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Genetic risks for type 2 diabetes do not influence diabetes progression
Recent study results show that genetic risk factors for developing type 2 diabetes are distinct from the factors that advance diabetes progression, suggesting that other mechanisms may accelerate progression. Data also indicated that elevated triacylglyceride and low HDL were linked to the progression rate of diabetes.
“Our results suggest that the genetic factors that predispose to diabetes are different from those that cause progression of diabetes, which may be mediated by other mechanisms such as glucolipotoxicity, endoplasmic reticulum and oxidative stress,” the researchers wrote. “Our findings that increased rate of progression of diabetes is associated with obesity, with low HDL and high [triacylglyceride] would certainly support this conjecture.”
The population-based observational study utilized data from the Genetics of Diabetes Audit and Research (GoDARTS) database, through which nearly 10,000 patients with type 2 diabetes have agreed to collection of their DNA. Patients selected for the current analysis included those who were diagnosed with diabetes after Jan. 1, 1994. All selected participants were diagnosed with type 2 diabetes after age 35 years, with no advancement to the need for insulin treatment within a year of diagnosis. Participants were required to undergo baseline BMI and HbA1c blood glucose measurements.
The researchers selected 5,250 patients from the GoDARTS database for inclusion in the study. They included for analysis the following clinical covariates: age at diabetes diagnosis, sex, BMI category, smoking status and social class (determined using the Scottish Index of Multiple Deprivation).
The investigators also designated genetic covariates, using a weighted genetic risk score covering 61 known type 2 diabetes risk variants to determine an individual’s genetic risk.
A Cox proportional hazards regression model was used to determine time to requirement for insulin treatment.
The researchers found there to be a faster rate of progression to insulin in patients with a low and a high BMI vs. the lowest risk group with a BMI between 24 and 26. In an analysis in which BMI and HbA1c were used as strata variables, faster progression was independently linked to younger age at diagnosis, higher log triacylglyceride levels (HR=1.28 per mmol/L; 95% CI, 1.15-1.42) and lower HDL levels (HR=0.7 per mmol/L; 95% CI, 0.55-0.87). Although a higher risk for diabetes was associated with younger age at diagnosis and a younger age at requirement of insulin, it was not linked to the advancement from diagnosis to requirement of insulin treatment.
Disclosure: Zhou is a Sir Henry Wellcome postdoctoral fellow.