Treating type 1 diabetes is good, preventing it would be better. And one approach to preventing type 1 diabetes is to target specific prevention measures to specific populations at specific stages in the progression from genetic predisposition to islet autoimmunity and clinical disease.
Jill M. Norris, MPH, PhD, discussed the interplay between genetic and dietary factors in reducing the risk of type 1 diabetes during her Kelly West Award for Outstanding Achievement in Epidemiology Lecture, Type 1 Diabetes and Diet: Moving from Epidemiology to Opportunities for Precision Prevention, on Sunday, June 5. Dr. Norris’ lecture was livestreamed and can be viewed on-demand by registered meeting participants at ADA2022.org. If you haven’t registered for the 82nd Scientific Sessions, register today to access the valuable meeting content.
Human leukocyte antigen (HLA) affects susceptibility to type 1 diabetes, rheumatoid arthritis, and other diseases, noted Dr. Norris, Professor and Chair of Epidemiology, University of Colorado School of Public Health. HLA-mediated susceptibility represents 50% of the genetic susceptibility to type 1 diabetes, and HLA-DR/DQ is the single strongest genetic risk factor for type 1 diabetes identified to date. One child in 15 with HLA-DR3/4 will develop type 1 diabetes by age 20.
“What is interesting is the incidence of type 1 diabetes has been increasing by 3% per year,” Dr. Norris said. “This increase is global and is too rapid to be due to genetic factors. This points to an environmental factor increasing risk or decreasing protective effects over time. It suggests we could target our prevention interventions.”
Multiple prospective cohorts of children at risk for type 1 diabetes, including Diabetes Autoimmunity Study in the Young, conducted in Colorado; The Environmental Determinants of Diabetes in the Young, conducted internationally; BabyDiab, conducted in Germany; and Type 1 Diabetes Prediction and Prevention, conducted in Finland, are exploring multiple environmental and dietary factors that may influence progression based on genetic susceptibility.
Higher omega-3 fatty acid intake and higher omega-3 levels, as well as higher vitamin D levels, appear to protect against progression to islet immunity. High glycemic index, total sugars, lactose intake, and nutrient patterns that are simultaneously high in sugars and low in linoleic acid and B vitamins appear to promote progression from islet immunity to clinical type 1 diabetes.
Multiple longitudinal cohort studies around the world have confirmed these factors, Dr. Norris said, but only in populations with specific genetic variants. Vitamin D can act as a protective factor, for example, but only in individuals with specific variants in the vitamin D receptor gene VDR. Similar associations have been found between vitamin D variants, vitamin D genetic risk score, and rheumatoid arthritis autoimmunity.
Nutritional patterns with higher glycemic index and total sugars and lower in linoleic acid and B vitamins can likewise contribute to progression to type 1 diabetes, while diets higher in omega-3 fatty acids reduce risk of progression—but only in individuals with specific genetic variations, Dr. Norris explained.
“We can target interventions to higher-risk individuals,” she said. “And we should be open to the fact that environmental exposures may have a larger impact in moderate-risk individuals because they don’t have as much of a genetic load. You might see more bang for your buck in moderate-risk individuals, but you first need the genetic epidemiology to tell you if that might be the case.”