Overlooked Risk Factors for Type 2 Diabetes

Study identifies multiple risk factors for type 2 diabetes, including insomnia, that need to be incorporated into diabetes prevention strategies. 

Previous studies identified possible risk factors for type 2 diabetes, but it remains uncertain whether or not these known associations are causal. Therefore, before determining causal risk factors, a review of previous studies on risk factors for type 2 diabetes was conducted. In addition, meta-analyses and review articles were used. Initially, 170 potential risk factors were found. Therefore, both causal risk factors and casual protective factors were identified in this study. Also, factors that did not have enough evidence were mentioned as suggestive factors.  

This study aimed to use Mendelian randomization (MR) to recognize causal risk factors in patients with type 2 diabetes. The results should inform the public health policies about the primary prevention of type 2 diabetes. A new observational study was published that identified risk factors that were causally associated with type 2 diabetes. This study’s name was An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomization study. Data from Diabetes Genetics Replication and Meta-analysis (DIAGRAM) consortium included 32 studies with 898,130 individuals of European descent. The mean age was 55 years old, and 51.8% were males. A total of 11,006 type 2 diabetes cases and 82,655 controls were used from the FinnGen consortium. For BMI, data from the Genome-Wide Association Study (GWAS) of 806,834 individuals of European ancestry, including the Genetic Investigation of Anthropometric Traits (GIANT) consortium UK Biobank was used. Sensitivity analyses were also performed. In addition, MR Egger regression methods were used to test consistency and to find possible pleiotropy.  

The estimates were completed with two-tailed p values. The Benhamini–Hochberg method was used to control the false discoverer rate for multiple testing. A confidence interval of 95% was used. A p-value of less than 0.05 was considered to be significant. An overall power analysis was conducted by using a web tool. The estimates were calculated using the random effects inverse variance weighted method when an exposure had greater than or equal to 3 single nucleotide polymorphisms. This method can provide accurate results; however, it is sensitive to invalid instrumental variables and pleiotropic effects.  

Among the 170 potential factors, only 97 were examined in this investigation. There were 29 factors nominally associated with type 2 diabetes. After adjusting for multiple comparisons with Benhamini-Hochberg, 20 elements were remaining. From previous MR studies, 14 risk factors were associated with type 2 diabetes. In total, there were 34 exposures. There were 19 risk factors and 15 protective factors. Insomnia was determined to be a novel risk factor for type 2 diabetes (OR 1.17 [95% CI 1.11, 1.23]). The other 18 risk factors were depression, systolic BP, smoking initiation, lifetime smoking, coffee (caffeine) consumption, plasma isoleucine, valine and leucine, liver alanine aminotransferase, childhood and adulthood BMI, body fat percentage, visceral fat mass, resting heart rate, and four plasma fatty acids.  

There were 21 suggestive risk factors (p < 0.05). After adjusting for adulthood BMI, only eight links remained. Alcohol consumption was showed to have a positive association with type 2 diabetes (OR 1.46 [95% CI 1.16, 1.83]). Also, daytime napping was found to be associated with an increased risk of type 2 diabetes. Additionally, short sleep and low sleep quality were further related to unhealthy eating habits and unbalanced eating patterns. 

The use of MR design intensified the casual implications on the different exposures. Numerous obesity independent risk factors were revealed. This can be a topic for future studies in preventing patients from developing type 2 diabetes. A weakness was the population’s homogenous nature. The majority of the population was of European descent. Some risk factors could have been overlooked due to the nature of initially pinpointing a more significant number of risk factors from meta-analyses and review articles. Also, some weak associations, like traits with minor variances explained by single nucleotide polymorphisms, could have been unnoticed. This MR study verified several previous well-known risk factors for patients with type 2 diabetes. This study was also able to identify a potential novel risk factor. 

Practice Pearls: 

• People living with insomnia are 17% more likely to acquire type 2 diabetes than people who do not have insomnia. 
• Multiple risk factors including mental health, sleep hygiene and education level should be taken into account when assessing type 2 diabetes risk. 
• Obesity is still a prevalent risk factor for type 2 diabetes.  

Yuan, S., Larsson, S.C. An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomization study. Diabetologia (2020).  

Alexandria Bartley, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences