Abstract
Aims: hyperglycemia impairs pancreatic β-cell function instantly, also known as glucotoxicity. It is unknown whether this insult is temporary or sustained, and little real-world evidence needs to reflect the relationship between hyperglycemic burden, per se, and glycemic durability. Materials and Methods: a retrospective observational cohort study was conducted to recruit newly-diagnosed type 2 diabetes mellitus (T2DM) patients. Durability was defined as the episode from first glycated hemoglobin A1c (HbA1c) below 7.0% to where it exceed 8.0% (with treatment failure) or where study ended (without treatment failure). Glycemic burden was defined with the area above a burden value line (HbA1c = 6.5%) but under the HbA1c curve (AUC), and it was then divided into two compartments with the demarcation timepoint once HbA1c was treated below or equal to 7.0%; the former AUC’ represented the initial insult; the latter AUC” represented the residual part. Multivariable regression models assessed factors associated with durability in whole participants and two distinct subgroups: patients with baseline HbA1c > 7.0% or ≤7.0%. Results: 1048 eligible participants were recruited and analyzed: 291 patients with treatment failure (durability 26.8 ± 21.1 months); 757 patients without treatment failure (durability 45.1 ± 31.8 months). Besides age, glycemic burden was the only constant determinant in the two subgroups. AUC’ or AUC” increased treatment failure, respectively, in baseline HbA1c > 7.0% or ≤7.0% subgroup [per 1%/90 days hazard ratio (95% confidence interval): 1.026 (1.018–1.034) and 1.128 (1.016–1.253)]. Other determinants include baseline HbA1c, initial OAD, and education level. Conclusions: in patients with newly-diagnosed T2DM, glycemic durability was negatively associated with greater glycemic burden.
Highlights
Glucotoxicity plays a pathogenic role in the early stages of type 2 diabetes mellitus (T2DM) as in vivo evidence reveals the loss of first-phase insulin secretion along with elevating plasma glucose [1]
oral antidiabetic (OAD), and initially prescribed insulin, we found that young age (p < 0.001), elementary school or uneducated, baseline hemoglobin A1c (HbA1c) (p < 0.001), high glycemic burden as initial glucotoxicity (AUC)’, SU use (p = 0.036), AGIs use (p = 0.021), and no OAD use were significantly associated with treatment failure
We found that glycemic burden, assessed by AUC, was associated with future long-term glycemic durability in real-world clinical care of newly-diagnosed
Summary
Glucotoxicity plays a pathogenic role in the early stages of type 2 diabetes mellitus (T2DM) as in vivo evidence reveals the loss of first-phase insulin secretion along with elevating plasma glucose [1]. The acute first-phase insulin response might be reversed after hyperglycemia is resolved, as T2DM remissions were found initially after bariatric surgery or intensive medication therapy in Remission Evaluation of Metabolic Interventions in Type 2 diabetes (REMIT study) [3,4]. We are curious about whether the insult of glucotoxicity in newlydiagnosed T2DM patients are not transient but persistent, which may be further presented in the form of secondary treatment failure. Hyperglycemia induces glucotoxicity and increases microvascular complications, macrovascular complications, and associated mortality in T2DM patients [7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
