Differential risk factor profile of diabetes and atherosclerosis in rural, sub-urban and urban regions of South India: The KMCH-Non-communicable disease studies.

AIMS: South Asia has emerged rapidly as an epicentre of non-communicable diseases (NCDs) specifically diabetes and cardiovascular diseases. The prevalence rate, risk factors and aetiology of NCDs in different socio-demographic settings are not clearly understood. This study was performed to assess the prevalence of diabetes and atherosclerosis and their risk factors in urban, sub-urban and rural communities of South India. METHODS: Three communities [Nallampatti (rural), Thadagam (sub-urban) and Kalapatti (urban)] in South India were selected for participation in the KMCH-NCD Studies. Study volunteers were administered a detailed questionnaire, underwent anthropometric measurements, clinical measurements including blood pressure, glycated haemoglobin (HbA1c ), non-fasting lipid profile and serum creatinine. Carotid intima-media thickness was measured using B-mode ultrasound. Multiple logistic regression analyses were performed to understand the association of risk factors with diabetes and atherosclerosis. RESULTS: A total of 2976 native participants, ≥20 years of age were screened. The prevalence of diabetes was 16%, 26% and 23% respectively in the rural, sub-urban and urban study populations. Association of obesity with diabetes was observed in only urban population while hypertension and dyslipidaemia showed association in both urban and semi-urban populations. Association of diabetes with atherosclerosis was observed in urban and semi-urban populations. Hypertension in semi-urban and obesity and dyslipidaemia in urban population showed association with atherosclerosis. CONCLUSIONS: Diabetes and atherosclerosis burden reported in the three different communities were higher than previous reports, especially in rural and sub-urban regions. No traditional risk factor is identified to be associated with prevalence of diabetes and atherosclerosis in rural population. These findings suggest an urgent need for investigation into the role of non-traditional risk factors like environmental or occupational exposures may help to better understand the aetiology of diseases in non-urbanized communities.

Correction to: Association of co-accumulation of arsenic and organophosphate insecticides with diabetes and atherosclerosis in a rural agricultural community: KMCH-NNCD-I study.

Authors would like to correct the error in the online publication, which is mentioned below.

Association of co-accumulation of arsenic and organophosphate insecticides with diabetes and atherosclerosis in a rural agricultural community: KMCH-NNCD-I study.

AIMS: In last few decades, the prevalence of diabetes and vascular diseases has intensified concurrently with increased use of synthetic chemicals in agriculture. This study is aimed to evaluate the association of co-accumulation of arsenic and organophosphate (OP) insecticides with diabetes and atherosclerosis prevalence in a rural Indian population. METHODS: This study included observations from KMCH-NNCD-I (2015) cross-sectional study (n = 865) from an Indian farming village. The participants had assessment of clinical parameters including HbA1c and carotid intima-media thickness and urinary heavy metals. Serum OP residues were extracted and quantified by GC-MS. Statistical analyses were performed to unravel the co-association of arsenic and OPs on prevalence of diabetes and atherosclerosis. RESULTS: On multivariate regression analyses, total organophosphate level and arsenic accumulation showed association with diabetes and atherosclerosis. Higher odds ratio with significant trends were observed for the sub-quartiles formed by the combination of higher quartiles of arsenic and total organophosphates in association with diabetes and atherosclerosis. CONCLUSIONS: We observed evidence of possible synergism between arsenic and OPs in association with prevalence of diabetes, pre-diabetes and atherosclerosis in the study population. Our findings highlight the importance of understanding health effects of mixed exposures and raises vital questions on the role of these agrochemicals in the etiology of diabetes and vascular diseases.

Metals in urine in relation to the prevalence of pre-diabetes, diabetes and atherosclerosis in rural India.

OBJECTIVE: Diabetes and cardiovascular diseases are growing burdens in rural communities worldwide. We have observed a high prevalence of diabetes among rural farming communities in India and sought to evaluate the association of non-traditional risk factors, such as metals, with diabetes and other cardiometabolic risk factors in this community. METHODS: Anthropometric measurements, chemistries and carotid intima-media thickness were determined in 865 participants of the Kovai Medical Center and Hospital-Nallampatti Non-Communicable Disease Study-I (KMCH-NNCD-I, 2015), a cross-sectional study conducted in a farming village in South India. Urinary metal levels were determined by inductively couped plasma-mass spectrometry analysis and corrected to urinary creatinine level. Statistical analyses were performed to study the association between urinary metal levels and clinical parameters. RESULTS: 82.5% of the study population were involved in farming and high levels of toxic metals were detected in the synthetic fertilisers used in the study village. The prevalence of pre-diabetes, diabetes and atherosclerosis was 43.4%, 16.2% and 10.3%, respectively. On logistic regression analysis, no association of traditional risk factors such as body mass index, blood pressure and total cholesterol with disease conditions was observed, but urinary levels of metals such as arsenic, chromium, aluminium and zinc showed an association with diabetes, while arsenic and zinc showed an association with pre-diabetes and atherosclerosis. CONCLUSIONS: Our data suggest a probable role of metals in the aetiology of diabetes and cardiovascular diseases in rural communities. Identifying and eliminating the causes of increased levels of these environmental chemicals could have a beneficial impact on the burden of non-communicable diseases in rural population.

Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis.

BACKGROUND: Organophosphates are the most frequently and largely applied insecticide in the world due to their biodegradable nature. Gut microbes were shown to degrade organophosphates and cause intestinal dysfunction. The diabetogenic nature of organophosphates was recently reported but the underlying molecular mechanism is unclear. We aimed to understand the role of gut microbiota in organophosphate-induced hyperglycemia and to unravel the molecular mechanism behind this process. RESULTS: Here we demonstrate a high prevalence of diabetes among people directly exposed to organophosphates in rural India (n = 3080). Correlation and linear regression analysis reveal a strong association between plasma organophosphate residues and HbA1c but no association with acetylcholine esterase was noticed. Chronic treatment of mice with organophosphate for 180 days confirms the induction of glucose intolerance with no significant change in acetylcholine esterase. Further fecal transplantation and culture transplantation experiments confirm the involvement of gut microbiota in organophosphate-induced glucose intolerance. Intestinal metatranscriptomic and host metabolomic analyses reveal that gut microbial organophosphate degradation produces short chain fatty acids like acetic acid, which induces gluconeogenesis and thereby accounts for glucose intolerance. Plasma organophosphate residues are positively correlated with fecal esterase activity and acetate level of human diabetes. CONCLUSION: Collectively, our results implicate gluconeogenesis as the key mechanism behind organophosphate-induced hyperglycemia, mediated by the organophosphate-degrading potential of gut microbiota. This study reveals the gut microbiome-mediated diabetogenic nature of organophosphates and hence that the usage of these insecticides should be reconsidered.

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India.

BACKGROUND: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. OBJECTIVES: To study the predispositions of HLA alleles/haplotypes with cervical cancer. MATERIALS AND METHODS: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. RESULTS: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions ß9 and ß37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. CONCLUSIONS: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.