Fasting C-peptide indicates hypoglycemia risk at basal insulin initiation
medwireNews: Fasting C-peptide levels can “provide valuable information” to guide the approach to titrating basal insulin in new users with type 2 diabetes, say researchers.
During the first 24 weeks after insulin initiation, the rate of hypoglycemia decreased with increasing fasting C-peptide level, report Wolfgang Landgraf (Sanofi, Frankfurt, Germany) and colleagues in Diabetes, Obesity and Metabolism.
Specifically, the average hypoglycemia incidence was 66.0% in the subgroup of people with C-peptide levels of 0.4 nmol/L or below, 51.0% for those with levels of 0.4 to 1.2 nmol/L, 43.2% for levels of 1.2 to 2.0 nmol/L, and 34.5% when levels were greater than 2.0 nmol/L.
The corresponding rates were 35.0%, 22.5%, 15.6%, and 11.3% for nocturnal hypoglycemia and 5.0%, 2.4%, 2.1%, and 0.0% for severe hypoglycemia. Each 0.4 nmol/L increase in C-peptide was associated with a significant 17% reduction in hypoglycemia risk on multivariate analysis.
The data, which come from 2165 participants of randomized trials who had fasting C-peptide measurements taken prior to initiating insulin glargine 100 U/mL, “further substantiates the broad heterogeneity” of insulin-naïve people with type 2 diabetes, says the team.
Landgraf and colleagues say that measuring C-peptide levels will tell clinicians whether patients are predominantly insulin-resistant or insulin-deficient, thus guiding personalized insulin initiation and titration.
“The more highly insulin-sensitive person may benefit from a cautious and slow initiation and titration of basal insulin, eventually requiring prandial supplementation, whereas the insulin-resistant individual will benefit from a more aggressive and forced titration of basal insulin,” they say.
In addition to baseline C-peptide levels, higher on-treatment glycated hemoglobin was associated with a lower hypoglycemia risk, and sulfonylurea use with a higher risk.
The largest proportion of people in the study – 58.5% – had C-peptide levels between 0.4 and 1.2 nmol/L, with 36.9% being above this range and just 4.6% below.
People with the lowest C-peptide levels experienced the most hypoglycemia despite having the lowest insulin dose at week 24. They had the longest diabetes duration, at a median of 8.8 years, the lowest average BMI, at 25.7 kg/m2, and were the least likely to achieve the glycated hemoglobin target of 7.0% (53 mmol/mol), at 26% versus 42–44% in the other groups.
The researchers also note that postprandial hyperglycemia was most common in this subgroup, “emphasising the need for additional treatment” targeting postprandial glucose levels.
They speculate that this group may have contained people with latent autoimmune diabetes in adults, or maturity onset diabetes of the young, and suggest that people with assumed type 2 diabetes and very low C-peptide levels should be further investigated for these alternative diabetes subtypes.
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