Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Diabetologia. 2019 May;62(5):779-788. doi: 10.1007/s00125-019-4829-x. Epub 2019 Feb 20.
AIMS/HYPOTHESIS: Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study.
We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed.
Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values.
CONCLUSIONS/INTERPRETATION: The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.
目的/假设：酮体可以被视为外周组织的节俭燃料，但它们的临床预后意义仍不清楚。我们在一项大型基于人群的观察性研究中，调查了自发禁食酮尿与糖尿病事件之间的关系，并结合代谢变量的变化进行了研究。
我们分析了韩国基因组和流行病学研究中 8703 名基线时无糖尿病的个体，这是一项基于社区的 12 年前瞻性研究。根据倾向评分，将有（n=195）或无禁食酮尿的个体按 1:4 匹配。糖尿病的定义为空腹血糖≥7.0mmol/L，2 小时餐后血糖≥11.1mmol/L，或使用降血糖药物。使用 Cox 回归模型，分析基线时存在酮尿与发生糖尿病的风险比（HR）。
在 12 年的随访中，在倾向评分匹配队列的 925 名参与者中，有 190 名（20.5%）发生了糖尿病。与无酮尿者相比，有自发性酮尿者的糖尿病发生率明显较低（HR 0.63；95%CI 0.41，0.97）。当将有禁食酮尿者与所有无酮尿者进行比较时，结果几乎相同（经过多变量调整后，HR 0.66；95%CI 0.45，0.96）。在随访期间，尽管基线值相当，有基线酮尿的参与者在 1 小时和 2 小时餐后血糖水平和胰岛素生成指数方面保持较低水平。
结论/解释：自发禁食酮尿的存在与糖尿病风险降低显著相关，独立于代谢变量。我们的研究结果表明，自发禁食酮尿可能在预防糖尿病发生方面具有潜在作用。
