To test the validity of internationally accepted waist circumference (WC) action levels for adult Asian Indians.
Analysis of data from multisite cross-sectional epidemiological studies in north ...India.
In all, 2050 adult subjects >18 years of age (883 male and 1167 female subjects).
Body mass index (BMI), WC, waist-to-hip circumference ratio, blood pressure, and fasting samples for blood glucose, total cholesterol, serum triglycerides, and high-density lipoprotein cholesterol.
In male subjects, a WC cutoff point of 78 cm (sensitivity 74.3%, specificity 68.0%), and in female subjects, a cutoff point of 72 cm (sensitivity 68.7%, specificity 71.8%) were appropriate in identifying those with at least one cardiovascular risk factor and for identifying those with a BMI >21 kg/m(2). WC levels of > or =90 and > or =80 cm for men and women, respectively, identified high odds ratio for cardiovascular risk factor(s) and BMI level of > or =25 kg/m(2). The current internationally accepted WC cutoff points (102 cm in men and 88 cm in women) showed lower sensitivity and lower correct classification as compared to the WC cutoff points generated in the present study.
We propose the following WC action levels for adult Asian Indians: action level 1: men, > or =78 cm, women, >/=72 cm; and action level 2: men, > or =90 cm, women, > or =80 cm.
Asian Indians exhibit unique features of obesity; excess body fat, abdominal adiposity, increased subcutaneous and intra-abdominal fat, and deposition of fat in ectopic sites (liver, muscle, etc.). ...Obesity is a major driver for the widely prevalent metabolic syndrome and type 2 diabetes mellitus (T2DM) in Asian Indians in India and those residing in other countries. Based on percentage body fat and morbidity data, limits of normal BMI are narrower and lower in Asian Indians than in white Caucasians. In this consensus statement, we present revised guidelines for diagnosis of obesity, abdominal obesity, the metabolic syndrome, physical activity, and drug therapy and bariatric surgery for obesity in Asian Indians after consultations with experts from various regions of India belonging to the following medical disciplines; internal medicine, metabolic diseases, endocrinology, nutrition, cardiology, exercise physiology, sports medicine and bariatric surgery, and representing reputed medical institutions, hospitals, government funded research institutions, and policy making bodies. It is estimated that by application of these guidelines, additional 10-15% of Indian population would be labeled as overweight/obese and would require appropriate management. Application of these guidelines on countrywide basis is also likely to have a deceleration effect on the escalating problem of T2DM and cardiovascular disease. These guidelines could be revised in future as appropriate, after another large and countrywide consensus process. Till that time, these should be used by clinicians, researchers and policymakers dealing with obesity and related diseases.
Determination of cutoff points of waist circumference is of paramount importance for prevention, optimum management, and prognostication of obesity, the metabolic syndrome, type 2 diabetes mellitus, ...and coronary heart disease. Heterogeneity of composition of abdominal tissues, in particular adipose tissue and skeletal muscle, and their location-specific and changing relations with metabolic factors and cardiovascular risk factors in different ethnic groups do not allow a simple definition of abdominal obesity that could be applied uniformly. In particular, Asians appear to have higher morbidity at lower cutoff points for waist circumference than do white Caucasians. International health agencies that deal with obesity (World Health Organization, International Obesity Task Force) should take cognizance of these data and consider formulating new cutoff points for waist circumference to define abdominal obesity for Asian populations.
Insulin resistance is associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). These abnormalities have been aggravated because of imbalanced and excess nutrition in ...developed countries, and rapid nutritional and lifestyle transition occurring in developing countries. This review presents evidence linking dietary nutrients with insulin resistance and its metabolic correlates, and also describes these issues from a Asian Indians and South Asian perspective. Despite possible influences from genetic and perinatal factors, diet and physical activity are likely to have greater and often overriding influence in pathogenesis of the insulin resistance, the metabolic syndrome, and T2DM. In animal studies, a link has been established between dietary nutrients and insulin resistance. However, in human studies evidence is not as strong as in animals. Data suggest that dietary omega-3 polyunsaturated fatty acids (PUFAs) improve lipid profile and may have beneficial effect on insulin resistance. Dietary saturated fatty acids intake is positively associated with insulin resistance. Also, low glycaemic index foods and whole grain intake decrease insulin resistance. Importantly, high carbohydrate diets increase plasma triglycerides, cause hyperinsulinaemia and decreases low-density lipoprotein cholesterol. Among micronutrients, high magnesium and calcium intake have been reported to decrease insulin resistance. High intake of dietary carbohydrate and omega-6 PUFAs, low intake of omega-3 PUFAs and fiber, and high omega -6/omega-3 PUFAs ratio have been reported in South Asians. Our recent investigations have shown that increased dietary omega-6 PUFAs and saturated fat intake are significantly associated with fasting hyperinsulinaemia and sub-clinical inflammation, respectively. Such imbalanced diets contribute to high prevalence of insulin resistance, the metabolic syndrome and T2DM in South Asians and Asian Indians.
Asian Indians have a high prevalence of insulin resistance and the metabolic syndrome. Currently, non-alcoholic fatty liver disease (NAFLD) is considered to be an integral part of the metabolic ...syndrome with insulin resistance as a central pathogenic factor. We studied anthropometric parameters, insulin resistance and metabolic co-variates in subjects with NAFLD as compared to those without NAFLD, and also developed a prediction score for NAFLD.
Thirty nine subjects with NAFLD and 82 controls were selected for the study after ultrasonography of 121 consecutive apparently healthy subjects. Anthropometric profile body mass index (BMI), waist circumference (WC) etc,, lipid profile, hepatic aminotransferases, fasting blood glucose (FBG), insulin were recorded and value of homeostasis model assessment of insulin resistance (HOMA-IR) was analysed. Step-wise logistic regression analysis and area under the receiver operator curve (aROC) were analysed to arrive at a prediction score.
Overall, prevalence of NAFLD was 32.2 per cent and prevalence of metabolic syndrome was seen in 41 per cent among cases and 19.5 per cent in controls (P<0.01). Subjects with NAFLD had significantly higher values of BMI, WC, hip circumference, FBG, fasting insulin, total cholesterol and serum triglycerides. Step-wise logistic regression analysis showed odds ratio (OR) and 95 per cent confidence interval (CI) for BMI 4.3 (1.6, 11.3), FBG 5.5 (1.5, 19.8) and fasting insulin 2.4 (1.0, 5.8) as independent predictors of NAFLD. The prediction score for NAFLD was; 1 (fasting insulin) +1.6 (BMI) + 1.9 (FBG) (sensitivity of 84.6%, specificity of 51.2% and aROC 76%).
In this study, presence of NAFLD indicated close relationship with multiple features of metabolic syndrome. The prediction score developed could be used as a screening tool to predict NAFLD among Asian Indians in north India.
OBJECTIVE:S--We aimed to evaluate eight candidate definitions of the metabolic syndrome (MS) against the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) definition as ...the reference for optimally defining MS in adult Asian Indians. RESEARCH DESIGN AND METHODS--We used clinical and biochemical data from our previous cross-sectional epidemiological studies. Candidate definitions of MS were proposed by modifying the NCEP ATPIII definition. These modifications included the following: waist circumference cutoffs as >90 cm in men and >80 cm in women, BMI cutoff as >23 kg/m², and a measure of truncal subcutaneous fat (subscapular skinfold thickness SST >18 mm). RESULTS:--The highest prevalence (29.9%) of MS was observed by the inclusion of modified cutoffs of waist circumference and BMI and SST in place of the existing cutoffs of waist circumference in the NCEP ATPIII criteria. Further, this modified definition showed the maximum absolute gain in the percentage of prevalence of MS over the NCEP ATPIII definition, and it was the best predictor for MS in subjects with impaired fasting glucose, type 2 diabetes, and different age-groups. The lowest percentage of prevalence of MS was observed with the definition that excluded biochemical variables and blood pressure. CONCLUSIONS:--The criteria for defining MS in adult Asian Indians need revision. Inclusion of modified cutoffs of waist circumference and BMI and measures of truncal subcutaneous fat in the NCEP ATPIII definition requires further validation.
The optimum definition of the metabolic syndrome (MS) is not known. We compared international definitions of MS recently proposed modified definition of National Cholesterol Education Programme, ...Adult Treatment Panel III (NCEP, ATP III) and International Diabetes Federation (IDF) with two proposed candidate definitions in adult Asian Indians.
Data from three previous cross-sectional studies carried out in North India were analyzed.
The study included 2050 adult (mean age: 40 +/- 18 years) Asian Indian subjects residing two metropolitan cities.
Candidate definitions of MS were proposed by modifying the NCEP, ATP III and IDF definitions by including the following modified variables into two combinations (MS-ATP1 and MS-IDF1); waist circumference cut-off points as >90 cm in males and >80 cm in females, body mass index (BMI) cut-off point as >23 kg/m2, impaired fasting glucose (IFG) cut-off point >100 mg/dl and waist circumference as an obligatory criterion.
Maximum overall and gender-specific prevalence of the MS (49.2% overall; 41.4% in males; 55.3% in females) was observed using the definition which included modified cut-off points of WC (non-obligatory), BMI, and IFG (>100 mg/dl) in addition to other defining parameters. Compared to other definitions this proposed candidate definition maximally detected presence of MS in subjects with IFG and T2DM Percentage prevalence: 78.1% (73.0-82.7) and 91.1% (84.2-95.6). Even in subjects without abdominal obesity, a high prevalence of other abnormal defining parameters of the metabolic syndrome; hypertension (> or = 130 or > or = 85 mmHg), 35.7%; BMI >23 kg/m2, 15.3%; hypertriglyceridemia (>150 mg/dl), 20.2% and low levels of HDL-C (<40 in males; <50 mg/dl in females), 55% were seen. Further, 10.5% of subjects who did not have abdominal obesity had presence of at least 3 risk variables of the metabolic syndrome. These data indicate that by making abdominal obesity a mandatory criterion would lead to missing of some cases of the metabolic syndrome.
By including BMI and making waist circumference as a non-obligatory criterion, more cases of the metabolic syndrome is detected. For Asian Indians, making waist circumference as mandatory variable in the definition of the metabolic syndrome would lead to non-inclusion of nearly 11% cases who would otherwise be diagnosed as metabolic syndrome according to modified NCEP, ATP III definition.
To assess the phenotypic correlations of insulin resistance with obesity and its relationship with the metabolic syndrome in Asian Indian adolescents.
We analyzed clinical, anthropometric (body mass ...index BMI, waist circumference WC) and laboratory (fasting blood glucose FBG, lipids and fasting serum insulin) data from 793 subjects (401 males and 392 females) aged 14–19 years randomly selected from Epidemiological Study of Adolescents and Young (ESAY) adults (
n
=
1447). The percentile cut-offs for 14–19 years age from ESAY cohort were used for defining abnormal values of variables. We devised three sets of definitions of metabolic syndrome by including BMI and fasting insulin levels with other defining variables.
Nearly 28.9% of adolescents had fasting hyperinsulinemia despite normal values of BMI, WC, FBG, lipids, and blood pressure. Remarkably, NCEP criteria with appropriate percentile cut-off points for Asian Indian adolescents identified metabolic syndrome in only six (0.8%) subjects. Inclusion of both BMI and WC in the definition resulted in increase in the prevalence of metabolic syndrome to 4.3%. With inclusion of hyperinsulinemia, the prevalence of metabolic syndrome increased to 4.2% (from 0.8%) in the modified NCEP definition, 5.2% (from 0.9%) when BMI was substituted for WC, and 10.2 (from 4.3%) when both BMI and WC were included.
Our data show marked heterogeneity of phenotypes of insulin resistance and poor value of NCEP definition to identify metabolic syndrome. We propose that BMI and fasting insulin should be evaluated in candidate definitions of metabolic syndrome in Asian Indian adolescents.
Aims/hypothesis
Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of ...dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Methods
Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (
n
= 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes.
Results
Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of −3.5% (95% CI −6.6, −0.4;
p
= 0.025) and relative change of −26.4% (−44.2, −8.6;
p
= 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference −13.1 U/l 95% CI −24.4, −1.8;
p
= 0.025) and non-significant reductions in aspartate aminotransferase (AST) (−9.3 U/l −19.5, 1.0;
p
= 0.075) and alanine aminotransferase (ALT) levels (−13.1 U/l −24.4, 2.5;
p
= 0.10). Absolute changes in PFC (−1.4% −3.2, 0.3;
p
= 0.106) and LSM (−1.31 kPa −2.99, 0.37;
p
= 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events.
Conclusions/interpretation
When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes.
Trial registration
ClinicalTrials.gov
NCT03590626
Funding
The current study was supported by an investigator-initiated study grant from Medanta–The Medicity’s departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India.
Graphical abstract
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