A nutrigenetic approach to investigate the relationship between metabolic traits and vitamin D status in an Asian Indian population

Studies in Asian Indians have examined the association of metabolic traits with vitamin D status. However, findings have been quite inconsistent. Hence, we aimed to explore the relationship between metabolic traits and 25-hydroxyvitamin D [25(OH)D] concentrations. We investigate whether this relationship was modified by lifestyle factors using a nutrigenetic approach in 545 Asian Indians randomly selected from the Chennai Urban Rural Epidemiology Study (219 normal glucose tolerant individuals, 151 with pre-diabetes and 175 individuals with type 2 diabetes). A metabolic genetic risk score (GRS) was developed using five common metabolic disease-related genetic variants. There was a significant interaction between metabolic GRS and carbohydrate intake (energy%) on 25(OH)D (Pinteraction = 0.047). Individuals consuming a low carbohydrate diet (≤62%) and those having lesser number of metabolic risk alleles (GRS ≤ 1) had significantly higher levels of 25(OH)D (p = 0.033). Conversely, individuals consuming a high carbohydrate diet despite having lesser number of risk alleles did not show a significant increase in 25(OH)D (p = 0.662). In summary, our findings show that individuals carrying a smaller number of metabolic risk alleles are likely to have higher 25(OH)D levels if they consume a low carbohydrate diet. These data support the current dietary carbohydrate recommendations of 50%–60% energy suggesting that reduced metabolic genetic risk increases 25(OH)D

Evidence for the association between FTO gene variants and vitamin B12 concentrations in an Asian Indian population

Background Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity. Methods A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model. Results The GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed. Conclusion The study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations

Lower dietary intake of plant protein is associated with genetic risk of diabetes-related traits in urban Asian Indian adults

The increasing prevalence of type 2 diabetes among South Asians is caused by a complex interplay between environmental and genetic factors. We aimed to examine the impact of dietary and genetic factors on metabolic traits in 1062 Asian Indians. Dietary assessment was performed using a validated semi-quantitative food frequency questionnaire. Seven single nucleotide polymorphisms (SNPs) from the Transcription factor 7-like 2 and fat mass and obesity-associated genes were used to construct two metabolic genetic risk scores (GRS): 7-SNP and 3-SNP GRSs. Both 7-SNP GRS and 3-SNP GRS were associated with a higher risk of T2D (p = 0.0000134 and 0.008, respectively). The 3-SNP GRS was associated with higher waist circumference (p = 0.010), fasting plasma glucose (FPG) (p = 0.002) and glycated haemoglobin (HbA1c) (p = 0.000066). There were significant interactions between 3-SNP GRS and protein intake (% of total energy intake) on FPG (Pinteraction = 0.011) and HbA1c (Pinteraction = 0.007), where among individuals with lower plant protein intake (1 risk allele had higher FPG (p = 0.001) and HbA1c (p = 0.00006) than individuals with ≤1 risk allele. Our findings suggest that lower plant protein intake may be a contributor to the increased ethnic susceptibility to diabetes described in Asian Indians. Randomised clinical trials with increased plant protein in the diets of this population are needed to see whether the reduction of diabetes risk occurs in individuals with prediabetes

Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians

Background: Plasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach and investigate whether these associations are modified by lifestyle factors. Methods: The study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Results: The ‘A’ allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p=1.90 x 10-47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p=7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of ‘A’ allele with cardiometabolic health status disappeared (p=0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). Conclusions: Our findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases

Postpartum development of type 1 diabetes in Asian Indian women with gestational diabetes

Aim: To study the postpartum conversion of gestational diabetes mellitus (GDM) to different types of diabetes among Asian Indian women. Materials and Methods: Using data from electronic medical records, 418 women with GDM seen at a tertiary diabetes care center for diabetes in Chennai in South India between 1991 and 2014 were evaluated for development of diabetes postpartum. Results: Of the 418 GDM women followed up postpartum, 388 progressed to diabetes. Of these 359 (92.5%) developed type 2 diabetes (T2DM) and 29 women (7.5%) developed type 1 diabetes (T1DM). The median time to development of T1DM was 2 years (interquartile range 2 [IQR]) while for T2DM it was 5 years (IQR 6). Women who developed T1DM had significantly lower mean body mass index (BMI) (20.4 ± 2.8 vs. 27.5 ± 4.4 kg/m 2 , P = 0.001), and higher fasting plasma glucose (222 ± 105 vs. 165 ± 62 mg/dl P = 0.008) and glycated hemoglobin levels (10.2 ± 2.7 vs. 8.5 ± 2.1% P < 0.001) compared to those who developed T2DM. Glutamic acid decarboxylase (GAD) autoantibodies were present in 24/29 (82.7%) of women who developed T1DM. Conclusion: A small but significant proportion of women with GDM progress to T1DM postpartum. Measurement of GAD antibodies in leaner women with more severe diabetes could help to identify women who are likely to develop T1DM and thus prevent their presentation with acute hyperglycemic emergencies after delivery

Causes and predictors of mortality in Asian Indians with and without diabetes-10 year follow-up of the Chennai Urban Rural Epidemiology Study (CURES - 150).

BACKGROUND:The incidence and prevalence of diabetes is increasing worldwide and it is the fifth leading cause of mortality accounting for over 3.8 million deaths annually. Despite the enormity of the diabetes-related health burdens, very few studies have evaluated the factors associated with mortality among people with diabetes in India. We sought to study the causes and predictors of mortality among urban Asian Indians with and without diabetes. METHODS AND FINDINGS:Of 2273 adults (27,850 person-years of follow-up) from the 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES), the cause of death could be ascertained in 552 individuals out of the 671 who had died (response rate 82.3%). Verbal autopsy was obtained from the family members of the deceased and this was adjudicated by trained physicians. The age-standardized mortality rate was 28.2 (95%CI 25.9-30.6) per 100,000 population. Mortality rates were significantly higher in individuals with diabetes compared to those without [27.9(95% CI 25.5-30.6) vs. 8.0 (6.6-9.9) per 1000 person years]. Compared to individuals of normal body mass index, underweight individuals had higher risk of mortality (Hazard ratio 1.49; 95% CI 1.11-2.0), whereas overweight and obese individuals did not show a higher risk. The population-attributable risk for all-cause mortality in the entire study cohort was highest for ischemic heart disease and diabetes. The excess mortality attributable to diabetes was highest in the age group of 51 to 70 years, and was mostly accounted for by renal disease (Rate ratio 5.68, 95%CI 2.43-6.23), ischemic heart disease (4.23,2.78-6.67), and cerebrovascular disease (4.00,1.87-9.81). CONCLUSION:Underweight (but not overweight or obesity) was strongly associated with mortality in this Asian Indian population. Ischemic heart disease and diabetes contributed the most to risk for all cause mortality. Excess mortality due to diabetes was higher in relatively younger individuals and was mostly accounted for by renal disease

Baseline characteristics of subjects with and without diabetes among the study cohort.

<p>Baseline characteristics of subjects with and without diabetes among the study cohort.</p

Hazard ratios of various risk factors for all-cause mortality in the overall study cohort.

<p>Hazard ratios of various risk factors for all-cause mortality in the overall study cohort.</p

Hazard ratios of various risk factors for all-cause mortality among subjects with and without diabetes.

<p>Hazard ratios of various risk factors for all-cause mortality among subjects with and without diabetes.</p

Causes of death in those with and without diabetes.

<p>Causes of death in those with and without diabetes.</p