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THE UNIQUE ROLE OF BETA CELLS IN T1D

BETA-CELL FUNCTION CAN IMPACT THE COURSE OF
PATIENTS' JOURNEYS WITH AUTOIMMUNE T1D1-6

BETA-CELL FUNCTION GOES BEYOND INSULIN

 

Although beta cells are best known for making insulin, they also have the vital role of maintaining glucose homeostasis, impacting a range of the body's organs and systems.7,8

An animated beta cell with a happy expression

T1D=type 1 diabetes.

BETA CELLS ARE KEY CONTRIBUTORS TO T1D PROGRESSION

Beta-cell function, as measured by C-peptide, can indicate patients' level of remaining beta-cell activity and help determine the extent of autoimmune T1D progression.9

Some of us working are better than none of us!; A cluster of animated beta cells with worried expressions

SOME FUNCTIONAL BETA CELLS ARE BETTER THAN NONE

It has been observed that in T1D even low beta cell function can produce adequate endogenous insulin to maintain glycemic control.10,11

C-PEPTIDE IS USED TO ASSESS PANCREATIC BETA-CELL FUNCTION

C-peptide is secreted by beta cells at a 1:1 ratio with insulin from proinsulin. It mirrors insulin production, and declining levels indicate loss of beta-cell function.3,6,13,14

C-PEPTIDE PROVIDES A MORE RELIABLE MEASURE OF BETA-CELL FUNCTION VS INSULIN14-16

C-PEPTIDE
Reliable measure of beta-cell function due to:
  • Constant rate of clearance
  • Not being affected by exogenous insulin
INSULIN
Difficult to measure accurately due to:
  • Variable rate of clearance
  • Being impacted by exogenous insulin

DYNAMIC C-PEPTIDE TESTING MORE CLOSELY REFLECTS PATIENT PHYSIOLOGY VS STATIC TESTING13

DYNAMIC
  • ✓ Measured via MMTT
  • ✓ Helps improve understanding of insulin secretion/sensitivity vs static measures
  • ✓ A reliable surrogate marker of beta-cell function in T1D and indicates endogenous insulin levels
STATIC
  • Measured via fasting/non-fasting random sample
  • Does not provide data on insulin secretion/sensitivity or beta-cell function

 

 

The C-peptide threshold for clinically meaningful beta-cell function is 0.2 pmol/mL or ≥0.6 ng/mL6,16

Based on a conversion from 0.2 pmol/mL using the molecular weight of 3020.3 g/mol for C-peptide.

ENDOGENOUS INSULIN PRODUCTION BY BETA CELLS REGULATES GLYCEMIC CONTROL

While exogenous insulin replaces endogenous insulin, it does not mimic the body’s natural ability to regulate glucose homeostasis.7,17

An animated beta cell with a happy expression; Efficiency suppresses glucose production in the liver; Facilitates uptake of glucose in the muscles; Helps maintain glucose homeostasis

References

  1. Jeyam A, Colhoun H, McGurnaghan S, et al. Clinical impact of residual C-peptide secretion in type 1 diabetes on glycemia and microvascular complications. Diabetes Care. 2021;44(2):390-398. 
  2. Gubitosi-Klug RA, Braffett BH, Hitt S, et al. Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia. J Clin Invest. 2021;131(3):e143011.  
  3. Palmer JP, Fleming GA, Greenbaum CJ, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004;53(1):250-264.  
  4. Lachin JM, McGee P, Palmer JP; DCCT/EDIC Research Group. Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes. 2014;63(2):739-748. 
  5. Steffes MW, Sibley S, Jackson M, Thomas W. β-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care. 2003;26(3):832-836. 
  6. Leighton E, Sainsbury CAR, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8(3):475-487. 
  7. Podobnik B, Korošak D, Skelin Klemen M, et al. β cells operate collectively to help maintain glucose homeostasis. Biophys J. 2020;118(10):2588-2595.  
  8. Röder PV, Wu B, Liu Y, Han W. Pancreatic regulation of glucose homeostasis. Exp Mol Med. 2016;48(3):e219. 
  9. Pociot F. Capturing residual beta cell function in type 1 diabetes. Diabetologia. 2019;62(1):28–32.
  10. Scheiner G, Weiner S, Kruger D, Pettus J. Screening for type 1 diabetes: Role of the diabetes care and education specialist. ADCES Pract. 2022;10(5):20-25. 
  11. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF. the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964-1974.
  12. Latres E, Greenbaum CJ, Oyaski ML, et al. Evidence for C-peptide as a validated surrogate to predict clinical benefits in trials of disease-modifying therapies for type 1 diabetes. Diabetes. 2024;73(6):823-833. 
  13. Galdierisi A, Carr ALJ, Martino M, et al. Quantifying beta cell function in the preclinical stages of type 1 diabetes. Diabetologia. 2023;66(12):2189‐2199.
  14. Maddaloni E, Bolli GB, Frier BM, et al. C-peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective. Diabetes Obes Metab. 2022;24(10):1912-1926. 
  15. Stankute I, Verkauskiene R, Dobrovolskiene R, et al. Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients. Diabetes Res Clin Pract. 2021;178:108938. 
  16. Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803-817.
  17. Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectr. 2004;17(3):183–190. 
  18. Lewis GF, Carpentier AC, Pereira S, Hahn M, Giacca A. Direct and indirect control of hepatic glucose production by insulin. Cell Metab. 2021;33(4):709-720. 
  19. Bekier M, Szkutnik-Fiedler D, Uruska A. Insulin resistance and iatrogenic hyperinsulinemia in type 1 diabetes — norm or complication? Role of metformin in type 1 diabetes mellitus. Acta Pol Pharm Drug Res. 2023;80(4):531-539.

MAT-US-2504443-v1.0-05/2025