Association Of Severe Hypoglycemia Research Articles

377-P: Effect of Severe Hypoglycemia on Myocardial Cardiac Function in Type 1 Diabetes

Objective: Associations between severe hypoglycemia (SH) and cardiovascular disease (CVD) have been reported in epidemiological studies. Mechanisms for the relationship between SH and CVD are not well understood. While associations of HbA1c and traditional CVD risk factors with myocardial function in subjects with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study have been reported, it is unknown whether an association of SH with myocardial function exists. Methods: We evaluated cardiac magnetic resonance (CMR) data of 1017 subjects. Associations of SH with CMR parameters using generalized linear models were examined. At time of CMR, subjects had been followed over ~ 22 years. SH was defined as SH requiring assistance of another party. A subset was defined as SH accompanied by coma and/or seizure (SHCS). Results: At time of CMR, 660 subjects had a SH history (407 subjects with coma and/or seizures). Median age [interquartile range] was 50 [44, 54] years, 48% were females, and median diabetes duration was 26.6 [23.5, 31.4] years. SH was positively associated with end diastolic volume (EDV) by +4 ml, p<0.01 and end systolic volume (ESV) by +2.7 ml, p<0.01, left ventricular mass (LVM) by +2.8 mg, p<0.05, and negatively correlated with ejection fraction by -0.8%, p<0.05. Its SHCS subset was positively associated with EDV by +3.4 ml, p<0.01, LVM by 2.6 mg, p<0.05, stroke volume by +1.9 ml, p<0.05, and cardiac output by +0.15 L/min, p<0.05. Sensitivity analyses were consistent with results. Conclusion: The effect of SH on cardiac function might be one of the mechanisms to explain the association between SH and CVD. It needs to be examined whether SH is associated with myocardial scars. Further studies are required to investigate whether the magnitude of SH effect on myocardial function increases with older age and leads to a clinically relevant CV event, especially in diabetic subjects with established coronary heart disease. Disclosure E. R. Fahrmann: None. L. J. Adkins: None. R. Lamichhane: None. H. Driscoll: None.

Abstract 16062: Hypoglycemia and Risk of Atherosclerotic Cardiovascular Disease (ascvd) in Patients With Diabetes

Introduction: Studies evaluating the relationship of severe hypoglycemia (SH) with the risk of atherosclerotic cardiovascular disease (ASCVD) events are limited by size, confounding and inconsistent outcome definitions. The aim of this study was to assess the association of SH, as defined by hypoglycemia-related hospital utilization, with risk of ASCVD. Methods: We conducted an observational cohort study of adults with diabetes with or without established ASCVD (as of 1/1/2014). All subjects were members of Kaiser Permanente Northern California, an integrated health care delivery system. Baseline was determined by the date of the first hypoglycemia-related utilization (primary diagnosis of hypoglycemia in the emergency department or principal diagnosis in the hospital) during 1/1/2013 - 12/31/2013. Baseline for those without SH, was a randomly assigned date in 2013. Multivariate Cox proportional hazard models were specified to estimate hazard ratios (HRs) for SH in adjusted models of time to incident ASCVD events. This outcome was defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through 12/31/2017. Results: Among 233,696 eligible individuals, mean age was 63.6 years, 47.6% were women, and mean follow-up was 3.8 years. There were 2,179 episodes of SH. Age-sex-race adjusted risk of ASCVD among those with SH versus those without was HR 2.59 (95% CI 2.3-2.9). When additionally adjusted for prior ASCVD, the HR was still more than double, HR 2.32 (95% CI 2.1-2.6). In a fully saturated model with additional adjustments for diabetes type, diabetes duration, HbA1c, GFR, Charlson score, insulin use, sulfonylureas, and quartiles of neighborhood deprivation, SH was associated with a 30% increased risk (HR 1.31, 95% CI 1.16-1.5). The substantial attenuation in risk after more comprehensive adjustment suggests that patients at higher risk of SH are likely at higher risk of ASCVD. Conclusions: In a large, diverse and contemporary cohort of patients with diabetes, SH as defined by hypoglycemia-related hospital utilization is associated with greater risk of ASCVD. Increased awareness in recognizing this risk and vigilance in care for this higher risk population is warranted.

Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID).

In children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial. We examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively. Thirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29). Among older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention.

Association of severe hypoglycemia with mortality for people with diabetes mellitus during a 20-year follow-up in Denmark: a cohort study.

Severe hypoglycemia has a significant deteriorating effect on quality of life of the individual and has been associated with increased mortality. The aim of this study was to investigate the mortality among people with type 1 and type 2 diabetes suffering from severe hypoglycemia in Denmark in the last two decades. People diagnosed with type 1 (n = 44,033) and type 2 diabetes (n = 333,581) were extracted from the complete population of Denmark from 1996 to 2017 via ICD-10 diabetes codes and ATC diabetes medication codes. People suffering from severe hypoglycemia (type 1 diabetes n = 8808, type 2 diabetes n = 5605) as identified from ICD-10 codes were then matched 1:1 by year of birth, gender and year of diabetes diagnosis with those without severe hypoglycemia. Cox proportional hazards models were constructed to analyze the effect of severe hypoglycemia on mortality. For both people with type 1 (HR 1.11, CI 95% 1.06 to 1.17) and type 2 diabetes (HR 1.77, CI 95% 1.67 to 1.87) suffering from hypoglycemia, an increased mortality risk was observed, compared to people without severe hypoglycemia. An investigation of the death causes did not indicate an association between the severe hypoglycemic episodes and death. In this study, severe hypoglycemic episodes increased the mortality risk for people with type 1 and type 2 diabetes. The risk was higher among people with type 2 diabetes. Whether severe hypoglycemia is a symptom of other underlying illnesses increasing mortality risk or a risk factor itself needs further investigation.

367-P: Severe Hypoglycemia and Risk of Falls in Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Diabetes is common among older adults and is associated with greater risk of falls, which can be fatal in this population. One hypothesized link between diabetes and falls is hypoglycemia. However, this has not been evaluated in an older, type 2 diabetes population. We included 1186 ARIC participants with diabetes at Visit 4 (1996-1998) followed through 2013 for severe hypoglycemia and falls. We identified severe hypoglycemia with ICD-9 codes in claims for hospitalization, emergency department and ambulance use. Falls were based on E-codes in inpatient and outpatient claims; secondary outcomes were hospitalized falls and falls with fracture. We used adjusted Cox regression models to evaluate the association of severe hypoglycemia as a time-varying exposure with risk of subsequent fall. Participants had a mean age of 64, 54% female, 32% black; 14 had hypoglycemia prior to baseline and 135 had a severe hypoglycemic episode during follow-up. The crude incidence rate of falls without severe hypoglycemia was 2.17 per 100 person-years (PY) (95% CI: 1.93-2.44) and 8.81 per 100PY (6.73-11.53) with severe hypoglycemia. After adjustment, hypoglycemia was associated with an over two-fold greater risk of falls (Table). Fall history and risk should be considered when deciding glycemic goals and medication use, as hypoglycemia may increase fall risk. Disclosure A.K. Lee: None. S.P. Juraschek: None. B. Windham: None. C. Lee: Consultant; Self; XOMA Corporation. Research Support; Self; Eiger BioPharmaceuticals. A. Sharrett: None. J. Coresh: None. E. Selvin: None. Funding National Institutes of Health

The Association of Severe Hypoglycemia With Incident Cardiovascular Events and Mortality in Adults With Type 2 Diabetes.

OBJECTIVEThere is suggestive evidence linking hypoglycemia with cardiovascular disease, but few data have been collected in a community-based setting. Information is lacking on individual cardiovascular outcomes and cause-specific mortality.RESEARCH DESIGN AND METHODSWe conducted a prospective cohort analysis of 1,209 participants with diagnosed diabetes from the Atherosclerosis Risk in Communities (ARIC) study (analytic baseline, 1996–1998). Severe hypoglycemic episodes were identified using first position ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls through 2013. Cardiovascular events and deaths were captured through 2013. We used adjusted Cox regression models with hypoglycemia as a time-varying exposure.RESULTSThere were 195 participants with at least one severe hypoglycemic episode during a median fellow-up of 15.3 years. After severe hypoglycemia, the 3-year cumulative incidence of coronary heart disease was 10.8% and of mortality was 28.3%. After adjustment, severe hypoglycemia was associated with coronary heart disease (hazard ratio [HR] 2.02, 95% CI 1.27–3.20), all-cause mortality (HR 1.73, 95% CI 1.38–2.17), cardiovascular mortality (HR 1.64, 95% CI 1.15–2.34), and cancer mortality (HR 2.49, 95% CI 1.46–4.24). Hypoglycemia was not associated with stroke, heart failure, atrial fibrillation, or noncardiovascular and noncancer death. Results were robust within subgroups defined by age, sex, race, diabetes duration, and baseline cardiovascular risk.CONCLUSIONSSevere hypoglycemia is clearly indicative of declining health and is a potent marker of high absolute risk of cardiovascular events and mortality.

Abstract 43: Association of Severe Hypoglycemia With Cardiovascular Disease and All-cause Mortality in Older Adults With Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: There is concern that the strong association of severe hypoglycemia with cardiovascular disease (CVD) and all-cause mortality is confounded by diabetes severity or may not be causal and simply reflects general vulnerability. Our objective was to determine if the association of hypoglycemia with CVD and death withstood rigorous adjustment for likely confounders that prior studies have not adequately accounted for. Methods: We included ARIC participants aged 65+ at Visit 4 (1996-1998) with diagnosed diabetes and CMS Part B insurance. Severe hypoglycemia was identified through 2013 with ICD-9 codes from hospitalizations, emergency department visits, and ambulance services. CVD events (coronary heart disease, stroke, or heart failure) and death were assessed through 2013. Hypoglycemia was a time-varying exposure in progressively adjusted Cox models that included demographics, clinical characteristics, comorbidities, cognitive function, and activities of daily living and instrumental activities of daily living. Results: Of the 464 eligible participants, hypoglycemic events occurred in 65 participants prior to CVD or censoring and in 94 participants prior to death or censoring. The crude incidence rates of CVD and death were higher in persons with hypoglycemia compared to those without (CVD: 10.6 vs. 5.08 per 100 person-years (PY), p<0.001; death: 14.3 vs. 4.5 per 100 PY, p<0.001). After adjustment for age, sex, and race-center, hypoglycemia was strongly associated with both CVD and death ( Figure ). After additional adjustment for confounders, the hazard ratios (HR) for hypoglycemia were substantially attenuated but remained significant (CVD HR: 1.61 (95%CI 1.06-2.46); death HR: 1.83 (95%CI 1.35-2.84)). Conclusion: After adjustment for rigorously measured shared risk factors, hypoglycemia was associated with both CVD and death. These results suggest that severe hypoglycemia may influence CVD risk and death independently of diabetes severity and general vulnerability.

Association of severe hypoglycemia with incident atrial fibrillation in type 2 diabetes: a nationwide population-based cohort study

Association of severe hypoglycemia with incident atrial fibrillation in type 2 diabetes: a nationwide population-based cohort study

Association of severe hypoglycemia with depressive symptoms in patients with type 2 diabetes: the Fukuoka Diabetes Registry

ObjectiveAlthough many studies have investigated the clinical characteristics of patients with diabetes with depression in Western populations, there is a lack of information regarding other ethnicities. We studied the association...

Hemoglobin A1c Levels and risk of severe hypoglycemia in children and young adults with type 1 diabetes from Germany and Austria: a trend analysis in a cohort of 37,539 patients between 1995 and 2012.

Severe hypoglycemia is a major complication of insulin treatment in patients with type 1 diabetes, limiting full realization of glycemic control. It has been shown in the past that low levels of hemoglobin A1c (HbA1c), a marker of average plasma glucose, predict a high risk of severe hypoglycemia, but it is uncertain whether this association still exists. Based on advances in diabetes technology and pharmacotherapy, we hypothesized that the inverse association between severe hypoglycemia and HbA1c has decreased in recent years. We analyzed data of 37,539 patients with type 1 diabetes (mean age ± standard deviation 14.4 ± 3.8 y, range 1-20 y) from the DPV (Diabetes Patienten Verlaufsdokumentation) Initiative diabetes cohort prospectively documented between January 1, 1995, and December 31, 2012. The DPV cohort covers an estimated proportion of >80% of all pediatric diabetes patients in Germany and Austria. Associations of severe hypoglycemia, hypoglycemic coma, and HbA1c levels were assessed by multivariable regression analysis. From 1995 to 2012, the relative risk (RR) for severe hypoglycemia and coma per 1% HbA1c decrease declined from 1.28 (95% CI 1.19-1.37) to 1.05 (1.00-1.09) and from 1.39 (1.23-1.56) to 1.01 (0.93-1.10), respectively, corresponding to a risk reduction of 1.2% (95% CI 0.6-1.7, p<0.001) and 1.9% (0.8-2.9, p<0.001) each year, respectively. Risk reduction of severe hypoglycemia and coma was strongest in patients with HbA1c levels of 6.0%-6.9% (RR 0.96 and 0.90 each year) and 7.0%-7.9% (RR 0.96 and 0.89 each year). From 1995 to 2012, glucose monitoring frequency and the use of insulin analogs and insulin pumps increased (p<0.001). Our study was not designed to investigate the effects of different treatment modalities on hypoglycemia risk. Limitations are that associations between diabetes education and physical activity and severe hypoglycemia were not addressed in this study. The previously strong association of low HbA1c with severe hypoglycemia and coma in young individuals with type 1 diabetes has substantially decreased in the last decade, allowing achievement of near-normal glycemic control in these patients. Please see later in the article for the Editors' Summary.