Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

S M Marren, S Hammersley, T J McDonald, B M Shields, B A Knight, A Hill, R Bolt, T I Tree, B O Roep, A T Hattersley, A G Jones, R A Oram, TIGI consortium, S M Marren, S Hammersley, T J McDonald, B M Shields, B A Knight, A Hill, R Bolt, T I Tree, B O Roep, A T Hattersley, A G Jones, R A Oram, TIGI consortium

Abstract

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 HbA1c , hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C-peptide on rate of hypoglycaemia and HbA1c 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), HbA1c , 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 HbA1c (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 HbA1c . 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.

© 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Figures

Figure 1
Figure 1
Total monthly rate of hypoglycaemia by C‐peptide group. Rates of aware (blue) and unaware (green) episodes with blood glucose P < 0.0001, for low (n = 118) vs. preserved (n = 39) C‐peptide. Error bars represent 95% confidence intervals.
Figure 2
Figure 2
Boxplot of study visit HbA1c by C‐peptide group. Study visit HbA1c was similar in the low (n = 148) and preserved (n = 70) C‐peptide groups P = 0.06. Outliers are shown in Fig. S3.
Figure 3
Figure 3
Boxplot of daily insulin dose by C‐peptide group. Insulin dose was lower in the preserved C‐peptide group (n = 70) vs. the low (n = 151) group, P = 0.01. Outliers are shown in Fig. S5.

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