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Diabetes Care. 2018 Mar;41(3):596-603. doi: 10.2337/dc17-1778. Epub 2018 Jan 8.

Increased Risk of Severe Hypoglycemic Events Before and After Cardiovascular Outcomes in TECOS Suggests an At-Risk Type 2 Diabetes Frail Patient Phenotype.

Author information

1
Munich Diabetes Research Group e.V. at Helmholtz Centre, Neuherberg, Germany eberhard.standl@lrz.uni-muenchen.de.
2
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
3
Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
4
University of North Carolina School of Medicine, Chapel Hill, NC.
5
Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.
6
The George Washington University Biostatistics Center, Rockville, MD.
7
Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, Centre Hospitalier Universitaire de Liège, University of Liège, Liège, Belgium.
8
Bichat-Claude Bernard Hospital, Paris 7 University, Paris, France.
9
University of Leuven, Leuven, Belgium.
10
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.

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). Patients with (versus without) SHEs were older with longer diabetes duration, lower body weight, and lower estimated glomerular filtration rate; were more frequently women, 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00790205.

PMID:
29311155
DOI:
10.2337/dc17-1778
[Indexed for MEDLINE]

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