Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women.

OBJECTIVE: To compare the concentrations of cytokines belonging to Th17 axis (interleukin (IL)-17 and IL-23) and Th1 axis (IL-12 and interferon (IFN)-gamma) in obese and lean women, and to investigate their relationships with the proinflammatory adipokine leptin, proinflammatory cytokine macrophage migration inhibitory factor (MIF) and anthropometric and metabolic parameters of obesity. DESIGN: Cross-sectional study. SUBJECTS: Twenty-six obese women (age 20-52 years, body mass index (BMI): 30-48 kg/m(2)) and 20 healthy lean women (age 23-46 years, BMI: 18-25 kg/m(2)). MEASUREMENTS: Plasma levels of cytokines and leptin, BMI, waist circumference (WC) and insulin resistance index HOMA (homeostatic model assessment). RESULTS: Blood concentrations of IL-17, IL-23, MIF and leptin, but not IL-12 or IFN-gamma, were higher in obese compared with lean women (P=0.002, 0.046, 0.006 and 0.002, respectively). There was a positive correlation between IL-17 and IL-23 (r(s)=0.530), which was at the border of statistical significance (P=0.065). Neither IL-17 nor IL-23 correlated with leptin or MIF, and there was no association between IL-17 and IL-23 levels with BMI, WC or HOMA index. CONCLUSION: Interleukin-23/IL-17 axis is stimulated in obese women independently of the increase in abdominal fat, insulin resistance, leptin and MIF levels.

Total ghrelin levels during acute insulin infusion in patients with polycystic ovary syndrome.

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance.

The effect of parathyroidectomy on insulin sensitivity in patients with primary hyperparathyroidism - an never ending story?

Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT.

Cardiovascular risk in adolescent and young adult obese females with polycystic ovary syndrome (PCOS).

Women with polycystic ovary syndrome (PCOS) could have associated risk for cardiovascular disease. The aim of the present study was to investigate the relationship between age and metabolic factors on cardiovascular risk in obese women with PCOS. Obese patients with PCOS were divided into an adolescent group (n=11; age 16.90 +/- 0.45 yr; BMI 35.04 +/- 1.70 kg/m2), and an adult group (n=18; age 29.66 +/- 1.31; BMI 34.57 +/- 1.46). We determined basal values of glucose, insulin, lipid and fibrinolytic parameters from blood samples taken in all patients and matched controls. Significantly different concentrations between the groups with PCOS were obtained for glucose, total cholesterol, triglycerides, LDL-cholesterol and Apo-B. Elevated concentrations of insulin (20.63 mU/l), both insulin sensitivity indexes--G:I ratio (7.52 mg/10(-4) U) and HOMA model (4.11 mmol/l x U/l(2))--and PAI-1 (5.49 U/ml) were obtained in the adolescent group with PCOS compared to controls, with further increase in the adult group with PCOS. It seems that the youngest obese population with PCOS represents a cohort with potential cardiovascular disease in adulthood.