Abstract
Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is one of the strongest diabetes loci identified to date; evidence suggests that it plays an important role in insulin secretion. Dietary factors that affect insulin demand might enhance the risk of diabetes associated with CDKAL1 variants. Our aim was to examine the interactions between dietary protein and fat intake and CDKAL1 genetic variants in relation to the risk of diabetes in Korean adults. Single nucleotide polymorphisms (SNPs) were selected with a genome-wide association study (GWAS) for diabetes after adjustment for age, gender, and examination site. Using data from the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), 3988 middle-aged Korean adults between 40–76 years of age (2034 men and 1954 women) were included in the study. Finally, rs7756992 located within the CDKAL1 gene region was selected from GWAS (p-value < 5 × 10−8). Multivariable logistic regression models were used to evaluate the interactions between genotypes and dietary protein and fat intake in relation to diabetes risk after adjustment for age, gender, BMI, waist circumference, physical activity, smoking status, drinking habits, and examination site. Significant interactions between CDKAL1 rs7756992 and dietary protein and fat intake for the risk of diabetes were observed in men (p-value < 0.05). In women, significant interactions between dietary protein and fat intake and CDKAL1 variants (rs7756992) were associated with increased risk of diabetes (p-value < 0.05). Dietary protein and fat intake interacted differently with CDKAL1 variants in relation to the risk of diabetes in Korean adults of both genders. These findings indicate that CDKAL1 variants play a significant role in diabetes and that dietary protein and fat intake could affect these associations.
Highlights
Diabetes is a rapidly growing public health issue which is associated with morbidity and premature mortality [1]
We investigated 3988 participants of the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), which included 2034 men (1297 with diabetes, 737 without diabetes) and 1954 women (1207 with diabetes, 747 without diabetes)
Dietary protein and fat intake interacted with CDKAL1 variants in relation to the risk of diabetes, which does vary depending on gender
Summary
Diabetes is a rapidly growing public health issue which is associated with morbidity and premature mortality [1]. Prevalence of diabetes is greater among Asians than in other populations from the rest of the world [2]. According to the Korea Health Statistics 2018, prevalence of diabetes in individuals aged 30 years and older (age standardized) was 12.4% (based on fasting blood glucose) and 13.8% (based on fasting blood glucose and glycated hemoglobin). More than one in 10 adults aged 30 years and older are diagnosed with diabetes mellitus in Korea [3]. Most individuals with type 2 diabetes suffer from serious complications such as nephropathy, neuropathy, retinopathy, cardiovascular disease, and dysfunction of pancreas, skeletal muscle, and liver physiology [4,5]. Diabetes is a complex disease caused by interactions between multiple genetic and environmental risk factors [6]. Genetic susceptibility synergistically acts in addition to environmental factors, leading to diabetes development [11]
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