DCD and Type 2 Diabetes Mellitus

DCD has been evaluated in several meta-analyses as a candidate gene associated with type 2 diabetes mellitus. The studies investigated a panel of risk loci and included DCD among several genes; however, associations with type 2 diabetes and its prediabetic traits have been at best modest. In a large-scale study involving 1,578 metabolically characterized subjects (PMID:18714373), the candidate single-nucleotide polymorphisms, including those mapping near DCD, failed to show reliable associations with adiposity, insulin sensitivity, or insulin secretion.

A subsequent replication study in a Japanese cohort further evaluated DCD along with six other loci (PMID:19455301). The authors reported only nominal associations that did not reach significance after correction for multiple testing. These findings suggest that if DCD contributes to type 2 diabetes risk, its effect is very minor and likely insufficient for straightforward diagnostic use.

Additional investigation in German populations assessed similar SNP loci and found that variants near DCD demonstrated very weak or absent associations with type 2 diabetes and related metabolic traits (PMID:19670153). The absence of significant segregation data among families further weakens its clinical validity.

Functional assessments remain scarce, as no direct experimental studies have been published that address the impact of DCD alterations on pancreatic beta-cell function or insulin signaling. In contrast to other diabetes risk genes, DCD has not been supported by in vitro or in vivo studies that recapitulate the human disease phenotype (PMID:19833888).

Moreover, studies investigating the association of diabetes risk loci with quantitative measures of adiposity did not reveal any conclusive evidence linking DCD variants to visceral or subcutaneous fat accumulation (PMID:22377712). Together, these genetic and experimental data indicate that the contribution of DCD to type 2 diabetes risk is limited.

In summary, while DCD has been consistently included in panels assessing diabetes susceptibility, the available evidence from genetic association studies and the lack of functional validation do not support a robust role for DCD in type 2 diabetes mellitus. Key take‑home: Current data on DCD suggest that it is not a major determinant of type 2 diabetes risk in clinical or commercial diagnostic settings.

References

• PloS One • 2008 • Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes PMID:18714373
• Diabetologia • 2009 • Replication study for the association of new meta-analysis-derived risk loci with susceptibility to type 2 diabetes in 6,244 Japanese individuals PMID:19455301
• Hormone and Metabolic Research • 2010 • Lack of significant effects of the type 2 diabetes susceptibility loci on diabetes and quantitative metabolic traits PMID:19670153
• Diabetes • 2010 • Gene variants in the novel type 2 diabetes loci affect different aspects of pancreatic beta‑cell function PMID:19833888
• Journal of Human Genetics • 2012 • Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography PMID:22377712

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