In findings from a novel global atlas study published today, 19 risk factors were identified to increase risk of developing type 2 diabetes, with insomnia identified as a risk factor for the first time.
In findings from a novel global atlas study published today in Diabetologia, 19 risk factors were found to increase the risk of developing type 2 diabetes (T2D), with insomnia identified as a risk factor for the first time.
Utilizing a technique called mendelian randomization (MR), researchers Susanna Larsson and Shuai Yuan of the Karolinska Institutet, Stockholm, Sweden, sought to identify the causal risk for T2D. MR, which is less likely to be affected by confounding or reverse causation than observational studies, uses “genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data,” stated the press release announcing the findings.
The researchers first conducted a review of meta-analyses and review articles (n = 1360) to delineate possible risk factors for T2D. From this initial analysis, 97 risk factors were indicated as being eligible to be investigated via MR.
For their MR analyses, the researchers used summary-level data from the DIAbetes Genetics Replication And Meta-analysis consortium (74,124 T2D cases; 824,006 controls of European ancestry), with potential causal associations replicated through the FinnGen consortium (11,006 T2D cases; 82,655 controls of European ancestry).
“The inverse-variance weighted method was used as the main analysis. Multivariable MR analysis was used to assess whether the observed associations with T2D were mediated by body mass index (BMI). We used the Benjamini–Hochberg method that controls false discovery rate for multiple testing,” explained the study authors.
In their findings, causal associations were identified between 34 exposures (19 risk factors and 15 protective factors) and T2D. Among people with insomnia, a 17% (odds ratio, 1.17; 95% CI, 1.11-1.23) greater risk was associated with the development of T2D compared with those who did not have insomnia.
The 18 other risk factors for T2D were depression; systolic blood pressure; starting smoking; lifetime smoking; coffee consumption; blood plasma levels of the amino acids isoleucine, valine, and leucine; the liver enzyme alanine aminotransferase; childhood and adulthood BMI; body fat percentage; visceral (internal) fat mass; resting heart rate; and blood plasma levels of 4 fatty acids.
After adjusting for adulthood BMI, 8 risk factors remained significantly associated with T2D risk, including insomnia. However, after stratifying for adulthood BMI, T2D risk among those with insomnia decreased to 7%. “Our study confirmed several previously established risk factors and identified novel potential risk factors for T2D using the latest summary-level data,” said the study authors. “Findings should inform public health policies for the primary prevention of T2D.”
Fifteen exposures were also found to decrease the risk of T2D: plasma alanine, high-density lipoprotein (good cholesterol) and total cholesterol, age at which women begin puberty, testosterone levels, sex hormone binding globulin levels (adjusted for BMI), birthweight, adulthood height, lean body mass in women, 4 separate plasma fatty acids, circulating vitamin D, and years of education.
“Prevention strategies should be constructed from multiple perspectives, such as lowering obesity and smoking rates and levels, and improving mental health, sleep quality, educational level and birthweight,” concluded the study authors.
Yuan S, Larsson SC. An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomization study. Diabetologia. Published online September 9, 2020. doi:10.1007/s00125-020-05253-x