improve insulin sensitivity in type 2 diabetes mellitus patients and has been discussed as a therapy for metabolic syndrome. Pioglitazone and other thiazolidinediones are associated with fluid retention and edema that may exacerbate existing or developing congestive heart failure, which is often present in these patients. Using a nonhuman primate model, our aims were to evaluate (1) whether fluid shifts were detectable in normoglycemic monkeys, (2) which fluid compartment changed, and (3) whether fluid retention was dose dependent. ⋯ Significant trends toward increases in interstitial fluid and extracellular water with increasing dose were apparent. Pioglitazone effectively improved metabolic status by significantly decreasing fasting glucose and triglycerides and increasing adiponectin. We conclude that thiazolidinedione-related plasma volume expansion occurs in nondiabetic primates and that fluid retention is detectable when compartments are directly measured.
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The complexity pathogenesis in the nonalcoholic fatty liver disease (NAFLD) involves an interplay between adipokines and neuroendocrine regulation of energy balance, including the role of neuropeptide Y (NPY)/agouti-related protein (AgRP) system. The first aim of this study was to assess the effect of long-term interdisciplinary intervention on NAFLD in obese adolescents, and the second objective was to establish the relationship between NPY/AgRP ratio and adiponectinemia. Fifty-five postpuberty obese adolescents were submitted to interdisciplinary intervention. ⋯ The most important finding was the positive correlation between AgRP and visceral fat in all patients and the negative correlation between NPY/AgRP and adiponectinemia only in NAFLD obese adolescents. The NAFLD patients presented more altered clinical parameters than the non-NAFLD subjects, including the negative correlation between adiponectinemia and NPY/AgRP. These results suggested that NAFLD obese adolescents presented an inflammatory profile that can influence the neuroendocrine regulation of energy balance, suggesting an additional impairment in the weight loss therapy.
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The aim of the study was to compare the impact of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) on vascular function among older Chinese people. A random sample of 671 men and 603 women aged 50 to 85 years without known diabetes from the Guangzhou Biobank Study-CVD was examined in a cross-sectional study. Subjects with no previously confirmed or treated diabetes but with both fasting plasma glucose less than 5.6 mmol/L and 2-hour glucose from 7.8 to less than 11.0 mmol/L were classified as having isolated IGT, and those with no previously confirmed and treated diabetes but with both fasting plasma glucose from 5.6 to less than 7.0 mmol/L and 2-hour glucose less than 7.8 mmol/L were classified as having isolated IFG. ⋯ Compared with subjects with isolated IFG, those with isolated IGT appeared to have a higher age- and sex-adjusted brachial-ankle pulse wave velocity (1543 +/- 22 vs 1566 +/- 17, P = .07) and to be more insulin resistant (2-hour postload insulin: 54.2 +/- 2.13 vs 26.8 +/- 2.99 muU/mL, P < .001), had a worse lipid profile (apolipoprotein [apo] B: 1.07 +/- 0.02 vs 0.97 +/- 0.02 g/L, P < .001; apo B/apo A-1 ratio: 0.80 +/- 0.02 vs 0.69 +/- 0.02, P < .001), but had lower glycosylated hemoglobin levels (6.03% +/- 0.06% vs 5.86% +/- 0.04%, P < .001) (values are mean +/- SE). Subjects with isolated IGT had greater arterial stiffness, probably as a result of being more insulin resistant, with a worse lipid profile than those with isolated IFG. The sole use of fasting glucose level to identify prediabetic people would fail to identify a significant proportion of the at-risk population.
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The metabolic syndrome is known to sometimes exist in the presence of normal aminotransferase levels. The purpose of this study was to determine the lowest sex-specific level of alanine aminotransferase associated with the metabolic syndrome in a nationwide, representative Korean population. We analyzed data from adults 20 years and older (n = 3405) assessed in the Third Korean National Health and Nutrition Examination Survey (2005). ⋯ In men, the odds ratio (95% confidence interval) of the metabolic syndrome was 2.71 (1.31-5.63) for alanine aminotransferase group 4 (> or =27 IU/L). In women, odds ratios were 1.69 (1.02-2.80) and 2.06 (1.23-3.43) for alanine aminotransferase groups 3 (15 < or = alanine aminotransferase < 19 IU/L) and 4 (> or =19 IU/L), respectively. High-normal alanine aminotransferase levels (> or =27 IU/L in men, > or =15 IU/L in women) were strongly associated with the metabolic syndrome in Korean adults.