Severe Hypoglycemia and Incident Heart Failure among Adults With Type 2 Diabetes

Author(s):  
Justin B Echouffo-Tcheugui ◽  
Arnaud D Kaze ◽  
Gregg C Fonarow ◽  
Sam Dagogo-Jack

Abstract Context The effect of severe hypoglycemia on the incidence of heart failure (HF) is unclear. Objective We evaluated the association of severe hypoglycemia with incident HF among individuals with type 2 diabetes. Methods We included participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Severe hypoglycemia episodes were assessed during the initial 24 months following randomization and defined using two methods: symptomatic, severe hypoglycemic event requiring medical assistance (first definition) or requiring any assistance (second definition). Participants without HF at baseline and during the first 24 months of the study were prospectively followed for incident HF hospitalization. Multivariable Cox regression was used to generate adjusted hazard ratios (HR) for the association of severe hypoglycemia and incident HF. Results Among 9,208 participants (mean age 63 years, 38% female, 62% White), 365 had ≥ 1 episode of severe hypoglycemic. Over a median follow-up of 3 years, there were 249 incident HF events. After multivariable adjustment for relevant confounders, participants with severe hypoglycemia requiring medical assistance had a 68% higher relative risk of incident HF (HR 1.68, 95% CI 1.06-2.66), as compared to individuals who never experienced any episode of hypoglycemia. Severe hypoglycemia requiring any assistance was also associated with a 49% higher relative risk of HF (HR 1.49, 95% CI 1.01-2.21). Conclusion In a large cohort of adults with type 2 diabetes, severe hypoglycemia was independently associated with greater risk of incident HF.

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
You-Bin Lee ◽  
Kyungdo Han ◽  
Bongsung Kim ◽  
Seung-Eun Lee ◽  
Ji Eun Jun ◽  
...  

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.


2018 ◽  
Vol 6 (1) ◽  
pp. e000527 ◽  
Author(s):  
Lisa S Chow ◽  
Rachel Zmora ◽  
Sisi Ma ◽  
Elizabeth R Seaquist ◽  
Pamela J Schreiner

ObjectiveWe constructed a predictive model of long-term risk for severe hypoglycemia (SH: hypoglycemia requiring assistance) in patients with type 2 diabetes (T2DM).Research design and methodsData from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (original n=10 251, n=5135 used in the current analysis), a randomized, multicenter, double 2×2 factorial design study examining the effect of glycemic, blood pressure, and lipid control on cardiovascular outcomes in patients with diagnosed T2DM, were used. Over the follow-up (3.76±1.12 years), the ACCORD participants experienced 607 incident SH events. Cox regression was used to identify the SH risk prediction model.ResultsWe identified 17 predictors—glycemic management, age, race, education, waist circumference, medications (insulin, antihypertensive, HMG-CoA reductase inhibitors, sulfonylurea, biguanide and meglitinide), years since diabetes diagnosis, history of hypoglycemia in the last week, systolic blood pressure, diastolic blood pressure, serum creatinine, and urinary albumin creatinine ratio—to construct a prediction model for SH (c-statistic=0.782). Using this information, we derived point scores to estimate the 5-year risk for SH in individual patients with T2DM. After adjusting for other variables in the model, the three strongest predictors for SH over 5 years were intensive glycemic management (HR=2.37, 95% CI 1.99 to 2.83), insulin use (HR=2.14, 95% CI 1.77 to 2.59), and antihypertensive medication use (HR=1.90, 95% CI 1.26 to 2.86).ConclusionUsing the ACCORD data, we identified attributes to predict 5-year risk of SH in patients with T2DM, which warrant evaluation in broader populations to determine applicability.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C H Tseng

Abstract Background A beneficial effect of metformin on heart failure requires confirmation. Purpose To investigate whether metformin might affect the risk of heart failure hospitalization in type 2 diabetes patients. Methods Patients with new-onset type 2 diabetes during 1999–2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed until December 31, 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort (42,367 ever users and 42,367 never users) and hazard ratios were estimated by Cox's hazard regression analysis incorporated with the inverse probability of treatment weighting using the PS. Results A total of 1,592 never users and 987 ever users were hospitalized for heart failure for the first time during follow-up, with a respective incidence of 843.34 and 499.18 per 100,000 person-years. The overall hazard ratio was 0.588 (95% confidence interval: 0.543–0.637), and the hazard ratios for the first (<29.13 months), second (29.13–61.63 months), and third (>61.63 months) tertiles of cumulative duration were 1.018 (0.914–1.135), 0.575 (0.511–0.647), and 0.340 (0.297–0.390), respectively. Sensitivity analyses conducted in an unmatched cohort before and after excluding patients who received an irregular refill of metformin or who were treated with incretin-based therapies during follow-up consistently supported such a protective effect of metformin on heart failure. Conclusion Metformin use is associated with a lower risk of hospitalization for heart failure. Acknowledgement/Funding The study was partly supported by the Ministry of Science and Technology (MOST 107-2221-E-002-129-MY3) of Taiwan.


2021 ◽  
Vol 10 (7) ◽  
pp. 1401
Author(s):  
You-Ting Lin ◽  
Wei-Lun Huang ◽  
Hung-Pin Wu ◽  
Man-Ping Chang ◽  
Ching-Chu Chen

Heart failure (HF) is a common presentation in patients with type 2 diabetes mellitus (T2DM). Previous studies revealed that the HbA1c level is significantly associated with HF. However, little is known about the association between HbA1c variability and HF. We aimed to evaluate the association of mean and variability of HbA1c with HF in patients with T2DM. Using Diabetes Share Care Program data, patients with T2DM who had mean HbA1c (HbA1c-Mean), and HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD) within 12–24 months during 2001–2008 were included. The cutoffs of HbA1c-Mean were set at <7%, 7–7.9%, and ≥8%. Hazard ratios (HRs) for HF during 2008–2018 were estimated using Cox proportional hazard models. A total of 3824 patients were included, of whom 315 patients developed HF during the observation period of 11.72 years. The associated risk of HF increased with tertiles of HbA1c variability and cutoffs of HbA1c-Mean. In mutually adjusted models, HbA1c-Mean showed a consistent dose-response association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean <7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%. In conclusion, mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with good glycemic control was also important for the development of HF in patients with T2DM.


2020 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O Luk ◽  
Claudia HT Tam ◽  
Baoqi Fan ◽  
Hongjiang Wu ◽  
...  

<b>Objective</b>: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes. <p><b>Research design and methods</b>: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code.</p> <p><b>Results: </b>Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA<sub>1c</sub>, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA<sub>1c</sub>, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001).</p> <p><b>Conclusions: </b>rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.</p> <b><br> </b>


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0244689 ◽  
Author(s):  
Chun-xing Li ◽  
Shuo Liang ◽  
Lingyan Gao ◽  
Hua Liu

Background and aims Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). Methods We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region. Results Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20–30)% or < 15%, (15–30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3–4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States. Conclusions The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Luc Djousse ◽  
Andrew Petrone ◽  
John M Gaziano

Background: While previous studies have reported a positive relation of fried food consumption with type 2 diabetes, hypertension, and obesity, no previous study has examined the relation of total fried food intake with risk of heart failure (HF) in a prospective cohort. Objective: To test the hypothesis that fried food consumption is positively associated with risk of HF in male physicians. Methods: A prospective cohort of 19,968 participants from the Physicians’ Health Study. Frequency of fried food consumption was assessed between 1999 and 2002 using a food frequency questionnaire and HF was ascertained through annual follow-up questionnaires with validation in a subsample. We used Cox regression to estimate multivariable adjusted hazard ratios of HF. Results: During a median follow-up of 10.6 years, 862 cases of HF occurred. The mean age at baseline was 66.4 ± 9.2 years. Median frequency of fried food consumption was <1 time per week. Multivariable adjusted hazard ratios (95% CI) were: 1.0 (ref), 1.18 (1.01-1.37), 1.25 (1.02-1.54), and 1.68 (1.19-2.36) for fried food consumption of <1/week, 1-3/week, 4-6/week, and 7+/week, respectively (p for linear trend: 0.0004), after adjustment for age, alcohol use, smoking, exercise, and history of myocardial infarction, coronary artery bypass graph or angioplasty (Fig). Additional adjustment of total trans fats did not alter the findings. In a secondary analysis, body mass index did not modify the relation of fried foods with HF risk. Conclusions: Our data show a positive association between fried food intake and risk of HF in US male physicians.


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duck-chul Lee ◽  
Carl J. Lavie ◽  
Timothy S. Church ◽  
Xuemei Sui ◽  
Steven N. Blair

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.


2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.


BMJ ◽  
2020 ◽  
pp. m2206 ◽  
Author(s):  
Yang Hu ◽  
Ming Ding ◽  
Laura Sampson ◽  
Walter C Willett ◽  
JoAnn E Manson ◽  
...  

Abstract Objective To examine the associations between the intake of total and individual whole grain foods and the risk of type 2 diabetes. Design Prospective cohort studies. Setting Nurses’ Health Study (1984-2014), Nurses’ Health Study II (1991-2017), and Health Professionals Follow-Up Study (1986-2016), United States. Participants 158 259 women and 36 525 men who did not have type 2 diabetes, cardiovascular disease, or cancer at baseline. Main outcome measures Self-reports of incident type 2 diabetes by participants identified through follow-up questionnaires and confirmed by a validated supplementary questionnaire. Results During 4 618 796 person years of follow-up, 18 629 participants with type 2 diabetes were identified. Total whole grain consumption was categorized into five equal groups of servings a day for the three cohorts. After adjusting for lifestyle and dietary risk factors for diabetes, participants in the highest category for total whole grain consumption had a 29% (95% confidence interval 26% to 33%) lower rate of type 2 diabetes compared with those in the lowest category. For individual whole grain foods, pooled hazard ratios (95% confidence intervals) for type 2 diabetes in participants consuming one or more servings a day compared with those consuming less than one serving a month were 0.81 (0.77 to 0.86) for whole grain cold breakfast cereal, 0.79 (0.75 to 0.83) for dark bread, and 1.08 (1.00 to 1.17) for popcorn. For other individual whole grains with lower average intake levels, comparing consumption of two or more servings a week with less than one serving a month, the pooled hazard ratios (95% confidence intervals) were 0.79 (0.75 to 0.83) for oatmeal, 0.88 (0.82 to 0.94) for brown rice, 0.85 (0.80 to 0.90) for added bran, and 0.88 (0.78 to 0.98) for wheat germ. Spline regression showed a non-linear dose-response association between total whole grain intake and the risk of type 2 diabetes where the rate reduction slightly plateaued at more than two servings a day (P<0.001 for curvature). For whole grain cold breakfast cereal and dark bread, the rate reduction plateaued at about 0.5 servings a day. For consumption of popcorn, a J shaped association was found where the rate of type 2 diabetes was not significantly raised until consumption exceeded about one serving a day. The association between higher total whole grain intake and lower risk of type 2 diabetes was stronger in individuals who were lean than in those who were overweight or obese (P=0.003 for interaction), and the associations did not vary significantly across levels of physical activity, family history of diabetes, or smoking status. Conclusion Higher consumption of total whole grains and several commonly eaten whole grain foods, including whole grain breakfast cereal, oatmeal, dark bread, brown rice, added bran, and wheat germ, was significantly associated with a lower risk of type 2 diabetes. These findings provide further support for the current recommendations of increasing whole grain consumption as part of a healthy diet for the prevention of type 2 diabetes.


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