Distribution of normal and pathological OGTTs among pregnant population and non-pregnant women with PCOS - the cross-sectional study.

ABSTRACT: Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition.We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B.The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P < .001) for abnormal OGTT results in pregnant women compared to non-pregnant women with PCOS.We might conclude that pregnancy could have a more challenging influence on glucose metabolism and that carries higher risks for abnormal glucose metabolism than PCOS. The awareness of obstetricians regarding physiological changes during pregnancy that predisposes abnormal glucose metabolism is decreasing over time and the compliance concerning OGTT testing of pregnant women is decreasing too.

In vitro models of insulin resistance: Mitochondrial coupling is differently affected in liver and muscle cells.

Mitochondrial dysfunction in diabetes is a widely studied topic, but inconsistency in literature data suggests a need for valid and reproducible models that will help to clarify this interaction. We aimed to establish insulin resistance models using chronic high insulin treatment in two cell types: myocytes and hepatocytes, characterise them in terms of mitochondrial function and compare them to the widely used palmitate-induced model of insulin resistance. We found that insulin lowered phosphorylation of Akt while not affecting cell viability, ROS production, mitochondrial morphology or respiration, and caused decrease in mitochondrial coupling only in muscle but not in liver cells.

The association of tumor necrosis factor alpha, lymphotoxin alpha, tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2 gene polymorphisms and serum levels with periodontitis and type 2 diabetes in Serbian population.

OBJECTIVES: Aiming to show that periodontitis (PD) and type 2 diabetes (T2D) are bidirectionally related and potentially linked by inflammatory cytokines, we searched for association between -308 G/A Tumor necrosis factor-alpha (TNFα), +252A/G Lymphotoxin-alpha (LTα), +36A/G Tumor necrosis factor receptor 1 (TNFR1) and +676 T/G tumor necrosis factor receptor 2 (TNFR2) single nucleotide polymorphisms (SNPs) and: risk of PD or PD + T2D; periodontitis parameters in PD and PD + T2D; serum levels of cytokines/their receptors. Relationship between periodontal inflammation and serum cytokine/receptor levels was also assessed. DESIGN: Subjects were stratified as: 57 healthy controls (HC); 58 PD; 65 PD + T2D. Sociodemographic, environmental, behavioral and periodontal clinical data were recorded. SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism, while cytokines/receptors levels were quantified by enzyme-linked immunosorbent assay. Impact of periodontal inflammation was measured using periodontal inflamed surface area (PISA). RESULTS: TNFα AA genotype showed protective effect in T2D + PD compared to PD, even adjusted for behavioral/environmental factors (OR 0.18; 95 %CI 0.037-0.886; p = 0.035). LTα AG heterozygotes had increased risk of PD (OR 3.27; 95 %CI 1.35-7.96; p = 0.016), while TNFR2 TG genotype had protective effect (OR = 0.44; 95 %CI 0.954-0.9794; p = 0.043). TNFR1 AA was predictor of periodontal pocket depth and clinical attachment loss in PD. Correlation between TNFR2 concentration and PISA was negative in PD, positive in PD + T2D. CONCLUSIONS: None of the SNPs showed cross-susceptibility between PD and T2D. + 252A/G LTα and +676 T/G TNFR2 SNPs are associated with PD risk. Periodontal destruction in healthy individuals is influenced by TNFR1 genotype. Impact of periodontal on systemic inflammation is masked by T2D.

Relationship between serum tumor necrosis factor receptor-2 concentration and periodontal destruction in patients with type 2 diabetes: Cross-sectional study.

Introduction: The role of tumor necrosis factor-α (TNFα) is well documented in pathogenesis of chronic periodontitis (CP) and type 2 diabetes (T2D). Considering short half-life of TNFα, tumor necrosis factor receptor-2 (TNFR2) is used as prosperous surrogate marker of TNFα activity. Objective: The aim was to detect TNFR2 serum concentration and correlate it with periodontal destruction in patients with diagnosed T2D and nondiabetics. Methods: The study included 85 patients divided into three groups: T2D + CP (group T2D, n = 34); nondiabetics + CP (Group PD, n = 27); and healthy controls (group HC, n = 24). T2D was diagnosed according to WHO criteria (2013) and periodontitis was diagnosed using International Workshop for a Classification of Periodontal Diseases and Conditions criteria (1999). TNFR2 level was measured by enzyme-linked immunosorbent assay (ELISA). Results: There was no difference in TNFR2 level among the groups (Kruskal­Wallis, p = 0.482). Significant correlation (Pearson's correlation coefficient) was observed between clinical attachment loss (CAL) and TNFR2 concentration in PD group (rp = -0.460, p = 0.016). In T2D group, correlations were observed between TNFR2 concentration and CAL (rp = 0.363, p = 0.005) and periodontal inflamed surface area (PISA) (rp = 0.345, p = 0.046) and periodontal epithelial surface area (PESA) (rp = 0.578, p = 0.000). Conclusion: Higher concentration of TNFR2 was associated with higher CAL, PESA, and PISA scores in T2D group. Contrary to that, nondiabetics with higher values of CAL exhibited lower concentration of TNFR2, presenting potential protective effect on periodontal destruction. These results imply that diabetes may alter TNFR2 secretion originated from periodontium.

Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). METHODS: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. RESULTS: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Hypertension in obese type 2 diabetes patients is associated with increases in insulin resistance and IL-6 cytokine levels: potential targets for an efficient preventive intervention.

Increased body weight as well as type 2 diabetes (T2D) are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2D or nondiabetic individuals are not clear. Therefore, in this study we compared the levels of insulin resistance (IR:OGIS), plasma insulin (PI:RIA) levels, and pro-inflammatory cytokines (IL-6 and TNF-α: ELISA), being risk factors previously found to be associated with hypertension, in T2D patients showing increased body weight (obese and overweight, BMI ≥ 25 kg/m²) with hypertension (group A, N = 30), or without hypertension (group B, N = 30), and in nonobese (BMI < 25 kg/m²), normotensive controls (group C, N = 15). We found that OGIS index was the lowest (A: 267 ± 35.42 vs. B: 342.89 ± 32.0, p < 0.01) and PI levels were the highest (A: 31.05 ± 8.24 vs. B: 17.23 ± 3.23, p < 0.01) in group A. In addition, IL-6 levels were higher in group A (A: 15.46 ± 5.15 vs. B: 11.77 ± 6.09; p < 0.05) while there was no difference in TNF-α levels. Our results have shown that appearance of hypertension in T2D patients with increased body weight was dependent on further increase in IR which was associated with the rise in pro-inflammatory IL-6 cytokine. The results imply that lifestyle intervention aimed to decrease IR might be beneficial in reducing the risk for hypertension in those T2D individuals.

Relationship between obesity, adipocytokines and inflammatory markers in type 2 diabetes: relevance for cardiovascular risk prevention.

This study aimed to analyse the impact of obesity in type 2 diabetes (T2D) on adipocytokines (adiponectin, leptin and resistin) and inflammatory markers (TNF-α, IL-6 and hsCRP) as cardiovascular risk factors. A cross-sectional study comparing the basal levels of adipocytokines and inflammatory markers was done in 18 obese (BMI ≥ 30 kg/m²) (group A), 21 overweight (25 kg/m² ≤ BMI < 30 kg/m²) (group B), 25 non-obese T2D patients (group C) and 15 non-obese controls (group D). The lowest levels of adiponectin and the highest levels of leptin, resistin, TNF-α, IL-6 and hsCRP were found in group A. Adiponectin levels were significantly lower, and resistin, TNF-α, and hsCRP levels were elevated in group C vs. D. However, leptin and IL-6 levels differed significantly between groups A and B, but not between groups C and D. Moreover, we found a significant negative correlation between adiponectin and TNF-α, but not with other markers, which was independent of the presence of obesity. In contrast, leptin and resistin correlated with the inflammatory markers, and this correlation was obesity-dependent. Our results suggest that obesity influences cardiovascular risk primarily through changes in leptin and resistin and less efficiently at the level of adiponectin.

Acute effects of ghrelin on insulin secretion and glucose disposal rate in gastrectomized patients.

CONTEXT: Plasma ghrelin concentration is diminished in gastrectomized patients. Acute ghrelin administration reduces insulin secretion, whereas insulin infusion has been shown to decrease ghrelin levels. Whether ghrelin has any effect on glucose utilization in humans is unknown. OBJECTIVE: Our objective was to reveal the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized patients. STUDY AND SETTING: We conducted a double-blind, randomized, placebo-controlled, hospital-based study. PATIENTS: Seven men and three women who all had a previous total gastrectomy and truncal vagotomy entered and completed the study. INTERVENTION: Each individual received infusion of saline alone or saline with ghrelin (5.0 pmol/kg.min) during a 5-h hyperinsulinemic (80 mU/m(2).min) euglycemic clamp on 2 separate days. MAIN OUTCOME MEASURES: We assessed glucose disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin. RESULTS: Glucose disposal rate decreased during ghrelin infusion (control study 8.6 +/- 0.2 vs. 7.2 +/- 0.1 mg/kg.min P < 0.001). In experiments with saline infusion, levels of ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP-1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration maintained at baseline, whereas leptin significantly rose (P < 0.001). In the ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 +/- 212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001) and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more suppressed than in the control study (P < 0.001). Other hormones and IGFBPs changed similarly as in the study with saline infusion. CONCLUSION: It appears that ghrelin might be involved in the negative control of insulin secretion and glucose consumption in gastrectomized patients, at least after acute administration.