Selenoprotein P is not elevated in gestational diabetes mellitus.

Selenoprotein P concentrations have been found to be associated with insulin resistance and elevated in patients with type 2 diabetes mellitus (DM). The aim of the present study was to investigate circulating selenoprotein P level and its possible relationship with metabolic parameters in gestational diabetes mellitus (GDM). Plasma selenoprotein P concentrations were measured in 30 pregnant women with GDM, 35 pregnant women without GDM and 22 healthy nonpregnant women. No difference in selenoprotein P levels was observed among the groups [6.2 (4.5-8.2), 7.9 (4.5-10.7) and 6.7 (5.3-9.1) ng/ml, respectively, p = 0.69]. In pregnant women with and without GDM, selenoprotein P did not correlate with age, gestational age, prepregnancy body mass index (BMI), HbA1c, glucose concentrations at oral glucose tolerance test (OGTT), area under curve (AUC) glucose, total cholesterol, LDL cholesterol and triglycerides levels (p > 0.05). But, there were statistically significant correlations between selenoprotein P and current BMI (r = -0.28, p = 0.04) and HDL cholesterol levels (r = 0.43, p = 0.01). We found that selenoprotein P concentrations are not elevated in women with GDM but associated with BMI and HDL cholesterol.

Serum levels of fetuin A are increased in women with gestational diabetes mellitus.

PURPOSE: Fetuin A is associated with insulin resistance and type 2 diabetes mellitus (DM). We aimed to investigate circulating fetuin A concentrations in gestational diabetes mellitus (GDM). METHODS: Serum fetuin A levels were studied in 26 pregnant women with GDM and 24 healthy pregnant women between 24th and 28th gestational weeks. Fetuin A levels were also evaluated in 18 of women with GDM at postpartum. RESULTS: Fetuin A concentrations were significantly increased in women with GDM compared to healthy pregnant women (35.0 ± 3.2 vs. 32.0 ± 4.4 ng/ml; p = 0.01). Also, fetuin A levels in women with GDM significantly decreased at postpartum period (35.0 ± 3.2 vs. 31.7 ± 3.9 ng/ml; p = 0.001). In whole pregnant women, there were positive correlations between fetuin A and HbA1c (r = 0.418, p = 0.002), total cholesterol (r = 0.332, p = 0.018) and triglycerides (r = 0.306, p = 0.031). Multivariate regression analysis demonstrated that HbA1c was the important predictor of circulating fetuin A level (beta = 0.375, p = 0.01). CONCLUSION: In conclusion, our results indicate that serum fetuin A concentrations are increased in women with GDM and decreased after delivery. Therefore, fetuin A might have a role in the development of insulin resistance and the metabolic changes in GDM.

Evaluation of body composition changes, epicardial adipose tissue, and serum omentin-1 levels in overt hypothyroidism.

Our aim was to investigate body composition changes, epicardial adipose tissue thickness (EATT), serum omentin-1 levels, and the relationship among them along with some atherosclerosis markers in overt hypothyroidism. Twenty-eight newly diagnosed overt hypothyroid patients were evaluated before and after 6 months of thyroid hormone replacement therapy (THRT) and compared to the healthy subjects in this prospective longitudinal study. Body compositions were measured with dual-energy X-ray absorptiometry, and EATT was measured by echocardiography. Carotid intima-media thickness (c-IMT), flow-mediated dilatation (FMD), thyroid hormone levels, lipid parameters, high sensitive c-reactive protein, homocysteine, and omentin-1 levels were measured in all subjects. Body weight and lean body mass were higher in patients with hypothyroidism compared to euthyroid state after THRT (p = 0.012, 0.034, respectively). EATT was higher in patients with hypothyroidism than the control group (p < 0.001) and decreased with THRT (p = 0.012) but still remained higher than the control group (p < 0.001). Free T4 levels were found to be an independent factor to predict EATT (p < 0.001). In hypothyroid state, omentin-1 levels were lower than controls (p = 0.037) but increased in 6 months with THRT (p = 0.001). The c-IMT was higher, and FMD was lower in hypothyroidism compared to euthyroid state and control group (p < 0.05). Increasing lean body mass, but not adipose tissue mass, was found to be responsible for weight gain in hypothyroidism. The increased amount of EATT and decreased omentin-1 levels can contribute to the development of atherosclerosis in addition to other factors in hypothyroidism.

The effect of calpain-10 gene polymorphism on the development of type 2 diabetes mellitus in a Turkish population.

INTRODUCTION: The variations in the Calpain-10 gene have been suggested to be related to susceptibility to type 2 diabetes mellitus (T2DM) in different populations. In this study, we investigated the relationship between single nucleotide polymorphism (SNP)-19, -44 and -63 in the Calpain-10 gene and the development of T2DM in a Turkish population. MATERIAL AND METHODS: A total of 211 subjects were recruited: 118 patients with a diagnosis of T2DM and 93 unrelated healthy subjects. RESULTS: There were no significant differences in the genotype and allele distribution of SNPs studied between the patients with T2DM and controls (p > 0.05), whereas the frequencies of 121 haplotype and 122/121 haplotype combination were found to be higher in patients with T2DM than in controls (p < 0.05). No association was observed between the variations in the Calpain-10 gene and glycaemic control and lipid parameters (p > 0.05). The SNP-19 insertion/insertion was significantly related to increased body mass index (BMI) in male diabetic patients (p < 0.05). CONCLUSIONS: The present study indicates that 121 haplotype and 122/121 haplotype combination of SNP-19, -44 and -63 in the Calpain-10 gene are associated with the development of T2DM in Turkish patients.

Circulating insulin and leptin in women with and without premenstrual disphoric disorder in the menstrual cycle.

Premenstrual dysphoric disorder (PMDD) is a syndrome related with mood and appetite changes during the late luteal phase. Leptin and insulin are the hormones related to appetite, and leptin may have a role in reproductive functions and mood. Our aim was to determine whether there are differences in serum leptin and insulin levels between women with and without PMDD during the follicular and luteal phases. In this study, 20 women with PMDD and 18 women without PMDD were included. Fasting blood glucose, insulin, leptin, progesterone levels and HOMA-IR were measured in the follicular and luteal phases separately. Repeated-measures analysis of variance revealed significant interactions for serum leptin, insulin and HOMA-IR levels between the diagnosis of PMDD and menstrual phases (F = 5.4, p = 0.025; F = 5.4, p = 0.026; and F = 4.7, p = 0.036, respectively). A significant correlation was found between progesterone and insulin levels in subjects without PMDD in the luteal phase (r = 0.58, p = 0.01). Whether the alterations in serum leptin and insulin are related with the changes of appetite and mood in PMDD or secondary to other factors should be clarified.

Relationship between serum osteoprotegerin, glycemic control, renal function and markers of atherosclerosis in type 2 diabetes.

We aimed to investigate the relationship between serum osteoprotegerin (OPG) level and glycemic control, lipids, renal function, microalbuminuria, insulin resistance and markers of atherosclerosis including C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) in patients with type 2 diabetes mellitus (DM). A total of 166 patients (99 women and 67 men) with type 2 DM were recruited in the study. Serum OPG level was higher in poorly controlled diabetic patients (HbA(1c) ≥ 7%) than in well-controlled diabetic patients (HbA(1c) < 7%) [4.0 (3.6-5.0) and 3.5 (2.9-4.4) pmol/L, p = 0.02]. There was no difference between the patients with and without microalbuminuria with respect to OPG levels (p > 0.05). LogOPG was correlated with age (r = 0.47, p = 0.0001). After adjustment for age, sex and BMI, logOPG correlated positively with fasting blood glucose (FBG) (r = 0.28, p = 0.001), prandial blood glucose (PBG) (r = 0.22, p = 0.009), glycated hemoglobin (HbA(1c)) (r = 0.26, p = 0.002), logHOMA-IR (r = 0.30, p = 0.006), fibrinogen (r = 0.17, p = 0.04), mean albumin excretion rate (MAER) (r = 0.20, p = 0.01) and negatively with creatinine clearance (r = - 0.20, p = 0.01). Regression analysis revealed that logOPG was independently associated with age (p = 0.0001), HbA(1c) (p = 0.01) and MAER (p = 0.02) (r(2) = 0.25). In conclusion; we found that serum OPG levels are increased in poorly controlled type 2 DM and associated with age, glycemic control and microalbuminuria.

The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes.

Adipocyte fatty acid binding protein-4 (A-FABP4) and retinol binding protein-4 (RBP4) have recently been linked to type 2 diabetes mellitus (DM). Serum A-FABP4 and RBP4 levels and their relationships with early diabetic nephropathy were examined in 87 type 2 diabetic patients. The patients with diabetic nephropathy showed high A-FABP4 levels compared to the patients without diabetic nephropathy (p=0.0001). Log A-FABP4 correlated positively with age (p=0.02), log duration of diabetes (p=0.04), log body mass index (BMI) (p=0.0001), log creatinine (p=0.007), log C-reactive protein (CRP) (p=0.01), log albumin excretion rate (AER) (p=0.001), and negatively with MDRD-GFR (p=0.0001). Serum RBP4 levels were similar between the patients with and without diabetic nephropathy. RBP4 correlated positively with triglycerides (p=0.001), log creatinine (p=0.009), and negatively with MDRD-GFR (p=0.04). In regression analysis, log A-FABP4 was associated with age, sex, log BMI, and log AER (r(2)=0.43) and RBP4 was associated with triglycerides and log creatinine (r(2)=0.22). In conclusion, we found high serum A-FABP4 but unchanged RBP4 concentrations and their associations with renal function and early diabetic nephropathy in type 2 DM.

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism.

INTRODUCTION: The 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. METHODS: Thirty-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 thyroid-related medication. RESULTS: Serum 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 microIU/ml and TSH <10 microIU/ml (in SCH patients, P>0.05). CONCLUSION: Our 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.

Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications.

The study was designed to examine serum IL-18 level and its relation to metabolic control parameters and microvascular complications in type 1 diabetes mellitus (DM). Sixty two patients with type 1 DM and 30 healthy individuals were enrolled in the study. Serum IL-18 levels of patients with type 1 DM were significantly increased compared to controls (293.4+/-133.4 vs 211.2+/-63.9 pg/ml, P=0.003). Patients with poor glycemic control had higher levels of IL-18 than patients with well glycemic control (329.9+/-141.0 vs 226.3+/-89.6 pg/ml, P=0.02). There was no significant difference between the serum IL-18 levels of patients with microvascular complications and those of patients without microvascular complications (307.6+/-127.6 vs 293.2+/-145.6 pg/ml, P>0.05). IL-18 correlated positively with HbA(1c) (r=0.32, P=0.01) and postprandial blood glucose (PPBG) (r=0.26, P=0.02); and negatively with HDL-cholesterol (HDL-C) (r=-0.38, P=0.007). By linear regression analysis, PPBG was determined as the most explanatory parameter for the alterations in serum IL-18 levels (P=0.02). High levels of IL-18 in patients with type 1 DM is related to short and long term glycemic control and HDL-C levels but not to microvascular complications.

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

Adiponectin and tumor necrosis factor-alpha (TNF-alpha) have been implicated in insulin resistance and diabetes mellitus (DM). In the present study we investigated levels of adiponectin and TNF-alpha 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-alpha 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-alpha levels were correlated with glycated hemoglobin in GDM. There was a significant positive correlation between TNF-alpha levels and pre-pregnancy and current BMI in GDM as well as NGT. HOMA-IR for adiponectin and pre-pregnancy BMI for TNF-alpha remained as significant determinants in multiple regression analyses. In conclusion, these data suggest that reduced adiponectin and increased TNF-alpha may be involved in the pathogenesis of GDM.

Uncomplicated type 1 diabetes is associated with increased asymmetric dimethylarginine concentrations.

CONTEXT: Asymmetric dimethylarginine (ADMA) has recently emerged as an independent risk marker for cardiovascular disease, but studies investigating the ADMA levels in type 1 diabetes mellitus (DM) are scarce. OBJECTIVE: We aimed to evaluate plasma ADMA, L-arginine concentrations, and L-arginine to ADMA ratio in uncomplicated type 1 diabetic patients and controls. DESIGN AND SUBJECTS: Forty patients with type 1 DM who did not have clinical evidence of vascular complications and 35 healthy controls were included in the study. RESULTS: Plasma ADMA concentrations were higher (2.6 +/- 1.9 vs. 1.7 +/- 0.7 micromol/liter, P < 0.01), and L-arginine levels were lower (79.3 +/- 22.6 vs. 89.6 +/- 19.4 micromol/liter, P < 0.05) in the diabetic group, compared with controls. The L-arginine to ADMA ratio was also lower in the diabetic group (38.7 +/- 17.1 vs. 62.0 +/- 27.9, P < 0.0001). In diabetic patients, logADMA correlated positively with body mass index (BMI) (P = 0.01), fasting blood glucose (P = 0.006), and low-density lipoprotein cholesterol (LDL-c) (P = 0.01) and negatively with high-density lipoprotein cholesterol (P = 0.03). L-arginine to ADMA ratio correlated negatively with BMI (P = 0.004), fasting blood glucose (P = 0.02), and LDL-c (P = 0.01) and positively with high-density lipoprotein cholesterol (P = 0.04). In controls, logADMA and L-arginine to ADMA ratio correlated with BMI and LDL-c (P < 0.05). In regression analysis, BMI predicted 15% variance of ADMA levels (P = 0.02). CONCLUSIONS: We demonstrated that ADMA increases and L-arginine to ADMA ratio decreases, even before the development of vascular complications in type 1 DM.

Decreased plasma adiponectin is associated with insulin resistance and HDL cholesterol in overweight subjects.

The purpose of this study was to investigate plasma adiponectin concentration and its relation with metabolic parameters in overweight and normal weight subjects. The study was carried out in 46 overweight subjects (20 male, 26 female; mean age 39.4 +/- 10.2 years) and 48 (19 male, 29 female; mean age 36.1 +/- 10.6 years) sex- and age-matched normal weight subjects. Anthropometric measurements were recorded and adiponectin, glucose, insulin, lipid profile, total homocysteine (tHcy) and fibrinogen levels were measured. The insulin resistance index was assessed by homeostasis model assessment for insulin resistance (HOMA-IR). Plasma mean adiponectin concentrations of the overweight subjects were significantly lower than those of normal weight subjects (15.0 +/- 4.2 vs 17.3 +/- 5.6 ng/ml) (P<0.05). In overweight subjects, adiponectin levels negatively correlated with body weight (r = -0.35, P<0.001), body mass index (BMI) (r = -0.28, P<0.006), systolic blood pressure (r = -0.21, P<0.04), fasting insulin (r = -0.19, P<0.01) and HOMA-IR (r = -0.20, P<0.01) and positively with high-density lipoprotein cholesterol (HDL-C) (r = 0.27, P<0.009). Overweight subjects with low HDL-C levels had significantly decreased plasma adiponectin levels compared to those with high HDL-C levels (P<0.05). Multiple regression analysis revealed that BMI, HOMA-IR and HDL-C explained 12%, 20% and 15% variance of the adiponectin concentrations. These findings may suggest that circulating adiponectin is associated with insulin resistance and HDL-C levels independent from BMI in overweight subjects.

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. PATIENTS AND MEASUREMENTS: Sixty-seven patients with hypothyroidism, 56 patients with hyperthyroidism and 52 age- and sex-matched euthyroid subjects were enrolled in the study. Adiponectin, C-reactive protein (CRP), homocysteine (Hcy), lipid parameters, Lipoprotein(a) [Lp (a)], Apolipoprotein (Apo) A, Apo B and fibrinogen levels were measured in all subjects. Insulin sensitivity was determined using the Homeostasis Model Assessment (HOMA-IR). RESULTS: Circulating adiponectin levels were not different between the groups (16.2 +/- 5.0, 15.1 +/- 3.7, 15.9 +/- 4.8 ng/ml; hypothyroid, hyperthyroid, euthyroid group, respectively). Plasma adiponectin levels correlated negatively with body mass index (BMI) and HOMA-IR index and positively with high-density lipoprotein cholesterol (HDL-C) in all groups. There was a significant correlation between adiponectin and CRP levels in both hypothyroid and hyperthyroid groups. In all groups, adiponectin levels did not correlate with age, systolic blood pressure, diastolic blood pressure and thyroid hormones. Multiple regression analysis revealed BMI and HDL-C levels to be the most important predictors of circulating adiponectin levels. CONCLUSIONS: Plasma adiponectin levels are associated with BMI and HDL-C levels in patients with hypothyroidism and hyperthyroidism. But there is not a direct relation of adiponectin with thyroid hormones in these patients.

Reduced serum acylated ghrelin levels in patients with hyperthyroidism.

BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = -0.26, p = 0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. CONCLUSION: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.

Serum Ghrelin Levels in patients with Hashimoto's thyroiditis.

OBJECTIVE: Hypothyroidism is associated with changes in appetite and body weight. Ghrelin is an orexigenic peptide, and it stimulates appetite and increases food intake. However, the potential relationship between circulating ghrelin levels, hypothyroidism, and thyroid antibodies has not been adequately studied. DESIGN: Forty-seven patients with hypothyroidism due to Hashimoto's thyroiditis and 48 euthyroid subjects were enrolled in the study. Thyroid hormones and antibodies, insulin, glucose, ghrelin levels, and lipid parameters were measured in all the subjects. MAIN OUTCOME: Hypothyroid group showed significantly decreased serum levels of ghrelin and ghrelin=body mass index (BMI) compared to euthyroid group (31.9 +/- 21.5 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.24 +/- 0.93 vs. 2.12 +/- 1.53, p < 0.0001). In hypothyroid group, 6 months after treatment, ghrelin levels and ghrelin/BMI remained lower than euthyroid group (33.2 +/- 21.1 pg/mL vs. 50.5 +/- 34.8 pg/mL, p < 0.001; and 1.27 +/- 0.86 vs. 2.12 +/- 1.53, p < 0.0001). Ghrelin levels were decreased in hypothyroid patients with high thyroid peroxidase antibody (TPOAb) titre compared to hypothyroid patients with low TPOAb titre (19.1 +/- 23.1 pg/ mL vs. 35.3 +/- 17.4 pg/mL, p < 0.01). Ghrelin levels correlated positively with free triiodothyronine (FT3) and free thyroxine (FT4), and negatively with age, thyroglobulin antibody (TAb), TPOAb, total cholesterol (T-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG) in hypothyroid group. In euthyroid group, circulating ghrelin levels correlated negatively with age, FT3, FT4, TG, and VLDL-C levels. No significant correlation was observed between ghrelin and homeostasis model assessment for insulin resistance (HOMA-IR) and between ghrelin and quantitative insulin sensitivity check index (QUICKI) in both groups. Regression analysis revealed that FT3 level is the most important predictor of ghrelin levels. CONCLUSION: Thyroid hormones and antibodies seem to have a potential effect on serum ghrelin levels in patients with hypothyroidism.