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1.  Adult metabolic syndrome and impaired glucose tolerance are associated with different patterns of body mass index gain during infancy; Data from the New Delhi birth cohort 
Diabetes care  2008;31(12):2349-2356.
Objective:
To describe patterns of infant, childhood and adolescent body mass index (BMI) and weight associated with adult metabolic risk factors for cardiovascular disease.
Research Design and Methods:
We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (NCEP-ATPIII definition) in 1,492 men and women aged 26-32 years in Delhi, India, whose weight and height were recorded 6-monthly throughout infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult).
Results:
Men and women with metabolic syndrome (29% overall), any of its component features, or higher (>upper quartile) insulin resistance (HOMA) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence, but with lower BMI in infancy.
Conclusions:
In this Indian population, patterns of infant BMI and weight gain differed for people who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.
doi:10.2337/dc08-0911
PMCID: PMC2584194  PMID: 18835958
Metabolic syndrome; diabetes; birthweight; infant weight; child growth
2.  Glucose tolerance, insulin resistance and insulin secretion in young south Indian adults; relationships to parental size, neonatal size and childhood body mass index 
Objective
To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.
Research design and Methods
2,218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages.
Results
Sixty-two (2.8%) subjects had type 2 diabetes (DM) and 362 (16.3%) had impaired glucose tolerance (IGT). IGT and DM combined (IGT/DM) and insulin resistance were associated with low childhood body mass index (BMI) (p<0.001 for both) and above-average BMI gain between childhood or adolescence and adult life (p<0.001 for both). There were no direct associations between birthweight or infant size and IGT/DM; however, after adjusting for adult BMI, lower birthweight was associated with an increased risk.
Conclusions
The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.
doi:10.1016/j.diabres.2009.11.015
PMCID: PMC3428893  PMID: 20115937
Type 2 diabetes mellitus; impaired glucose tolerance; insulin resistance; childhood body mass index; young adulthood
3.  Adult Metabolic Syndrome and Impaired Glucose Tolerance Are Associated With Different Patterns of BMI Gain During Infancy 
Diabetes Care  2008;31(12):2349-2356.
OBJECTIVE—The purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease.
RESEARCH DESIGN AND METHODS—We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult).
RESULTS—Men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy.
CONCLUSIONS—In this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.
doi:10.2337/dc08-0911
PMCID: PMC2584194  PMID: 18835958
4.  Comparison of metabolic syndrome prevalence using eight different definitions: a critical approach 
Archives of Disease in Childhood  2007;92(12):1067-1072.
Objective
Multiple definitions of the metabolic syndrome (MS) have been proposed for children, adolescents and adults. The aim of this study was to analyse the variations in the MS prevalence using different definitions and to examine which factors influence the frequency of the MS in childhood and adolescence.
Methods and design
The prevalence of the MS according to eight proposed definitions was studied in 1205 Caucasian overweight children and adolescents aged 4–16 years (mean body mass index (BMI) 27.3 kg/m2, mean age 11.8 years, 46% males, 39% prepubertal). Blood pressure, waist circumference and fasting triglycerides, HDL‐cholesterol, total cholesterol, insulin and glucose concentrations were determined. Overweight was defined according to the International Task Force of Obesity in Childhood. Degree of overweight was calculated as standard deviation score of BMI (SDS‐BMI). Insulin resistance was estimated based on the HOMA model.
Results
The prevalence of the MS varied significantly (p<0.001), being between 6% and 39% depending on the different definitions. Only 2% of the children fulfilled the criteria of the MS in all definitions. Insulin resistance and degree of overweight were associated with the MS. In most definitions, pubertal stage did not influence the occurrence of the MS. In a principal component analysis, total cholesterol, triglycerides and waist circumference showed high final communality estimates.
Conclusions
Since the prevalence of the MS varied widely in overweight children and adolescents depending on the proposed definition used, an internationally accepted uniform definition of the MS is necessary to compare different populations and studies.
doi:10.1136/adc.2006.104588
PMCID: PMC2066078  PMID: 17301109
5.  Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK. 
OBJECTIVE: To compare the prevalence of glucose intolerance (impaired glucose tolerance and diabetes), and its relationship to body mass index (BMI) and waist-hip ratio in Chinese and Europid adults. DESIGN: This was a cross sectional study. SETTING: Newcastle upon Tyne. SUBJECTS: These comprised Chinese and Europid men and women, aged 25-64 years, and resident in Newcastle upon Tyne, UK. MAIN OUTCOME MEASURES: Two hour post load plasma glucose concentration, BMI, waist circumference, and waist-hip ratio. METHODS: Population based samples of Chinese and European adults were recruited. Each subject had a standard WHO oral glucose tolerance test. RESULTS: Complete data were available for 375 Chinese and 610 Europid subjects. The age adjusted prevalences of glucose intolerance in Chinese and Europid men were 13.0% (p = 0.04). Mean BMIs were lower in Chinese men (23.8 v 26.1) and women (23.5 v 26.1) than in the Europids (p values < 0.001), as were waist circumferences (men, 83.3 cm v 90.8, p < 0.001; women, 77.3 cm v 79.2, p < 0.05). Mean waist-hip ratios were lower in Chinese men (0.90 v 0.91, p = 0.02) but higher in Chinese women (0.84 v 0.78, p < 0.001) compared with Europids. In both Chinese and Europid adults, higher BMI, waist circumference, and waist-hip ratio were associated with glucose intolerance. CONCLUSIONS: The prevalence of glucose intolerance in Chinese men and women, despite lower BMIs, is similar to or higher than that in local Europid men and women and intermediate between levels found in China and those in Mauritius. It is suggested that an increase in mean BMI to the levels in the Europid population will be associated with a substantial increase in glucose intolerance in Chinese people.
PMCID: PMC1060438  PMID: 9196645
6.  Diabetes and pre-diabetes are associated with cardiovascular risk factors and carotid/femoral intima-media thickness independently of markers of insulin resistance and adiposity 
Background
Impaired glucose regulation (IGR) is associated with detrimental cardiovascular outcomes such as cardiovascular disease risk factors (CVD risk factors) or intima-media thickness (IMT). Our aim was to examine whether these associations are mediated by body mass index (BMI), waist circumference (waist) or fasting serum insulin (insulin) in a population in the African region.
Methods
Major CVD risk factors (systolic blood pressure, smoking, LDL-cholesterol, HDL-cholesterol,) were measured in a random sample of adults aged 25–64 in the Seychelles (n = 1255, participation rate: 80.2%).
According to the criteria of the American Diabetes Association, IGR was divided in four ordered categories: 1) normal fasting glucose (NFG), 2) impaired fasting glucose (IFG) and normal glucose tolerance (IFG/NGT), 3) IFG and impaired glucose tolerance (IFG/IGT), and 4) diabetes mellitus (DM). Carotid and femoral IMT was assessed by ultrasound (n = 496).
Results
Age-adjusted levels of the major CVD risk factors worsened gradually across IGR categories (NFG < IFG/NGT < IFG/IGT < DM), particularly HDL-cholesterol and blood pressure (p for trend < 0.001). These relationships were marginally attenuated upon further adjustment for waist, BMI or insulin (whether considered alone or combined) and most of these relationships remained significant. With regards to IMT, the association was null with IFG/NGT, weak with IFG/IGT and stronger with DM (all more markedly at femoral than carotid levels). The associations between IMT and IFG/IGT or DM (adjusted by age and major CVD risk factors) decreased only marginally upon further adjustment for BMI, waist or insulin. Further adjustment for family history of diabetes did not alter the results.
Conclusion
We found graded relationships between IGR categories and both major CVD risk factors and carotid/femoral IMT. These relationships were only partly accounted for by BMI, waist and insulin. This suggests that increased CVD-risk associated with IGR is also mediated by factors other than the considered markers of adiposity and insulin resistance. The results also imply that IGR and associated major CVD risk factors should be systematically screened and appropriately managed.
doi:10.1186/1475-2840-6-32
PMCID: PMC2148037  PMID: 17958881
7.  Increased incidence of glucose disorders during pregnancy is not explained by pre-pregnancy obesity in London, Canada 
Background
The increasing incidence of impaired glucose tolerance (IGT), gestational diabetes (GDM) and type 2 diabetes (T2D) during pregnancy was hypothesized to be associated with increases in pre-pregnancy body mass index (BMI). The aims were to 1) determine the prevalence of IGT/GDM/T2 D over a 10 year period; 2) examine the relationship between maternal overweight/obesity and IGT/GDM/T2D; and 3) examine the extent to which maternal metabolic complications impact maternal and fetal pregnancy outcomes.
Methods
Data arose from a perinatal database which contains maternal characteristics and perinatal outcome for all singleton infants born in London, Canada between January 1, 2000 and December 31, 2009. Univariable and multivariable odds ratios (OR) were estimated using logistic regression with IGT/GDM/T2 D being the outcome of interest.
Results
A total of 36,597 women were included in the analyses. Population incidence of IGT, GDM and T2 D rose from 0.7%, 2.9% and 0.5% in 2000 to 1.2%, 4.2% and 0.9% in 2009. The univariable OR for IGT, GDM and T2 D were 1.65, 1.52 and 2.06, respectively, over the ten year period. After controlling for maternal age, parity and pre-pregnancy BMI the OR did not decrease. Although there was a positive relationship between pre-pregnancy BMI and prevalence of IGT/GDM/T2 D, this did not explain the time trends in the latter. Diagnosis of IGT/GDM/T2 D increased the risk of having an Apgar score <7 at 5 minutes, which was partially explained by gestational hypertension, high placental ratio, gestational age and large for gestational age babies.
Conclusions
We found a significant increase in the incidence of IGT/GDM/T2 D for the decade between 2000-2009 which was not explained by rising prevalence of maternal overweight/obesity.
doi:10.1186/1471-2393-10-85
PMCID: PMC3022738  PMID: 21184681
8.  Acrochordons as a Cutaneous Sign of Metabolic Syndrome: A Case-Control Study 
Background:
Acrochordons (known as skin tags) are benign skin tumors. A few studies with contradictory results have been reported regarding the abnormalities of carbohydrate and/or lipid metabolisms in patients with skin tags.
Aim:
The aim of this study is to determine if the presence of acrochordons could be a marker of Metabolic syndrome by comparing with a control group.
Subjects and Methods:
A total of 110 patients having two or more acrochordons and age- and gender-matched 110 controls were included in the study. Localization, size and the total number of acrochordons were recorded in the patient group. Age, sex, body mass index (BMI), waist circumference, smoking status, fasting plasma glucose (FPG), impaired glucose tolerance (IGT) test, insulin resistance, serum lipids and liver enzyme levels were estimated in cases and controls. Arterial blood pressures were measured in two groups.
Results:
A total of 58 patients and 12 controls were diagnosed with overt diabetes mellitus (DM). 15% (16/110) of patients and 8% (9/110) of controls had an IGT test. The difference was statistically significant for the diagnosis of DM and not significant for the IGT. The mean levels of FPG, BMI, insulin resistance, total cholesterol, low-density lipoprotein cholesterol and triglyceride were significantly higher in patients than those in controls. Serum levels of high-density lipoprotein were less in patients. Patients with acrochordons had higher systolic and diastolic blood pressures than controls.
Conclusion:
Acrochordons may represent a cutaneous sign for Metabolic syndrome. Changing the life-style of these patients may have a beneficial role.
doi:10.4103/2141-9248.129040
PMCID: PMC3991940  PMID: 24761238
Acrochordons; Metabolic; Syndrome
9.  Impact of ADMA, endothelial progenitor cells and traditional cardiovascular risk factors on pulse wave velocity among prediabetic individuals 
Background
Central arterial stiffness represents a well-established predictor of cardiovascular disease. Decreased circulating endothelial progenitor cells (EPCs), increased asymmetric dimethyl-arginine (ADMA) levels, traditional cardiovascular risk factors and insulin resistance have all been associated with increased arterial stiffness. The correlations of novel and traditional cardiovascular risk factors with central arterial stiffness in prediabetic individuals were investigated in the present study.
Methods
The study population consisted of 53 prediabetic individuals. Individuals were divided into groups of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IGT-IFG. Age, sex, family history of diabetes, smoking history, body mass index (BMI), waist to hip ratio (WHR), waist circumference (WC), blood pressure, lipid profile, levels of high sensitive C-reactive protein (hsCRP), glomerular filtration rate (GFR), and history of antihypertensive or statin therapy were obtained from all participants. Insulin resistance was evaluated using the Homeostatic Model Assessment (HOMA-IR). Carotid -femoral pulse wave velocity was used as an index of arterial stiffness. Circulating EPC count and ADMA serum levels were also determined.
Results
Among studied individuals 30 (56.6%) subjects were diagnosed with isolated IFG, 9 (17%) with isolated IGT (17%) and 14 with combined IFG-IGT (26.4%). In univariate analysis age, mean blood pressure, fasting glucose, total cholesterol, LDL cholesterol, and ADMA levels positively correlated with pulse-wave velocity while exercise and GFR correlated negatively. EPC count did not correlate with PWV. In multivariate stepwise regression analysis PWV correlated independently and positively with LDL-Cholesterol (low density lipoprotein) and ADMA levels and negatively with exercise.
Conclusions
Elevated ADMA and LDL-C levels are strongly associated with increased arterial stiffness among pre-diabetic subjects. In contrast exercise inversely correlated with arterial stiffness.
doi:10.1186/1475-2840-11-141
PMCID: PMC3527304  PMID: 23153108
Pre-diabetes; ADMA; Pulse wave velocity; Endothelial progenitor cells
10.  Childhood Obesity Predicts Adult Metabolic Syndrome: The Fels Longitudinal Study 
The Journal of pediatrics  2007;152(2):191-200.
Objectives
To determine the age of significant divergence in body mass index (BMI) and waist circumference in adults with and without the metabolic syndrome, and to provide age- and sex-specific childhood values that predict adult metabolic syndrome.
Study design
Part 1 of this study is a retrospective cohort study of 92 men and 59 women (mean age, 51 years) who had metabolic syndrome and 154 randomly selected adults matched for age and sex who did not have the syndrome. Part 2 is a study of predictive accuracy in a validation sample of 743 participants.
Results
The first appearance of differences between adults with and without metabolic syndrome occurred at ages 8 and 13 for BMI and 6 and 13 for waist circumference in boys and girls, respectively. Odds ratios (ORs) for the metabolic syndrome at 30 years and older ranged from 1.4 to 1.9 across age groups in boys and from 0.8 to 2.8 across age groups in girls if BMI exceeded criterion values in childhood. The corresponding ORs for waist circumference ranged from 2.5 to 31.4 in boys and 1.7 to 2.5 in girls. These ORs increased with the number of examinations.
Conclusions
Children with BMI and waist circumference values exceeding the established criterion values are at increased risk for the adult metabolic syndrome.
doi:10.1016/j.jpeds.2007.07.055
PMCID: PMC3988700  PMID: 18206688
11.  The Metabolic Syndrome among Postmenopausal Women in Gorgan 
Introduction. The present study aimed to assess the metabolic syndrome among postmenopausal women in Gorgan, Iran. Materials and Methods. The study was conducted on hundred postmenopausal women who were referred to the health centers in Gorgan. Metabolic syndrome was diagnosed using Adult Treatment Panel III (ATP III) guidelines. Results. The mean body mass index, waist circumference, hip, circumference waist-to-hip ratio, diastolic blood pressure, and triglyceride and fasting blood glucose levels were significantly high among postmenopausal women with metabolic syndrome, but the mean HDL-cholesterol was significantly low (P < 0.05). Overall prevalence of metabolic syndrome was 31%. Body mass index and waist circumference had a positive correlation with a number of metabolic syndrome factors (P < 0.001). Body mass index, waist circumference, and waist-to-hip ratio had a positive correlation with each other (P < 0.001). BMI had relatively high correlation with WC (P < 0.001). Conclusions. Our results show that postmenopausal status might be a predictor of metabolic syndrome. Low HDL-cholesterol level and high abdominal obesity are the most frequent characteristics in comparison to other metabolic components. Our study also showed some related factors of metabolic syndrome among postmenopausal women. These factors may increase cardiovascular risk among postmenopausal women with metabolic syndrome.
doi:10.1155/2012/953627
PMCID: PMC3296160  PMID: 22518135
12.  Anthropometric predictors of incident type 2 diabetes mellitus in Iranian women 
Annals of Saudi Medicine  2009;29(3):194-200.
BACKGROUND AND OBJECTIVES:
Studies have shown a strong association between excess weight and risk of incident diabetes in Iranian women. Therefore, we investigated anthropometric indices in the prediction of diabetes in Iranian women.
SUBJECTS AND METHODS:
We examined 2801 females aged ≥220 years (mean [SD] age, 45.2 [12.9] years) in an Iranian urban population who were non-diabetic or had abnormal glucose tolerance at baseline. We estimated the predictive value of central obesity parameters (waist circumference [WC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR], body mass index [BMI]) in the prediction of diabetes. We classified each parameter in quartiles and compared the lowest with the highest quartile after adjusting for confounding variables, including age, hypertension, triglyceride levels, HDL-cholesterol, family history of diabetes, and abnormal glucose tolerance in a multivariate model. Receiver operator characteristic (ROC) curves were used to determine the predictive power of each variable.
RESULTS:
Over a median follow up of 3.5 years (11 months-6.3 years), 114 individuals developed diabetes (4.1%). The risk for developing diabetes was significantly higher for the highest quartile of BMI, WC, WHR and WHtR, respectively, compared to the lowest quartile, and the risk decreased but remained statistically significant when abnormal glucose tolerance was included in the multivariate model. WHtR had the highest area under the ROC curve.
CONCLUSIONS:
In Iranian women, BMI, WC, WHR, WHtR were predictive of development of type 2 diabetes, but WHtR was a better predictor than BMI.
doi:10.4103/0256-4947.51788
PMCID: PMC2813660  PMID: 19448363
13.  Predictive Ability of Childhood Metabolic Components for Adult Metabolic Syndrome and Type 2 Diabetes 
The Journal of pediatrics  2009;155(3):S6.e1-S6.e7.
Objective
To estimate sensitivity, specificity, and positive and negative predictive values of components of the metabolic syndrome (MetS) during childhood for MetS and type 2 diabetes (T2D) in adulthood.
Study design
Data from 3 major studies—the Fels Longitudinal Study, the Muscatine Study, and the Princeton Follow-up Study—were combined to examine how thresholds of metabolic components during childhood determine adult MetS and T2D. Available metabolic components examined in the 1789 subjects included high-density lipoprotein, triglyceride levels, glucose, and percentiles for body mass index, waist circumference, triglycerides, and systolic and diastolic blood pressures. Sensitivity, specificity, and positive and negative predictive values for a refined set of component threshold values were examined individually and in combination.
Results
Sensitivity and positive predictive values remained low for adult MetS and T2D for individual components. However, specificity and negative predictive values were fairly high for MetS and exceptionally so for T2D. In combination, having 1 or more of the components showed the highest sensitivity over any individual component and high negative predictive value. Overall, specificity and negative predictive values remained high whether considering individual or combined components for T2D.
Conclusions
Sensitivity and positive predictive values on the basis of childhood measures remained relatively low, but specificity and negative predictive values were consistently higher, especially for T2D. This indicates that these components, when examined during childhood, may provide a useful screening approach to identifying children not at risk so that further attention can be focused on those who may be in need of future intervention.
doi:10.1016/j.jpeds.2009.04.048
PMCID: PMC3777811  PMID: 19732565
14.  Additive Utility of Family History and Waist Circumference to Body Mass Index in Childhood for Predicting Metabolic Syndrome in Adulthood 
The Journal of pediatrics  2009;155(3):S6.e9-S6.13.
Objective
To determine whether waist circumference (WC) and family history of disease increase the predictive utility of body mass index (BMI) for adult metabolic syndrome (MetS).
Study design
A subsample of 161 men and women from the Fels Longitudinal Study with childhood and adulthood measures were analyzed. Using logistic regression, childhood BMI categories (50th, 75th, and 85th percentiles), WC categories (75th and 90th percentiles), and family history of type 2 diabetes mellitus or cardiovascular disease were modeled separately and in combinations to predict adult MetS. Predicted probabilities and c-statistics were compared across models.
Results
The addition of family history to BMI improved the predicted probability of adult MetS from 29% to 52% (Δc-statistic = 0.13). The combination of WC and BMI was more predictive than BMI alone but did not outperform the combination of family history and BMI. In 3 of the 4 models with a combination of family history, WC, and BMI, the predicted probability of adult MetS did not exceed that from the combination of family history and BMI.
Conclusions
Family history of type 2 diabetes or cardiovascular disease is a useful addition to BMI in childhood to predict the future risk of adult MetS.
doi:10.1016/j.jpeds.2009.05.024
PMCID: PMC3988675  PMID: 19732567
15.  Age at Menarche and Its Association with the Metabolic Syndrome and Its Components: Results from the KORA F4 Study 
PLoS ONE  2011;6(10):e26076.
Objective
The metabolic syndrome is a major public health challenge and identifies persons at risk for diabetes and cardiovascular disease. The aim of this study was to examine the association between age at menarche and the metabolic syndrome (IDF and NCEP ATP III classification) and its components.
Design
1536 women aged 32 to 81 years of the German population based KORA F4 study were investigated. Data was collected by standardized interviews, physical examinations, and whole blood and serum measurements.
Results
Young age at menarche was significantly associated with elevated body mass index (BMI), greater waist circumference, higher fasting glucose levels, and 2 hour glucose (oral glucose tolerance test), even after adjusting for the difference between current BMI and BMI at age 25. The significant effect on elevated triglycerides and systolic blood pressure was attenuated after adjustment for the BMI change. Age at menarche was inversely associated with the metabolic syndrome adjusting for age (p-values: <0.001 IDF, 0.003 NCEP classification) and additional potential confounders including lifestyle and reproductive history factors (p-values: 0.001, 0.005). Associations remain significant when additionally controlling for recollected BMI at age 25 (p-values: 0.008, 0.033) or the BMI change since age 25 (p-values: 0.005, 0.022).
Conclusion
Young age at menarche might play a role in the development of the metabolic syndrome. This association is only partially mediated by weight gain and increased BMI. A history of early menarche may help to identify women at risk for the metabolic syndrome.
doi:10.1371/journal.pone.0026076
PMCID: PMC3196515  PMID: 22028807
16.  Changes in Insulin Sensitivity and Insulin Release in Relation to Glycemia and Glucose Tolerance in 6,414 Finnish Men 
Diabetes  2009;58(5):1212-1221.
OBJECTIVE
We evaluated insulin sensitivity and insulin secretion across the entire range of fasting (FPG) and 2-h plasma glucose (PG), and we investigated the differences in insulin sensitivity and insulin release in different glucose tolerance categories.
RESEARCH DESIGN AND METHODS
A total of 6,414 Finnish men (aged 57 ± 7 years, BMI 27.0 ± 3.9 kg/m2) from our ongoing population-based METSIM (Metabolic Syndrome in Men) study were included. Of these subjects, 2,168 had normal glucose tolerance, 2,859 isolated impaired fasting glucose (IFG), 217 isolated impaired glucose tolerance (IGT), 701 a combination of IFG and IGT, and 469 newly diagnosed type 2 diabetes.
RESULTS
The Matsuda index of insulin sensitivity decreased substantially within the normal range of FPG (−17%) and 2-h PG (−37%) and was approximately −65 and −53% in the diabetic range of FPG and 2-h PG, respectively, compared with the reference range (FPG and 2-h PG <5.0 mmol/l). Early-phase insulin release declined by only approximately −5% within the normal range of FPG and 2-h PG but decreased significantly in the diabetic range of FPG (by 32–70%) and 2-h PG (by 33–51%). Changes in insulin sensitivity and insulin secretion in relation to hyperglycemia were independent of obesity. The predominant feature of isolated IGT was impaired peripheral insulin sensitivity. Isolated IFG was characterized by impaired early and total insulin release.
CONCLUSIONS
Peripheral insulin sensitivity was already decreased substantially at low PG levels within the normoglycemic range, whereas impairment in insulin secretion was observed mainly in the diabetic range of FPG and 2-h PG. Obesity did not affect changes in insulin sensitivity or insulin secretion in relation to hyperglycemia.
doi:10.2337/db08-1607
PMCID: PMC2671053  PMID: 19223598
17.  Should the first degree relatives of type 2 diabetic patients with isolated impaired fasting glucose be considered for a diabetes primary prevention program? 
BACKGROUND:
The aim of this study is to investigate the need for diabetes primary prevention program in isolated impaired fasting glucose (i-IFG) of the first degree relatives of type 2 diabetics.
METHODS:
In a cross sectional study, 793 individuals with prediabetes [543 with i-IFG and 250 with isolated impaired glucose tolerance (i-IGT)] who were the first degree relatives of type 2 diabetic patients, were enrolled. Isolated IFG was considered as fasting plasma glucose between 100-125 mg/dl and 2 hour plasma glucose < 140 mg/dl and isolated IGT as FPG < 100 mg/dl and 2 hour plasma glucose between 140-199 mg/dl during an overnight fasting 75 g oral glucose tolerance test. Mean of the age, weight, waist circumference, body mass index, systolic and diastolic blood pressure, plasma glucose, HbA1C, and lipid profile were compared between two groups (i-IFG and i-IGT). The prevalence of cardiometabolic risk factors (BMI ≥ 25 kg/m2, hypertension, cholesterol ≥ 200 mg/dl, LDL-C ≥ 100 mg/dl, HDL-C ≤ 40 mg/dl, and triglyceride ≥ 150 mg/dl) adjusted by age, sex and BMI were compared.
RESULTS:
The prevalence of cardiometabolic risk factors is higher in i-IFG group than i-IGT. The mean level of LDL-C is significantly higher in i-IFG than i-IGT group.
CONCLUSIONS:
First degree relatives of T2DM with isolated impaired fasting glucose should probably be included in the primary preventive program for diabetes. However, longitudinal cohort study is required to show high progression of i-IFG to T2DM.
PMCID: PMC3082819  PMID: 21526094
Prediabetic States; Diabetes Mellitus; Type II; Oral Glucose Tolerance Test; Primary Prevention; Dyslipidemia; Risk Factor; Iran
18.  Receiver-operating characteristic of adiposity for metabolic syndrome: HANDLS study 
Public health nutrition  2010;14(1):77-92.
Objective
To assess the predictive values of various adiposity indices for the metabolic syndrome (MetS) among adults using baseline data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort.
Design
In a cross-sectional study, body mass index (BMI), waist circumference (WC), body composition by dual-energy x-ray absorptiometry (DXA) and metabolic risk factors such as triglycerides, HDL-cholesterol, blood pressure, fasting glucose and insulin, uric acid and C-reactive protein were measured. Receiver-operating characteristic (ROC) curves and logistic regression analyses were conducted.
Setting
Baltimore, Maryland.
Subjects
1,981 White and African-American US adults, aged 30-64 years.
Results
In predicting risk of MetS using obesity-independent National Cholesterol Education Program Adult Treatment Panel III criteria, % body fat mass (TtFM) assessed using DXA measuring overall adiposity had no added value over WC. This was true among both men (Areas under curve; AUC=0.680 vs. 0.733 for TtFM and WC, respectively, p<0.05) and women (AUC=0.581 vs. 0.686). Rib fat mass (RbFM) was superior to TtFM only in women for MetS (AUC=0.701 and 0.581 for RbFM and TtFM, respectively, p<0.05), particularly among African-American women. Elevated Leg fat mass (LgFM) was protective against MetS among African-American men. Among White men, BMI was inferior to WC in predicting MetS. Optimal WC cut points varied across ethnic-sex groups and differed from those recommended by the NIH/NAASO.
Conclusion
We provide evidence that WC is among the most powerful tools to predict MetS, and that optimal cut-points for various indices including WC may differ by sex and race.
doi:10.1017/S1368980010002648
PMCID: PMC3017668  PMID: 20854721
Metabolic syndrome; percent body fat mass; central obesity; body mass index
19.  Predicting Adult Body Mass Index–Specific Metabolic Risk From Childhood 
Abstract
Background
Metabolic risk varies within adult body mass index (BMI) categories; however, the development of BMI-specific metabolic risk from childhood is unknown.
Methods
The sample included 895 adults (20–38 years of age; 43% male, 34% black) from the Bogalusa Heart Study (1995–2002), who had been measured as children (5–18 years of age) in 1981–1982. Adult metabolic risk was assessed using two definitions: Cardiometabolic risk factor clustering (RFC) included two or more abnormal risk factors [blood pressure, high-density lipoprotein cholesterol (HDL-C), triglycerides, and fasting glucose] and insulin resistance (IR), comprising the top quartile of the homeostasis model of insulin resistance (HOMA-IR) distribution. Logistic regression, within BMI categories, was used to predict adult metabolic risk from childhood mean arterial pressure (MAP), HDL-C, low-density lipoprotein cholesterol (LDL-C), glucose, and triglycerides. Covariates included childhood age, race, sex, adult BMI, and length of follow-up.
Results
The prevalence of the adult abnormal metabolic risk profile varied by definitions of metabolic risk (normal weight, 5%–9%; overweight, 15%–23%; and obese, 40%–53%). The adult abnormal profile was associated with higher childhood LDL-C [IR, odds ratio (OR), 1.95; 95% confidence interval (CI), 1.06–3.58) and insulin (IR, OR, 1.69; CI, 1.10–2.58) in normal-weight adults; lower childhood HDL-C in overweight adults (RFC, OR, 0.61; CI, 0.40–0.94); and higher childhood MAP (RFC, OR, 1.75; CI, 1.24–2.47) and glucose (IR, OR,1.38; CI, 1.06–1.81) in obese adults.
Conclusions
Some childhood metabolic risk factors are moderately associated with adult BMI-specific metabolic risk profiles. The ability to identify children with high future adult cardiovascular risk may initiate early treatment options.
doi:10.1089/met.2009.0063
PMCID: PMC3035100  PMID: 20156071
20.  Identifying Adolescent Metabolic Syndrome Using Body Mass Index and Waist Circumference 
Preventing Chronic Disease  2008;5(4):A115.
Introduction
Metabolic syndrome is increasing among adolescents. We examined the utility of body mass index (BMI) and waist circumference to identify metabolic syndrome in adolescent girls.
Methods
We conducted a cross-sectional analysis of 185 predominantly African American girls who were a median age of 14 years. Participants were designated as having metabolic syndrome if they met criteria for 3 of 5 variables: 1) high blood pressure, 2) low high-density lipoprotein cholesterol level, 3) high fasting blood glucose level, 4) high waist circumference, and 5) high triglyceride level. We predicted the likelihood of the presence of metabolic syndrome by using previously established cutpoints of BMI and waist circumference. We used stepwise regression analysis to determine whether anthropometric measurements significantly predicted metabolic syndrome.
Results
Of total participants, 18% met the criteria for metabolic syndrome. BMI for 118 (64%) participants was above the cutpoint. Of these participants, 25% met the criteria for metabolic syndrome, whereas only 4% of participants with a BMI below the cutpoint met the criteria for metabolic syndrome (P <.001). Girls with a BMI above the cutpoint were more likely than girls with a BMI below the cutpoint to have metabolic syndrome (P = .002). The waist circumference for 104 (56%) participants was above the cutpoint. Of these participants, 28% met the criteria for metabolic syndrome, whereas only 1% of participants with a waist circumference below the cutpoint met the criteria for metabolic syndrome (P <.001). Girls with a waist circumference above the cutpoint were more likely than girls with a waist circumference below the cutpoint to have metabolic syndrome (P = .002). Stepwise regression showed that only waist circumference significantly predicted metabolic syndrome.
Conclusion
Both anthropometric measures were useful screening tools to identify metabolic syndrome. Waist circumference was a better predictor of metabolic syndrome than was BMI in our study sample of predominantly African American female adolescents living in an urban area.
PMCID: PMC2578768  PMID: 18793503
21.  Association between insulin resistance and metabolic syndrome risk factors in Japanese 
Abstract
Aims/Introduction:  It is important to identify individuals at risk of metabolic syndrome (MetS), namely those with insulin resistance. Therefore, the aim of the present study was to find anthropometric and metabolic parameters that can better predict insulin resistance.
Subjects and Methods:  We selected 3899 individuals (2058 men and 1841 women), excluding those with fasting plasma glucose (FPG) ≥126 mg/dL, on medication for hypertension, dyslipidemia or diabetes, and those with a history of advanced macrovascular disease. Using multivariate analyses, we selected components for obesity, lipids, and blood pressure based on the strength of their association with the homeostasis model assessment of insulin resistance (HOMA‐IR).
Results:  In multiple linear regression analysis, body mass index (BMI), waist circumference (WC), triglycerides (TG), high‐density lipoprotein–cholesterol (HDL‐C), and systolic blood pressure (SBP) were selected in men and women, and the effect of BMI on HOMA‐IR outweighed that of WC. In multiple logistic regression analysis, BMI, TG, and SBP were significantly associated with HOMA‐IR ≥2.5 in both genders, but WC and HDL‐C were only selected in men. Combinations of BMI, TG, SBP, and FPG showed higher HOMA‐IR values than those of the existing MetS components, considered useful for the identification of individual with higher insulin resistance.
Conclusions:  Body mass index, TG and SBP were selected as components significantly related to insulin resistance. The selected components were fundamentally adherent to the existing MetS criteria, the only difference being the measure of obesity, in which a stronger association with insulin resistance was observed for BMI than WC. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00162.x, 2011)
doi:10.1111/j.2040-1124.2011.00162.x
PMCID: PMC4020738  PMID: 24843564
HOMA‐IR; Insulin resistance; Metabolic syndrome
22.  Obesity and the Metabolic Syndrome in Korean Adolescents 
Journal of Korean Medical Science  2007;22(3):513-517.
This study evaluated the prevalence of metabolic syndrome and investigated its association with being overweight in Korean adolescents. Data were obtained from 1,393 students between 12 and 13 yr of age in a cross-sectional survey. We defined the metabolic syndrome using criteria analogous to the Third Report of the Adult Treatment Panel (ATP III) as having at least three of the following: fasting triglycerides ≥100 mg/dL; HDL <50 mg/dL; fasting glucose ≥110 mg/dL; waist circumference >75th percentile for age and gender; and systolic blood pressure >90th percentile for age, gender, and height. Weight status was assessed using the age- and gender-specific body mass index (BMI), and a BMI ≥85th percentile was classified as overweight. Of the adolescents, 5.5% met the criteria for the metabolic syndrome, and the prevalence increased with weight status; it was 1.6% for normal weight and 22.3% in overweight (p<0.001). In multivariate logistic regression analyses among adolescents, overweight status was independently associated with the metabolic syndrome (odds ratio, 17.7; 95% confidence interval, 10.0-31.2). Since childhood metabolic syndrome and obesity likely persist into adulthood, early identification helps target interventions to improve future cardiovascular health.
doi:10.3346/jkms.2007.22.3.513
PMCID: PMC2693647  PMID: 17596663
Metabolic Syndrome; Overweight; Adolescents
23.  Insulin‐secretion capacity in normal glucose tolerance, impaired glucose tolerance, and diabetes in obese and non‐obese Japanese patients 
Abstract
Aims/Introduction:  Pronounced reduction of insulin secretion in response to a rise in glucose level has been reported in Japanese patients compared with Caucasian patients, but the mean body mass index (BMI) is also lower in Japanese patients. As BMI is a determinant of insulin secretion, we examined insulin‐secretion capacity in obese and non‐obese Japanese patients.
Materials and Methods:  Using the oral glucose tolerance test (OGTT), we estimated the insulin‐secreting capacity in obese (BMI ≥ 25) and non‐obese (BMI < 25) Japanese patients, including 1848 patients with normal glucose tolerance (NGT), 321 patients with impaired glucose tolerance (IGT) and 69 diabetes (DM) patients.
Results:  The insulinogenic index (I.I.), calculated by dividing the increment in serum insulin by the increment in plasma glucose from 0 to 30 min during OGTT, decreased from NGT to IGT and to DM in patients with and without obesity. In patients with NGT, IGT and DM, the I.I. values of obese patients were higher than those of the non‐obese patients. The peak of insulin concentration in OGTT appeared at 60 min in NGT and at 120 min in IGT in both obese and non‐obese patients, but in DM it was observed at 120 min in obese patients and at 60 min in non‐obese patients.
Conclusions:  These results show that early‐phase insulin secretion in obese Japanese patients is higher than in non‐obese patients in all stages of glucose tolerance, and delayed insulin‐secretion capacity is also conserved in obese Japanese patients, even in IGT and DM, which is similar to Caucasian patients. (J Diabetes Invest, doi:10.1111/j.2040‐1124.2011.00180.x, 2011)
doi:10.1111/j.2040-1124.2011.00180.x
PMCID: PMC4014949  PMID: 24843576
Insulin secretion; Non‐obese Japanese; Obese Japanese
24.  Effects of exercise intervention on vascular endothelium functions of patients with impaired glucose tolerance during prediabetes mellitus 
Endothelial dysfunction (ED) is an early pathophysiological change in patients with impaired glucose tolerance (IGT) during prediabetes mellitus. This study was designed to test the hypothesis that exercise intervention contributes to the reversal of vascular endothelium-dependent dysfunction in middle-aged patients with IGT. Following exercise intervention, significant changes in endothelin (ET)-1, C-type natriuretic peptide (CNP), ΔDia-P, oral glucose tolerance test (OGTT)2h, fasting insulin, homeostasis model of assessment-insulin resistance (HOMA-IR), body fat percentage, waist circumference and waist to hip ratio were measured. However, no marked changes in carotid artery intima-media thickness (IMT), fasting blood glucose and BMI were observed following exercise intervention. Validity analysis of index changes in the two exercise intervention groups further confirmed there was no change. Exercise intervention increased CNP levels, decreased ET-1 levels and increased ΔDia-P, indicating improved vascular endothelium function. Decreased HOMA-IR following exercise suggests enhanced insulin sensitivity. Exercise intervention also improved glucose metabolism via decreased OGTT2h and fasting insulin. In addition, decreased waist circumference, ratio of waist to hip and body fat percentage following exercise intervention improved changes of body composition, including BMI, body fat and waist circumference. These results indicate that exercise intervention may reverse vascular endothelium-dependent dysfunction in middle-aged patients with IGT. This study also provided direct clinical data supporting the use of exercise intervention to prevent diabetes mellitus (DM) during the early stage.
doi:10.3892/etm.2013.1064
PMCID: PMC3702621  PMID: 23837031
exercise intervention; impaired glucose tolerance; diabetes mellitus
25.  Prediction of metabolic syndrome in women with polycystic ovary syndrome 
Objective
To identify biochemical factors that serve as predictors for the metabolic syndrome (MetS) in patients with polycystic ovary syndrome (PCOS) and to investigate the value of adipocytokines in the prediction of metabolic syndrome.
Material and Methods
A total of 91 pre-menopausal women with PCOS diagnosed according to the Rotterdam consensus criteria were recruited as study subjects. Waist circumference, blood pressure, body mass index (BMI), fasting glucose, serum lipids, insulin, FSH, LH, E2, total testosteron, homeostatic model assessment–insulin resistance (HOMA-IR), serum leptin and adiponectin levels were evaluated for all patients.
Results
Of the 91 women with PCOS, 15 patients met the criteria for MetS. Body weight, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, and VLDL concentrations were significantly higher and HDL was significantly lower in women with PCOS+MetS compared with those with PCOS only. However, the level of LDL, FSH, LH, E2 and total testesterone was not significantly different between these two groups. Women with PCOS+MetS had significantly higher levels of leptin and HOMA-IR, and significantly lower levels of adiponectin compared to the women with PCOS only. In the multiple logistic regression model, the association between HOMA-IR and leptin, and MetS remained statistically significant (p=0.001 and 0.018), while the association between adiponectin and MetS was no longer statistically significant.
Conclusion
Aside from the biochemical markers such as glucose, cholesterol and triglyceride, adipose tissue factors and insulin resistance are valuable parameters in the prediction of MetS in patients with PCOS.
doi:10.5152/jtgga.2012.24
PMCID: PMC3939237  PMID: 24592034
Metabolic syndrome; polycystic ovary syndrome; leptin; adiponectin; HOMA-IR

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