Residual β cell function in long-term type 1 diabetes associates with reduced incidence of hypoglycemia

Abstract

BACKGROUNDWe investigated residual β cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM).METHODSSerum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among nonresponders (all C-peptide values after meal <0.003 nmol/L) and 3 categories of responders, classified by peak C-peptide concentration (nmol/L) as high (>0.2), intermediate (>0.03 to ≤0.2), and low (≥ 0.003 to ≤0.03).RESULTSOf the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C-peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and nonresponders demonstrated similar rates of advanced microvascular complications.CONCLUSIONβ Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of >0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia.TRIAL REGISTRATIONClinicalTrials.gov NCT00360815 and NCT00360893.FUNDINGDivision of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157).

Keywords: Autoimmunity; Diabetes; Endocrinology.

Conflict of interest statement

Conflict of interest: ABK declares research support from Siemens Healthcare Diagnostics. DR declares that her spouse is employed by Roche.

Figures

Figure 1. Plasma C-peptide MMTT response curves for high and intermediate responders in EDIC.

Plasma C-peptide MMTT response curves in EDIC for high responders (>0.2 nmol/L, n = 11) are shown in black and those for intermediate responders (>0.03 to ≤0.2 nmol/L, n = 60) are shown in gray.

Figure 2. Comparison of DCCT and EDIC plasma peak C-peptide concentrations for high responders (>0.2 nmol/L, n = 11).

Figure 3. Flow chart of participation in the C-peptide study.

A“Refused” included participants with scheduling conflicts, the inability to come in for an in-person clinic visit, or general unwillingness to participate. “Ineligible” participants included those with competing medical issues (e.g., gastrointestinal issues, cardiovascular or renal disease, cancer, dialysis, and kidney or pancreas transplant) or the inability to obtain venous access at the start of the study. “Other” includes participants with erratic blood sugars at the start of testing, who were unable to stabilize their glucose.