Diet with a low n‐6/n‐3 essential fatty acid ratio when started immediately after the onset of overt diabetes prolongs survival of type 1 diabetes model NOD mice

Abstract

Type 1 diabetes is a multifactorial disease involving genetic and environmental factors and results from the destruction of pancreatic islet β cells, virtually the only source of insulin. When the majority of β cells are lost, a 'honeymoon' period of variable length follows: namely, a fleeting phase of residual endogenous insulin production, during which glycemic control is achieved with modest or no doses of insulin. However, the remaining β cells are eventually lost, causing the individual to become insulin-dependent and to require long-term insulin therapy or islet transplantation. Here we show that NOD mice, a type 1 diabetes model, survived significantly longer when their diet was changed from one chow with a high essential fatty acid (EFA) ratio (n-6/n-3, 14.5) to another with a low n-6/n-3 ratio (3.0) within 6 days after the onset of overt diabetes (i.e. the 'honeymoon' period), than mice that were continuously fed with the chow with the high n-6/n-3 ratio. This effect was not observed when the chow was changed later than 9 days after the onset. Significantly larger number of islets remained with suggestive islet neogenesis from the pancreatic duct and pathological changes in renal glomeruli were significantly milder in NOD mice fed the chow with the low n-6/n-3 ratio within 6 days after the onset of overt diabetes than those continuously fed with the high-n-6/n-3-ratio chow. These findings indicate that a diet with a low n-6/n-3 ratio prolongs the 'honeymoon' period by retaining the β cell mass, suggesting its potential therapeutic merit.