ABSTRACT
There has been a huge increase in diabetes and its associated cardiovascular complications over the last decade, predominantly in the middle- and low-income countries. In these countries, the majority live in rural areas. The Rural Epidemiology of Diabetes in South India (REDSI) study was aimed to analyze the prevalence of diabetes, cardiovascular risk factors, and its complications in rural farming and non-farming villages in Tamil Nadu, South India. A research survey on the prevalence of self-reported diabetes, cardiovascular risk factors (age, sex, obesity, hypertension, hypercholesterolemia, alcohol and tobacco use) and agricultural occupational exposure was executed among 106,111 people from 61 villages in the state of Tamil Nadu, South India, during 2015-2018. Overall, we observed a diabetes prevalence of 11.9% in rural South India. A nearly two-fold higher prevalence of diabetes was observed among the farming community (15.0%) compared to that among the non-farming population (8.7%). Logistic regression analyses revealed a strong association with agrochemical exposure (P < 0.0001) and diabetes prevalence among rural farming people. Our survey indicates a high prevalence of diabetes in rural South India particularly among the farming community. This survey in conjunction with other epidemiological and experimental studies raises the need for understanding the etiology of diabetes and other cardiovascular risk factors in rural communities.
ABSTRACT
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.
