Clinical study of risk factors and ultrasonographic correlation of endometrial hyperplasia according to the WHO classification 2014

Background: Type 1 endometrial carcinoma is usually preceded by atypical hyperplasia. Nonatypical hyperplasia should be managed conservatively and atypical hyperplasia have to be managed aggressively. So, the diagnosis is crucial for its management.Methods: The study population included women diagnosed with endometrial hyperplasia by histopathology as per WHO classification 2014 from the year January 2015 to February 2020.Women with endometrial polyp diagnosed by transvaginal ultrasonography and histopathology were excluded. Primary objective was to compare the endometrial thickness between the two types of hyperplasia. Secondary objective was to analyses the risk factors of the two types.Results: In multivariate analysis of logistic regression, diabetic women have 1.57 times risk of developing atypia and obese women have 3.12 times risk of developing atypia. Polycystic ovarian disease is having borderline significance for causing atypia. There was significant difference in endometrial thickness between atypical and nonatypical hyperplasia (P=0.040). In premenopausal women, (P=0.069) the thickness difference in atypia is of only borderline significance. Heteroechoic pattern or cystic spaces in the endometrium also didn’t predict atypia.Conclusions: Mean endometrial thickness is significantly different in atypical hyperplasia. Heteroechoic pattern of endometrium do not predict atypia. We need color doppler sonography to gain knowledge about atypia. Obesity and diabetes mellitus are significant risk factors of atypia

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

Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the 'T' allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions between the SNPs and lifestyle factors were statistically significant after correction for multiple testing. Our findings indicate that the association between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in this Asian Indian population

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

Potentially Heterogeneous Cross-Sectional Associations of Seafood Consumption with Diabetes and Glycemia in Urban South Asia.

Aims: In this study, we aimed to estimate cross-sectional associations of fish or shellfish consumption with diabetes and glycemia in three South Asian mega-cities. Methods: We analyzed baseline data from 2010-2011 of a cohort (n = 16,287) representing the population ≥20 years old that was neither pregnant nor on bedrest from Karachi (unweighted n = 4017), Delhi (unweighted n = 5364), and Chennai (unweighted n = 6906). Diabetes was defined as self-reported physician-diagnosed diabetes, fasting plasma glucose ≥126 mg/dL (7.0 mmol/L), or glycated hemoglobin A1c (HbA1c) ≥6.5% (48 mmol/mol). We estimated adjusted and unadjusted odds ratios for diabetes using survey estimation logistic regression for each city, and differences in glucose and HbA1c using survey estimation linear regression for each city. Adjusted models controlled for age, gender, body mass index, waist-height ratio, sedentary lifestyle, educational attainment, tobacco use, an unhealthy diet index score, income, self-reported physician diagnosis of high blood pressure, and self-reported physician diagnosis of high cholesterol. Results: The prevalence of diabetes was 26.7% (95% confidence interval: 24.8, 28.6) in Chennai, 36.7% (32.9, 40.5) in Delhi, and 24.3% (22.0, 26.6) in Karachi. Fish and shellfish were consumed more frequently in Chennai than in the other two cities. In Chennai, the adjusted odds ratio for diabetes, comparing more than weekly vs. less than weekly fish consumption, was 0.81 (0.61, 1.08); in Delhi, it was 1.18 (0.87, 1.58), and, in Karachi, it was 1.30 (0.94, 1.80). In Chennai, the adjusted odds ratio of prevalent diabetes among persons consuming shellfish more than weekly versus less than weekly was 1.08 (95% CI: 0.90, 1.30); in Delhi, it was 1.35 (0.90, 2.01), and, in Karachi, it was 1.68 (0.98, 2.86). Conclusions: Both the direction and the magnitude of association between seafood consumption and glycemia may vary by city. Further investigation into specific locally consumed seafoods and their prospective associations with incident diabetes and related pathophysiology are warranted

A systematic review of the effect of gene–lifestyle interactions on metabolic-disease-related traits in South Asian populations

Context Recent data from the South Asian subregion have raised concern about the dramatic increase in the prevalence of metabolic diseases, which are influenced by genetic and lifestyle factors. Objective The aim of this systematic review was to summarize the contemporary evidence for the effect of gene–lifestyle interactions on metabolic outcomes in this population. Data sources PubMed, Web of Science, and SCOPUS databases were searched up until March 2023 for observational and intervention studies investigating the interaction between genetic variants and lifestyle factors such as diet and physical activity on obesity and type 2 diabetes traits. Data extraction Of the 14 783 publications extracted, 15 were deemed eligible for inclusion in this study. Data extraction was carried out independently by 3 investigators. The quality of the included studies was assessed using the Appraisal Tool for Cross-Sectional Studies (AXIS), the Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I), and the methodological quality score for nutrigenetics studies. Data analysis Using a narrative synthesis approach, the findings were presented in textual and tabular format. Together, studies from India (n = 8), Pakistan (n = 3), Sri Lanka (n = 1), and the South Asian diaspora in Singapore and Canada (n = 3) reported 543 gene–lifestyle interactions, of which 132 (∼24%) were statistically significant. These results were related to the effects of the interaction of genetic factors with physical inactivity, poor sleep habits, smoking, and dietary intake of carbohydrates, protein, and fat on the risk of metabolic disease in this population. Conclusions The findings of this systematic review provide evidence of gene–lifestyle interactions impacting metabolic traits within the South Asian population. However, the lack of replication and correction for multiple testing and the small sample size of the included studies may limit the conclusiveness of the evidence. Note, this paper is part of the Nutrition Reviews Special Collection on Precision Nutrition. Systematic Review Registration PROSPERO registration No. CRD42023402408

Physical activity patterns and gestational diabetes outcomes – The wings project

AbstractObjectiveTo compare physical activity (PA) patterns in pregnant woman with and without gestational diabetes (GDM) and to assess the effects of an exercise intervention on change in PA patterns, blood glucose levels and pregnancy outcomes in GDM women.MethodsFor the first objective, PA patterns were studied in 795 pregnant women with and without GDM. For the second objective, the Women in India with Gestational Diabetes Strategy-Model of Care (WINGS-MOC) intervention were evaluated in 151 women out of 189 with GDM. PA was assessed using a validated questionnaire and a pedometer. Changes in PA patterns, glycemic parameters and neonatal outcomes were evaluated.ResultsOverall, only 10% of pregnant women performed recommended levels of PA. Women with GDM were significantly more sedentary compared to those without GDM (86.2 vs. 61.2%, p<0.001). After the MOC was implemented in women with GDM, there was a significant improvement in PA and a decrease in sedentary behaviour amongst women (before MOC, moderate activity: 15.2%, sedentary: 84.8% vs. after MOC-moderate: 26.5%, sedentary: 73.5%; p<0.001), and an increase in their daily step count from 2206/day to 2476/day (p<0.001). Fasting 1 and 2-h postprandial glucose values significantly decreased (p<0.001 for all). Sedentary behaviour was associated with a fourfold higher risk (p=0.02), and recreational walking with 70% decreased risk, of adverse neonatal outcomes (p=0.04) after adjusting for potential confounders.ConclusionsPA levels are inadequate amongst this group of pregnant women studied i.e. those with and without GDM. However, a low-cost, culturally appropriate MOC can bring about significant improvements in PA in women with GDM. These changes are associated with improved glycemic control and reduction in adverse neonatal outcomes

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