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Association of Mean and Variability of HbA1c with Heart Failure in Patients with Type 2 Diabetes.

ABSTRACT: 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.

SUBMITTER: Lin YT

PROVIDER: S-EPMC8037774 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Prognostic impact of HbA1c variability on long-term outcomes in patients with heart failure and type 2 diabetes mellitus.

Project description:BackgroundThe prognostic impact of long-term glycemic variability on clinical outcomes in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) remains unclear. We determined and compared hemoglobin A1c (HbA1c) variability and clinical outcomes for patients with HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced ejection fraction (HFrEF) in a prospective longitudinal study.MethodsPatients with HF and T2DM, undergone 3 or more HbA1c determinations during the first 18 months, were then followed for 42 months. The primary outcome was death from any cause. Secondary outcome was composite endpoints with death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF and HFrEF.ResultsOf 902 patients enrolled, 32.2% had HFpEF, 14.5% HFmrEF, and 53.3% HFrEF. During 42 months of follow-up, 270 (29.9%) patients died and 545 (60.4%) patients experienced composite endpoints of death and HF readmission. The risk of all-cause death or composite endpoints was lower for HFpEF than HFrEF. Moreover, higher HbA1c variability was associated with higher all-cause mortality or composite endpoints and HbA1c variability was an independent predictor of all-cause mortality or composite endpoints, regardless of EF.ConclusionsThis prospective longitudinal study showed that the all-cause death and composite events was lower for HFpEF than HFrEF. HbA1c variability was independently and similarly predictive of death or combined endpoints in the three HF phenotypes.

| S-EPMC6026342 | biostudies-literature

What is the best predictor of mortality in patients with type 2 diabetes and chronic kidney disease: mean, variability of HbA1c or HbA1c-Hemoglobin ratio?

Project description:Limitations in the measurement of glycated hemoglobin (HbA1c) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) result in uncertainty about the best predictor of mortality among these patients. Our study aimed to determine the association between the mean and average real variability (ARV) of HbA1c, as well as HbA1c-hemoglobin (HH) ratio with mortality among patients with T2D and CKD. We identified 16,868 T2D patients with stage 3 or above CKD from outpatient visits during 2003-2018. We ascertained all-cause and cardiovascular mortality through linkage to Taiwan's National Death Registry. Mortality rates were estimated using the Poisson distribution, and we conducted Cox proportional hazards regressions to assess relative risks of mortality corresponding to the mean HbA1c, ARV of HbA1c and HH ratio. Compared to patients with a mean HbA1c of 7.0-7.9%, a mean HbA1c < 7.0% was persistently associated with highest risk of all-cause but not cardiovascular mortality after adjusting for confounders. On the contrary, patients with HbA1c-ARV in the second to fourth quartiles and HH ratios in the higher quartiles showed increased risk of all-cause and cardiovascular mortality compared to those in the first quartiles. HbA1c-ARV was more effective than mean HbA1c or HH ratio in predicting mortality in T2D patients with CKD. Apart from optimal glucose control, multidisciplinary care focusing on glycemic variability is essential for reducing mortality in these patients.

| S-EPMC11293112 | biostudies-literature

Both high and low HbA1c predict incident heart failure in type 2 diabetes mellitus.

Project description:Type 2 diabetes mellitus is an independent risk factor for heart failure development, but the relationship between incident heart failure and antecedent glycemia has not been evaluated.The Genetics of Diabetes Audit and Research in Tayside Study study holds data for 8683 individuals with type 2 diabetes mellitus. Dispensed prescribing, hospital admission data, and echocardiography reports were linked to extract incident heart failure cases from December 1998 to August 2011. All available HbA1c measures until heart failure development or end of study were used to model HbA1c time-dependently. Individuals were observed from study enrolment until heart failure development or end of study. Proportional hazard regression calculated heart failure development risk associated with specific HbA1c ranges accounting for comorbidities associated with heart failure, including blood pressure, body mass index, and coronary artery disease. Seven hundred and one individuals with type 2 diabetes mellitus (8%) developed heart failure during follow up (mean 5.5 years, ±2.8 years). Time-updated analysis with longitudinal HbA1c showed that both HbA1c <6% (hazard ratio =1.60; 95% confidence interval, 1.38-1.86; P value <0.0001) and HbA1c >10% (hazard ratio =1.80; 95% confidence interval, 1.60-2.16; P value <0.0001) were independently associated with the risk of heart failure.Both high and low HbA1c predicted heart failure development in our cohort, forming a U-shaped relationship.

| S-EPMC4366571 | biostudies-literature

Association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.

Project description:AimTo investigate the association between visit-to-visit HbA1c variability and the risk of cardiovascular disease in patients with type 2 diabetes.Materials and methodsWe performed a retrospective cohort study of 29 260 patients with at least four HbA1c measurements obtained within 2 years of their first diagnosis of type 2 diabetes. Different HbA1c variability markers were calculated, including the standard deviation (SD), coefficient of variation (CV) and adjusted SD. Cox proportional hazards regression models were used to estimate the association of these HbA1c variability markers with incident cardiovascular disease.ResultsDuring a mean follow-up of 4.18 years, a total of 3746 incident cardiovascular disease cases were diagnosed. Multivariate-adjusted hazard ratios for cardiovascular disease across the first, second, third and fourth quartiles of HbA1c SD values were 1.00, 1.30 (95% confidence interval [CI] 1.18-1.42), 1.40 (95% CI 1.26-1.55) and 1.59 (95% CI 1.41-1.77) (P for trend <.001), respectively. When we utilized HbA1c CV and adjusted HbA1c SD values as exposures, similar positive associations were observed. HbA1c variability was also associated with the risk of first and recurrent severe hypoglycaemic events. A mediating effect of severe hypoglycaemia was observed between HbA1c variability and incident cardiovascular disease.ConclusionsLarge visit-to-visit HbA1c variability is associated with an increased risk of cardiovascular disease in patients with type 2 diabetes. Severe hypoglycaemia may mediate the association between HbA1c variability and incident cardiovascular disease.

| S-EPMC9092602 | biostudies-literature

Does glucose variability influence the relationship between mean plasma glucose and HbA1c levels in type 1 and type 2 diabetic patients?

Project description:ObjectiveThe A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA(1c) and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA(1c) relationship.Research design and methodsAnalyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA(1c) relationship.ResultsGV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA(1c) relationship in type 1 diabetic patients so that high GV led to a higher HbA(1c) level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA(1c) level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency.ConclusionsIn only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA(1c). This effect is more pronounced at higher HbA(1c) levels. However, the impact of GV on the HbA(1c) level in type 1 diabetes is modest, particularly when HbA(1c) is close to the treatment target of 7%.

| S-EPMC3142023 | biostudies-literature

Dependence of Heart Rate Variability Indices on the Mean Heart Rate in Women with Well-Controlled Type 2 Diabetes.

Project description:Heart rate variability (HRV) is a method used to evaluate the presence of cardiac autonomic neuropathy (CAN) because it is usually attributed to oscillations in cardiac autonomic nerve activity. Recent studies in other pathologies suggest that HRV indices are strongly related to mean heart rate, and this does not depend on autonomic activity only. This study aimed to evaluate the correlation between the mean heart rate and the HRV indices in women patients with well-controlled T2DM and a control group. HRV was evaluated in 19 T2DM women and 44 healthy women during basal supine position and two maneuvers: active standing and rhythmic breathing. Time-domain (SDNN, RMSSD, pNN20) and frequency-domain (LF, HF, LF/HF) indices were obtained. Our results show that meanNN, age, and the maneuvers are the main predictors of most HRV indices, while the diabetic condition was a predictor only for pNN20. Given the known reduced HRV in patients with T2DM, it is clinically important that much of the HRV indices are dependent on heart rate irrespective of the presence of T2DM. Moreover, the multiple regression analyses evidenced the multifactorial etiology of HRV.

| S-EPMC8509544 | biostudies-literature

Variability of adiposity indices and incident heart failure among adults with type 2 diabetes.

Project description:BackgroundIt remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM).MethodsWe included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF.ResultsOver a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91-6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36-4.53) and 2.88 (1.52-5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11-3.26), 1.79 (95% CI 1.07-3.01), and 1.73 (1.01-2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively.ConclusionsIn a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

| S-EPMC8805255 | biostudies-literature

Different levels of hypoglycemia in patients with type 2 diabetes, their achieved mean HbA1c vs. all-cause and cardiovascular mortality.

Project description:AimIn patients with type 2 diabetes (T2D), levels of hypoglycemia and their risk of mortality are not well understood. The aim of this study was to ascertain the correlation among disparate levels of hypoglycemia and patients with T2D's achieved mean glycated hemoglobin A1c (HbA1c) with all-cause and cardiovascular mortality.Methods27,932 T2D patients taking hypoglycemic medications at outpatient visits for more than 6 months between 2008 and 2018 were linked to Taiwan's National Death Registry. We determined the respective mortality rates with Poisson assumption, and explored the relative risks of all-cause and cardiovascular mortality according to dissimilar levels of hypoglycemia with their achieved mean HbA1c by Cox proportional hazard regression model with adjustment of potential confounders.ResultsT2D patients with level 3 hypoglycemia had the highest rates of all-cause and cardiovascular mortality. Compared with those who never encountered hypoglycemia, study subjects with level 1 and level 2 hypoglycemia did not show excessive risks of either all-cause or cardiovascular mortality. Only those with level 3 hypoglycemia revealed marginal risk of all-cause (Hazard ratio [HR]: 1.18; 95% Confidence Interval [CI] 1.04-1.33) but not cardiovascular mortality (HR: 1.16; 95% CI 0.88-1.53). In T2D patients with hypoglycemia, only those with mean HbA1c ≥9.0% increased all-cause mortality in level 3 hypoglycemia, and cardiovascular mortality in level 1 hypoglycemia.ConclusionsElevated risk of all-cause mortality was exclusively found in patients with level 3 hypoglycemia. In T2D patients with hypoglycemia, mean HbA1c ≥ 9% increased all-cause or cardiovascular mortality. Aggressive treatment of accompanying serious illness in severe hypoglycemia may help reduce mortality in patients with T2DM.

| S-EPMC10370691 | biostudies-literature

Association of long-term visit-to-visit variability of HbA1c and fasting glycemia with hypoglycemia in type 2 diabetes mellitus.

Project description:BackgroundSelf-management of blood glucose levels to avoid hypoglycemia is vital for patients with type 2 diabetes mellitus (T2DM). The association between specific metrics of glycemic variability (glycosylated hemoglobin A1c [HbA1c] and fasting plasma glucose [FPG]) and severe hypoglycemia has not been fully studied in patients with T2DM.MethodsIn this post hoc analysis, patients with established T2DM with a high risk of cardiovascular disease were included in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards model was used to investigate the relationship between glycemic variability and hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any third-party assistance (HAA). The prognostic value of HbA1c/FPG variability for our predefined outcomes was compared using Harrell's C method.ResultsAfter adjusting for confounders, each increase in HbA1c variability of 1 standard deviation (SD) indicated a higher risk of HAA (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.03-1.16; P < 0.01) and HMA events (HR: 1.11; 95% CI: 1.03-1.20; P < 0.01). Meanwhile, each increase in FPG variability of 1 SD increased the risk of HAA (HR: 1.40; 95% CI: 1.31-1.49; P < 0.01) and HMA events (HR: 1.46; 95% CI: 1.35-1.57; P < 0.01). Meanwhile, models, including FPG variability, had better prognostic value for our predefined outcomes than HbA1c variability (P < 0.01).ConclusionsIncreased visit-to-visit variability in HbA1c and fasting glycemia is associated with a greater risk of severe hypoglycemic events in T2DM patients. FPG variability is a more sensitive indicator than HbA1c variability.Trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT00000620.

| S-EPMC9402888 | biostudies-literature

Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus.

Project description:BackgroundThis study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.MethodsIn this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ?6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.ResultsA total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).ConclusionCAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

| S-EPMC6300446 | biostudies-literature

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