Efficacy of a virtual assistance-based lifestyle intervention in reducing risk factors for Type 2 diabetes in young employees in the information technology industry in India: LIMIT, a randomized controlled trial.

AIMS: To investigate a virtual assistance-based lifestyle intervention to reduce risk factors for Type 2 diabetes in young employees in the information technology industry in India. METHODS: LIMIT (Lifestyle Modification in Information Technology) was a parallel-group, partially blinded, randomized controlled trial. Employees in the information technology industry with ≥3 risk factors (family history of cardiometabolic disease, overweight/obesity, high blood pressure, impaired fasting glucose, hypertriglyceridaemia, high LDL cholesterol and low HDL cholesterol) from two industries were randomized to a control or an intervention (1:1) group. After initial lifestyle advice, the intervention group additionally received reinforcement through mobile phone messages (three per week) and e-mails (two per week) for 1 year. The primary outcome was change in prevalence of overweight/obesity, analysed by intention to treat. RESULTS: Of 437 employees screened (mean age 36.2 ± 9.3 years; 74.8% men), 265 (61.0%) were eligible and randomized into control (n=132) or intervention (n=133) group. After 1 year, the prevalence of overweight/obesity reduced by 6.0% in the intervention group and increased by 6.8% in the control group (risk difference 11.2%; 95% CI 1.2-21.1; P=0.042). There were also significant improvements in lifestyle measurements, waist circumference, and total and LDL cholesterol in the intervention group. The number-needed-to-treat to prevent one case of overweight/obesity in 1 year was 9 (95% CI 5-82), with an incremental cost of INR10665 (£112.30) per case treated/prevented. A total of 98% of participants found the intervention acceptable. CONCLUSIONS: A virtual assistance-based lifestyle intervention was effective, cost-effective and acceptable in reducing risk factors for diabetes in young employees in the information technology industry, and is potentially scalable.

Body size and body composition: a comparison of children in India and the UK through infancy and early childhood.

BACKGROUND: Indian babies are characterised by the 'thin-fat phenotype' which comprises a 'muscle-thin but adipose' body composition compared with European babies. This body phenotype is of concern because it is associated with an increased risk of diabetes and cardiovascular disease. We examined whether the 'thin-fat phenotype' persists through early childhood, comparing Indian children with white Caucasians in the UK at birth, infancy and childhood, using comparable measurement protocols. METHODS: We used data from two cohorts, the Pune Maternal Nutrition Study (N=631) and the Southampton Women's Survey (N=2643). Measurements of weight, head circumference, mid-upper arm circumference, height, triceps and subscapular skinfold thickness were compared at birth, 1, 2, 3 and 6 years of age. SD scores were generated for the Pune children, using the Southampton children as a reference. Generalised estimating equations were used to examine the changes in SD scores across the children's ages. RESULTS: The Indian children were smaller at birth in all body measurements than the Southampton children and became relatively even smaller from birth to 2 years, before 'catching up' to some extent at 3 years, and more so by 6 years. The deficit for both skinfolds was markedly less than for other measurements at all ages; triceps skinfold showed the least difference between the two cohorts at birth, and subscapular skinfold at all ages after birth. CONCLUSIONS: The 'thin-fat phenotype' previously found in Indian newborns, remains through infancy and early childhood. Despite being shorter and lighter than UK children, Indian children are relatively adipose.

Differences in body composition and metabolic status between white U.K. and Asian Indian children (EarlyBird 24 and the Pune Maternal Nutrition Study).

BACKGROUND/AIMS: The concept of the 'thin-fat' Indian baby is well established, but there is little comparative data in older children, and none that examines the metabolic correlates. Accordingly, we investigated the impact of body composition on the metabolic profiles of Asian Indian and white U.K. children. METHODS: Body mass index (BMI), waist circumference, sum of four skin-folds, % body fat (by dual-energy X-ray absorptiometry), glucose, insulin, insulin resistance (Homeostasis Model Assessment), trigylcerides, cholesterol [total, low-density lipoprotein, high-density lipoprotein {HDL}, total/HDL ratio] and blood pressure (systolic, diastolic and mean arterial) were measured in 262 white Caucasian children from Plymouth, U.K. (aged 6.9 ± 0.2 years, 57% male), and 626 Indian children from rural villages around Pune, India (aged 6.2 ± 0.1 years, 53% male). RESULTS: Indian children had a significantly lower BMI (boys: -2.1 kg m(-2) , girls: -3.2 kg m(-2) , both P < 0.001), waist circumference (P < 0.001) and skin-fold thickness (P < 0.001) than white U.K. children, yet their % body fat was higher (boys +4.5%, P < 0.001, girls: +0.5%, P = 0.61). Independently of the differences in age and % body fat, the Indian children had higher fasting glucose (boys +0.52 mmol L(-1) , girls +0.39 mmol L(-1) , both P < 0.001), higher insulin (boys +1.69, girls +1.87 mU L(-1) , both P < 0.01) and were more insulin resistant (boys +0.25, girls +0.28 HOMA-IR units, both P < 0.001). CONCLUSIONS: The 'thin-fat' phenotype observed in Indian babies is also apparent in pre-pubertal Indian children who have greater adiposity than white U.K. children despite significantly lower BMIs. Indian children are more insulin resistant than white U.K. children, even after adjustment for adiposity.

Analysis of 32 common susceptibility genetic variants and their combined effect in predicting risk of Type 2 diabetes and related traits in Indians.

AIMS: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians. METHODS: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis. RESULTS: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 × 10(-17)) and individuals with extremes of genetic risk score (≥ 29.0 and ≤ 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 × 10(-4)), fat mass per cent (P = 2.4 × 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 × 10(-3) for both), as well as insulin resistance (P =0.02). CONCLUSIONS: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Effect of physiological doses of oral vitamin B12 on plasma homocysteine: a randomized, placebo-controlled, double-blind trial in India.

BACKGROUND/OBJECTIVES: Vitamin B(12) (B(12)) deficiency is common in Indians and a major contributor to hyperhomocysteinemia, which may influence fetal growth, risk of type II diabetes and cardiovascular disease. The purpose of this paper was to study the effect of physiological doses of B(12) and folic acid on plasma total homocysteine (tHcy) concentration. SUBJECTS/METHODS: A cluster randomized, placebo-controlled, double-blind, 2 x 3 factorial trial, using the family as the randomization unit. B(12) was given as 2 or 10 microg capsules, with or without 200 microg folic acid, forming six groups (B(0)F(0), B(2)F(0), B(10)F(0), B(0)F(200), B(2)F(200) and B(10)F(200)). Plasma tHcy concentration was measured before and after 4 and 12 months of supplementation. RESULTS: From 119 families in the Pune Maternal Nutrition Study, 300 individuals were randomized. There was no interaction between B(12) and folic acid (P=0.14) in relation to tHcy concentration change and their effects were analyzed separately: B(0) vs. B(2) vs. B(10); and F(0) vs. F(200). At 12 months, tHcy concentration reduced by a mean 5.9 (95% CI: -7.8, -4.1) micromol/l in B(2), and by 7.1 (95% CI: -8.9, -5.4) micromol/l in B(10), compared to nonsignificant rise of 1.2 (95% CI: -0.5, 2.9) micromol/l in B(0). B(2) and B(10) did not differ significantly. In F(200), tHcy concentration decreased by 4.8 (95% CI: -6.3, -3.3) micromol/l compared to 2.8 (95% CI: -4.3, -1.2) micromol/l in F(0). CONCLUSION: Daily oral supplementation with physiological doses of B(12) is an effective community intervention to reduce tHcy. Folic acid (200 microg per day) showed no additional benefit, neither had any unfavorable effects.

Adiposity, inflammation and hyperglycaemia in rural and urban Indian men: Coronary Risk of Insulin Sensitivity in Indian Subjects (CRISIS) Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether the higher prevalence of insulin resistance and glucose intolerance in urban compared with rural Indian men is related to their higher adiposity (percentage body fat) and the associated inflammatory state. METHODS: We studied 149 rural, 142 urban slum and 150 urban middle-class male residents (age 30-50 years), who were selected by stratified random sampling. We measured body fat (bioimpedance), waist circumference, glucose tolerance (75 g OGTT), insulin resistance [homeostasis model assessment (HOMA-IR)], beta cell function (insulinogenic index) and inflammatory markers (total leucocyte count, IL-6, TNF-alpha and C-reactive protein). RESULTS: Adiposity, waist circumference, HOMA-IR, insulinogenic index and both fasting and 120 min plasma glucose concentrations increased progressively from rural through to urban slum and urban middle-class men. Inflammatory markers were higher in urban than in rural men. Adiposity was strongly related to HOMA-IR (r = 0.57, p < 0.001) and to insulinogenic index and glycaemic parameters (r = 0.25, p < 0.001 for both). Adiposity explained approximately two thirds of the difference in HOMA-IR between the urban middle-class men and the rural and slum residents, but its contribution to the difference in insulinogenic index and 120 min plasma glucose concentration was not significant. Inclusion of C-reactive protein, IL-6 and total leucocyte count in the models did not further explain these results, nor did the inclusion of waist circumference. There was a significant residual difference after these adjustments. CONCLUSIONS/INTERPRETATION: Adiposity is a major contributor to the difference in insulin resistance between rural and urban Indian men; there was no additional contribution from inflammation or central obesity. Other unmeasured factors also seem to contribute to the metabolic differences between rural and urban men.

Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study.

AIMS/HYPOTHESIS: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. METHODS: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. RESULTS: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India.

Newborn size, infant and childhood growth, and body composition and cardiovascular disease risk factors at the age of 6 years: the Pune Maternal Nutrition Study.

OBJECTIVE: To study associations of size and body proportions at birth, and growth during infancy and childhood, to body composition and cardiovascular disease (CVD) risk factors at the age of 6 years. DESIGN: The Pune Maternal Nutrition Study, a prospective population-based study of maternal nutrition and CVD risk in rural Indian children. METHODS: Body composition and CVD risk factors measured in 698 children at 6 years were related to body proportions and growth from birth. MEASUREMENTS: Anthropometry was performed every 6 months from birth. At 6 years, fat and lean mass (dual X-ray absorptiometry) and CVD risk factors (insulin resistance, blood pressure, glucose tolerance, plasma lipids) were measured. RESULTS: Compared with international references (NCHS, WHO) the children were short, light and thin (mean weight <-1.0 s.d. at all ages). Larger size and faster growth in all body measurements from birth to 6 years predicted higher lean and fat mass at 6 years. Weight and height predicted lean mass more strongly than fat mass, mid-upper arm circumference (MUAC) predicted them both approximately equally and skinfolds predicted only fat mass. Neither birthweight nor the 'thin-fat' newborn phenotype, was related to CVD risk factors. Smaller MUAC at 6 months predicted higher insulin resistance (P<0.001) but larger MUAC at 1 year predicted higher systolic blood pressure (P<0.001). After infancy, higher weight, height, MUAC and skinfolds, and faster growth of all these parameters were associated with increased CVD risk factors. CONCLUSIONS: Slower muscle growth in infancy may increase insulin resistance but reduce blood pressure. After infancy larger size and faster growth of all body measurements are associated with a more adverse childhood CVD risk factor profile. These rural Indian children are growing below international 'norms' for body size and studies are required in other populations to determine the generalizability of the findings.

Bone mass in Indian children--relationships to maternal nutritional status and diet during pregnancy: the Pune Maternal Nutrition Study.

CONTEXT/OBJECTIVE: Bone mass is influenced by genetic and environmental factors. Recent studies have highlighted associations between maternal nutritional status during pregnancy and bone mass in the offspring. We hypothesized that maternal calcium intakes and circulating micronutrients during pregnancy are related to bone mass in Indian children. DESIGN/SETTING/PARTICIPANTS/MAIN OUTCOME MEASURES: Nutritional status was measured at 18 and 28 wk gestation in 797 pregnant rural Indian women. Measurements included anthropometry, dietary intakes (24-h recall and food frequency questionnaire), physical workload (questionnaire), and circulating micronutrients (red cell folate and plasma ferritin, vitamin B12, and vitamin C). Six years postnatally, total body and total spine bone mineral content and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA) in the children (n = 698 of 762 live births) and both parents. RESULTS: Both parents' DXA measurements were positively correlated with the equivalent measurements in the children (P < 0.001 for all). The strength of these correlations was similar for fathers and mothers. Children of mothers who had a higher frequency of intake of calcium-rich foods during pregnancy (milk, milk products, pulses, non-vegetarian foods, green leafy vegetables, fruit) had higher total and spine bone mineral content and BMD, and children of mothers with higher folate status at 28 wk gestation had higher total and spine BMD, independent of parental size and DXA measurements. CONCLUSIONS: Modifiable maternal nutritional factors may influence bone health in the offspring. Fathers play a role in determining their child's bone mass, possibly through genetic mechanisms or through shared environment.

Neonatal anthropometry: the thin-fat Indian baby. The Pune Maternal Nutrition Study.

OBJECTIVE: To examine body size and fat measurements of babies born in rural India and compare them with white Caucasian babies born in an industrialised country. DESIGN: Community-based observational study in rural India, and comparison with data from an earlier study in the UK, measured using similar methods. SUBJECTS: A total of 631 term babies born in six rural villages, near the city of Pune, Maharashtra, India, and 338 term babies born in the Princess Anne Hospital, Southampton, UK. MEASUREMENTS: Maternal weight and height, and neonatal weight, length, head, mid-upper-arm and abdominal circumferences, subscapular and triceps skinfold thicknesses, and placental weight. RESULTS: The Indian mothers were younger, lighter, shorter and had a lower mean body mass index (BMI) (mean age, weight, height and BMI: 21.4 y, 44.6 kg, 1.52 m, and 18.2 kg/m(2)) than Southampton mothers (26.8 y, 63.6 kg, 1.63 m and 23.4 kg/m(2)). They gave birth to lighter babies (mean birthweight: 2.7 kg compared with 3.5 kg). Compared to Southampton babies, the Indian babies were small in all body measurements, the smallest being abdominal circumference (s.d. score: -2.38; 95% CI: -2.48 to -2.29) and mid-arm circumference (s.d. score: -1.82; 95% CI: -1.89 to -1.75), while the most preserved measurement was the subscapular skinfold thickness (s.d. score: -0.53; 95% CI: -0.61 to -0.46). Skinfolds were relatively preserved in the lightest babies (below the 10th percentile of birthweight) in both populations. CONCLUSIONS: Small Indian babies have small abdominal viscera and low muscle mass, but preserve body fat during their intrauterine development. This body composition may persist postnatally and predispose to an insulin-resistant state.

Adiposity and hyperinsulinemia in Indians are present at birth.

We studied body size and cord blood leptin and insulin concentrations in newborn urban Indian (Pune, India) and white Caucasian (London, UK) babies to test the hypothesis that the adiposity and hyperinsulinemia of Indians are present at birth. Indian babies (n = 157) were lighter in weight compared with white Caucasian babies [n = 67; median weight, 2805 g vs. 3475 g, respectively; P < 0.001, adjusted for gestational age and sex; -1.52 SD score; confidence interval (CI), -1.66, -1.42] and had smaller abdominal (-2.39 SD score; CI, -2.52, -2.09), midarm (-1.47 SD score; CI, -1.58, -1.34), and head (-1.23 SD score; CI, -1.42, -1.13) circumferences. However, their skinfolds were relatively preserved: subscapular (central) skinfold (-0.32 SD score; CI, -0.43, -0.20) was better preserved than triceps (peripheral) skinfold (-0.86 SD score; CI, -0.97, -0.75). Cord plasma leptin (median, 6.2 ng/ml Pune and 6.4 ng/ml London) and insulin (median, 34.7 pmol/liter Pune and 20.8 pmol/liter London) concentrations were comparable in the two populations but were higher in Indians when adjusted for birth weight, confirming relative adiposity and hyperinsulinemia of Indian babies. Indian mothers were smaller in all respects, compared with white Caucasian mothers, except subscapular skinfold, which was similar in the two populations. Our results support the intrauterine origin of adiposity, central adiposity, and hyperinsulinemia in Indians. Further research should concentrate on elucidating genetic and environmental influences on fetal growth and body composition. Prevention of insulin resistance syndrome in Indians will need to address regulation of fetal growth in addition to prevention of obesity in later life.

Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.

Circulating lipids and cardiovascular risk in newly diagnosed non-insulin-dependent diabetic subjects in India.

Circulating concentrations of total cholesterol, triglycerides, non-esterified fatty acids (NEFA), glycerol, and 3-hydroxybutyrate (3-HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired-glucose-tolerance (IGT) and 189 non-insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3-7.5) mmol l-1, median (range)), IGT (4.7 (2.7-6.3)) and NIDDM (4.3 (2.3-6.9)). Plasma triglycerides (NGT 0.88 (0.37-2.80), IGT 1.26 (0.43-3.82) and NIDDM 1.38 (0.62-3.91) mmol l-1) and NEFA (NGT 0.81 (0.29-1.58), IGT 1.02 (0.33-1.87) and NIDDM 1.02 (0.48-2.77) mmol l-1) were higher in the two hyperglycaemic groups, but blood 3-HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations.