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.