Researchers used a technique called “Mendelian Randomization” (MR), which uses genetic variation as a natural experiment to investigate the causal relationships between modifiable risk factors and health outcomes in observational data.
For the study, the authors conducted a review of meta-analyses and review articles in the PubMed database. Overall, 1,360 relevant articles were used to find the possible risk factors for type 2 diabetes. A total of 97 risk factors were found that could be investigated using the MR method.
For the study population, researchers used 74,124 type 2 diabetes cases and 824,006 controls of European ancestry from the Diabetes Genetics Replication and Meta-analysis consortium. This data was compared to a separate independent population to check that the potential casual associations could be replicated. The independent population consisted of 11,006 type 2 diabetes cases and 82,655 controls of European ancestry from the FinnGen consortium.
Researchers concluded that there were 34 exposures to type 2 diabetes, including 19 risk factors and 15 protective factors. Insomnia was identified as a novel risk factor showing a 17% higher risk factor for people to develop type 2 diabetes compared to people without the sleep disorder.
The other 18 risk factors for type 2 diabetes were identified as depression, systolic blood pressure, starting smoking, lifetime smoking, coffee (caffeine) consumption, blood plasma levels of the amino acids isoleucine, valine and leucine, liver enzyme alanine aminotransferase (a sign of liver function), childhood and adulthood body mass index (BMI), body fat percentage, visceral (internal) fat mass, resting heart rate, and blood plasma levels of four fatty acids.
The 15 factors that were associated with a decreased risk of type 2 diabetes were plasma alanine (an amino acid), high-density lipoprotein (good cholesterol) and total cholesterol, age at beginning puberty in women (menarche), testosterone levels, sex hormone-binding globulin levels (adjusted for BMI), birth weight, adulthood height, lean body mass (for women), four plasma fatty acids, circulating vitamin D, and years of education.
Body Mass Index
When the study results were adjusted for Body Mass Index (BMI), it was found that those who had insomnia with a lower percentage of BMI also had a lower risk of type 2 diabetes. Suggesting that the effect of insomnia on T2D risk is mediated by BMI, the researchers found that the risk of type 2 diabetes fell from 17% to 7% in those with a lower BMI.
The authors conclude: “Our study confirmed several previously established risk factors and identified novel potential risk factors for type 2 diabetes using the latest summary-level data. Findings should inform public health policies for the primary prevention of type 2 diabetes. 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 birth weight.”