Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, United States of America.
Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States of America.
PLoS One. 2024 Jun 3;19(6):e0302643. doi: 10.1371/journal.pone.0302643. eCollection 2024.
The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828.
We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables.
By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (β = -0.05 mmol/L/year per allele, p = 0.058 among women; β = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes.
Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting.
CREB3 调节因子 rs373863828 的 A 等位基因与高体重指数相关，但与 2 型糖尿病的几率较低相关。这些关联已在其他地方得到复制，但迄今为止，所有研究都是横断面研究。我们的目的是：(1)描述无 2 型糖尿病或基线时未使用糖尿病药物的成年萨摩亚人纵向队列中，2010 年至 2018 年间 2 型糖尿病的发展和空腹血糖的变化；(2)检查空腹血糖变化率（mmol/L/年）与 rs373863828 的 A 等位基因之间的关联。
我们描述并测试了 2010 年至 2018 年间 n = 401 名成年萨摩亚人队列中空腹血糖、2 型糖尿病的发展、体重指数、年龄、吸烟状况、身体活动、居住的城市性和家庭资产评分之间的差异，这些人被选择为具有 GG:AG:AA rs373863828 基因型的~2:2:1 比值。多元线性回归用于检验空腹血糖变化率与 rs373863828 基因型和其他基线变量之间的关系。
到 2018 年，所有基因型组的空腹血糖和体重指数均显著升高，且大部分样本发生 2 型糖尿病。A 等位基因与空腹血糖变化率降低相关（女性中每等位基因β=-0.05mmol/L/年，p=0.058；男性中每等位基因β=-0.004mmol/L/年，p=0.863），在考虑了基线变量后。在 8 年期间，空腹血糖和平均体重指数均升高，到 2018 年，大量个体发生 2 型糖尿病。然而，AG 和 AA 基因型女性的空腹血糖变化率和 2 型糖尿病的发展较低。
需要进一步研究以了解 A 等位基因对空腹血糖和 2 型糖尿病发展的影响。基于我们观察到随着时间的推移其他风险因素增加的结果，我们主张在这种情况下继续促进糖尿病预防和治疗计划，并减少可改变的风险因素。
