Exploring genetic risk factors for β-cell deterioration in type 2 diabetes mellitus: Insights from longitudinal C-peptide analysis.

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes research and clinical practice Pub Date : 2025-02-17 DOI:10.1016/j.diabres.2025.112049

Shuhei Morita, Yoshinori Shimajiri, Yuko Matsuoka, Yoshiki Kadoya, Shoichi Yamada, Taka-Aki Matsuoka, Tokio Sanke

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Abstract

Aims: Insulin secretion in type 2 diabetes mellitus deteriorates over time, but the factors influencing the degree of deteriorates remain unclear. This study aims to specifically identify genetic factors associated with this decline.

Methods: Fasting serum C-peptide was observed over 10.5 ± 4.7 years in 116 Japanese patients with type 2 diabetes mellitus without significant obesity or renal dysfunction. The individual annual decline of fasting serum C-peptide (IAD) was calculated using regression analysis. We evaluated the IAD in patients with or without susceptible allele of candidate single nucleotide polymorphisms (SNPs) in genes (KCNQ1, TCF7L2, CDKN2A/B, CDKAL1, UBE2E2, HHEX, and KCNJ11), which linked to insulin secretion in previous cross-sectional studies.

Results: The IAD was -1.513 [-2.635: -0.129] × 10^-2 nmol/L/year. Among the candidate SNPs, only KCNJ11 (rs5219) showed a significant difference in IAD between the patients with homozygous susceptibility allele TT (-2.583 [-3.285: -0.893] × 10^-2 nmol/L/year, N = 20) and those with TC/CC (-1.367 [-2.273: -0.767] × 10^-2 nmol/L/year, N = 96) (P = 0.035).

Conclusions: Using IAD calculated by fasting serum C-peptide over 10 years, KCNJ11 (rs5219) was identified as a genetic factor that was associated with the decline in insulin secretion in Japanese patients with type 2 diabetes mellitus.

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.