Department of Cell Physiology and Metabolism, University of Geneva Medical Center, 1206 Geneva, Switzerland.
Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, Switzerland.
J Clin Endocrinol Metab. 2022 Sep 28;107(10):2833-2843. doi: 10.1210/clinem/dgac444.
During an asymptomatic prediabetic state, the functional ß-cell mass decreases to a critical threshold, triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.
Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts.
We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy.
Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (P < 0.0001) and hemoglobin A1c (P < 0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (P = 0.004) and Homeostatic Model Assessment of Insulin Resistance %S (P < 0.03) and was particularly high in nondiabetic obese individuals, potentially accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (P = 0.002), regardless their glucose tolerance status.
In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its noninvasive monitoring may alert about the loss of ß cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.
在无症状糖尿病前期，功能性β细胞群减少到临界阈值，引发糖尿病和相关症状。迄今为止，尚无可靠的检测方法能够在体内捕捉到β细胞群的潜在下降。
除了作为短期血糖控制标志物外，脱氧己糖 1,5-脱水葡萄糖醇在啮齿动物中被确定为功能性β细胞群的循环生物标志物，即使在无症状糖尿病前期阶段也是如此。本研究调查了不同人类队列中循环 1,5-脱水葡萄糖醇的潜在相关性。
我们分析了已确诊的 2 型糖尿病患者和被认为有发生糖尿病高风险的患者以及无糖尿病病史拟行胰十二指肠切除术的患者的临床和血液参数。
循环 1,5-脱水葡萄糖醇在 2 型糖尿病患者中降低，与空腹血糖（P<0.0001）和糖化血红蛋白（HbA1c）（P<0.0001）呈负相关。在健康受试者中，1,5-AG 水平与体重指数（P=0.004）和稳态模型评估的胰岛素抵抗 %S（P<0.03）呈正相关，在非糖尿病肥胖个体中尤其高，可能是由于β细胞代偿性扩张。无糖尿病病史的行胰十二指肠切除术的患者在手术后β细胞群急性损失，循环 1,5-脱水葡萄糖醇水平降低 50%（P=0.002），无论其血糖耐量状态如何。
总之，血浆 1,5-脱水葡萄糖醇浓度与β细胞群相关，其非侵入性监测可能会提示糖尿病高危人群β细胞的损失，这一事件无法通过其他血糖控制的临床参数来捕捉。
