Hemoglobin glycation index among adults with type 1 diabetes: Association with double diabetes features

Abstract

Background: The hemoglobin glycation index (HGI) represents the discrepancy between the glucose management indicator (GMI) based on mean blood glucose levels and laboratory values of glycated hemoglobin (HbA1c). The HGI is a promising indicator for identifying individuals with excessive glycosylation, facilitating personalized evaluation and prediction of diabetic complications. However, the factors influencing the HGI in patients with type 1 diabetes (T1D) remain unclear. Autoimmune destruction of pancreatic β cells is central in T1D pathogenesis, yet insulin resistance can also be a feature of patients with T1D and their coexistence is called "double diabetes" (DD). However, knowledge regarding the relationship between DD features and the HGI in T1D is limited.

Aim: To assess the association between the HGI and DD features in adults with T1D.

Methods: A total of 83 patients with T1D were recruited for this cross-sectional study. Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI. DD features included a family history of type 2 diabetes, overweight/obesity/central adiposity, hypertension, atherogenic dyslipidemia, an abnormal percentage of body fat (PBF) and/or visceral fat area (VFA) and decreased estimated insulin sensitivity. Skin autofluorescence of advanced glycation end products (SAF-AGEs), diabetic complications, and DD features were assessed, and their association with the HGI was analyzed.

Results: A discrepancy was observed between HbA1c and GMI among patients with T1D and DD. A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy (P = 0.030), particularly retinopathy (P = 0.031). Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI, compared with those without DD features (adjusted odds ratio = 8.12; 95% confidence interval: 1.52-43.47). Specifically, an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI. Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.

Conclusion: In patients with T1D, DD features are associated with a higher HGI, which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.

Keywords: Advanced glycation end products; Diabetic complications; Double diabetes; Hemoglobin glycation index; Insulin resistance; Type 1 diabetes.

Figure 1

Relationships among glucose management indicator, laboratory glycated hemoglobin, and skin autofluorescence of advanced glycation end products. A: The correlation plot between glucose management indicator (GMI) and laboratory glycated hemoglobin (HbA1c); B: The discrepancy of GMI and laboratory HbA1c among different hemoglobin glycation index (HGI) groups (error bars represent standard error of the mean); C: The correlation plot between HGI and skin autofluorescence of advanced glycation end products. HGI groups were determined by HGI value tertile (low HGI: ≤ 0.12%; moderate HGI: 0.13%-0.70%; high HGI: ≥ 0.71%). ^bP < 0.01. ^cP < 0.001. GMI: Glucose management indicator; HbA1c: Glycated hemoglobin; HGI: Hemoglobin glycation index; SAF-AGEs: Skin autofluorescence of advanced glycation end products.

Figure 2

Prevalence of diabetic microangiopathy among different hemoglobin glycation index groups. ^aP < 0.05. Significant difference between high and low hemoglobin glycation index group, corrected for multiple comparisons using the Bonferroni method. HGI: Hemoglobin glycation index.

Figure 3

Odds ratios and 95% confidence intervals for the association between double diabetes features and hemoglobin glycation index groups. Forest plots display odds ratios and 95% confidence intervals. ¹Moderate hemoglobin glycation index group compared to low hemoglobin glycation index group. ²High hemoglobin glycation index group compared to low hemoglobin glycation index group. Confounding variables adjusted: Age, gender, duration of diabetes and hemoglobin. OR: Odds ratio; 95%CI: 95% confidence interval; HGI: Hemoglobin glycation index; DD: Double diabetes; T2D: Type 2 diabetes; PBF: Percent total body fat; VFA: Visceral fat area; eIS: Estimated insulin sensitivity.