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A Simple Way to Calculate Beta Cell Functional Decline in People with Diabetes

Nov 17, 2018
 
Editor: Steve Freed, R.PH., CDE

Author: Arsalan Hashmi, PharmD. Candidate, LECOM College of Pharmacy

Study looks at using easy-to-measure variables to calculate the decline of a patient’s beta cells and incorporating this into routine tests.

Properly functioning beta cells are releasing both insulin and C-peptide on a 1:1 ratio. The C-peptide test is an excellent resource as it can tell the provider exactly what is going on inside the pancreas. As of today, the C-peptide test is the only test to confirm the destruction of beta cells in the autoimmune type 1 diabetes.

 

Current clinical trials are showing that monoclonal antibodies can be used to increase autoimmunity of the beta cells, which is a crucial factor in type 1 diabetes. As these new treatments for T1D are approved, the measures by which we treat the disease should also be updated for convenience of providers. As of today, the only way to test the function of beta cells is through the average C-peptide plasma concentration (CPAVE), which is a long and tedious process involving a liquid meal and numerous blood samples. Studies have shown a correlation between C-peptide’s response to glucose and a patients A1c, age, and BMI suggesting that these easy-to-measure factors can be used to analyze beta cell function. This study looked at data from eight trials to develop a simple test to determine the CPave using routine clinical measures and a fasting CPAVE.

Clinical and biochemical data were taken from the TrialNet trials at 0, 3, 6, and 12 months, and from Immune Tolerance Network trials at 0, 6, and 12 months. Plasma-C peptide concentrations conferred a sensitivity of 0.017 and 0.05 nmol/l respectively. After receiving this data, any missing variable was estimated and the two trials were corrected for differences. Statistical test included correlation and ROC curve analysis. Half the participants under 21 were used to train the Linear Mixed Models to determine CPEST (Estimate C-peptide) using a combination of 1 to 8 variables, discussed later in this article.

The remaining half of those under 21 validated the models. The reasons this age group was chosen was because it reflects the majority of patients who have type 1, beta cell function will decline faster in this group, and there is a higher chance of preserving beta cells. Ranking and validation of models was through Imer, which enabled the A1C to be determined. The lowest A1C was seen in the model, which took the following variables into consideration; BMI, diabetes duration, insulin dose/kg, Fasting C-Peptide, Fasting Plasma Glucose, and HbA1c. This model was strongly correlated to CPAVE (r2= 0.816, p<0.001). This model was applied to both males and females of ranging ages and stood true.

In this study, a clinical decline in beta cell function was defined as a decrease of at least 7.5% from baseline. The ROC curves tested if the CP(est) could recognize significant loss in beta cell function at 3, 6 and 12 months; AUROC was statistically significant:  0.89 (CI 0.87-0.92). When tested against the TN-05, TN-09 and ITN-27 trials for rituximab, abatacept and teplizumab respectively, CPEST showed no difference from CPAVE. Both tests agreed therapy preserved beta cells. CPEST showed to be better then IDAA1c and equivalent to CPAVE.

The variables that the model uses are easily measurable, and the accuracy of CPEST was at the same level as the CPAVE in detecting changes in beta cell function. Although age is looked at as a protective factor when it comes to beta cell dysfunction, the various models did not show that it plays a role in testing for beta cell decline. The study suggests that the other variables have corrected for age. This study is underpowered by up to 17%, however, there is also less deviation in CPEST than in CPAVE because of fasting, and less samples taken, so this may not be an issue. Larger phase 3 and 4 trials are needed. This study showed that CPEST is better than IDAA1c in identifying the declining beta cell function in diabetes. The study also suggests that the CPEST should be implemented in routine checkups due to its’ simplicity and accuracy.

Practice Pearls:

  • The CPEST uses a number of easy-to-measure variables and is equivalent to the C-peptide (CPAVE) test used to measure beta cell function.
  • The best variables the study found to measure beta cell health were BMI, diabetes duration, insulin dose/kg, Fasting C-Peptide, Fasting Plasma Glucose, and HbA1c.
  • The study population was largely European; larger stage 3 and 4 studies should be conducted to increase generalizability.

References:

Wentworth, John M., et al. “Beta Cell Function in Type 1 Diabetes Determined from Clinical and Fasting Biochemical Variables.” Philosophical Transactions of the Royal Society B: Biological Sciences, The Royal Society, 30 Aug. 2018, doi.org/10.1007/s00125-018-4722-z.

“C-Peptide Test: MedlinePlus Lab Test Information.” MedlinePlus, U.S. National Library of Medicine, 27 July 2018, medlineplus.gov/labtests/cpeptidetest.html.

Arsalan Hashmi, PharmD. Candidate, LECOM College of Pharmacy