Göksun Ayvaz

Circulating concentrations of adiponectin and tumor necrosis factor-α in gestational diabetes mellitus

Adiponectin and tumor necrosis factor-α (TNF-α) have been implicated in insulin resistance and diabetes mellitus (DM). In the present study we investigated levels of adiponectin and TNF-α and their relationships with each other and metabolic factors in women with gestational DM (GDM). Thirty-four pregnant women with GDM and 31 pregnant women with normal glucose tolerance (NGT) were included in the study. Plasma adiponectin levels were lower in GDM than in NGT (36.9 ± 6.7 vs. 61.3 ± 13.0 ng/ml, p = 0.028). Serum TNF-α levels were increased in GDM compared with NGT (20.5 ± 2.4 vs. 14.0 ± 1.5 pg/ml, p = 0.042). After adjustment for pre-pregnancy and current body mass index (BMI), adiponectin levels correlated negatively with insulin resistance by homeostasis model assessment-insulin resistance (HOMA-IR) and 0-h and 1-h glucose both at glucose challenge test and oral glucose tolerance test in GDM. Adiponectin levels were correlated only with very low-density lipoprotein cholesterol and triglyceride levels in NGT. TNF-α levels were correlated with glycated hemoglobin in GDM. There was a significant positive correlation between TNF-α levels and pre-pregnancy and current BMI in GDM as well as NGT. HOMA-IR for adiponectin and pre-pregnancy BMI for TNF-α remained as significant determinants in multiple regression analyses. In conclusion, these data suggest that reduced adiponectin and increased TNF-α may be involved in the pathogenesis of GDM.

The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome

Aim: The aim of this study was to assess the effects of metformin and rosiglitazone on insulin resistance and serum androgen levelsin both obese and lean patients with polycystic ovary syndrome (PCOS). Materials and methods: Forty lean [body mass index (BMI) <25 kg/m2] and 40 overweight and obese (BMI>²5 kg/m2) patients were included in the study. Waist and hip measurements, serum sex steroid levels, insulin response to 75-g oral glucose tolerance test, fasting insulin, fasting C-peptide levels and homeostasis modelassessment of insulin resistance (HOMA-IR) were determined in all patients. The degree of hirsutism was determined by the Ferriman-Gallwey scoring system. Patients were divided into two groups, with 40 (20 overweight and obese; 20 non-obese) patients each. One group was treated with metformin (MET group) 850 mg bid while the other received rosiglitazone (ROSI group) 4 mg/day for 12 weeks. All measurements were repeated at the end of this period. Results: After the 12-week treatment period, HOMA-IR, area under the curve of insulin, fasting insulin and C-peptide levels were observed to have be decreased significantly in all groups. The decrease in the parameters mentioned above was similar in the four groups. The serum levels of free testosterone, androstenedione and DHEA-S decreased in all groups, but the decrease was statistically significant only in the ROSI groups. Within the lean MET group one patient became pregnant and was hence excluded from the final data analysis. Menstruations became regular after metformin therapy in 41.6% of lean and 35.7% of obese patients who had menstrual disturbance prior to the study. Rosiglitazone therapy improved menstrual disturbance in 61.5 % of lean and 53.8% of obese patients. Conclusions: Our data showed that both metformin and rosiglitazone increased insulin sensitivity in obese patients with PCOS as expected, and in lean patients as well. Rosiglitazone seemed to be more effective in decreasing the androgen levels and in achieving slightly greater improvement in menstrual disturbance than metformin.

The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome.

Objective. The aim of the present study was to assess the effects of metformin and rosiglitazone on menstrual cyclicity and hirsutism in patients with polycystic ovary syndrome (PCOS). Materials and methods. Ninety-six patients were included in the study. Serum sex steroids, serum fasting glucose and insulin levels, and insulin response to a 75-g oral glucose tolerance test were assessed in all patients. Menstrual cyclicity, with recording of menses in the 6-month periods before the study and during treatment, was evaluated in each patient. Patients were divided into two groups: one was treated with metformin (MET group, n = 48), while the other received rosiglitazone (ROSI group, n = 48). At baseline and after 24 weeks of treatment all patients underwent hormonal and clinical assessments, including body mass index (BMI), waist and hip measurements and Ferriman – Gallwey (FG) scores. Results. Of the 96 patients included in the study, 88 (91.7%) were able to complete it and yielded data for analyses. After the 24-week treatment period, fasting insulin levels and area under the curve for serum insulin decreased significantly, while the glucose/insulin ratio increased in both groups. The degree of reduction in serum free testosterone and androstenedione levels was similar in the two groups. The decreases in luteinizing hormone/follicle-stimulating hormone ratio and serum dehydroepiandrosterone sulfate levels were significantly greater in the ROSI group compared with the MET group. BMI increased in the ROSI group, while it decreased in the MET group. In patients with menstrual disturbance treated with rosiglitazone, menstrual cycles became regular in 87.8%, while improvement occurred in 79.3% of the patients treated with metformin. FG score decreased in both ROSI and MET groups, but the degree of decrease was significantly greater in the ROSI group than in the MET group. Conclusion. Our data show that both metformin and rosiglitazone improve ovarian function and hirsutism in patients with PCOS. Rosiglitazone appears better than metformin in the treatment of hirsutism and has better patient tolerance.

Serum resistin and adiponectin levels in women with polycystic ovary syndrome.

Aim. This study was performed to compare the serum levels of resistin and adiponectin in women with polycystic ovary syndrome (PCOS) and normal controls. Materials and methods. Seventy-six patients (36 obese, 40 non-obese) with PCOS and 42 healthy subjects were included in the study. Serum levels of resistin, adiponectin, follicle-stimulating hormone, luteinising hormone, dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxy progesterone, free testosterone, androstenedione, glucose, insulin and lipid parameters were measured. Insulin resistance and carbohydrate metabolism were evaluated by using the homeostasis model (HOMA) and the area under the insulin curve (AUCI). Results. Plasma resistin levels, HOMA-IR and AUCI were significantly higher and adiponectin level was lower in women with PCOS than those in healthy women. Plasma resistin levels were similar among obese and non-obese women with PCOS. No correlation was observed between resistin, body mass index (BMI), HOMA-IR, AUCI, insulin, lipid parameters and serum androgen levels. In obese PCOS patients, adiponectin levels were lower than in the lean PCOS patients. A negative correlation was observed among adiponectin, HOMA-IR, AUCI, BMI, testosterone, DHEAS, total-cholesterol, LDL-cholesterol and lipoprotein (a) levels. Conclusion. These results suggest that the serum adiponectin level may be involved in the pathogenesis of PCOS. But resistin levels were independently associated with insulin resistance and BMI in PCOS patients. Nevertheless, wider-scale trials are required to be performed on this subject.

Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes

Aims  Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low‐density lipoprotein (LDL) size and all seven subclasses, as well as the ‘atherogenic–lipoprotein phenotype’[ALP, e.g. concomitant presence of elevated triglycerides, reduced high‐density lipoprotein (HDL)‐cholesterol and increased small, dense LDL].

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

IntroductionThe relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls.MethodsThirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroidrelated medication.ResultsSerum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 μIU/ml and TSH <10 μIU/ml (in SCH patients, P>0.05).ConclusionOur results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject’s TSH level.

Adiponectin levels and cardiovascular risk factors in hypothyroidism and hyperthyroidism.

Objective  Adiponectin, an adipose tissue‐derived hormone, has been reported to have anti‐inflammatory and anti‐atherogenic effects. The physiological effect of adiponectin on the metabolic changes and its relation with cardiovascular risk factors in thyroid dysfunction states is still not clear. The aim of the study was to evaluate plasma adiponectin level and its relation to cardiovascular risk factors in patients with thyroid dysfunction.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene in first-degree relatives of subjects with polycystic ovary syndrome.

Aim. This study was designed to examine the relationship between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and insulin resistance (IR) in first-degree relatives of subjects with polycystic ovary syndrome (PCOS). Materials and methods. One hundred and twenty family members of 55 patients with PCOS and 80 unrelated healthy control subjects without a family history of diabetes or PCOS were studied. IR was assessed by homeostatic model assessment (HOMA-IR) and area under the curve (AUC) for insulin during an oral glucose tolerance test in subjects with normal glucose tolerance and controls. Genetic analysis of the PPAR-γ gene Pro12Ala polymorphism was performed by restriction fragment length polymorphism. Results. Fasting insulin, HOMA-IR and AUC insulin were significantly higher in first-degree relatives of PCOS subjects than in controls. A significantly different allele distribution of the Pro12Ala polymorphism of PPAR-γ was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the first-degree relatives of PCOS subjects (10.8%, 13 subjects) compared with the control group (22.5%, 18 subjects). All Pro12Ala polymorphisms of the PPAR-γ gene were heterozygous. Compared with first-degree relatives of PCOS subjects with the Pro12Pro polymorphism of PPAR-γ, first-degree relatives of PCOS subjects with the Pro12Ala polymorphism had low fasting insulin, HOMA-IR and AUC insulin levels. The combined prevalence rate for impaired glucose tolerance, impaired fasting glucose and diabetes was 40% (16 subjects) in mothers and 52% (20 subjects) in fathers of PCOS women. Conclusion. Our findings suggest that Pro12Ala PPAR-γ gene polymorphism may be protective against IR and might prevent the development of diabetes mellitus in the first-degree relatives of subjects with PCOS.

PREGO (presentation of Graves’ orbitopathy) study: changes in referral patterns to European Group On Graves’ Orbitopathy (EUGOGO) centres over the period from 2000 to 2012

Background/aims The epidemiology of Graves’ orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. Methods Prospective observational study of European Group On Graves’ Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. Results The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). Conclusions These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Frequency of adiponectin gene polymorphisms in polycystic ovary syndrome and the association with serum adiponectin, androgen levels, insulin resistance and clinical parameters

Aim. Although the association between adiponectin gene polymorphisms and insulin resistance has been investigated in many studies, there are only a few studies, which have investigated adiponectin gene polymorphisms in patients with polycystic ovary syndrome (PCOS). The objectives of this study were to determine the frequency of T45G polymorphisms localised in exon 2 of the adiponectin gene in a Turkish population with PCOS and to determine the association of T45G polymorphisms with insulin resistance and serum adiponectin levels in PCOS. Materials and methods. Ninety-six patients with PCOS and 93 healthy control subjects were included in the study. Insulin resistance was estimated via HOMA-IR. Serum adiponectin levels were measured by ELISA. For determination of adiponectin gene polymorphisms, PCR was performed with appropriate primers after genomic DNA was obtained from the peripheral blood of the patients and control subjects. Results. Adiponectin levels were low in patients with PCOS than control subjects. There was no significant statistical difference between the PCOS and control groups with respect to the frequency of polymorphisms and the genotype distribution. Adiponectin gene polymorphisms were not associated with the anthropometric parameters, hyperandrogenism and adiponectin levels in PCOS. However, the fasting insulin level and insulin resistance were significantly higher and more frequent, respectively, in the polymorphic group compared to the other genotypes among patients with PCOS. Conclusion. The risk of PCOS, hyperandrogenism in patients with PCOS and low serum adiponectin levels cannot be directly attributed to T45G adiponectin gene polymorphisms in exon 2, rather these polymorphisms may be associated with insulin resistance and hyperinsulinemia in PCOS.