Insecticidal exposure triggers gut microbes to produce glucose in liver, leading to high blood sugar or hyperglycaemia in the body, says a new study, conducted by researchers from Madurai Kamaraj University (MKU), Madurai. The study was published in Genome Biology.
The researchers observed an alarming number of farmers in villages around the university, undergoing medical management for diabetes. Diabetes is routinely associated with lack of exercise, a high cholesterol diet and obesity. However, farmers seeking diabetes treatment were most often engaged in intense physical work, ate a balanced diet and were not overweight. Intrigued by this observation the authors conducted a study with 3,080 villagers of Vadapalanji panchayat of Madurai district, Tamil Nadu.The participants were divided into two groups - those with direct pesticide exposure (pesticide applicators, farmers, and pesticide vendors) and the ones with indirect exposure (people not associated with agricultural activities). Individuals with family history of diabetes were not part of the survey. Blood samples were analysed for insecticide residues and glycosylated haemoglobin - a marker for determining the average blood glucose levels in last three months.
“We observed a three-fold higher prevalence of diabetes in humans with farming as profession compared to humans with other profession”, said Ganesan Velmurugan, one of the authors of the paper, who was a PhD student at MKU earlier. Insecticide residues of different types of orthophosphates (OPs) like: monocrotophos (MCP), chlorpyrifos, malathion and methyl parathion were found in 87.3%, 73.2%, 70.9%, and 68.3% of the study population, respectively. In people who were directly exposed to pesticides, the authors found a positive correlation between amount of insecticide residues in plasma and levels of glycosylated haemoglobin.
After the global ban of organochloride pesticides like dichloro-diphenyl-trichloroethane (DDT), biodegradable OPs have taken its place. Despite being toxic to humans they occupy 40% of the pesticide market. Farmers work without gloves, shoes, mask and their skin is in direct contact with pesticides. Only 0.1% of sprayed pesticide reaches the target, i.e. insects and pests. The remaining enters plant tissues, soil, water, air and affects off target organisms like humans.
The authors tested their hypothesis further in the lab using mice. To check whether chronic exposure of OPs is a risk factor for high blood sugar, mice were made to drink water mixed with MCP for 180 days. The dose was equivalent to 12-15 years of exposure in humans. After 60 days, MCP-fed mice showed presence of glucose in plasma, and after 180 days, they showed glucose intolerance - a pre-diabetic state. The control mice, who drank normal water showed no such symptoms. Subbiah Ramasamy, Assistant Professor at MKU and principal investigator of the study said, “The primary mode of action of organophosphates (OPs) is inhibition of acetylcholine esterase (AChE) - an enzyme required for neurotransmission. But both in our human and animal studies we noticed that chronic exposure to OPs induced hyperglycemia with no change in AChE.”
Previous studies on degradation of OPs by intestinal bacteria prompted the researchers to focus on the role of gut microbiota. They studied proteins and enzymes produced by the entire intestinal microbial community and found that enzymes like esterases, hydrolases and lipases are being produced in higher amounts. These very enzymes are known to be involved in degradation of OPs. Upon degradation, OPs produces short chain fatty acids, like acetates that are converted to glucose (by gluconeogenesis) in liver. This is what contributes to high glucose level in body and results in diabetes.
Dr. Yogesh S. Shouche, principal investigator at National Centre for Cell Sciences (NCCS), Pune, who also studies microbial ecology and is unrelated to this study said, the researchers have done a “thorough job by proving their hypothesis in animal experiments.”
To take their work further the authors are now “collecting samples from sub-urban and urban areas to understand the impact of OPs on prevalence of diabetes in these areas”, said Velmurugan.