Sepsis uncouples serum C-peptide and insulin levels in critically ill patients with type 2 diabetes mellitus.

Objective: To assess the effects of sepsis and exogenous insulin on C-peptide levels and C-peptide to insulin ratios in intensive care unit (ICU) patients with type 2 diabetes mellitus (T2DM). Design, setting and participants: In this prospective, observational, single-centre study, we enrolled 31 ICU-admitted adults with T2DM. We measured serum C-peptide and insulin levels during the first 3 days of ICU stay and recorded characteristics of exogenous insulin therapy. Patients were compared on the basis of the presence of sepsis, and their exposure to exogenous insulin therapy. C-peptide levels were also measured in eight healthy subjects. Main outcome measures: Serum insulin and C-peptide levels during the first 3 days in ICU. Results: Median C-peptide levels were higher in the ICU population compared with healthy subjects (10.9 [IQR, 8.2-14.1] v 4.8 [IQR, 4.6-5.1] nmol/L, P < 0.01). Sepsis was present in 25 ICU patients (81 %). Among ICU patients unexposed to exogenous insulin, the 11 patients with sepsis had higher median C-peptide levels compared with the six non-septic patients (2.5 [IQR, 1.8-3.7] v 1.7 [IQR, 0.8-2.2] nmol/L, P = 0.04), and a threefold higher C-peptide to insulin ratio (45 [IQR, 37-62] v 13 [IQR, 11-17], P = 0.03). However, septic patients exposed to exogenous insulin had lower median C-peptide levels (1.2 [IQR, 0.7-2.3] nmol/L, P = 0.01) and C-peptide to insulin ratios (5 [IQR, 2-10], P < 0.01) compared with insulin-free septic patients. The C-peptide to insulin ratio was significantly associated with white cell count and severity of illness in insulin-free septic patients. Conclusion: C-peptide levels were elevated in critically ill patients with T2DM. In this population, sepsis increased C-peptide levels and uncoupled serum C-peptide and insulin levels. Exogenous insulin decreased both C-peptide levels and C-peptide to insulin ratios.