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Biomarkers associated with severe hypoglycaemia and death in ACCORD
Author(s) -
Chow L. S.,
Chen H.,
Miller M. E.,
Marcovina S. M.,
Seaquist E. R.
Publication year - 2016
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.12883
Subject(s) - medicine , hypoglycemia , diabetes mellitus , intensive care medicine , endocrinology
Aims and hypothesis In patients with Type 2 diabetes, intensive glycaemic control is associated with hypoglycaemia and possibly increased mortality. However, no blood biomarkers exist to predict these outcomes. Using participants from the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) study, we hypothesized that insulin deficiency and islet autoantibodies in patients with clinically diagnosed Type 2 diabetes would be associated with severe hypoglycaemia and death. Methods A nested case–control study design was used. A case ( n = 86) was a participant who died with at least one episode of severe hypoglycaemia, defined as hypoglycaemia requiring assistance, at any point during ACCORD follow‐up. A control ( n = 344) was a participant who did not die and did not have severe hypoglycaemia during follow‐up. Each case was matched to four controls (glycaemic intervention arm, race, age and BMI ). Baseline insulin deficiency (fasting C–peptide ≤ 0.15 nmol/l) and islet autoantibodies [glutamic acid decarboxylase ( GAD ), tyrosine phosphatase‐related islet antigen 2 ( IA 2), insulin ( IAA ) and zinc transporter (ZnT8)] were measured. Conditional logistic regression with and without adjustment for age, BMI and diabetes duration was used. Results Death during ACCORD in those who experienced at least one episode of severe hypoglycaemia was associated with insulin deficiency [ OR 4.8 (2.1, 11.1): P < 0.0001], GAD antibodies [ OR 2.3 (1.1, 5.1): P = 0.04], the presence of IAA or baseline insulin use [ OR 6.1 (3.5,10.7): P < 0.0001], which remained significant after adjusting for age, BMI , and diabetes duration. There was no significant association with IA 2 or ZnT8 antibodies. Conclusions In patients with Type 2 diabetes, C–peptide or GAD antibodies may serve as blood biomarkers predicting higher odds of subsequent severe hypoglycaemia and death. (Clinical Trial Registry No: NCT 620, www.clinicaltrials.gov for original ACCORD study)