Rapid loss of C-peptide tied to risk of severe hypoglycemia in children with type 1 diabetes: Study

A rapid beta-cell function loss in children having T1D is predicted by the presence of multiple autoantibodies and low age at diagnosis. The study published in BMJ Open Diabetes Research & Care further stated that a high BMI SD score at diagnosis is predictive of remaining beta-cell function during the follow-up of 6 years.

It is already known that ketoacidosis, low age at onset and high HbA1c are linked with rapid loss of beta-cell function following the onset of type 1 diabetes. Higher frequency of the HLADR3 genotype and lower HbA1c during the first years are associated with long-term preservation of C-peptide. Considering this, Annika Grönberg, Uppsala University, Uppsala, Sweden, and colleagues aimed to identify early characteristics linked with the rapid or slow decline of beta-cell function and by what means it impacts the clinical course.

For this purpose, the researchers assessed stimulated C-peptide in 50 children by mixed meal tolerance test during 2004–2017, at regular intervals for six years from the diagnosis of type 1 diabetes. There was a rapid decline of stimulated C-peptide in 40% of children; the rapid decline was defined as no measurable C-peptide (<0.03 nmol/L) after 30 months of diagnosis.

The study led to the following findings:

• At diagnosis, higher frequencies of detectable glutamic acid decarboxylase antibodies (GADA) and islet cell autoantibodies islet antigen 2 (IA-2A) were linked with rapid loss of beta-cell function.
• By age at 18 months and 30 months duration, C-peptide was predicted positively.
• BMI SD scores at diagnosis predicted higher C-peptide at diagnosis, three months, nine months, 30 months, three years, four years and six years. In contrast, high blood glucose and HbA1c at diagnosis predicted a lower C-peptide at diagnosis for both comparisons.
• IA-2A and GADA were negative predictors of C-peptide at nine months, 18 months and 30 months.
• Ten children experienced 22 events of severe hypoglycemia and had lower mean C-peptide at 18 months, 30 months and six years compared with others.
• Seven had a rapid decline of C-peptide, and there was a nearly fivefold increase (OR=4.846) in the odds of experiencing severe hypoglycemia.

"The findings indicate that multiple autoantibodies and low age at diagnosis predict a rapid decline in the beta-cell function. C-peptide loss is linked with greater risk and higher frequency of severe hypoglycemia events and less control of good blood sugar," the researchers stated. "A higher BMI SD score at diagnosis predicts a slow decline of beta-cell function."

Results imply that repeated C-peptide measurements during follow-up of type 1 diabetes are warranted and critical for identifying children and adolescents at the highest severe hypoglycemia risk.

Reference:

Grönberg A, Espes D, Carlsson P, et alHigher risk of severe hypoglycemia in children and adolescents with a rapid loss of C-peptide during the first 6 years after type 1 diabetes diagnosisBMJ Open Diabetes Research and Care 2022;10:e002991. doi: 10.1136/bmjdrc-2022-002991