Dataset Information

Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults.

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.

SUBMITTER: Choi WJ

PROVIDER: S-EPMC7460637 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults.

Choi Woo Jeong WJ Jin Hyun-Seok HS Kim Sung-Soo SS Shin Dayeon D

International journal of molecular sciences 20200805 16

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 adu ...[more]

PMID: 32764395

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Project description:BACKGROUND/OBJECTIVE:The CDKAL1 gene is among the best-replicated susceptibility loci for type 2 diabetes, originally identified by genome-wide association studies in humans. To clarify a physiological importance of CDKAL1, we examined effects of a global Cdkal1-null mutation in mice and also evaluated the influence of a CDKAL1 risk allele on body mass index (BMI) in Japanese subjects. METHODS:In Cdkal1-deficient (Cdkal1?/?) mice, we performed oral glucose tolerance test, insulin tolerance test, and perfusion experiments with and without high-fat feeding. Based on the findings in mice, we tested genetic association of CDKAL1 variants with BMI, as a measure of adiposity, and type 2 diabetes in Japanese. PRINCIPAL FINDINGS:On a standard diet, Cdkal1?/? mice were modestly lighter in weight than wild-type littermates without major alterations in glucose metabolism. On a high fat diet, Cdkal1?/? mice showed significant reduction in fat accumulation (17% reduction in %intraabdominal fat, P?=?0.023 vs. wild-type littermates) with less impaired insulin sensitivity at an early stage. High fat feeding did not potentiate insulin secretion in Cdkal1?/? mice (1.0-fold), contrary to the results in wild-type littermates (1.6-fold, P<0.01). Inversely, at a later stage, Cdkal1?/? mice showed more prominent impairment of insulin sensitivity and glucose tolerance. mRNA expression analysis indicated that Scd1 might function as a critical mediator of the altered metabolism in Cdkal1?/? mice. In accordance with the findings in mice, a nominally significant (P<0.05) association between CDKAL1 rs4712523 and BMI was replicated in 2 Japanese general populations comprising 5,695 and 12,569 samples; the risk allele for type 2 diabetes was also associated with decreased BMI. CONCLUSIONS:Cdkal1 gene deletion is accompanied by modestly impaired insulin secretion and longitudinal fluctuations in insulin sensitivity during high-fat feeding in mice. CDKAL1 may affect such compensatory mechanisms regulating glucose homeostasis through interaction with diet.

Project description:Abstract Objectives Genetic variation contributes to individual differences in food preference, dietary habit, and nutrient intake, thus affecting nutritional status. Although studies which showed the relevance between genetic differences and the intake of nutrients such as carotenoid, vitamin E, and fat are available, more studies are needed for implementation of precision nutrition. Objective of the study was to investigate genetic variations that are associated with nutrient intake and taste sensitivity. Methods A total of 100 healthy adults (50 men and 50 women) aged 25–35 y who were free of diseases were recruited. Anthropometric measurements, clinical parameters including CBC, lipid profile, glucose level, and liver function tests, dietary intake data using 3-day food record, and taste sensitivity for salty and sweet tastes were determined. A total of 800,000 single nucleotide polymorphisms (SNPs) were analyzed by Theragen Etex using Theragen Precision Medicine Research Array (PMRA) chips. Results A total of 577,164 qualified SNPs were analyzed and three SNPs that might have significant relevance with energy intake (rs75052357, rs1125186, rs73471118) were identified. Carriers of the C allele in rs75052357 (C > T), which is identified in IQGAP1 loci, showed significantly higher fat mass (CC: 16.16 ± 3.52 kg, TC: 14.26 ± 3.58 kg, TT: 12.43 ± 3.83 kg) and higher % body fat (CC: 25.68 ± 5.40%, TC: 22.79 ± 6.10%, TT: 20.60 ± 7.52%) despite a lower energy intake (CC: 1782.2 ± 445.5 kcal, TC: 2212.5 ± 424.1 kcal, TT: 2315.0 ± 892.6 kcal). Carriers of G allele in rs1125186 (G > C) had significantly higher fat mass (CC: 13.34 ± 16.22 kg, CG: 16.22 ± 3.48 kg, GG: 15.67 ± 3.63 kg) in spite of lower energy intake compared with CC carriers (CC: 2222.5 ± 515.9 kcal, CG: 1927.9 ± 452.6 kcal, GG: 1745.7 ± 476.7 kcal). Carriers of T allele in rs73471118 (C > T) had significantly higher energy intake (CC: 1815.5 ± 445.0 kcal, TC: 2726.5 ± 490.6 kcal), while having lower threshold for sweet taste (CC: 8.94 ± 8.51 g/L TC: 0.40 ± 0.00 g/L). Conclusions Novel SNPs showing associations between energy consumption and fat mass or sugar taste sensitivity have been identified. This finding can help developing personalized recommendation for energy intake, however, further studies to delineate the mechanisms are needed. Funding Sources Supported by Seoul National University Research Grant in 2018.

Project description:The relationship between the variants of bitter taste receptor gene TAS2R4, dietary intake, and incidence of type 2 diabetes mellitus (T2DM) remains unclear. Hence, we aimed to examine the association of TAS2R4 rs2233998 variants with T2DM incidence in middle-aged and older Korean adults to understand if their association was modulated by dietary intake. Data of the Ansan-Ansung cohort from the Korean Genome and Epidemiology Study were used in this study. A total of 4552 Korean adults aged 40-69 years with no history of T2DM or cancer at baseline were followed-up for 16 years. Dietary intake was assessed using a 103-item food frequency questionnaire, and new T2DM cases were defined based on the World Health Organization and International Diabetes Federation criteria. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM incidence. During the mean follow-up period of 11.97 years, 1082 (23.77%) new T2DM cases were identified. Women carrying the TT genotype of TAS2R4 rs2233998 exhibited 1.48 times higher incidence of T2DM (HR: 1.48; 95 CI: 1.13-1.93) than those carrying the CC genotype. TAS2R4 rs2233998 variants were positively associated with the incidence of T2DM among Korean women with high intakes of carbohydrates or sugars and low intakes of fruits or vegetables. TT carrier women in the highest tertile of carbohydrate or sugar intake exhibited an increased incidence of T2DM (HR: 2.08, 95% CI: 1.33-3.27 for carbohydrates; HR: 2.31, 95% CI: 1.53-3.51 for sugars) than CC carrier women. Women carrying the TT genotype in the lowest tertile exhibited an increased incidence of T2DM (HR: 1.55, 95% CI: 1.02-2.37 for vegetables; HR: 1.62, 95% CI: 1.06-2.48 for fruits) than women carrying the CC genotype in the highest tertile of vegetable or fruit consumption. However, no association was observed between TAS2R4 rs2233998 variants and dietary intake with T2DM incidence in Korean men. Our findings suggest that variants of TAS2R4 rs2233998 are associated with T2DM incidence, and their associations are strengthened by excessive intake of carbohydrates or sugars and inadequate intake of fruits or vegetables. Diet encompassing optimal intake of carbohydrates or sugars and high intake of fruits or vegetables may minimize the risk of developing T2DM.

Dataset Information

Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults.

Publications

Dietary Protein and Fat Intake Affects Diabetes Risk with <i>CDKAL1</i> Genetic Variants in Korean Adults.

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