title: Association between mild and severe hypoglycemia in people with type 2 diabetes initiating insulin.
abstract: OBJECTIVE
  Primary objective: Identify risk factors associated with severe hypoglycemia (SH) and investigate the association between mild hypoglycemia and SH in people with type 2 diabetes starting insulin. Secondary objectives: Investigate the association of demographics and clinical factors with SH incidence.
  
  
  METHODS
  Integrated trial database data were obtained for 3 randomized controlled trials that included insulin-naïve people with type 2 diabetes initiating basal (insulin glargine) versus biphasic (insulin lispro mixture) insulin. Standard definitions were used for SH; mild hypoglycemia was defined as all non-SH. Cox regression identified risk factors associated with SH and the correlation between SH and mild hypoglycemia.
  
  
  RESULTS
  Data were pooled (N=2931). During 24-48weeks' treatment, 2127 (72.6%) participants experienced ≥1 mild hypoglycemic event but no SH (mean mild hypoglycemia rate=2.33/month). 56 participants (1.9%) experienced ≥1 SH event plus mild hypoglycemia (mean mild hypoglycemia rate=3.95/month); 748 participants (25.5%) had no hypoglycemia. Among factors tested, only mild hypoglycemia rate/month was associated with SH. SH risk was higher (HR=4.24; 95%CI=2.57-6.99;p<0.0001) for participants experiencing multiple mild hypoglycemic events/month compared with those experiencing ≤1 mild hypoglycemic event/month.
  
  
  CONCLUSIONS
  Mild hypoglycemia may predict the first SH event, which is important because SH is a strong and consistent risk factor for morbidity/mortality.
authors.affiliation: Eli Lilly Regional Operations Ges.m.b.H., Vienna, Austria. Electronic address: andreasfesta@icloud.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Festa
authors.affiliation: Sheffield Teaching Hospitals Foundation Trust, University of Sheffield, Sheffield, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Heller
authors.affiliation: University of Minnesota, Medical School, Minneapolis, MN, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Seaquist
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Duan
authors.affiliation: Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Hadjiyianni
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Haoda
authors.initials: H
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000473:pathology*; D007328:Insulin / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000627:therapeutic use; D061268:Insulin Lispro / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D007328:Insulin; D061268:Insulin Lispro; D000069036:Insulin Glargine
keywords: Database research; Glycemic control; Hypoglycemia; Insulin therapy; Type 2 diabetes