Increased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOSSuggests an at-risk type 2 diabetes frail patient phenotype

Eberhard Standl, Susanna R. Stevens, Paul W. Armstrong, John B. Buse, Juliana C.N. Chan, Jennifer B. Green, John M. Lachin, Andre Scheen, Florence Travert, Frans Van De Werf, Eric D. Peterson, Rury R. Holman

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE Severe hypoglycemic events (SHEs) in type 2 diabetes are associated with subsequent cardiovascular (CV) event risk.We examined whether CV events were associated with subsequent SHE risk. RESEARCH DESIGN AND METHODS Time-dependent associations between SHEs and a composite CV end point (fatal/ nonfatal myocardial infarction or stroke, hospitalization for unstable angina, hospitalization for heart failure [hHF]) were examined post hoc in 14,671 TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) participants with type 2 diabetes and CV disease followed for a median of 3.0 years. RESULTS SHEs were uncommon and unassociated with sitagliptin therapy (N = 160 [2.2%], 0.78/100 patient-years vs. N = 143 [1.9%], 0.70/100 patient-years for placebo; hazard ratio [HR] 1.12 [95%CI 0.89, 1.40], P = 0.33). Patientswith (versus without) SHEswere older with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate;weremore frequentlywomen, nonwhite, and insulin treated; and more often had microalbuminuria or macroalbuminuria. Analyses adjusted for clinical factors showed SHEs were associated with increased risk of the primary composite CV end point (1.55 [1.06, 2.28], P = 0.025), all-cause death (1.83 [1.22, 2.75], P = 0.004), and CV death (1.72 [1.02, 2.87], P = 0.040). Conversely, nonfatal myocardial infarction (3.02 [1.83, 4.96], P < 0.001), nonfatal stroke (2.77 [1.36, 5.63], P = 0.005), and hHF (3.68 [2.13, 6.36], P < 0.001) were associated with increased risk of SHEs. Fully adjusted models showed no association between SHEs and subsequent CV or hHF events, but the association between CV events and subsequent SHEs remained robust. CONCLUSIONS These findings, showing greater risk of SHEs after CV events and greater risk of CV events after SHEs, suggest a common at-risk type 2 diabetes frail patient phenotype.

Original languageEnglish (US)
Pages (from-to)596-603
Number of pages8
JournalDiabetes care
Volume41
Issue number3
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Fingerprint

Dive into the research topics of 'Increased risk of severe hypoglycemic events before and after cardiovascular outcomes in TECOSSuggests an at-risk type 2 diabetes frail patient phenotype'. Together they form a unique fingerprint.

Cite this