9-LB: Hypoglycemia in Patients with Diabetes: Therapeutic Strategies and Associated Risk Factors

Use of insulin or sulfonylureas (SU) carries a risk of hypoglycemia, but the risk with different diabetes therapies, such as premixed insulin, is not well known. We conducted a case-control analysis of 297,263 patients with DIAB and 487,226 NONDIAB in the national VA database who had ≥4 primary care visits, ≥1 A1c, and ≥3 outpatient random plasma glucoses (RPG) in 2002-2003, and examined hypoglycemia by diabetic medication use and other risk factors, through 2012. Hypoglycemia was defined as severe (Emergency Department visit with hypoglycemia [EDHypo]) and by outpatient lab (RPGHypo = RPG <70 mg/dl); both were associated with increased mortality (2.1- and 1.5-fold, respectively, p<0.001). At baseline, DIAB had mean age 66 year, BMI 31 kg/m², and A1c 7.5%; and were 98% male, 80% white, and 18% with retinopathy; NONDIAB were similar but had lower BMI. Among DIAB, 49% were on SU, 29% insulin (5% basal, 5% basal+SU, 1% bolus, 8% basal+bolus, 10% premixed), 11% otherRx (non-insulin/non-SU), 11% no meds. RPGHypo and EDHypo occurred in 6.8% and 0.3% of DIAB, respectively, vs. 2.1% and <0.1% of NONDIAB, p<0.001. During mean follow-up 7.5 year, 35% of DIAB (n=102,063; 229,612 events) had ≥1 RPGHypo, an incidence rate of 0.10 events/pt-year, and 4% had EDHypo. In adjusted models compared to otherRx, the risk of any hypo and EDHypo, respectively, was highest with basal+bolus (OR 1.4 and 17.8) and premixed insulin (OR 1.4 and 13.8), and lower with basal Insulin (OR 1.4 and 10.5), and SU (OR 1.2 and 5.1), all p<0.001. Black race and retinopathy also conferred higher risk of both any hypoglycemia and EDHypo (black race, OR 1.9 and 2.1; retinopathy OR 1.3 and 1.6, respectively; all p<0.001), much higher than the risk with A1c <6.0% (OR 1.0 and 1.3).

Conclusions: Clinically significant hypoglycemia, including both outpatient RPG <70 mg/dl and ED visits, is common in DIAB patients, particularly in those using basal+bolus or premixed insulin, and with black race or retinopathy, and should prompt consideration of altered management.