Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a global epidemic associated with increased health expenditure, and low quality of life. Many non-genetic risk factors have been suggested, but their overall epidemiological credibility has not been assessed.

Methods: We searched PubMed to capture all meta-analyses and Mendelian randomization studies for risk factors of T2DM. For each association, we estimated the summary effect size, its 95% confidence and prediction interval, and the I2 metric. We examined the presence of small-study effects and excess significance bias. We assessed the epidemiological credibility through a set of predefined criteria.

Results: We captured 86 eligible papers (142 associations) covering a wide range of biomarkers, medical conditions, and dietary, lifestyle, environmental and psychosocial factors. Adiposity, low hip circumference, serum biomarkers (increased level of alanine aminotransferase, gamma-glutamyl transferase, uric acid and C-reactive protein, and decreased level of adiponectin and vitamin D), an unhealthy dietary pattern (increased consumption of processed meat and sugar-sweetened beverages, decreased intake of whole grains, coffee and heme iron, and low adherence to a healthy dietary pattern), low level of education and conscientiousness, decreased physical activity, high sedentary time and duration of television watching, low alcohol drinking, smoking, air pollution, and some medical conditions (high systolic blood pressure, late menarche age, gestational diabetes, metabolic syndrome, preterm birth) presented robust evidence for increased risk of T2DM.

Conclusions: A healthy lifestyle pattern could lead to decreased risk for T2DM. Future randomized clinical trials should focus on identifying efficient strategies to modify harmful daily habits and predisposing dietary patterns.

Fig 1. Flow chart of literature search.

Fig 2. Manhattan plot for 142 associations between risk factors and T2DM.

The horizontal line corresponds to the significance threshold of P <10⁻⁶.

Fig 3. Schematic representation of risk factors for T2DM with convincing or highly suggestive evidence.

The symbol ↑ denotes a higher exposure to a risk factor, and the symbol ↓ represents a lower exposure to a risk factor. For alcohol consumption, never drinkers presented a higher risk for T2DM than moderate drinkers.

Fig 4. Forest plot of risk factors (measured as continuous variables) for T2DM supported by convincing or highly suggestive evidence.

Fig 5. Forest plot of risk factors (measured as dichotomous variables) for T2DM supported by convincing or highly suggestive evidence.