The dual role of diabetes on oral potentially malignant disorders.

Background: Observational studies suggest a link between diabetes and oral potentially malignant disorders (OPMDs), such as oral lichen planus (OLP) and oral leukoplakia (OLK). The causal relationship, as well as the type of diabetes that promotes OPMDs development, remains unclear. This Mendelian randomization (MR) study estimated the causal effects of diabetes-related traits on OPMDs.

Methods: Large-scale genome-wide association study data on type 1 diabetes (T1D), type 2 diabetes (T2D), fasting glucose (FG), fasting insulin (FI), glycated hemoglobin (HbA1c), OLP, OLK, and actinic cheilitis (AC) were used. Causal effects were assessed using inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Multivariable MR analyses evaluated the independent roles of these traits, with extensive sensitivity analyses.

Results: Genetic susceptibility to T1D (IVW OR = 1.09, 95% CI 1.02-1.17, P = 0.007) and T2D (IVW OR = 0.91, 95% CI 0.86-0.97, P = 0.002) showed protective effects against AC. T1D was associated with an increased risk of OLP (IVW OR = 1.09, 95% CI 1.02-1.17, P = 0.007). The effect of T1D on AC and OLP remained robust after adjusting for FI, FG, and HbA1c, while T2D's effect on AC was not significant when considering these glycemic traits. No potential pleiotropy was detected (P > 0.05).

Conclusions: T1D may have a causal role in the development of OLP independent of glycemic traits, emphasizing the need for routine oral examinations in T1D patients. Conversely, genetically predicted T1D and T2D are significantly associated with a reduced risk of AC, challenging previous assumptions and offering new insights into the relationship between diabetes and OPMDs. Further extensive investigations are required to address the limitations of this study and to clarify these associations.