Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study

Khunti, Kamlesh; Davies, Melanie J.; Majeed, Azeem; Thorsted, Brian Larsen; Wolden, Michael Lyng; Paul, Sanjoy K.

doi:10.2337/dc14-0920

Cited by 304 publications

(225 citation statements)

References 31 publications

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“…Investigators et al, 2013, Khunti et al, 2015, Majumdar et al, 2013, McCoy et al, 2012, Zhao et al, 2012, Zoungas et al, 2010. Despite the heterogeneity, we note that direction of association was consistent across all the studies in the Forest plot.…”

Section: Association Between Hypoglycaemia and Mortality (Figure 3)supporting

confidence: 57%

“…We screened 1273 citations and included 17 studies with a total of 1498358 participants in the meta-analysis (Bonds et al, 2010, Chiba et al, 2015, Duckworth et al, 2011, Hsu et al, 2013, Origin Trial Investigators et al, 2013, Johnston et al, 2012, Johnston et al, 2011, Khunti et al, 2015, Majumdar et al, 2013, McCoy et al, 2012, Rajpathak et al, 2015, Rathmann et al, 2013, Signorovitch et al, 2013, Zhao et al, 2012, Zoungas et al, 2010. The flow chart of the study selection in shown in the supplementary eFigure.…”

Section: Resultsmentioning

confidence: 99%

“…Our findings indicate that hypoglycaemia was associated with incident cardiovascular events, even in those patients with no cardiovascular history. Khunti et al assessed the association between hypoglycaemia and cardiovascular events in subgroups of patients with, or without cardiovascular history, and found that the risk was similarly elevated in both subgroups, (Khunti et al, 2015) thus refuting Yun's hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…We focused on vascular adverse events because patients with diabetes have an increased risk of micro-and macro-vascular disease (Bloomfield et al, 2012) and cardiovascular events remains the primary cause of death among insulin-treated people with diabetes (Khunti et al, 2015). We also aimed to evaluate falls and fractures because injuries are a leading cause of death in older people and can result in significant physical, psychological and social consequences (Thapa et al, 1996).…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…Association between hypoglycaemia and vascular disease (Figure 1) We included eight studies in the meta-analysis for macrovascular complications (Duckworth et al, 2011, Hsu et al, 2013 , Johnston et al, 2011, Khunti et al, 2015, Rathmann et al, 2013, Zhao et al, 2012, Zoungas et al, 2010 There are two studies in the meta-analysis which reported on the association between hypoglycaemia and microvascular complications (Zhao et al, 2012, Zoungas et al, 2010. The pooled odds ratio was 1.77 (95% Confidence Interval 1.49, 2.10) with no evidence of heterogeneity (chi-squared p= 0.90, I 2 =0%).…”

Section: Meta-analysismentioning

confidence: 99%

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Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

Mattishent

Loke

2016

Journal of Diabetes and its Complications

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Aims:We aimed to conduct a meta-analysis of serious adverse events (macro-and micro-vascular events, falls and fractures, death) associated with hypoglycaemia in older patients. Methods:We searched MEDLINE and EMBASE spanning a ten-year period up to March 2015 (with automated PubMed updates to October 2015). We selected observational studies reporting on hypoglycaemia and associated serious adverse events, and conducted a meta-analysis. We assessed study validity based on ascertainment of hypoglycaemia, adverse events and adjustment for confounders. Conclusion:Our meta-analysis raises major concerns about a range of serious adverse events associated with hypoglycaemia. Clinicians should prioritize individualized therapy and closer monitoring strategies to avoid hypoglycaemia in susceptible older patients.

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Section: Association Between Hypoglycaemia and Mortality (Figure 3)supporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

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Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

Mattishent

Loke

2016

Journal of Diabetes and its Complications

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Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes

et al. 2018

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IMPORTANCE Understanding cardiovascular outcomes of initiating second-line antidiabetic medications (ADMs) may help inform treatment decisions after metformin alone is not sufficient or not tolerated. To date, no studies have compared the cardiovascular effects of all major second-line ADMs during this early decision point in the pharmacologic management of type 2 diabetes. OBJECTIVE To examine the association of second-line ADM classes with major adverse cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study among 132 737 insured adults with type 2 diabetes who started therapy with a second-line ADM after taking either metformin alone or no prior ADM. This study used 2011-2015 US nationwide administrative claims data. Data analysis was performed from January 2017 to October 2018. EXPOSURES Dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, thiazolidinediones (TZDs), basal insulin, and sulfonylureas or meglitinides (both referred to as sulfonylureas hereafter). The DPP-4 inhibitors served as the comparison group in all analyses. MAIN OUTCOMES AND MEASURES The primary outcome was time to first cardiovascular event after starting the second-line ADM. This composite outcome was based on hospitalization for the following cardiovascular conditions: congestive heart failure, stroke, ischemic heart disease, or peripheral artery disease. RESULTS Among 132 737 insured adult patients with type 2 diabetes (men, 55%; aged 45-64 years, 58%; white, 63%), there were 3480 incident cardiovascular events during 169 384 person-years of follow-up. Patients were censored after the first cardiovascular event, discontinuation of insurance coverage, transition from International Classification of Diseases, Ninth Revision (ICD-9) to end of ICD-9 coding, or 2 years of follow-up. After adjusting for patient, prescriber, and health plan characteristics, the risk of composite cardiovascular events after starting GLP-1 receptor agonists was lower than DPP-4 inhibitors (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96), but this finding was not significant in all sensitivity analyses. Cardiovascular event rates after starting treatment with SGLT-2 inhibitors (HR, 0.81; 95% CI, 0.57-1.53) and TZDs (HR, 0.92; 95% CI, 0.76-1.11) were not statistically different from DPP-4 inhibitors. The comparative risk of cardiovascular events was higher after starting treatment with sulfonylureas (HR, 1.36; 95% CI, 1.23-1.49) or basal insulin (HR, 2.03; 95% CI, 1.81-2.27) than DPP-4 inhibitors.

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Association of Cumulative Multimorbidity, Glycemic Control, and Medication Use With Hypoglycemia-Related Emergency Department Visits and Hospitalizations Among Adults With Diabetes

et al. 2020

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IMPORTANCE Severe hypoglycemia is a serious and potentially preventable complication of diabetes, with some of the most severe episodes requiring emergency department (ED) care or hospitalization. A variety of health conditions increase the risk of hypoglycemia. People with diabetes often have multiple comorbidities, and the association of such multimorbidity with hypoglycemia risk in the context of other risk factors is uncertain. OBJECTIVE To examine the associations of age, cumulative multimorbidity, glycated hemoglobin (HbA 1c) level, and use of glucose level-lowering medication with hypoglycemia-related ED visits and hospitalizations. DESIGN, SETTING, AND PARTICIPANTS Cohort study of claims and laboratory data from OptumLabs Data Warehouse, an administrative claims database of commercially insured and Medicare Advantage beneficiaries in the United States. Participants were adults (aged Ն18 years) with diabetes who had an available HbA 1c level result in 2015. Data from January 1, 2014, to December 31, 2016, were analyzed. Final analyses were conducted from December 2017 to September 2018. MAIN OUTCOMES AND MEASURES This study calculated rates of hypoglycemia-related ED visits and hospitalizations during the year after the index HbA 1c level was obtained, stratified by patient demographic characteristics, diabetes type, comorbidities (from 16 guideline-specified high-risk conditions), index HbA 1c level, and glucose level-lowering medication use. The association of each variable with hypoglycemia-related ED and hospital care was examined using multivariable Poisson regression analysis overall and by diabetes type. RESULTS The study cohort was composed of 201 705 adults with diabetes (mean [SD] age, 65.8 [12.1] years; 102 668 [50.9%] women; 118 804 [58.9%] white; mean [SD] index HbA 1c level, 7.2% [1.5%]). Overall, there were 9.06 (95% CI, 8.64-9.47) hypoglycemia-related ED visits and hospitalizations per 1000 persons per year. The risk of hypoglycemia-related ED visits and hospitalizations was increased by age 75 years or older (incidence rate ratio [IRR], 1.56 [95% CI, 1.23-2.02] vs 18-44 years), black race/ethnicity (IRR, 1.30 [95% CI, 1.16-1.46] vs white race/ethnicity), lower annual household income (IRR, 0.63 [95% CI, 0.

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Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study

Cited by 304 publications

References 31 publications

Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

Meta-analysis: Association between hypoglycaemia and serious adverse events in older patients

Association of Second-line Antidiabetic Medications With Cardiovascular Events Among Insured Adults With Type 2 Diabetes

Association of Cumulative Multimorbidity, Glycemic Control, and Medication Use With Hypoglycemia-Related Emergency Department Visits and Hospitalizations Among Adults With Diabetes

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