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Published on: June 25, 2014
Exploring genetic risk factors for β-cell deterioration in type 2 diabetes mellitus: Insights from longitudinal
Shuhei Morita1, Yoshinori Shimajiri2, Yuko Matsuoka3
1First Department of Medicine, Wakayama Medical University, 811-1 Kimi-idera, Wakayama City, Wakayama 641-8509, Japan.
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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