Phenotypic and metabolic dichotomy in obesity: clinical, biochemical and immunological correlates of metabolically divergent obese phenotypes in healthy South Asian adults

<p><b>INTRODUCTION</b>Metabolic heterogeneity among obese individuals is thought to translate into variations in cardiovascular risk. Identifying obese people with an unfavourable metabolic profile may allow preventive strategies to be targeted at high-risk groups. This study aimed to identify clinical, biochemical and immunological differences between insulin-sensitive and insulin-resistant obese subgroups, to understand the population-specific pathophysiological basis of the adverse cardiovascular risk profile in the latter group.</p><p><b>METHODS</b>Cardiovascular risk indicators, including anthropometric parameters, blood pressure, acanthosis nigricans area, and related biochemical, endocrine and inflammatory markers, were determined in 255 healthy South Asian volunteers aged 18-45 years, with a 2:1 ratio of obese/overweight to normal-weight individuals. Lifetime atherosclerotic cardiovascular disease (ASCVD) risk was also calculated.</p><p><b>RESULTS</b>Body mass index (BMI) and insulin sensitivity-based tertiles independently showed incremental trends in waist-hip ratio, skinfold thickness, acanthosis nigricans area, blood pressure, serum lipids, hepatic enzymes, adipokines, inflammatory markers and ten-year ASCVD risk. The anthropometric, biochemical and inflammatory parameters of obese insulin-sensitive and obese insulin-resistant groups differed significantly. Extreme group analysis after excluding the middle tertiles of both insulin resistance and BMI also showed significant difference in anthropometric indicators of cardiovascular risk and estimated lifetime ASCVD risk between the two obese subgroups.</p><p><b>CONCLUSION</b>Obese insulin-sensitive individuals had a favourable metabolic profile compared to the obese insulin-resistant group. The most consistent discriminative factor between these phenotypic classes was anthropometric parameters, which underscores the importance of clinical parameters as cardiovascular risk indicators in obesity.</p>

Slowing the diabetes epidemic in the World Health Organization South-East Asia Region: the role of diet and physical activity.

The nutrition transition occurring in the World Health Organization South-East Asia Region, as a result of rapid urbanization and economic development, has perhaps made this region one of the epicentres of the diabetes epidemic. This review attempts to evaluate the role of diet and physical inactivity in the South-East Asia Region in promoting this epidemic and points to strategies to slow it down by lifestyle modification. The emerging new food-production technologies and supermarkets have made energy-dense foods more easily available. This includes refined carbohydrate foods like those with added sugars, and refined grains and unhealthy fats. In addition, increased availability of modern technology and motorized transport has led to decreased physical activity. South Asian diets tend to be based on high-carbohydrate foods, with a predominance of refined grains. All of these accentuate the risk of diabetes in people of this region, who already have a unique “south Asian phenotype”. However, there is increasing evidence that altering diet by replacing refined cereals like white rice with whole grains (e.g. brown rice) and increasing physical activity can help to prevent diabetes in highrisk individuals. An urgent, concerted effort is now needed to improve diet quality and encourage physical activity, by introducing changes in policies related to food and built environments, and improving health systems to tackle noncommunicable diseases like diabetes.

Appropriate anthropometric indices to identify cardiometabolic risk in South Asians.

Background: South Asians show an elevated cardiometabolic risk compared to Caucasians. They are clinically metabolically obese but are considered normal weight based on current international cut-off levels of several anthropometric indices. This study has two main objectives: (i) to predict the most sensitive anthropometric measures for commonly studied cardiometabolic risk factors, and (ii) to determine optimal cut-off levels of each of the anthropometric indices in relation to these cardiometabolic risk factors in South Asians. Methods: The study was conducted on a random sample of 1178 adults of 20–80 years of age from an urban population of eastern India. Obesity, as evaluated by standard anthropometric indices of BMI (body mass index), WC (waist circumference), WHpR (waist-to-hip ratio) and WHtR (waist-to-height ratio), was individually correlated with cardiometabolic risk factors. Receiver operating characteristic (ROC) curve analyses were performed which includes: (i) the area under the receiver operating characteristic curve (AUROC) analysis to assess the predictive validity of each cardiometabolic risk factor; and (ii) Youden index to determine optimal cut-off levels of each of the anthropometric indices. Results: Overall, AUROC values for WHtR were the highest, but showed variations within the sexes for each of the cardiometabolic risk factors studied. Further, WHpR cut-offs were higher for men (0.93–0.95) than women (0.85–0.88). WC cut-offs were 84.5–89.5 cm in men and 77.5–82.0 cm in women. For both sexes the optimal WHtR cut-off value was 0.51–0.55. The optimal BMI cut-offs were 23.4–24.2 kg/m2 in men and 23.6–25.3 kg/m2 in women. Conclusion: WHtR may be a better anthropometric marker of cardiometabolic risks in South Asian adults than BMI, WC or WHpR.

Prevalence of metabolic syndrome in a north Indian hospital-based population with obstructive sleep apnoea.

Background & objectives: Obstructive sleep apnoea (OSA) is known to be associated with cardiovascular risk factors and metabolic syndrome (MS). The burden of MS in patients with OSA in India is unknown. We investigated the prevalence of MS and its components in a cross-sectional study in patients with and without OSA in a hospital-based population of a tertiary health care centre in New Delhi, India. Methods: Consecutive patients undergoing overnight polysomnography in the Sleep Laboratory of the Department of Internal Medicine of All India Institute of Medical Sciences (AIIMS) hospital, New Delhi, were studied. Anthropometry and body composition analysis, blood pressure (BP), fasting blood glucose, insulin resistance by homeostasis model assessment (HOMA-IR) and fasting blood lipid profile were measured. MS was defined using the National Cholesterol Education Program Adult treatment panel III criteria, with Asian cut-off values for abdominal obesity. Results: Of the 272 subjects recruited, 187 (82%) had OSA [apnoea-hypopnoea index (AHI)>5 events/h] while 40 (18%) had a normal sleep study. Prevalence of MS in OSA patients was 79 per cent compared to 48 per cent in non-OSA individuals [OR 4.15, (2.05-8.56), P<0.001]. Prevalence of OSA in mild, moderate and severe OSA was 66, 72 and 86 per cent, respectively (P<0.001). Patients with OSA were more likely to have higher BP [OR: 1.06 (1.02-1.11)], fasting insulin [OR: 1.18 (1.05-1.32)], HOMA-IR [OR: 1.61 (1.11-2.33)] and waist circumference [OR: 1.20 (1.13-1.27)]. Interpretation & conclusions: Our findings suggest that OSA is associated with a 4-fold higher occurrence of MS than patients without OSA. The prevalence of MS increases with increasing severity of OSA, therefore, early detection will be beneficial.

Screening with OGTT alone or in combination with the Indian diabetes risk score or genotyping of TCF7L2 to detect undiagnosed type 2 diabetes in Asian Indians.

Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 ( 201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population.

Association of hypoadiponectinemia with non-alcoholic fatty liver disease in urban south Indians - (CURES - 81).

Background & objective: Association between adiponectin and non-alcoholic fatty liver disease (NAFLD) has been reported in west. Studies in Indian population are lacking. This study was undertaken to assess the association of hypoadiponectinemia with NAFLD in Asian Indians. Method: In this cross-sectional study, subjects were randomly selected from Phase 5 of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study based on a representative population of Chennai in south India. One hundred twenty one subjects without NAFLD and 72 subjects with NAFLD were selected. NAFLD was diagnosed by ultrasonography. Serum adiponectin levels were measured using radioimmunoassay. Insulin resistance was calculated using Homeostasis Assessment model (HOMA-IR). Results: Serum adiponectin values were significantly lower in subjects with NAFLD compared to those without [5.6 μg/ml (95% Confidence Interval (CI) 5.0 - 6.3 μg/ml] vs 7.4 μg/ml (95% CI: 6.7 - 8.1 μg/ml, P<0.01). Adiponectin levels decreased with increasing severity of NAFLD. Subjects with moderate to severe steatosis had significantly lower adiponectin levels (5.1μg/ml, 95% CI: 4.1- 6.4 μg/ml) compared to subjects with mild steatosis (5.9 μg/ml, 95% CI: 5.0 - 6.9 μg/ml; P<0.001) and subjects without NAFLD (7.3 μg/ml, 95% CI: 6.6 - 8.0 μg/ml; P<0.01). Multiple logistic regression analysis revealed adiponectin to be negatively associated with NAFLD [Odds Ratio (OR): 0.865, 95% Confidence Interval (CI): 0.792- 0.944, P=0.001]. This remained statistically significant even after adjusting for confounding factors age, gender, body mass index, insulin resistance, waist circumference, total cholesterol, triglycerides and glucose intolerance (OR: 0.873, 95% CI: 0.793 - 0.961; P=0.005). Interpretation & conclusion: NAFLD is associated with lower serum adiponectin levels independent of conventional cardiovascular risk factors in Asian Indians known to have high prevalence of diabetes and coronary artery disease.

Are metabolic syndrome, obstructive sleep apnoea & syndrome Z sequential? - A hypothesis.

Background & objectives: The metabolic syndrome (MS) is a risk factor for development of cardiovascular disease and is closely associated with obstructive sleep apnoea (OSA). Co-occurrence of both OSA and MS is called syndrome Z. It has been hypothesized that the OSA may be a manifestation of MS. We collected data on polysomnography (PSG) and biochemical investigations on middle aged urban Indians during a community based study in South Delhi while studying prevalence of obstructive sleep apnoea and analysed to find out the ages at which the OSA, MS and syndrome Z exist in these subjects. Methods: A 2-stage, cross-sectional, population-based study in subjects of either gender between 30-65 yr of age in 4 different socio-economic zones of the South Delhi, India, was performed earlier (from April 2005 through June 2007). In-hospital, supervised PSG studies were performed and biochemical investigations for the MS using National Cholesterol Education Programmme Adult Treatment Panel (NCEP ATP) III criteria were carried out. In this communication, the data were further analysed to estimate the prevalences of MS alone, OSA alone and syndrome Z and average ages of 3 conditions. Results: Three hundred and fifty one subjects had satisfactory PSG studies. The MS alone was present in 105 [29.9%; (95% CI 25.1-34.7)] while OSA alone was present in 24 [6.8%; (95% CI 4.2-9.5)] subjects and the syndrome Z was present in 70 [19.9%; (95% CI 15.8-24.1)] subjects. Median ages of normal subjects, and subjects with MS, OSA and syndrome Z were 40, 43, 43 and 47 yr respectively. Minimum ages of normal subjects, and subjects with MS, OSA and syndrome Z were 30, 30, 32 and 32 yr respectively. Interpretation & conclusions: When body mass index (BMI) was normal, the increasing median ages of these conditions indicated that the MS may be the first event followed by OSA and eventually syndrome Z develops. With BMI >25 or >30 no clear-cut difference was noted, indicating that the BMI itself could have an independent role in MS, OSA and syndrome Z.

Can novel Apo A-I polymorphisms be responsible for low HDL in South Asian immigrants.

Coronary artery disease (CAD) is the leading cause of death in the world. Even though its rates have decreased worldwide over the past 30 years, event rates are still high in South Asians. South Asians are known to have low high-density lipoprotein (HDL) levels. The objective of this study was to identify Apolipoprotein A-I (Apo A-I) polymorphisms, the main protein component of HDL and explore its association with low HDL levels in South Asians. A pilot study on 30 South Asians was conducted and 12-h fasting samples for C-reactive protein, total cholesterol, HDL, low-density lipoprotein (LDL), triglycerides, Lipoprotein (a), Insulin, glucose levels, DNA extraction, and sequencing of Apo A-I gene were done. DNA sequencing revealed six novel Apo A-I single nucleotide polymorphisms (SNPs) in South Asians, one of which (rs 35293760, C938T) was significantly associated with low (<40 mg/dl) HDL levels (P = 0.004). The association was also seen with total cholesterol (P = 0.026) and LDL levels (P = 0.032). This pilot work has highlighted some of the gene-environment associations that could be responsible for low HDL and may be excess CAD in South Asians. Further larger studies are required to explore and uncover these associations that could be responsible for excess CAD risk in South Asians.