Low levels of C‐peptide have clinical significance for established Type 1 diabetes

Abstract

Aim To determine whether the low C-peptide levels (<50 pmol/l) produced by the pancreas for decades after onset of Type 1 diabetes have clinical significance. Methods We evaluated fasting C-peptide levels, duration of disease and age of onset in a large cross-sectional series (n=1272) of people with Type 1 diabetes. We then expanded the scope of the study to include the relationship between C-peptide and HbA1c control (n=1273), as well as diabetic complications (n=324) and presence of hypoglycaemia (n=323). The full range of C-peptide levels was also compared with 1,5-Anhydroglucitol, a glucose responsive marker. Results C-peptide levels declined for decades after diagnosis, and the rate of decline was significantly related to age of onset (P<0.0001), after adjusting for disease duration. C-peptide levels > 10 pmol/l were associated with protection from complications (e.g. nephropathy, neuropathy, foot ulcers and retinopathy; P=0.03). Low C-peptide levels were associated with poor metabolic control measured by HbA1c (P<0.0001). Severe hypoglycaemia was associated with the lowest C-peptide levels compared with mild (P=0.049) or moderate (P=0.04) hypoglycaemia. All levels of measurable C-peptide were responsive to acute fluctuations in blood glucose levels as assessed by 1,5-Anhydroglucitol (P<0.0001). Conclusions Low C-peptide levels have clinical significance and appear helpful in characterizing groups at-risk for faster C-peptide decline, complications, poorer metabolic control and severe hypoglycaemia. Low C-peptide levels may be a biomarker for characterizing at-risk patients with Type 1 diabetes.

Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes

“…To the best of our knowledge, this was the first study of the effect of MSC infusion on patients with severe diabetes and our novel data extended previous findings111213 and support the notion that infusion with MSCs benefits T1D patients by preserving β-cell function. Notably, preservation of β-cell function and control of hyperglycemia are crucial for reducing and preventing long-term hyperglycemia-related complication, which is a leading cause of morbidity and mortality of diabetic patients1718. Our findings may aid in design of new therapies for patients with severe T1D.…”

Correlation Among Hypoglycemia, Glycemic Variability, and C-Peptide Preservation After Alefacept Therapy in Patients with Type 1 Diabetes Mellitus: Analysis of Data from the Immune Tolerance Network T1DAL Trial

“…17, 18, 20 It is known that the rate of decline of β-cell function after diagnosis in T1D is highly variable and many patients retain detectable insulin secretion (as measured by stimulated C-peptide production) for years or decades. 19 The basis for this variability is not understood but is partly a function of age at disease onset as well as the intensity of diabetes management in the early period after diagnosis. 32 Regardless of the mechanism of this variability, those with better preserved C-peptide secretion have lower rates of hypoglycemia and decreased microvascular complications.…”

“…17 The original analyses suggested that these clinical benefits were associated with C-peptide levels above a minimum threshold of 0.2 pmol/mL (“responders”), but more recent analyses indicate that reduced rates of hypoglycemia and microvascular complications are observed across a range of C-peptide values with no threshold or breakpoint, 18 suggesting that even very low levels of preserved C-peptide secretion in T1D can confer clinical benefits. 19 …”

GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis

“…to fully support a clinical benefit for it. However, some experts argue that C-peptide retention is a clinically important endpoint in its own right, pointing to research suggesting that residual C-peptide confers clinical benefits including better long-term glycaemic control [17–19]. Nonetheless, our study was designed to answer the question of whether or not GAD therapy should be developed further, so we await optimisation of this vaccine before a robust appraisal of its full clinical benefit can be attempted.…”