Sena Yesil

Prediction of developing metabolic syndrome after gestational diabetes mellitus

OBJECTIVE To determine the predictors of subsequent development of metabolic syndrome (MS) in women with previous gestational diabetes mellitus (GDM). DESIGN Controlled clinical study. SETTING University hospital. PATIENT(S) One hundred sixty-four consecutive women with previous GDM were evaluated after a mean follow-up of 40.54 months from index pregnancy. Sixty-five lean women with negative screening for GDM were included as a control group. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Subjects were evaluated for diagnosis of MS according to criteria of the National Cholesterol Education Program and the International Diabetes Federation. Tests were performed including a 75-g oral glucose tolerance test (OGTT), fasting insulin, lipids, plasma fibrinogen, blood pressure, and body measurements. The homeostasis model assessment score was calculated. RESULT(S) The MS prevalence was higher in women with previous GDM, according to both definitions. Univariate analysis showed that prepregnancy obesity, weight gain during follow-up, and fasting glucose level at the OGTT of the index pregnancy were predictors of developing MS. Multivariate analysis showed that fasting glucose level >100 mg/dL at the OGTT of the index pregnancy was an independent predictor of the MS development. CONCLUSION(S) We suggest that early prediction of women with previous GDM who are at high risk for developing MS is possible, and it is vital to prevent MS-related complications.

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration. Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m2; Group 2 (overweight), BMI 25 kg/m2 to 29.9 kg/m2; and Group 3 (obese), BMI≥30 kg/m2. Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. Conclusion: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

Serum osteoprotegerin is associated with carotid intima media thickness in women with previous gestational diabetes

Circulating levels of osteoprotegerin (OPG) have been shown to be increased in patients with cardiovascular disorders and diabetes. The aim of this study was to determine serum OPG levels in women with previous gestational diabetes (GDM), and to investigate the relationship between OPG and carotid intima media thickness (IMT) and circulating cardiovascular risk factors. Serum OPG was measured in 46 women with previous GDM and 30 age-matched healthy controls. Carotid IMT was evaluated. Serum lipid, insulin and hsCRP levels, plasma fibrinogen, vWF and PAI-1 levels were measured. Serum OPG levels tended to be increased in women with previous GDM (p=0.058). Carotid IMT was increased in the study group. Women with previous GDM had elevated levels of hsCRP and PAI-1. OPG levels were positively correlated with age, fasting and post-load glucose levels, hsCRP, and carotid IMT. Multiple regression analysis showed that serum OPG was a statistically significant predictor for elevated carotid IMT. Our results revealed that OPG levels tended to be elevated in women with previous GDM. Significant association of OPG with carotid IMT suggested that OPG might play a role in the pathogenesis of endothelial dysfunction in women with previous GDM.

Is fasting glucose level during oral glucose tolerance test an indicator of the insulin need in gestational diabetes

Maintenance of a good metabolic control improves foetal and maternal outcomes in gestational diabetes mellitus (GDM). The aim of this study is to investigate the utility of diagnostic oral glucose tolerance test (OGTT) in prediction of the need of insulin in patients with GDM. One hundred and fifty five consecutive patients with GDM were included in the study. Patients were ordered MNT first. Those who failed to maintain glycemic targets were treated with insulin. Glucose levels obtained from the diagnostic OGTT were evaluated regarding the need of insulin during the rest of pregnancy. Fasting, 1h and 3h post-load glucose levels were significantly elevated in patients who required insulin. Multivariate analysis showed that fasting glucose level on OGTT was an independent predictor for the insulin need. A cut-off value of 105mg/dl had a fair specificity (91.89%) and positive predictive value (80.64%) for the prediction of patients who required insulin during the rest of their pregnancy. Our results suggest that fasting glucose level on OGTT is a predictor of the need for insulin treatment in GDM. A cut-off level of 105mg/dl seems to effectively determine high-risk patients for additional treatment other than MNT in GDM.

Evaluation of postpartum carbohydrate intolerance and cardiovascular risk factors in women with gestational diabetes

We aimed to evaluate the predictors of subsequent development of postpartum carbohydrate intolerance, metabolic syndrome and cardiovascular risk factors in women with previous GDM. Two hundred fifty-two consecutive women with GDM were enrolled. After exclusion of women who did not attend to the hospital for follow-up visits for minimum 1 year, data of 195 patients were evaluated. Seventy-one lean women with negative screening for GDM were included as a control group. The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose and metabolic syndrome was significantly higher in women with previous GDM than healthy controls. Women with previous GDM were more insulin resistant, had an atherogenic lipid profile and increased carotid IMT. The most important predictors of postpartum diabetes were the need for insulin treatment during index pregnancy and glucose values on antepartum OGTT. Among women with previous GDM, the development of postpartum diabetes and metabolic syndrome was associated with increased carotid IMT. Our data show that women with previous GDM are at high risk for developing carbohydrate intolerance, metabolic syndrome and atherosclerosis. Antepartum prediction of high risk subjects for the subsequent development of postpartum carbohydrate intolerance and metabolic syndrome seems to be vital to prevent cardiovascular outcomes.

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.

The effects of body fat distribution on pulmonary function tests in the overweight and obese.

Objectives: To determine the predominant pulmonary function abnormality in overweight and moderately obese subjects and to evaluate the correlation between the severity of lung function impairment and the degree of obesity. Methods: Fifty-three volunteers underwent physical examination, skin fold measurements, and standardized pulmonary function tests. Thirty-one women and 22 men with a mean age of 40.2 (18–66) years were studied. Results: The reduction in functional residual capacity (FRC) and expiratory reserve volume (ERV) were the most common abnormalities in overweight and obese subjects. The reduction in static lung volume was correlated with the degree of obesity in women and men. Stepwise multiple regression coefficients were obtained separately for women and men. Subscapular skinfold was the best predictor in women for FRC and waist-to-hip ratio (WHR) and BMI were found the best for ERV. WHR was found predictive for forced vital capacity, total lung capacity, and FRC in men. Conclusions: The lung volumes are substantially affected in our overweight and obese subjects. This influence is focused on different parameters of respiratory functions in men and women in relation to body fat distribution.

Serum Leptin Levels in Patients with Liver Cirrhosis and Chronic Viral Hepatitis

BACKGROUND The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. METHODS Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. RESULTS Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. CONCLUSIONS These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.Background: The aim of the present study was to investigate serum leptin levels in relation to anthropometric features in patients with liver cirrhosis (LC) and chronic viral hepatitis (CVH), and to determine the effect of the severity and aetiology of the LC on serum leptin levels. Methods: Forty-nine patients with LC, 32 patients with CVH and 69 control subjects were age, body mass index (BMI) and sex-matched and included in the study. Plasma glucose, serum leptin and insulin levels were determined. Insulin resistance was assessed using homoeostasis model assessment (HOMA). Body composition was estimated by skinfold thickness. Results: Female patients with Child-A LC had higher levels of leptin, and female and male patients with Child-A LC had higher absolute leptin (leptin/BFM) levels compared to patients with Child-C LC and control subjects. Serum leptin levels of the patients with alcohol LC were higher than the control subjects, but the absolute leptin levels were comparable. When alcoholic and post-viral hepatitis cirrhotic patients were compared with each other on an aetiologic basis, there was no significant difference between them in leptin and absolute leptin levels. There were significant correlations between leptin and BMI, body fat percentage (BFP), BFM (body fat mass) in all three groups in both sexes. Conclusions: These data suggest that the physiologic correlations among serum leptin level, sex, BMI and BFM were well preserved in patients with chronic liver disease. Patients with alcohol LC had higher leptin levels. In early stages of liver disease, leptin levels and absolute leptin levels are higher than in normal subjects. However, in advanced stages of the disease the significant decline in leptin levels and similar levels of leptin expressed in relation to BFM compared to control subjects predominantly represent the expression of fat mass.

Increased osteoprotegerin levels in women with previous gestational diabetes developing metabolic syndrome

Osteoprotegerin (OPG), a novel soluble member of tumour necrosis factor receptor superfamily, has been shown to link cardiovascular disorders. The aim of this study is to investigate the potential relationship between serum OPG levels, cardiovascular risk factors and metabolic syndrome in a relatively large group of women with previous GDM. In this cross-sectional case-control study, 128 women with previous GDM and 67 age-matched controls were enrolled. Subjects were evaluated for the diagnosis of metabolic syndrome according to the criteria of the American Heart Association (AHA). Fasting glucose, insulin, serum lipids, CRP and OPG were assayed. HOMA score was calculated. Carotid intima media thickness (IMT) was measured. There was no significant increase in OPG levels in women with previous GDM when compared to controls. On the other hand, women with previous GDM developing metabolic syndrome had higher OPG levels than those without metabolic syndrome and healthy controls. Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT. Serum OPG is related to cardiovascular risk factors and metabolic syndrome, and might be involved in the development of cardiovascular disorders in women with previous GDM.

Allergic reactions to human insulin: a review of current knowledge and treatment options

Although the incidence of insulin allergy decreased after the introduction of recombinant human insulin preparations, it is still a major problem which may be life-threatening in some cases. In this article, we attempted to review current knowledge concerning allergic reactions to human insulin and discuss the available treatment options of insulin allergy.