BETA IMPACTS OUTCOMES

RESIDUAL BETA-CELL FUNCTION IS ASSOCIATED WITH LOWER HBA1C LEVELS⁸

Chart depicts HbA1C levels based on residual beta-cell function as measured by C-peptide.⁸

Study overview and limitations: Results from Danish Study Group for Childhood Diabetes (DanDiabKids) evaluating 342 pediatric patients aged 4.8-18.9 years with T1D for 3 to 6 years. Limitations were reported for this study. Thirty-nine percent of children eligible for the study according to the DanDiabKids registry did not participate. The HbA1c used for the study was analyzed locally.⁸

*Logistic regression analysis adjusted for sex, age, pubertal status, diabetes duration, and insulin administration technique.⁸

^†Standard meal–stimulated C-peptide was used to assess residual beta cell function.⁸

Figure adapted from Sørensen JS, et al. Diabetes Care. 2013.

CI=confidence interval; HbA1c=hemoglobin A1c; OR=odds ratio.

ASSOCIATION OF BETA-CELL FUNCTION AND TIME IN RANGE⁸

Chart depicts time in range based on residual beta-cell function as measured by urinary C-peptide-to-creatinine ratio (UCPCR)⁸

Study overview and limitations: Results of a cross-sectional cohort study examining the association between residual beta-cell function and glucose control (as metrics of continuous glucose monitoring) in patients with T1D (N=499). Limitations were reported for this study. First, because of the cross-sectional design, it is impossible to make claims of causality. Second, the UCPCR is not considered as gold standard for measuring beta-cell function. Therefore, this study may underestimate the contribution of beta-cell function to CGM-derived metrics and HbA1c. Finally, in the Netherlands, individuals with inadequate glycemic control generally have access to more devices. It is seen that participants with less beta-cell function more often use pumps, but did not obtain a better TIR, suggesting that the association between TIR and UCPCR may be further underestimated in this cohort of individuals with access to advanced tools of diabetes management.⁸

*Estimated using post-meal urinary C-peptide–to–creatinine ratio (UCPCR): undetectable (<0.01 nmol/mmol), low (0.01-0.2 nmol/mmol), intermediate (0.2-0.6 nmol/mmol), or high (>0.6 nmol/mmol).⁸

Figure adapted from Fuhri Snethlage CM, et al. Diabetes Care. 2024

BMI=body mass index; CGM=continuous glucose monitoring; HbA1c=hemoglobin A1c; T1D=type 1 diabetes; TIR=time in range.

ASSOCIATION OF RESIDUAL BETA-CELL FUNCTION AND INCIDENCE OF SEVERE HYPOGLYCEMIC EVENTS^1-6

Chart depicts incidence of severe hypoglycemic events with a mean of 6.5 years of follow-up based on residual beta-cell function as measured by C-peptide levels.^2¶

Figure adapted from Gubitosi-Klug RA, et al. J Clin Invest. 2021.

Study overview and limitations: An analysis conducted within the DCCT- EDIC cohort that evaluated residual beta-cell function in individuals with a mean T1D duration of 35 years. Beta-cell function was assessed through C-peptide concentrations, measured at 9 time points during a 4-hour MMTT. Participants were categorized by peak C-peptide concentration (nonresponder, low, intermediate, or high), and associations with metabolic outcomes, severe hypoglycemia, and microvascular complications were examined. ​ No limitations were reported for this study.^2,5

Data from the DCCT/EDIC studies, which included study participants from US and Canada. C-peptide studies, were carried out between 2015 and 2017.

*Hypoglycemia requiring assistance.^2
†Based on Cochran–Armitage trend test.^2
‡1 nmol/L C-peptide=3.0203 ng/mL. 
^§During a 4-hour MMTT, all C-peptide values were <0.003 nmol/L, which was the lower limit of detection for the C-peptide assay used in the study.^2 
||Peak C-peptide during 4-hour MMTT.^2 
¶During the DCCT study, participants were asked to report all episodes of suspected severe hypoglycemia immediately, and all participants were interviewed regarding the episodes using a standard series of questions. During the EDIC study, the ascertainment of events was restricted to the 3-month window prior to the annual visit and used the same standardized questions.²

DCCT=Diabetes Control and Complications Trial; EDIC=Epidemiology of Diabetes 
Interventions and Complications; MMTT=mixed-meal tolerance test; T1D=type 1 diabetes.

ASSOCIATION OF RESIDUAL BETA-CELL FUNCTION AND MOTOR SPEED PRESERVATION¹¹

After an 18-year follow-up, motor speed z-score increased with higher baseline stimulated C-peptide levels¹¹

Data presentation adapted from Wang T, et al. Diabetes. 2025.

Study overview: An analysis conducted of 1144 participants within the DCCT/EDIC aimed to determine whether baseline-stimulated C-peptide levels are associated with cognitive performance over an 18-year follow-up in adults with T1D. Baseline-stimulated C-peptide levels were measured using standardized assays and cognitive performance was assessed using a comprehensive neuropsychological test battery. Multivariable linear regression models were used to evaluate the association between baseline-stimulated C-peptide and cognitive z-scores adjusting for covariates including demographics, HbA1c, and diabetes-related complications (retinopathy, neuropathy, nephropathy).¹¹*

*During the DCCT study, participants were asked to report all episodes of suspected severe hypoglycemia immediately, and all participants were interviewed regarding the episodes using a standard series of questions. During the EDIC study, the ascertainment of events was restricted to the 3-month window prior to the annual visit and used the same standardized questions.²

DCCT=Diabetes Control and Complications Trial; EDIC=Epidemiology of Diabetes Interventions and Complications; HbA1c=hemoglobin A1c; T1D=type 1 diabetes.