Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, 100 Cambridge, Boston, MA, USA.
Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cardiovasc Diabetol. 2021 Feb 27;20(1):56. doi: 10.1186/s12933-021-01246-1.
Impaired fasting glucose (IFG) is a prevalent and potentially reversible intermediate stage leading to type 2 diabetes that increases risk for cardiometabolic complications. The identification of clinical and molecular factors associated with the reversal, or regression, from IFG to a normoglycemia state would enable more efficient cardiovascular risk reduction strategies. The aim of this study was to identify clinical and biological predictors of regression to normoglycemia in a non-European population characterized by high rates of type 2 diabetes.
We conducted a prospective, population-based study among 9637 Mexican individuals using clinical features and plasma metabolites. Among them, 491 subjects were classified as IFG, defined as fasting glucose between 100 and 125 mg/dL at baseline. Regression to normoglycemia was defined by fasting glucose less than 100 mg/dL in the follow-up visit. Plasma metabolites were profiled by Nuclear Magnetic Resonance. Multivariable cox regression models were used to examine the associations of clinical and metabolomic factors with regression to normoglycemia. We assessed the predictive capability of models that included clinical factors alone and models that included clinical factors and prioritized metabolites.
During a median follow-up period of 2.5 years, 22.6% of participants (n = 111) regressed to normoglycemia, and 29.5% progressed to type 2 diabetes (n = 145). The multivariate adjusted relative risk of regression to normoglycemia was 1.10 (95% confidence interval [CI] 1.25 to 1.32) per 10 years of age increase, 0.94 (95% CI 0.91-0.98) per 1 SD increase in BMI, and 0.91 (95% CI 0.88-0.95) per 1 SD increase in fasting glucose. A model including information from age, fasting glucose, and BMI showed a good prediction of regression to normoglycemia (AUC = 0.73 (95% CI 0.66-0.78). The improvement after adding information from prioritized metabolites (TG in large HDL, albumin, and citrate) was non-significant (AUC = 0.74 (95% CI 0.68-0.80), p value = 0.485).
In individuals with IFG, information from three clinical variables easily obtained in the clinical setting showed a good prediction of regression to normoglycemia beyond metabolomic features. Our findings can serve to inform and design future cardiovascular prevention strategies.
空腹血糖受损（IFG）是导致 2 型糖尿病的一种普遍且潜在可逆的中间阶段，会增加患心血管代谢并发症的风险。确定与从 IFG 向正常血糖状态逆转或消退相关的临床和分子因素，将使心血管风险降低策略更加有效。本研究的目的是在一个以 2 型糖尿病发病率高为特征的非欧洲人群中，确定向正常血糖状态逆转的临床和生物学预测因子。
我们在 9637 名墨西哥个体中进行了一项前瞻性、基于人群的研究，使用临床特征和血浆代谢物。其中，491 名个体被分类为 IFG，定义为基线时空腹血糖在 100-125mg/dL 之间。在随访时，空腹血糖<100mg/dL 被定义为向正常血糖状态的逆转。通过核磁共振谱对血浆代谢物进行了分析。使用多变量 Cox 回归模型来研究临床和代谢组学因素与向正常血糖状态逆转的相关性。我们评估了仅包含临床因素的模型和包含临床因素和优先代谢物的模型的预测能力。
在中位随访 2.5 年期间，22.6%的参与者（n=111）向正常血糖状态逆转，29.5%的参与者进展为 2 型糖尿病（n=145）。年龄每增加 10 岁，向正常血糖状态逆转的多变量调整相对风险为 1.10（95%置信区间 [CI] 1.25-1.32），BMI 增加 1 SD 的相对风险为 0.94（95% CI 0.91-0.98），空腹血糖增加 1 SD 的相对风险为 0.91（95% CI 0.88-0.95）。包含年龄、空腹血糖和 BMI 信息的模型对向正常血糖状态逆转的预测效果良好（AUC=0.73（95% CI 0.66-0.78）。添加优先代谢物（大 HDL 中的 TG、白蛋白和柠檬酸盐）信息后的改善不显著（AUC=0.74（95% CI 0.68-0.80），p 值=0.485）。
在 IFG 个体中，在临床环境中容易获得的三个临床变量的信息，在代谢组学特征之外，对向正常血糖状态的逆转有较好的预测作用。我们的研究结果可用于指导和设计未来的心血管预防策略。
