SAN FRANCISCO – Patients with type 2 diabetes who were insulin deficient were 36 times more likely to develop severe hypoglycemia on treatment and to fail to get hemoglobin A1c levels below 6% after starting intensive therapy in a retrospective analysis of data on 1,401 patients.
In addition, patients with any of four antibodies against islet cells at baseline were 4-12 times more likely to develop severe hypoglycemia and fail to reach the glycemic target on intensive therapy, compared with patients without those biomarkers, Dr. Lisa Chow reported at the annual scientific sessions of the American Diabetes Association.
Dr. Lisa Chow
The study defined insulin deficiency as a fasting C-peptide level no higher than 0.45 ng/mL. Investigators measured levels of three of the autoantibodies and considered the fourth – insulin autoantibody (IAA) – to be present if the patient used insulin at baseline.
In unadjusted analyses, the likelihood of severe hypoglycemia and failure to reach the glycemic target was four times higher in patients with IAA or antibodies against glutamic acid decarboxylase (GAD) or zinc transporter 8 (ZnT8), compared with patients without those autoantibodies. Severe hypoglycemia and failure to get hemoglobin A1c (HbA1c) below 6% were 11 times more likely in patients with antibodies against tyrosine phosphatase–related islet antigen 2 (IA-2), reported Dr. Chow, an endocrinologist at the University of Minnesota, Minneapolis.
She and her associates studied data on 1,401 patients who were randomized to the intensive glycemic control arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. They compared 326 patients ("cases") who developed severe hypoglycemia and whose HbA1c levels did not reach the target of less than 6% with 1,075 control patients (matched 4:1 by age, race, and body mass index) who did not have severe hypoglycemia and who reached the HbA1c target.
Overall, 17% of cases and 1% of controls were insulin deficient. Excluding IAA (present in 62% of cases and 26% of controls), the most common islet antibody was GAD, in 17% of cases and 6% of controls. IA-2 was present in 4% of cases and 0.4% of controls, and ZnT8 was present in 2% of cases and 0.7% of controls.
"We propose that measuring C-peptide and GAD antibodies in patients with type 2 diabetes may serve as a biomarker to help tailor and individualize therapy" by predicting which patients are more likely to have adverse outcomes on intensive glycemic treatment, Dr. Chow said.
At baseline, the case group was significantly more likely to use insulin, compared with controls (89% and 24%, respectively) and less likely to be male (50% vs. 59%). The case patients had a higher HbA1c at baseline, compared with controls (8.54% vs. 8.08%, respectively) and a longer duration of diabetes (15 vs. 9 years).
After adjusting for the effects of age and body mass index, the combined outcome of severe hypoglycemia and failure to reach the glycemic target was 32 times more likely in patients with insulin deficiency at baseline, 3 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 9 times more likely in patients with IA-2, compared with patients without those markers, Dr. Chow said.
A third analysis removed data for any case patients who died and their associated controls and found that severe hypoglycemia and failure to reach the glycemic target was 30 times more likely in patients with insulin deficiency at baseline, 4 times more likely in patients with GAD or ZnT8, 5 times more likely in patients with IAA, and 12 times more likely in patients with IA-2, compared with patients without those markers.
The study defined severe hypoglycemia as any hypoglycemia requiring assistance. Patients who developed severe hypoglycemia were four times less likely to get their HbA1c levels below 6%.
Dr. Chow reported having no financial disclosures. The National Institutes of Health funded the study.
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