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Waist Circumference (waist + circumference)
Selected AbstractsInteractive effect of central obesity and hypertension on cognitive function in older out-patients with Type 2 diabetesDIABETIC MEDICINE, Issue 12 2008E. Kim Abstract Aim Central obesity, hypertension and diabetes mellitus have been related individually to cognitive dysfunction. We aimed to study the interactive effects of these co-occurring risk factors on cognitive decline, which remain unclear in older patients with diabetes. Methods We assessed metabolic profiles and neuropsychological functions in 60 older out-patients with Type 2 diabetes to examine the associations of central obesity with cognitive functions, while controlling for other confounding factors in these subjects. Results Waist circumference was associated with poor performance in digits forward (r2 = 0.11, P = 0.02), choice reaction time (r2 = 0.08, P = 0.04) and cognitive reaction time (r2 = 0.07, P < 0.05) even after adjustment for potential confounders including age, gender, education and HbA1c. There were also significant interactions between central obesity and hypertension with respect to performance of digits forward (P = 0.04) and delayed verbal cued recall (P = 0.03). Conclusion Our findings suggest that, in addition to glycaemic control, central obesity and hypertension influence cognitive functions, such as attention and psychomotor speed in older patients with Type 2 diabetes. [source] Endogenous testosterone levels and smoking in men.INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2007The fifth Tromsø study Summary Smoking is a risk factor of coronary heart disease (CHD), while the role of testosterone in the development of CHD is controversial. The reported effects of cigarette smoking on testosterone levels in men are conflicting, and smoking may be an important confounding factor when evaluating the relationship between testosterone levels and CHD. Thus, the objective of the present study was to examine the associations of smoking status and number of cigarettes smoked per day with total and free testosterone levels in a cross-sectional population-based study of 3427 men participating in the fifth Tromsø study. Total testosterone, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin levels were measured with immunoassay while free testosterone levels were calculated. Waist circumference was also measured and two standardized questionnaires were completed, including smoking status and number of cigarettes smoked. The data were analysed with analysis of variance and covariance and multiple regression analysis. Smoking men had significantly higher levels of total and free testosterone compared with men who never smoked (p < 0.001 and <0.01 respectively). Both total and free testosterone levels increased significantly with increasing number of cigarettes smoked daily (p < 0.001). Smoking men had 15% higher total and 13% higher free testosterone levels compared with men who never smoked. Thus, smoking seems to be an important confounding factor when evaluating testosterone levels, and could possibly mask borderline hypogonadism. [source] Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohortINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2008A. S. Wierzbicki Summary Objective:, To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. Methods:, A prospective case,control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. Results:, The patients were divided into two groups by QuickI score. Waist circumference (90 ± 10 vs. 90 ± 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 ± 3.7 vs. 24.2 ± 3.5 kg/m2; p < 0.001) and waist:hip ratio (0.94 ± 0.09 vs. 0.90 ± 0.06; p < 0.001). Lipid parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 ± 0.23 vs. 0.82 ± 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08,3.98) vs. 1.12 (0.37,3.61) mmol/l; p = 0.01], but no difference in low-density lipoprotein cholesterol (LDL-C) (2.75 ± 1.00 vs. 2.90 ± 0.94 mmol/l; p = 0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3,175.1) vs. 3.9 (0.2,57.9) mg/l: p < 0.001], sialic acid (82 ± 14 vs. 77 ± 15 mg/l; p < 0.001) aspartate transaminase [24 (7,171) vs. 21 (7,83) IU/l; p < 0.001] and gamma-glutamyl transferase [27 (8,482) vs. 21 (7,168) IU/l; p = 0.005] levels were increased. In insulin-resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (, = 1.62; p < 0.001), HDL-C (, = ,53.2; p < 0.001), lipoprotein (a) (, = 11.4; p = 0.007), smoking (, = 7.98; p = 0.004), CRP (, = 6.06; p = 0.03) and QuickI index (, = ,146; p = 0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL-C (, = 10.0; p = 0.02), CRP (, = 7.13; p = 0.03), HDL-C (, = ,38.1; p = 0.03), and weakly with age (, = 0.73; p = 0.07) and smoking (, = 5.52; p = 0.09). Conclusions:, Indian Asians show a dichotomous insulin-resistance phenotype. Atheroma is associated with low HDL-C and inflammation associated in all but LDL-C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant. [source] Factors that predict cecal insertion time during sedated colonoscopy: The role of waist circumferenceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2008Yu-Hsi Hsieh Abstract Background and Aim:, Various factors have been closely linked to the cecal insertion time. These factors include age, sex, body mass index, quality of bowel preparation, doctor's technique, a history of prior hysterectomy, diverticulosis, and constipation. Waist circumference is better than body mass index in assessing abdominal obesity and therefore may be better than body mass index in predicting cecal insertion time. The aim of this study was to evaluate the factors influencing cecal insertion time and the impact of waist circumference. Methods:, This prospective study was conducted between August 2004 and June 2005 in Buddhist Dalin Tzu Chi General Hospital. Asymptomatic patients admitted to our physical check-up department were enrolled. A single endoscopist performed all colonoscopies under sedation with a single-handed method. Age, sex, body mass index, waist circumference, history of hysterectomy, constipation, bowel cleansing status, and diverticulosis were analyzed. Results:, A total of 1022 patients were enrolled. Among them, 996 (97.5%) completed the colonoscopic examinations (472 men and 524 women). The mean ± SD insertion time was 307 ± 166 s for men and 403 ± 195 s for women (P < 0.01). Female sex, poor bowel preparation, smaller waist circumference, lower body mass index and older age were associated with longer insertion time. Waist circumference was better than body mass index in predicting cecal insertion time. Conclusion:, Female sex, poor bowel preparation, smaller waist circumference, lower body mass index and older age were associated with a longer insertion time. Waist circumference was a better predictor than body mass index in assessing cecal insertion time. [source] Methods for measuring abdominal obesity in the prediction of severe acute pancreatitis, and their correlation with abdominal fat areas assessed by computed tomographyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010A. Duarte-Rojo Aliment Pharmacol Ther 2010; 32: 244,253 Summary Background, Obesity increases the risk for severe acute pancreatitis, although abdominal obesity may be a better prognostic marker. Aim, To determine if a single anthropometric parameter best predicts severe acute pancreatitis and correlates with intra-abdominal fat. Methods, Ninety-nine patients with acute pancreatitis were studied prospectively. Anthropometry included body mass index (BMI) and girths (umbilical/minimum waist, iliac/trochanter hip, thigh). Several waist-to-hip/waist-to-thigh ratios (WHR/WTR) were constructed. A CT-scan with calculation of cross-sectional abdominal fat areas was obtained in 37 cases. Results, Severe acute pancreatitis occurred in 25 patients. Waist circumference (WC), WHR and WTR , all using the umbilical reference , most accurately predicted severe acute pancreatitis. Only umbilical WC was retained in multivariate analysis: the risk for severe acute pancreatitis increased 16% with every 1 cm (OR 1.16, 95%CI: 1.1,1.3). Abdominal obesity caused a 6-fold increase in risk. Umbilical WC correlated best with subcutaneous fat area (r = 0.791, P < 0.001), whereas WHR with intra-abdominal (r = 0.594, P < 0.001). Conclusions, Abdominal obesity according to umbilical WC is a better predictor for development of severe acute pancreatitis than BMI, minimum WC, WHR and WTR. The protocol for anthropometry must be standardized as it may affect results. Both subcutaneous and intra-abdominal fat appears to affect the likelihood of a severe outcome. [source] Change in waist circumference over 11 years and current waist circumference independently predict elevated CRP in Filipino women,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Julienne N. Rutherford C-reactive protein, a marker of chronic, low-grade inflammation, is strongly associated with current central adiposity, and has been linked to elevated risk of cardiovascular disease. Less is known about the contribution of longitudinal change in waist circumference to current inflammation. We evaluated the extent to which current waist circumference and change over an 11-year interval contribute independently to low-grade systemic inflammation measured in a group of 1,294 women, 35,69 years, participating in the Cebu Longitudinal Nutrition and Health Survey in the Philippines. Waist circumference was measured at the time of blood draw for CRP analysis in 2005 and during an earlier survey in 1994. A waist circumference delta variable was constructed by subtracting current circumference from past circumference. We used logistic regression models to predict having an elevated plasma CRP concentration (3 mg L,1 < CRP < 10 mg L,1). Waist circumference in 2005 was a strong predictor of elevated CRP (OR 1.10, 95% CI = 1.08, 1.12, P < 0.001). In combined models, increase in circumference over 11 years was a significant and independent predictor of elevated CRP risk (OR = 1.023, 95% CI = 1.00, 1.05, P < 0.05). Considering the average increase over time, the cumulative risk of elevated CRP due to increased central adiposity was 25.7%. However, women who reduced their waist circumference between 1994 and 2005 had greatly reduced risk (6.2%), suggesting that even long-term inflammatory burden can be reversed by weight loss. Although current waist circumference is an important contributor to risk of elevated systemic inflammation in this as in other populations, history of central adiposity may be an independent phenomenon. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] High fitness is associated with a healthier programming of body composition at adolescenceAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 6 2008Francisco B. Ortega The programming effect of birth weight on later body composition has become of increasing interest in recent years. This programming effect is affected by factors such as gender. Physical fitness could be another factor of influence. This study aimed to examine whether handgrip strength (HG) or cardiovascular fitness (CVF) modify the associations between birth weight and body composition in adolescents. A sample of 1,740 (942 females) adolescents aged 13 to 18.5 years, born at more than 35 weeks of gestation, from the AVENA study was studied. Waist circumference was measured, percentage body fat was calculated from skinfold thicknesses and fat free mass was derived by subtracting fat mass from total body weight. HG and CVF were assessed using the HG test and the 20 m shuttle run test, respectively. Birth weight was positively associated with fat free mass in females with high (above the median) CVF (P < 0.001), but not in those with low (below the median) CVF. In contrast, birth weight was positively associated with total and central adiposity in males with low HG (both P = 0.002), but not in those with high HG. These results suggest that the programming effect of birth weight on later body composition is dependent on gender and fitness level. A high birth weight may have a healthy programming effect on body composition in those adolescents with a high fitness level, being associated with increased fat free mass levels in females and not showing the increased adiposity levels observed in unfit males. Am. J. Hum. Biol., 2008. © 2008 Wiley-Liss, Inc. [source] Anthropometric correlates of lipoprotein profile and blood pressure in high BMI African American childrenACTA PAEDIATRICA, Issue 6 2010A Raman Abstract Objective:, To explore the association of anthropometric indices with lipoprotein profile and blood pressure as risk factors of cardiovascular disease, in African American (AA) children. Methods:, A cross-sectional analysis was carried out on children aged 9,13 years with BMI >85th percentile. Height, weight, waist and hip circumferences, % body fat and blood pressure [systolic (sBP) and diastolic (dBP)] were measured. Fasting plasma levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), intermediate density lipoprotein cholesterol (IDL-C) and very low-density lipoprotein cholesterol (VLDL-C) were analysed. Results:, After accounting for age, gender and pubertal status of the child, multiple linear regression models showed that waist circumference and BMIz were strong predictors for lipoprotein variables. In independent analysis, waist circumference and BMI z-scores were found to be interdependently associated with TG, LDL-C:HDL-C ratio, VLDL-C and sBPz. However, for HDL-C, TG:HDL-C ratio and dBPz, waist circumference was independently and more strongly associated with these risk factors than BMI. Conclusion:, Waist circumference was a stronger predictor for lipoprotein variables and blood pressure in high BMI AA children than other anthropometric indices, and may be adequate as a screening test to identify children who are at increased risk for cardiovascular disease. [source] Population-based waist circumference and waist-to-height ratio reference values in preschool childrenACTA PAEDIATRICA, Issue 10 2009Josefine Roswall Abstract Aim:, To establish new reference values for measurements of waist circumference and waist-to-height ratio in preschool children. Methods:, A population-based, cross-sectional study of 4502 children aged 0,5 years derived from child health care in a Swedish county. Measurements of weight, height and waist circumference were recorded using a standardized procedure. Results:, New reference values for waist circumference and waist-to-height ratio for preschool children are presented. Reference charts were constructed and are presented. Waist circumference increased with age (r = 0.80, p < 0.001). After adjustment to the individual height, expressed as waist-to-height ratio, there was an inverse correlation to age during the first 5 years of age (r = ,0.87, p < 0.001). Conclusion:, The new reference values for waist circumference and waist-to-height ratio for Swedish preschool children enable future identification of new risk populations for childhood obesity. For clinicians, new reference charts for these two variables are provided for practical use. [source] Waist circumference in relation to body perception reported by Finnish adolescent girls and their mothersACTA PAEDIATRICA, Issue 3 2009JS Van Vliet Abstract Aim: To study how waist circumference (WC) relates to body perception in adolescent girls and to maternal perception of the girl's body size. Methods: Three hundred and four girls, 11,18 years, were measured for height, weight and WC. 294 girls provided self-report data on weight, height and body image before anthropometric measurements. Paired data from 237 girls and mothers on perception of the girls' body size were collected. Results: In girls, self-reported weight indicated awareness of actual body size. The girls' body perception showed an overestimation of body size relative to international reference values for body mass index (BMI) (p < 0.05), but not for WC. Girls' body perception exceeded that of their mothers (p < 0.05). Maternal perception agreed better than the girls' perception with international reference values for BMI (p < 0.05). No significant difference between mothers and girls were found concerning agreement of body perception with international reference values for WC. Conclusion: WC rather than BMI agrees with perception of body size, possibly due to its relation to abdominal fat at different ages. For effective prevention and treatment programmes for weight-related health problems among adolescent girls, we recommend measuring WC to diminish the discrepancy between measured and perceived body size. [source] Waist circumference percentiles for 7- to 15-year-old Australian childrenACTA PAEDIATRICA, Issue 9 2005Joey C. Eisenmann Abstract Aim: The purpose of this study was to develop age- and sex-specific reference values for waist circumference using data obtained from Australian children and adolescents. Methods: Subjects were 8439 7-to-15 y olds (4277 males and 4162 females) who participated in the 1985 Australian Health and Fitness Survey. Waist circumference (WC) was measured in the standing position at the level of the umbilicus to the nearest 0.1 cm using a constant tension tape. Descriptive statistics for each whole-year age group (e.g., 10.0,10.99 y, etc.) within sex were calculated. Construction of the smoothed centile curves was performed using the LMS method. Results: Mean WC increases in both males and females, with the values being similar between males and females prior to age 11 y, after which values are slightly higher in males. The range of values varied by age and sex groups but approximated 30,60 cm. Smoothed percentile curves and percentile values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles are presented for boys and girls. WC increases with age in boys and girls, and boys have higher values than girls at nearly every age-specific percentile. Conclusions: These data can be added to the existing international reference values for WC of children and adolescents which should be used to create international cut-off points similar to those for the body mass index (BMI). Future studies should consider the immediate and long-term consequences of an elevated WC in children and also examine the interaction of BMI and WC on chronic disease risk factors. [source] Does smoking in adolescence affect body mass index, waist or height?ADDICTION, Issue 9 2007Findings from a longitudinal study ABSTRACT Aim To assess the effect of smoking uptake on body mass index (BMI), waist circumference and height during adolescence. Design Five-year longitudinal study. Setting Thirty-six schools in South London, England, selected by a stratified random sampling procedure designed to ensure ethnic and socio-economic diversity. Participants A total of 5863 students took part in the HABITS (Health and Behaviour in Teenagers) Study between 1999 and 2003. Measurements Self-reported smoking behaviour, saliva cotinine concentrations and measured weight, waist circumference and height were obtained, along with information on gender, ethnicity, socio-economic deprivation, pubertal status, self-reported exercise and dieting. Students were examined annually from school year 7 (ages 11,12) to year 11 (ages 15,16), with response rates ranging from 74 to 84%. A total of 2665 never smokers at year 7 with complete data for years 7 and 11 were included in the analyses. Findings Adjusting for year 7 BMI and other potential confounders, regular smokers (more than six cigarettes a week) at year 11 had significantly lower BMI (P = 0.002) than other students. Smokers defined by a cotinine above 15 ng/ml also had lower BMI (P < 0.0001). Waist circumferences were lower in regular smokers (P = 0.014) and cotinine-defined smokers (P < 0.011). No consistent association was found between smoking and height. The adjusted difference in weight between regular smokers and other students amounted to 1.8 kg (95% CI, 0.52,3.17) for an average-height student. Conclusion Taking up regular smoking during adolescence may result in a lower BMI, but the effect is small and of uncertain significance. [source] Depression and the metabolic syndrome: gender-dependent associationsDEPRESSION AND ANXIETY, Issue 8 2008Sharon Toker Ph.D. Abstract This study was designed to test the extent to which depressive symptoms are associated with the presence of the metabolic syndrome (MS) and each of its components, and whether these relationships are gender dependent. Participants were apparently healthy employed men (N=2,355) and women (N=1,525) who underwent a routine health check between the years 2003 and 2005. We used logistic regression analysis, predicting the MS by depressive symptoms, as assessed by the Patient Health Questionnaire, and the following control variables: age, education, smoking status, physical exercise, anxiety, and burnout. As hypothesized, we found that depression among women, but not men, was associated with a 1.94-fold risk of having the MS, and with an elevated risk of having two of its five components: elevated waist circumference (odds ratio, OR=2.23) and elevated glucose levels (OR=2.44). In addition, a positive trend was observed toward an association with the other three components: low high-density lipoprotein, hypertension, and elevated triglycerides. Among men depression was associated with elevated waist circumference only (OR=1.77). These findings suggest that especially among women, the association between depression and cardiovascular diseases might be linked to metabolic processes. If replicated in longitudinal studies, these findings may have important health-care policy implications with regard to depression management interventions. Depression and Anxiety 0:1,9, 2007. © 2007 Wiley-Liss, Inc. [source] PROCEED: Prospective Obesity Cohort of Economic Evaluation and Determinants: baseline health and healthcare utilization of the US sample,DIABETES OBESITY & METABOLISM, Issue 12 2008A. M. Wolf Aim:, To summarize baseline characteristics, health conditions, resource utilization and resource cost for the US population for the 90-day period preceding enrolment, stratified by body mass index (BMI) and the presence of abdominal obesity (AO). Methods:, PROCEED (Prospective Obesity Cohort of Economic Evaluation and Determinants) is a multinational, prospective cohort of control (BMI 20,24.0 kg/m2), overweight (BMI 25,29.9 kg/m2) and obese (BMI , 30 kg/m2) subjects with AO and without AO [non-abdominal obesity (NAO)], defined by waist circumference (WC) >102 and 88 cm for males and females, respectively. Subjects were recruited from an Internet consumer panel. Outcomes were self-reported online. Self-reported anthropometric data were validated. Prevalence of conditions and utilization is presented by BMI class and AO within BMI class. Differences in prevalence and means were evaluated. Results:, A total of 1067 overweight [n = 474 (NAO: n = 254 and AO: n = 220)] and obese [n = 493 (NAO: n = 39 and AO: n = 454)] subjects and 100 controls were recruited. Self-reported weight (r = 0.92) and WC (r = 0.87) were correlated with measured assessments. Prevalence of symptoms was significantly higher in groups with higher BMI, as were hypertension (p < 0.0001), diabetes (p < 0.0001) and sleep apnoea (p < 0.0001). Metabolic risk factors increased with the BMI class. Among the overweight class, subjects with AO had significantly more reported respiratory, heart, nervous, skin and reproductive system symptoms. Overweight subjects with AO reported a significantly higher prevalence of diabetes (13%) compared with overweight subjects with NAO (7%, p = 0.04). Mean healthcare cost was significantly higher in the higher BMI classes [control ($456 ± 937) vs. overweight ($1084 ± 3531) and obese ($1186 ± 2808) (p < 0.0001)]. Conclusion:, An increasing gradient of symptoms, medical conditions, metabolic risk factors and healthcare utilization among those with a greater degree of obesity was observed. The independent effect of AO on health and healthcare utilization deserves further study with a larger sample size. [source] Genetic variation and decreased risk for obesity in the Atherosclerosis Risk in Communities StudyDIABETES OBESITY & METABOLISM, Issue 4 2007M. L. Hart Sailors Aim:, To investigate the effects of variation in the leptin [LEP (19A>G)] and melanocortin-4 receptor [MC4R (V103I)] genes on obesity-related traits in 13,405 African-American (AA) and white participants from the Atherosclerosis Risk in Communities (ARIC) Study. Methods:, We tested the association between the single-locus and multilocus genotypes and obesity-related measures [body mass index (BMI), body weight (BW), waist,hip ratio, waist circumference and leptin levels], adjusted for age, physical activity level, smoking status, diabetic status, prevalence of coronary heart disease, hypertension, stroke or transient ischaemic attack. Results:, AA and white female carriers of the MC4R I103 allele exhibited significantly lower BW than non-carriers of this allele (p < 0.05 and p < 0.01 respectively). AA female carriers of both the LEP A19 allele and the MC4R I103 allele were 63% [odds ratio (OR) = 0.37, 95% confidence interval (CI) (0.18,0.78)] less likely to be obese, and white female carriers of the same two alleles were 46% [OR = 0.54, 95% CI (0.32,0.91)] less likely to be obese, than non-carriers of the variant alleles. Female carriers of both the LEP A19 and MC4R I103 alleles had significantly lower BW (p < 0.05), BMI (p < 0.05) and plasma leptin (p < 0.01) than the non-carriers of both the alleles. Carriers of the two variant alleles had lower BMI over the 9-year course of the ARIC study and significantly lower weight gain from age 25 years. No significant joint effect of these two variants was observed in males. Conclusion:, These results suggest that variation within the LEP and MC4R genes is associated with reduced risk for obesity in females. [source] Elevated C-reactive protein in Native Canadian children: an ominous early complication of childhood obesityDIABETES OBESITY & METABOLISM, Issue 5 2006R. Retnakaran Aim:, Subclinical inflammation has been proposed as a pathophysiologic mechanism linking obesity with vascular and metabolic disease. Native North American populations are experiencing high prevalence rates of both (i) childhood obesity and (ii) adult cardiovascular disease (CVD) and type 2 diabetes. Thus, we sought to determine whether subclinical inflammation is an early complication of obesity in Native children. Methods:, Serum concentrations of the inflammatory biomarker C-reactive protein (CRP) were assessed in a population-based, cross-sectional study of the Sandy Lake Oji-Cree community of Northern Ontario, Canada, involving 228 children aged 10,19 years (mean age 14.8). Results:, Median CRP in this population was 0.5 mg/l (interquartile range 0.18,1.79 mg/l). CRP levels were higher than age-matched reference data from the Third National Health and Nutrition Examination Survey (NHANES III). Importantly, fully 15.8% of the children of this community had CRP concentrations between 3 and 10 mg/l, a range that identifies adults at high risk of CVD. Moreover, increasing CRP concentration in this paediatric population was associated with an enhanced CV risk profile, consisting of increased adiposity, higher insulin resistance, worsening lipid profile (higher total cholesterol, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B and total cholesterol : high-density-lipoprotein cholesterol ratio), increased leptin and decreased adiponectin. On multivariate analysis, waist circumference and interleukin-6 (IL-6) emerged as independent determinants of CRP concentration. Conclusion:, Subclinical inflammation is an early complication of childhood obesity in Native children and may foreshadow an increased burden of CVD and type 2 diabetes in the future. [source] Association of the metabolic syndrome with depression and anxiety in Japanese men: A 1-year cohort studyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2009Takeaki Takeuchi Abstract Background Recent studies on the association between the metabolic syndrome (MetS) and depression have reported conflicting findings. This 1-year cohort study aims to evaluate the association of MetS with the development of both depression and anxiety. Methods The cohort comprised 956 Japanese male employees of an enterprise (mean age, 42.7 years; SD, 10.2 years). MetS was diagnosed according to the International Diabetes Federation criteria. The psychological conditions of depression and anxiety were assessed in 2 successive years by using the profile of mood states (POMS) questionnaire and by conducting clinical interviews as per the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). We evaluated the temporal and dose-response relationships between MetS and the development of depression and anxiety, controlling for potential confounding factors like age and lifestyle-related factors. Results We identified a positive relationship between MetS at baseline and new-onset depression in the subsequent year (OR 2.14, 95% CI 1.10,4.17). Of the five MetS components examined, only waist circumference was significantly related to new-onset depression (OR 2.08, 1.23,3.50). Trend analysis revealed a significant positive trend of association between the number of MetS components identified and new-onset depression (Ptrend < 0.01), but not between Mets and new-onset anxiety. Conclusions Our results suggest that MetS is a predictive factor for the development of depression, and that waist circumference largely contributes to the association between MetS and depression. Copyright © 2009 John Wiley & Sons, Ltd. [source] Independent predictive roles of eotaxin Ala23Thr, paraoxonase 2 Ser311Cys and ,3 -adrenergic receptor Trp64Arg polymorphisms on cardiac disease in Type 2 Diabetes,an 8-year prospective cohort analysis of 1297 patientsDIABETIC MEDICINE, Issue 4 2010Y. Wang Diabet. Med. 27, 376,383 (2010) Abstract Aims, To examine the independent and joint effects of multiple genetic variants on a cardiac end-point in an 8-year prospective study of a Chinese diabetic cohort. Methods, Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for inflammation, thrombosis, vascular tone regulation and lipid metabolism were genotyped in 1297 Chinese patients with no prior history of coronary heart disease (CHD) or heart failure at baseline. Cardiac end-point was defined by the occurrence of CHD and/or heart failure. Results, In Cox regression model, after adjustment for baseline confounding variables including age, sex, smoking status, duration of diabetes, glycaemic control, lipid levels, waist circumference, blood pressure, albuminuria and estimated glomerular filtration rate, genetic variants, including Ala/Ala of SCYA11 (eotaxin) Ala23Thr, Cys/Cys or Cys/Ser of PON2 (paraoxonase 2) Ser311Cys and Arg/Arg of ADRB3 (,3 -adrenergic receptor) Trp64Arg, were independently associated with incident cardiac end-point, with respective hazard ratios (95% confidence interval) of 1.70 (1.10,2.61, P = 0.037), 1.42 (1.08,1.88, P = 0.013) and 3.84 (1.18,12.50, P = 0.025). Analysis of the joint effect of the risk alleles showed significant increased risk of the cardiac end-point with increasing number of risk alleles (P < 0.001). The adjusted risk for the cardiac end-point was 4.11 (P = 0.002) for patients carrying four risk alleles compared with those carrying one or no risk allele. Conclusions, The independent risk conferred by genetic variants encoding pathways such as inflammation and lipid metabolism, not adequately reflected by conventional biomarkers, may identify high-risk individuals for intensified control of modifiable risk factors. [source] Following in mother's footsteps?DIABETIC MEDICINE, Issue 3 2010Mother, cardiovascular disease 15 years after gestational diabetes, daughter risks for insulin resistance Diabet. Med. 27, 257,265 (2010) Abstract Aims, To determine effects on mothers and daughters of gestational diabetes mellitus/gestational impaired glucose tolerance (GDM/GIGT) on their future metabolic and cardiovascular risks. Methods, Case mothers who had GDM/GIGT in pregnancy (cases; n = 90) and normoglycaemic control women (n = 99) and their daughters underwent lifestyle assessment and metabolic tests 15-years post-partum. Results, Prevalence of glucose intolerance (GI) in daughters was 1.1%. Maternal prevalence was 44.4% in cases compared to 13.1% in controls, with conversion best predicted by weight gain. Case daughters had higher insulin resistance (IR) and greater waist circumference (WC) (51.2%) relative to control daughters (36.4%, p < 0.05) made worse if case mothers became GI at follow-up (65%) (relative risk =1.8; 95% confidence interval 1.2,2.9). In multivariable linear regression analyses adjusting for daughters' birthweight, maternal obesity (> 30.0 kg/m2) at 15years and mothers' case-control status were strong predictors of daughters' WC (p < 0.01; P < 0.01, respectively). For daughters' body mass index (BMI) percentile and percentage of body fat, maternal obesity was a stronger predictor (p < 0.01; p < 0.001)) than mothers' case-control status (p < 0.01; P = 0.09). Conclusions, GDM/GIGT pregnancies led to increased conversion to GI in mothers, minimal in daughters. Case daughters have increased risk of central adiposity and insulin resistance, whereas maternal obesity strongly predicted daughters' BMI percentile and per cent of body fat. Controlling hyperglycaemia in pregnancy and family weight management may provide the key to preventing offspring obesity and glucose intolerance post GDM/GIGT. [source] Efficacy and safety of insulin glargine and glimepiride in subjects with Type 2 diabetes before, during and after the period of fasting in RamadanDIABETIC MEDICINE, Issue 12 2009I. Salti Abstract Aims, To determine the safety and efficacy of insulin glargine and glimepiride in patients with Type 2 diabetes before and after Ramadan and during fasting for Ramadan. Methods, In this open, descriptive, multi-centre, prospective study, insulin-naïve (n = 100) or previously insulin-treated (n = 249) patients with Type 2 diabetes received insulin glargine [titrated from 10 U daily according to fasting blood glucose (FBG)] and glimepiride (4 mg daily). The number and type of hypoglycaemic episodes and glycaemic control were assessed before, during and after Ramadan. Bivariate logistic regression analyses were used to identify factors which predicted hypoglycaemia during Ramadan. Results, Only one episode of severe hypoglycaemia occurred in each time period before, during and after Ramadan. Mild hypoglycaemic episodes increased from 156 pre-Ramadan to 346 during Ramadan (P < 0.001) and decreased to 153 post-Ramadan (P = 0.0002). The increase during Ramadan was mainly attributed to increased symptomatic hypoglycaemic episodes. FBG and glycated haemoglobin improved during the titration period and did not change during the rest of the study. Risk of hypoglycaemic events during Ramadan was higher in countries where fasting is strict [odds ratio (OR) 3.69 (2.06,6.63), P < 0.0001]. Lower weight [< 70.0 kg; OR 2.56 (1.46,4.48), P = 0.001] and waist circumference [< 90 cm; OR 3.06 (1.62,5.78), P = 0.001] increased the risk of hypoglycaemia during Ramadan whilst FBG > 6.7 mmol/l [OR 0.3 (0.17,0.54), P < 0.0001] had a protective effect. Conclusions, Combination of insulin glargine and glimepiride may be used during Ramadan in patients with Type 2 diabetes who wish to fast, provided glimepiride is given at the time of breaking the fast and insulin glargine titrated to provide FBG > 6.7 mmol/l. [source] J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes: an 8-year follow-up of relatively lean Japanese individualsDIABETIC MEDICINE, Issue 8 2009M. Sakurai Abstract Aims, This study investigated the relationship between waist circumference and the subsequent incidence of Type 2 diabetes and the association with insulin resistance and pancreatic B-cell function in relatively lean Japanese individuals. Methods, The study participants were 3992 employees (2533 men and 1459 women, aged 35,55 years) of a metal-products factory in Japan. The incidence of diabetes was determined in annual medical examinations during an 8-year follow-up. We calculated age- and sex-adjusted hazard ratios (HRs) according to the sex-specific quintile of waist circumference at baseline. Differences in baseline insulin resistance [homeostatis model assessment (HOMA)-IR] and pancreatic B-cell function (HOMA-B) were compared between participants who developed diabetes and those who did not. Results, During the follow-up, 218 participants developed diabetes. Age- and sex-adjusted HRs across the quintiles of waist circumference were 1.78, 1.00 (reference), 1.59, 3.11 and 3.30, respectively (P for trend, < 0.0001). The HR for the lowest quintile was significantly higher than that for the second quintile. Among participants with waist circumference of the lowest quintile, HOMA-B was lower in those who developed diabetes than in those who did not [33.1 (24.1,45.0) vs. 54.3 (37.9,74.6) median (interquartile range), P < 0.0001], but HOMA-IR did not differ between these groups. Conclusions, There was a J-shaped relationship between waist circumference and subsequent risk for Type 2 diabetes in relatively lean Japanese individuals; lower pancreatic B-cell function may also increase the risk of diabetes in very lean Japanese people. [source] HbA1c levels in non-diabetic Dutch children aged 8,9 years: the PIAMA birth cohort studyDIABETIC MEDICINE, Issue 2 2009H. Jansen Abstract Aim, Glycated haemoglobin (HbA1c) is considered the best index of glycaemic control in established diabetes. It may also be useful in the diagnosis of diabetes and as a screening tool. Little is known about the distribution of HbA1c in healthy children and its predictors. The aim of this study is to describe the distribution of HbA1c in non-diabetic Dutch children aged 8,9 years and to investigate potential associations of HbA1c in this group. Methods HbA1c was measured in 788 non-diabetic children aged 8,9 years participating in the PIAMA birth cohort study. Data on parents and children were collected prospectively by questionnaires. Weight, height and waist and hip circumference of the children were measured when blood samples were taken. Results, Mean (sd) HbA1c was 4.9 ± 0.33%, range 3.5,6.0%. HbA1c was significantly higher in boys (4.9 ± 0.31 vs. 4.9 ± 0.33%) and in children of mothers with gestational diabetes (5.0 ± 0.37 vs. 4.9 ± 0.32%). We found a significant inverse association between HbA1c and haemoglobin (regression coefficient: ,0.169 (95% CI ,0.221 to ,0.118), P < 0.001). HbA1c was not significantly associated with age, body mass index, waist circumference, parental diabetes or maternal body mass index. Conclusions, We found no significant relation between known risk factors for Type 2 diabetes and HbA1c at age 8,9 years. Moreover, there was a significant inverse association between haemoglobin and HbA1c. These results suggest that HbA1c may not only reflect the preceding blood glucose levels, but seems to be determined by other factors as well. [source] Insulin resistance is an independent correlate of increased urine albumin excretion: a cross-sectional study in Iranian Type 2 diabetic patientsDIABETIC MEDICINE, Issue 2 2009A. Esteghamati Abstract Aims, To assess the association of insulin resistance with increased urinary albumin excretion (UAE) in a cohort of Iranian Type 2 diabetic patients. Methods, Three hundred and sixty-one men and 472 women with Type 2 diabetes were enrolled from three different outpatient clinics (Tehran, Iran) during the period 2005,2008. Patients with obstructive uropathy, severe heart failure, liver disease, cancer, autoimmune disease and macroalbuminuria were not included. Microalbuminuria (MA; defined as UAE , 30 mg/day) was found in 242 (29.1%) patients; 591 (70.9%) subjects had normoalbuminuria (UAE < 30 mg/day). Insulin resistance was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Results, HOMA-IR index values were higher in subjects with MA than those with normoalbuminuria (P < 0.00001). Adjusted values (for age, sex and duration of diabetes) of UAE and HOMA-IR were 11.81 ± 7.51 (mg/day) and 3.30 ± 2.21 in normoalbuminuric and 75.36 ± 55.57 (mg/day) and 4.98 ± 3.22 in the MA group, respectively (P < 0.00001 for all). Multiple regression analysis showed that UAE was predicted by HOMA-IR, independently of age, duration of diagnosed diabetes, triglycerides, waist circumference, metabolic control, blood pressure and related treatments (P < 0.00001). When patients were categorized into quartiles of HOMA-IR, those of the fourth quartile (i.e. the most insulin resistant) were at a higher risk of increased UAE than other quartiles [odds ratio (OR) 3.7 (95% confidence intervals 2.7,6.2)]. Conclusions, In Iranian Type 2 diabetic patients, albuminuria was strongly associated with insulin resistance. HOMA-IR is an independent predictor of UAE. [source] Risk factor control in patients with Type 2 diabetes and coronary heart disease: findings from the Swedish National Diabetes Register (NDR)DIABETIC MEDICINE, Issue 1 2009S. Gudbjörnsdottir Abstract Aims Patients with Type 2 diabetes and coronary heart disease (CHD) are infrequently treated to risk factor targets in current guidelines. We aimed to examine risk factor management and control levels in a large sample of patients with Type 2 diabetes with CHD. Methods This was an observational study of 1612 patients with first incidence of CHD before 2002, and of 4570 patients with first incidence of CHD before 2005, from the Swedish National Diabetes Register (NDR). Results In patients with CHD 1,2 years before follow-up, the achievement of cardiovascular risk factor targets (follow-up 2002/follow-up 2005) was: HbA1c < 7%, 47%/54% (P < 0.01); blood pressure , 130/80 mmHg, 31%/40% (P < 0.001); total cholesterol < 4.5 mmol/l, 47%/60% (P < 0.001); and low-density lipoprotein-cholesterol < 2.5 mmol/l, 49%/65% (P < 0.001). Use of medication: antihypertensives, 90%/94% (P < 0.01); lipid-lowering drugs, 75%/86% (P < 0.001); and aspirin, 85%/89% (P < 0.05). A high prevalence of adverse lifestyle characteristics prevailed (2002/2005): overweight [body mass index (BMI) , 25 kg/m2], 86%/85%; obesity (BMI , 30 kg/m2), 41%/42%; smokers in age group < 65 years, 16,23%/18,19%; as well as waist circumference , 102 cm (men) or , 88 cm (women), 68% in 2005. Conclusions Patients with a combination of Type 2 diabetes and CHD showed an increased use of lipid-lowering drugs over time, corresponding to improving blood lipid levels. A discrepancy existed between the prevalent use of antihypertensive drugs and the low proportion reaching blood pressure targets. Regretfully, a high prevalence of adverse lifestyle characteristics prevailed. Evidence-based therapy with professional lifestyle intervention and drugs seems urgent for improved quality of secondary prevention in these patients. [source] Prevalence and projections of diabetes and pre-diabetes in adults in Sri Lanka,Sri Lanka Diabetes, Cardiovascular Study (SLDCS)DIABETIC MEDICINE, Issue 9 2008P. Katulanda Abstract Aims To determine the prevalence of diabetes mellitus and pre-diabetes (impaired fasting glucose and impaired glucose tolerance) in adults in Sri Lanka. Projections for the year 2030 and factors associated with diabetes and pre-diabetes are also presented. Methods This cross-sectional study was conducted between 2005 and 2006. A nationally representative sample of 5000 adults aged , 18 years was selected by a multi-stage random cluster sampling technique. Fasting plasma glucose was tested in all participants and a 75-g oral glucose tolerance test was performed in non-diabetic subjects. Prevalence was estimated for those > 20 years of age. Results Response rate was 91% (n = 4532), males 40%, age 46.1 ± 15.1 years (mean ± standard deviation). The age,sex standardized prevalence (95% confidence interval) of diabetes for Sri Lankans aged , 20 years was 10.3% (9.4,11.2%) [males 9.8% (8.4,11.2%), females 10.9% (9.7,12.1%), P = 0.129). Thirty-six per cent (31.9,40.1%) of all diabetic subjects were previously undiagnosed. Diabetes prevalence was higher in the urban population compared with rural [16.4% (13.8,19.0%) vs. 8.7% (7.8,9.6%); P < 0.001]. The prevalence of overall, urban and rural pre-diabetes was 11.5% (10.5,12.5%), 13.6% (11.2,16.0%) and 11.0% (10.0,12.0%), respectively. Overall, 21.8% (20.5,23.1%) had some form of dysglycaemia. The projected diabetes prevalence for the year 2030 is 13.9%. Those with diabetes and pre-diabetes compared with normal glucose tolerance were older, physically inactive, frequently lived in urban areas and had a family history of diabetes. They had higher body mass index, waist circumference, waist,hip ratio, systolic/diastolic blood pressure, low-density lipoprotein cholesterol and triglycerides. Insulin was prescribed to 4.4% (2.7,6.1%) of all diabetic subjects. Conclusions One in five adults in Sri Lanka has either diabetes or pre-diabetes and one-third of those with diabetes are undiagnosed. [source] Evidence for distinct effects of GH and IGF-I in the metabolic syndromeDIABETIC MEDICINE, Issue 9 2007P. Maison Abstract Aims, The metabolic syndrome is a cluster of cardiovascular risk factors which include central obesity, dyslipidaemia, glucose intolerance and hypertension. These risk factors are common in patients with growth hormone (GH) deficiency, suggesting a role for the somatotropic axis in the development of metabolic syndrome. Methods, We used factor analysis to investigate the relationships linking serum levels of GH and insulin-like growth factor I (IGF-I) to metabolic syndrome variables (high-density lipoprotein cholesterol, triglycerides, fasting glucose, blood pressure and waist circumference). We studied 359 men and 388 women from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR). Their age range was 30,64 years. Results, Three independent latent factors explained 61% of the total variance in women and four factors explained 73% in men. In both men and women, IGF-I showed a strong positive correlation with the lipid factor and a negative correlation with the obesity/glucose factor. In women, GH showed a strong negative correlation with the obesity/glucose factor but not the lipid factor. In men, GH was unrelated to the lipid and obesity/glucose factors. The blood pressure factor was not related to GH or IGF-I. In contrast with IGF-I, GH was significantly lower in women with metabolic syndrome (1575 ± 449 pg/ml) than in the other women (2121 ± 520 pg/ml, P = 0.002). No significant difference was observed in men for GH or IGF-I. Conclusion, Our results support a link between the somatotropic axis and several features of the metabolic syndrome, and suggest distinct effects of GH and IGF-I on these parameters. [source] Relationship of glucose concentrations with PAI-1 and t-PA in subjects with normal glucose toleranceDIABETIC MEDICINE, Issue 8 2006P. E. Heldgaard Abstract Aims To study metabolic risk factors for the development of cardiovascular disease (CVD), including markers of the fibrinolytic system in relation to blood glucose levels in subjects with normal glucose tolerance and fasting blood glucose levels below 5.6 mmol/l. Methods Cross-sectional, community-based study from a primary health-care centre of adult subjects with normal glucose tolerance. Analysis of fasting and 2-h post-load blood glucose concentrations were centralized and related to anthropometric characteristics, metabolic variables, inflammatory markers, and coagulation and fibrinolytic variables. Results Increasing fasting blood glucose concentrations within the normal range in subjects with normal glucose tolerance were associated with increasing age, body mass index, and waist circumference, and with increasing concentrations of metabolic risk factors for development of CVD. After adjustment for gender, age, body mass index (BMI), and fasting insulin, levels of plasmin activator inhibitor (PAI-1) and tissue type plasminogen activator (t-PA) increased significantly with increasing levels of fasting glucose within the normal range (P = 0.012 and P < 0.0001, respectively). Conclusions We found risk factors for CVD, specifically key components of the fibrinolytic system, PAI-1 and t-PA, increased with increasing fasting glucose levels even in subjects with normal glucose tolerance. This observation may help to explain the increased risk of CVD with increasing values of fasting glucose in the normal range. [source] The metabolic syndrome and changing relationship between blood pressure and insulin with age, as observed in Aboriginal and Torres Strait Islander peoplesDIABETIC MEDICINE, Issue 11 2005A. E. Schutte Abstract Aims To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age. Methods A cross-sectional population-based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2-h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids. Results The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15,29 years, and an inverse correlation for Aborigines aged 40 years and older. Conclusion Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin. [source] Prevalence of the metabolic syndrome among the Inuit in Greenland.DIABETIC MEDICINE, Issue 11 2004A comparison between two proposed definitions Abstract Aims To estimate the prevalence of the metabolic syndrome among Greenland Inuit according to the World Health Organization (WHO) definition and the definition suggested by the National Cholesterol Education Program (NCEP). Methods From 1999 to 2001, 917 adult Inuit participated in a health survey in Greenland. The examination included a 75-g oral glucose tolerance test (OGTT). Body mass index (BMI), waist circumference, waist-to-hip ratio and blood pressure were measured. Plasma glucose, serum insulin, lipids and urine albumin/creatinine ratio were measured. The metabolic syndrome was diagnosed according to the WHO criteria 1999 and to the working definition suggested by the NCEP 2001. Results Using the WHO and the NCEP criteria, 20.7% and 17.9% of the participants had the metabolic syndrome, respectively. There was a moderate agreement between the two definitions, , = 0.56 (95% CI 0.51,0.61). Of those with the WHO metabolic syndrome, 37.9% did not have the NCEP syndrome, and 28.5% of those with the NCEP syndrome were not classified with the metabolic syndrome under the WHO criteria. Compared with the WHO syndrome, men with the NCEP syndrome had higher mean values of waist circumference, BMI and triglycerides, and lower mean values of high-density lipoprotein (HDL) cholesterol; among women, triglycerides were higher with the NCEP syndrome. Conclusion The metabolic syndrome is common among Inuit using either the WHO definition or the proposed NCEP definition. The classification disagreement is considerable and a universally accepted definition is needed. [source] Ethnic differences and determinants of diabetes and central obesity among South Asians of PakistanDIABETIC MEDICINE, Issue 7 2004T. H. Jafar Abstract Aims To study the within ethnic subgroup variations in diabetes and central obesity among South Asians. Methods Data from 9442 individuals age , 15 years from the National Health Survey of Pakistan (NHSP) (1990,1994) were analysed. Diabetes was defined as non-fasting blood glucose , 7.8 mmol/l, or known history of diabetes. Central obesity was measured at the waist circumference. Distinct ethnic subgroups Muhajir, Punjabi, Sindhi, Pashtun, and Baluchi were defined by mother tongue. Results The age-standardized prevalence of diabetes varied among ethnic subgroups (P = 0.002), being highest among the Muhajirs (men 5.7%, women 7.9%), then Punjabis (men 4.6%, women 7.2%), Sindhis (men 5.1%, women 4.8%), Pashtuns (men 3.0%, women 3.8%), and lowest among the Baluchis (men 2.9%, women 2.6%). While diabetes was more prevalent in urban vs. rural dwellers [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.24, 1.82], this difference was no longer significant after adjusting for central obesity (OR 1.15, 95% CI 0.95, 1.42). However, the ethnic differences persisted after adjusting for major sociodemographic risk factors (unadjusted OR for Pashtun vs. Punjabi 0.59, 95% CI 0.42, 0.84, adjusted OR 0.54, 95% CI 0.37, 0.78). Ethnic variation was also observed in central obesity, which varied with gender, and did not necessarily track with ethnic differences in diabetes. Conclusions Unmeasured environmental or genetic factors account for ethnic variations in diabetes and central obesity, and deserve further study. [source] | |||||||||||||||||||||||||||||||||||||