The relative contribution of diurnal and nocturnal glucose exposures to HbA1c in type 1 diabetes males: a pooled analysis

Abstract

Purpose The exact contribution of daily glucose exposure to HbA1c in people with type 1 diabetes (T1D) remains controversial. We examined the contribution of pre- and postprandial glycaemia, nocturnal and early-morning glycaemia, and glycaemic variability to HbA1c levels in T1D. In this analysis, we used clinical data, namely age, BMI and HbA1c, as well as glycaemic metrics (24-h glycaemia, postprandial, nocturnal, early-morning glycaemia, wake-up glucose, and glycaemic variability) obtained over a four-week period of continuous glucose monitoring (CGM) wear in thirty-two males with T1D. Methods The trapezoid method was used estimate the incremental area under the glucose curve (iAUC) for 24-h, postprandial (3-h period following breakfast, lunch, and dinner, respectively), nocturnal (between 24:00–04:00 AM), and early-morning (2-h period 2-h prior to wake-up) glycaemia. Linear regression analysis was employed whereby CGM-derived glycaemic metrics were explanatory variables and HbA1c was the outcome. Results Thirty-two T1D males (mean ± SD: age 29 ± 4 years; HbA1c 7.3 ± 0.9% [56 ± 13 mmol/mol]; BMI 25.80 ± 5.01 kg/m2) were included in this analysis. In linear models adjusted for age and BMI, HbA1c was associated with 24-h mean glucose (r2 = 0.735, p < 0.001), SD (r2 = 0.643, p = 0.039), and dinner iAUC (r2 = 0.711, p = 0.001). CGM-derived metrics and non-glycaemic factors explained 77% of the variance in HbA1c, in which postprandial glucose accounted for 32% of the variance explained. The single greatest contributor to HbA1c was dinner iAUC resulting in 0.6%-point (~7 mmol/mol) increase in HbA1c per SD increase in dinner iAUC. Conclusions Using comprehensive CGM profiling, we show that postprandial glucose, specifically evening-time postprandial glucose, is the single largest contributing factor to HbA1c in T1D. Trial registration number NCT02204839 (July 30th 2014); NCT02595658 (November 3rd 2015).

Relative contributions of fasting and postprandial glucose increments, glycemic variability, and non‐glycemic factors to HbA1c in individuals with type 1 diabetes

“…Previously, it has been demonstrated that variances existed between CGM metrics and HbA1c and could be determined by many factors such as time period, variation in glycation rates, and factors such as anemia. In this study, the factors derived from CGM data contributed >70% of the variance in HbA1c, which is in line with the recently published data conducted among T1D males from Europe 13 . Of note, the non‐glycemia factors included in our study, such as age, BMI, diabetic duration, and Hb level, have a small contribution in HbA1c and there was still approximately 20%–30% of the variance in HbA1c undefined even though the contribution of glycemia was higher among those with HbA1c >7.3% .…”

“…In this study, the factors derived from CGM data contributed >70% of the variance in HbA1c, which is in line with the recently published data conducted among T1D males from Europe. 13 Of note, the non‐glycemia factors included in our study, such as age, BMI, diabetic duration, and Hb level, have a small contribution in HbA1c and there was still approximately 20%–30% of the variance in HbA1c undefined even though the contribution of glycemia was higher among those with HbA1c >7.3% . Recently, Ajjan and his colleagues had reported a model that incorporated erythrocyte lifespan, attempting to address limitations in laboratory HbA1c.…”

“…Since Monnier et al pivotally demonstrated the relative contribution of blood glucose in T2D, 6 , 7 the increasing bulk of evidence in T2D had been reported although few had concentrated on T1D, either focusing on adolescents 11 or only males, 13 or using self‐monitoring blood glucose (SMBG) data. 12 Therefore, in our study, focusing on adults with T1D, we found that BHG contributes the majority of diurnal hyperglycemia regardless of levels of HbA1c.…”

“… 6 , 7 , 8 , 9 However, most of these studies have focused on type 2 diabetes (T2D) particiapnts treated with or without insulin, 10 or mixed cohorts but composed of only a small percentage of T1D populations, 8 or analyzed glucose exposure from limited 24‐hour or single glucose value collected via fingerstick blood glucose monitoring (see Supplementary Table S1 ). Evidence for the exact contribution of daily postprandial glucose exposure in HbA1c in individuals with T1D is few, 11 , 12 , 13 with even less for Asian populations. Considering the biochemical and pathophysiological differences between T1D and T2D, a further discussion in T1D is essential to help improve its clinical management.…”

Macronutrient Intake in Children and Adolescents with Type 1 Diabetes and Its Association with Glycemic Outcomes

“…Postprandial hyperglycemia is independently associated with the development of cardiovascular disease (CVD) in people with T1D [5,6]. Additionally, a recent study found that postprandial glucose exposure is a stronger determinant of HbA1c, than preprandial glucose, nocturnal glucose, and glycemic variability in people with T1D, with the evening meal postprandial period being the single largest contributing factor to HbA1c [7].…”