Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic.
Measuring endogenous insulin secretion using C-peptide can assist diabetes management, but standard stimulation tests are impractical for clinical use. Random non-fasting C-peptide assessment would allow testing when a patient is seen in clinic.



We compared C-peptide at 90 min in the mixed meal tolerance test (sCP) with random non-fasting blood C-peptide (rCP) and random non-fasting urine C-peptide creatinine ratio (rUCPCR) in 41 participants with insulin-treated diabetes [median age 72 (interquartile range 68-78); diabetes duration 21 (14-31) years]. We assessed sensitivity and specificity for previously reported optimal mixed meal test thresholds for severe insulin deficiency (sCP < 200 pmol//l) and Type 1 diabetes/inability to withdraw insulin (< 600 pmol//l), and assessed the impact of concurrent glucose.



rCP and sCP levels were similar (median 546 and 487 pmol//l, P = 0.92). rCP was highly correlated with sCP, r = 0.91, P < 0.0001, improving to r = 0.96 when excluding samples with concurrent glucose < 8 mmol//l. An rCP cut-off of 200 pmol//l gave 100% sensitivity and 93% specificity for detecting severe insulin deficiency, with area under the receiver operating characteristic curve of 0.99. rCP < 600 pmol//l gave 87% sensitivity and 83% specificity to detect sCP < 600 pmol//l. Specificity improved to 100% when excluding samples with concurrent glucose < 8 mmol//l. rUCPCR (0.52 nmol/mmol) was also well-correlated with sCP, r = 0.82, P < 0.0001. A rUCPCR cut-off of < 0.2 nmol/ mmol gave sensitivity and specificity of 83% and 93% to detect severe insulin deficiency, with area under the receiver operating characteristic curve of 0.98.



Random non-fasting C-peptide measures are strongly correlated with mixed meal C-peptide, and have high sensitivity and specificity for identifying clinically relevant thresholds. These tests allow assessment of C-peptide at the point patients are seen for clinical care.
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.|Department of Geriatrics, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
S V
SV
Hope
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.
B A
BA
Knight
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.
B M
BM
Shields
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.|Department of Diabetes & Endocrinology, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
A T
AT
Hattersley
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.|Department of Blood Sciences, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK.
T J
TJ
McDonald
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK. Angus.Jones@exeter.ac.uk.|Department of Diabetes & Endocrinology, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK. Angus.Jones@exeter.ac.uk.
A G
AG
Jones
D000368:Aged; D002096:C-Peptide / Q000097:blood*; D019411:Clinical Laboratory Techniques / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis*; D003940:Diagnostic Techniques, Endocrine; D005215:Fasting / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D062407:Meals
D002096:C-Peptide; D007328:Insulin