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

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 HbA 1c 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 HbA 1c ( 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.