Genetic Risk Score in Diabetes Associated With Chronic Pancreatitis Versus Type 2 Diabetes Mellitus

Area of Science:

• Genetics
• Endocrinology
• Gastroenterology

Background:

• Diabetes mellitus (DM) is a known complication of chronic pancreatitis (CP).
• The distinct pathophysiologic nature of CP-DM compared to type 2 DM (T2DM) is uncertain.
• Clarifying this distinction is crucial for developing targeted CP-DM management strategies.

Purpose of the Study:

• To investigate whether CP-DM is genetically distinct from T2DM.
• To determine if a genetic risk score (GRS) for T2DM can differentiate between CP-DM and T2DM patients.

Main Methods:

• A weighted GRS was constructed using 60 validated T2DM single nucleotide polymorphisms.
• The GRS was applied to subjects from the North American Pancreatitis Study 2 (n=1,613) and the Multi-Ethnic Study of Atherosclerosis (n=2,685).
• Subjects included individuals with CP-DM (n=321), T2DM (n=423), and nondiabetic controls (n=3,554).

Main Results:

• The mean GRS was statistically identical between CP-DM and T2DM groups (P = 0.95).
• Both diabetic groups exhibited significantly higher GRS compared to nondiabetic controls (P < 0.0001).
• Exploratory analyses, including stricter definitions for CP-DM, did not enhance the GRS's ability to distinguish between the groups.

Conclusions:

• The findings suggest that CP-DM may represent a subtype of T2DM, rather than a distinct entity.
• Further large-scale prospective studies are warranted to validate this hypothesis.
• This has implications for understanding and managing diabetes in chronic pancreatitis patients.