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?

Diabet Med. 2019 Sep;36(9):1092-1099. doi: 10.1111/dme.13960. Epub 2019 Jun 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Blood Glucose Self-Monitoring
  • C-Peptide / blood*
  • C-Peptide / metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / epidemiology
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Practice Patterns, Physicians' / statistics & numerical data
  • United Kingdom / epidemiology
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents