Persistent C‐peptide is associated with reduced hypoglycaemia but not HbA 1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Aims Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA 1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C‐peptide on rate of hypoglycaemia and HbA 1c in those with long duration (> 5 years) Type 1 diabetes. Methods We conducted a cross‐sectional case–control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C‐peptide after a mixed‐meal tolerance test. We compared self‐reported hypoglycaemia ( n  = 160), HbA 1c , insulin dose and microvascular complications ( n  = 140) in those with preserved and low C‐peptide. Results Stimulated median ( IQR ) C‐peptide was 114 (43, 273) pmol/l and < 3 (< 3, < 3) pmol/l in those with preserved and low C‐peptide respectively. Participants with preserved C‐peptide had lower reported monthly rates of hypoglycaemia, with 21% fewer symptomatic episodes, 5.9 vs. 7.5 [incidence rate ratio ( IRR ) 0.79, P  = 0.001], and 65% fewer asymptomatic episodes, 1.0 vs. 2.9 ( IRR 0.35, P  < 0.001). Those with preserved C‐peptide had a lower insulin dose (0.68 vs. 0.81 units/kg, P  = 0.01) but similar HbA 1c (preserved 69 vs. low 67 mmol/mol, P  = 0.06). Conclusions Adults with Type 1 diabetes and preserved endogenous insulin production receiving usual care in the UK have lower daily insulin doses and fewer self‐reported hypoglycaemic episodes, but no difference in HbA 1c . This is consistent with non‐intensive treatment in previous studies, and suggests a need to consider therapy intensification to gain full benefit of preserved endogenous insulin.