Measuring extremely low levels of C-peptide in patients with type 1 diabetes may help predict future complications and HbA1c control, according to a presenter at the 50th European Association for the Study of Diabetes Annual Meeting.

 

Denise L. Faustman

 

Building on previous research that showed insulin production persists for decades, Faustman and colleagues investigated the clinical relevance of that production. They looked at the relationship between extremely low levels of C-peptide, defined as less than 10 pmol/L, and age of onset of diabetes (n=1,273), diabetes complications (n=324), HbA1c control (n=807), risk for hypoglycemia (n=331) and response to a mixed-meal tolerance test (n=9).

Comparing age of onset younger than 20 years to age of onset older than 20 years, Faustman showed a significant difference in the decline of C-peptide (P=.005).

“Indeed, when we start to stratify that data based on age of onset, you rapidly see that if you have an age of onset of young type of less than 10 years of age, your C-peptide falls very rapidly,” she said. “Age of onset is an influencing factor for how rapid the C-peptide declines.”

After adjusting for duration of disease, Faustman said extremely low levels of C-peptide were associated with risk for diabetes-related complications such as nephropathy, neuropathy and cardiovascular disease (P=.03) and worse metabolic control, as measured by HbA1c (P=.01).

“When we do this kind of stratification and the biostatistics department at Harvard corrects for disease duration, we rapidly start to see that very low levels of C-peptide, even low levels of 10 pmol/L, start to protect from complications. In other words, the persistence of C-peptide greater than 10 (pmol/L) prevents complications and that C-peptide less than 10 (pmol/L) biases you toward complications,” Faustman said. “Unlike past C-peptide levels in the 50 (pmol/L) to 60 (pmol/L) range, these lower levels are helping to subdivide patients into at risk vs. protection.”

Similarly, she showed data in which C-peptide levels less than 50 pmol/L offered a protective HbA1c effect.

“When C peptide got into these micro secretor ranges, we started seeing a flaring of the HbA1c, suggesting, like the complications data, that this was perhaps protective,” Faustman said. “Low C-peptide levels help to dramatically control HbA1c better than the standard of care.”

Lastly, Faustman showed data based on mass spectrometry analysis of the metabolite 1,5-anhydroglucitol (1,5-AG) that resulted in a “tight correlation” between C-peptide and 1,5-AG (P=.015).

“These low levels of C-peptide — though not totally protective of blood sugar — help to maintain glucose control,” she said. “Low levels of C-peptide are very responsive, even though they’re tiny levels, to direct blood sugar measurements as measured by mass spectrometry.”

Faustman DL. Abstract #91. Presented at: 50th EASD Annual Meeting; Sept. 16-19, 2014; Vienna