Largest Amplitude of Glycemic Excursion Calculating from Self-Monitoring Blood Glucose Predicted the Episodes of Nocturnal Asymptomatic Hypoglycemia Detecting by Continuous Glucose Monitoring in Outpatients with Type 2 Diabetes

AIMS: Nocturnal asymptomatic hypoglycemia (NAH) is a serious complication of diabetes, but it is difficult to be detected clinically. This study was conducted to determine the largest amplitude of glycemic excursion (LAGE) to predict the episodes of NAH in outpatients with type 2 diabetes. METHODS: Data were obtained from 313 outpatients with type 2 diabetes. All subjects received continuous glucose monitoring (CGM) for consecutive 72 hours. The episodes of NAH and glycemic variability indices (glucose standard deviation [SD], mean amplitude of plasma glucose excursion [MAGE], mean blood glucose [MBG]) were accessed via CGM. LAGE was calculated from self-monitoring blood glucose (SMBG). RESULTS: A total of 76 people (24.3%) had NAH. Compared to patients without NAH, patients with NAH showed higher levels of glucose SD (2.4 ± 0.9 mmol/L vs 1.7 ± 0.9 mmol/L, p <0.001), MAGE (5.2 ± 2.1 mmol/L vs 3.7 ± 2.0, p<0.001) and LAGE (4.6 ± 2.3 mmol/L vs 3.8 ± 1.9 mmol/L, p=0.007), and lower level of MBG (7.5 ± 1.5 mmol/L vs 8.4 ± 2.2 mmol/L, p=0.002). LAGE was significantly associated with the incidence of NAH and time below rang (TBR) in model 1 [NAH: 1.189 (1.027-1.378), p=0.021; TBR: 0.008 (0.002-0.014), p=0.013] with adjustment for age, BMI, sex, work, hyperlipidemia, complication and medication, and in model 2 [NAH: 1.177 (1.013-1.367), p=0.033; TBR: 0.008 (0.002-0.014), p=0.012] after adjusting for diabetes duration based on model 1, as well as in model 3 [NAH: 1.244 (1.057-1.464), p=0.009; TBR: 0.009 (0.002-0.016), p=0.007] with further adjustment for HbA1c based on model 2. In addition, no significant interactions were found between LAGE and sex, age, HbA1c, duration of diabetes, BMI and insulin therapy on the risk of NAH. The receiver operator characteristic (ROC) curve shows the ideal cutoff value of LAGE for the prediction of NAH was 3.48 mmol/L with 66.7% sensitivity, 50% specificity and 0.587 (95% CI: 0.509-0.665) of area under the ROC curve. CONCLUSIONS: High glycemic variability is strongly associated with the risk of NAH. The LAGE based on SMBG could be an independent predictor of NAH for outpatients with type 2 diabetes, and LAGE greater than 3.48 mmol/L could act as a warning alarm for high risk of NAH in daily life.