August 30, 2021
3 min read
People at high genetic risk are more likely to develop type 2 diabetes at some point in their lifetime, but maintaining normal weight may mitigate the increased risk, according to a study published in Diabetic Medicine.
“Estimation of lifetime risk of diabetes with the use of genetic data may inform individuals at an early age of their diabetes risk,” Symen Ligthart, MD, MSc, PhD, a resident of internal medicine in the department of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands, told Healio. “Maintaining normal weight may mitigate a high genetic risk.”
Ligthart and colleagues analyzed data from two prospective population-based cohort studies. The Atherosclerosis Risk in Communities (ARIC) study included adults aged 45 to 64 years at baseline from 1987 to 1989 from four U.S. communities. Participants underwent six follow-up exams through 2019. The analysis included 8,243 participants in ARIC with genetic data available and free of type 2 diabetes at enrollment. The Rotterdam Study included adults aged 55 years or older in Rotterdam and began in 1990. The study was extended with a second cohort of adults aged 55 years or older in 2000, and a third cohort aged 45 years or older in 2006. The analysis included 7,428 participants with genetic data available with diabetes at baseline. Using 403 genetic variants identified in the study, a weighted polygenic score was created, with participants in ARIC and the Rotterdam Study categorized to low, intermediate or high genetic risk categories.
In ARIC, 31% of participants were diagnosed with type 2 diabetes during a median follow-up time of 19.4 years, including 24% of those with low genetic risk, 31% of those with intermediate genetic risk and 38% in the high genetic risk category. Of the ARIC cohort, 31% died without diabetes, including 34% with low genetic risk, 32% with intermediate risk and 29% with high genetic risk.
In the Rotterdam Study, 9% of participants were diagnosed with type 2 diabetes over a median follow-up time of 6.9 years, including 7% with low genetic risk, 9% with intermediate genetic risk and 11% with high genetic risk. About 20% of Rotterdam participants died without diabetes, including 19% of those with low genetic risk and 20% each in the intermediate and high genetic risk subgroups.
Adults with intermediate or high genetic risk had an increased risk for type 2 diabetes compared with those in the low genetic risk category, with the high genetic risk group having a nearly twofold greater risk than the low genetic risk group. Participants with normal body weight also had a lower risk for diabetes compared with those with overweight and obesity in the intermediate and high genetic risk categories. Among those with a high genetic risk, normal weight was associated with a 56% lower risk for diabetes in ARIC and 55% lower risk in the Rotterdam Study.
In the Rotterdam Study, adults aged 45 years had a 22.8% remaining lifetime risk for type 2 diabetes with low genetic risk, a 30.6% risk with intermediate genetic risk and a 35.5% remaining lifetime diabetes risk in the high genetic risk group. A similar trend was observed in ARIC. The highest lifetime risk was for adults with obesity at high genetic risk with a 59.7% risk for diabetes in ARIC and 55.3% risk in the Rotterdam Study. Adults with normal weight at low genetic risk had the lowest risk for type 1 diabetes at 23.8% in ARIC and 16.8% in the Rotterdam Study.
“In agreement with findings from earlier reports, the high lifetime risk of type 2 diabetes in individuals with obesity at all genetic risk strata highlight the importance of lifestyle interventions that maintain a normal weight, and from a public health intervention perspective, it would therefore be logical to focus at older ages on individuals with obesity,” the researchers wrote.
Ligthart said future research should focus on estimating genetic lifetime risk for type 2 diabetes among younger people with long-term follow-up to establish more precise risk estimates.
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Symen Ligthart, MD, MSc, PhD, can be reached at email@example.com.