Is Hemoglobin A1c the Right Outcome for Studies of Diabetes?
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ABSTRACT:
SUBMITTER: Lipska KJ
PROVIDER: S-EPMC5350060 | biostudies-literature | 2017 Mar
REPOSITORIES: biostudies-literature
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Is Hemoglobin A1c the Right Outcome for Studies of Diabetes?
Lipska Kasia J KJ Krumholz Harlan M HM
JAMA 20170301 10
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Project description:Hemoglobin A1c (HbA1c) is a biomarker used for population-level screening of type 2 diabetes (T2D) and risk stratification. Large-scale, genome-wide association studies have identified multiple genomic loci influencing HbA1c. We discuss the challenges of classifying these genomic loci as influencing HbA1c through glycemic or nonglycemic pathways, based on their probable biology and pleiotropic associations with erythrocyte traits. We show that putative nonglycemic genetic variants have a measurable, albeit small, impact on the classification of T2D status by HbA1c in white and Asian populations. Accounting for their effect on HbA1c may be relevant when screening populations with higher frequencies of nonglycemic HbA1c-altering alleles. As carriers of such HbA1c-altering alleles have HbA1c levels that may not accurately reflect overall glycemia, we describe how accounting for genotype may improve the performance of HbA1c in T2D prediction models and risk stratification, allowing for lifestyle intervention strategies to be directed towards those who are truly at elevated risk for developing T2D. In a Mendelian randomization framework, genetic variants can be used as instrumental variables to estimate causal relationships between HbA1c and T2D-related complications. This approach may help to support or refute HbA1c as an appropriate biomarker for long-term health outcomes in the general population.
| S-EPMC5275759 | biostudies-literature
Project description:ObjectivesGiven the long-term consequences of untreated diabetes, patients benefit from timely diagnoses. Payer policies often recognize glucose but not hemoglobin A1c (HbA1c) for diabetes screening. This study evaluates the different information that glucose and HbA1c provide for diabetes screening.MethodsWe conducted a retrospective review of national clinical laboratory testing during 2020 when glucose and HbA1c were ordered for routine diabetes screening, excluding patients with known diabetes, out-of-range glucose, or metabolic syndrome.ResultsOf 15.47 million glucose and HbA1c tests ordered simultaneously, 672,467 (4.35%) met screening inclusion criteria; 116,585 (17.3%) were excluded because of diabetes-related conditions or the specimen was nonfasting, leaving 555,882 result pairs. More than 1 in 4 patients 60 years of age or older with glucose within range had an elevated HbA1c level. HbA1c claims were denied more often for Medicare beneficiaries (38,918/65,273 [59.6%]) than for other health plans combined (23,234/291,764 [8.0%]).ConclusionsAlthough many health plans do not cover HbA1c testing for diabetes screening, more than 1 in 4 glucose screening patients 60 years of age or older with an in-range glucose result had a concurrent elevated HbA1c result. Guideline developers and health plans should explicitly recognize that glucose and HbA1c provide complementary information and together offer improved clinical utility for diabetes screening.
| S-EPMC8742979 | biostudies-literature
Project description:BackgroundHemoglobin A1c (HbA1c) is the product of a non-enzymatic chemical reaction between hemoglobin (Hb) and glucose. However, the association between Hb and HbA1c remains to be fully elucidated in view of the controversial findings reported to date. Therefore, our aim in this study was to evaluate the association between Hb levels within the normal range and HbA1c levels among Chinese non-diabetes adults using cross-sectional data from the China Health and Nutrition Survey 2009.MethodsOur analysis was based on the data of 1659 non-diabete adults 20-49 years of age. Multivariable linear models were applied to examine the association between Hb and HbA1c levels. Subgroup analyses stratified by age and sex were also performed.ResultsThe association between Hb and HbA1c levels was positive in the unadjusted model (β =0.020, 95% CI: 0.008, 0.032). However, this association did not remain significant when the regression model was minimally adjusted for age and sex (β =0.006, 95% CI: - 0.014, 0.024); this association became negative when the model was further adjusted for covariates whose effect estimates of HbA1c levels more than 10% (β = - 0.042, 95% CI: - 0.064, - 0.020). The association remained negative on subgroup analyses stratified by age (20-34 years: β = - 0.052, 95% CI: - 0.091, - 0.013; 35-49 years: β = - 0.041, 95% CI: - 0.068, - 0.014) and sex (men: β = - 0.042, 95% CI: - 0.074, - 0.010; women: β = - 0.042, 95% CI: - 0.073, - 0.012) when controlling for covariates.ConclusionsOur findings revealed that Hb levels within the normal range were negatively associated with HbA1c levels among Chinese non-diabetes adults. Confounding factors, such as red blood cell counts can affect the association between Hb and HbA1c levels.
| S-EPMC7916310 | biostudies-literature
Project description:Despite advances in diabetes technology and treatment, a majority of children and adolescents with type 1 diabetes (T1D) fail to meet hemoglobin A1c (HbA1c) targets. Among high-income nations, the United States has one of the highest mean HbA1c values. We tracked the HbA1c values of 261 patients diagnosed with T1D in our practice over a 2.5-year period to identify inflection points in the HbA1c trajectory. The HbA1c declined until 5 months postdiagnosis. There was a rise in the HbA1c between the fifth and sixth month postdiagnosis. The HbA1c continued to steadily rise and by 18 months postdiagnosis, the mean HbA1c was 8.2%, which is also our clinic mean. Understanding the HbA1c trajectory early in the course of diabetes has helped to identify opportunities for intensification of diabetes management to flatten the trajectory of HbA1c and improve clinical outcomes.
| S-EPMC7001422 | biostudies-literature
Project description:BackgroundOnly a subset of patients at risk for ARDS go on to develop it, and the contribution of preexisting comorbidities (eg, diabetes) to ARDS risk is not well understood. Prior studies of the association between diabetes and ARDS have yielded conflicting results.Research questionDoes assessing ARDS risk based on hemoglobin A1c (HbA1c) as a marker of long-term blood glucose levels, rather than a charted diagnosis of diabetes, clarify the relationship between diabetes and ARDS?Study design and methodsUsing data from two prospective observational cohorts of critically ill adults (Validating Acute Lung Injury Biomarkers for Diagnosis [VALID] and Early Assessment of Renal and Lung Injury [EARLI]), we analyzed the association between clinical HbA1c category and development of ARDS in patients with a risk factor for ARDS and at least one clinical HbA1c measurement within the 180 days prior through 14 days after enrollment.ResultsA total of 599 patients in VALID and 276 in EARLI met inclusion criteria, of whom 164 and 58 developed ARDS, respectively. Patients with a charted diagnosis of diabetes were not shown to be more likely to develop ARDS (VALID: 24.6% ARDS in those categorized as nondiabetic vs 30.0% in those categorized as diabetic, P = .14; EARLI: 19.6% vs 22.8%, respectively; P = .55). However, in VALID, patients categorized as diabetic with inadequate glycemic control based on their HbA1c had an increased risk of developing ARDS compared with those with nondiabetic HbA1c (20.9% vs 34.0%, respectively; P = .0073), a finding that persisted in multivariable analysis (OR for those categorized as diabetic with inadequate glycemic control vs those categorized as nondiabetic range HbA1c, 1.25; 95% CI, 1.01-1.57). These findings were not reproduced in the smaller EARLI cohort, but were appreciated when the cohorts were combined for analysis.InterpretationElevated HbA1c may be associated with risk of developing ARDS, independent of clinical diagnosis of diabetes, but prospective validation is needed. If confirmed, these findings suggest that inadequate glycemic control could be an unrecognized risk factor for ARDS.
| S-EPMC11485198 | biostudies-literature
Project description:Annual hemoglobin A1c testing is recommended for patients with diabetes mellitus. However, it is unknown how consistently patients with diabetes mellitus receive hemoglobin A1c testing over time, or whether testing consistency is associated with adverse cardiovascular outcomes. We identified 1 574 415 Medicare patients (2002-2012) with diabetes mellitus over the age of 65. We followed each patient for a minimum of 3 years to determine their consistency in hemoglobin A1C testing, using 3 categories: low (testing in 0 or 1 of 3 years), medium (testing in 2 of 3 years), and high (testing in all 3 years). In unweighted and inverse propensity-weighted cohorts, we examined associations between testing consistency and major adverse cardiovascular events, defined as death, myocardial infarction, stroke, amputation, or the need for leg revascularization. Overall, 70.2% of patients received high-consistency testing, 17.6% of patients received medium-consistency testing, and 12.2% of patients received low-consistency testing. When compared to high-consistency testing, low-consistency testing was associated with a higher risk of adverse cardiovascular events or death in unweighted analyses (hazard ratio [HR]=1.21; 95% CI, 1.20-1.23; P<0.001), inverse propensity-weighted analyses (HR=1.16; 95% CI, 1.15-1.17; P<0.001), and weighted analyses limited to patients who had at least 4 physician visits annually (HR=1.15; 95% CI, 1.15-1.16; P<0.001). Less-consistent testing was associated with worse results for each cardiovascular outcome and in analyses using all years as the exposure. Consistent annual hemoglobin A1c testing is associated with fewer adverse cardiovascular outcomes in this observational cohort of Medicare patients of diabetes mellitus.
| S-EPMC5015285 | biostudies-literature
Project description:ImportanceIndividuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence.ObjectiveTo examine the association between HbA1c TIR and incidence of ADRD in older veterans with diabetes.Design, setting, and participantsThe study sample for this cohort study was obtained from administrative and health care utilization data from the Veterans Health Administration and Medicare from January 1, 2004, to December 31, 2018. Veterans 65 years or older with diabetes were assessed. Participants were required to have at least 4 HbA1c tests during the 3-year baseline period, which could start between January 1, 2005, and December 31, 2014. Data analysis was conducted between July and December 2023.Main outcomes and measuresHemoglobin A1c TIR was calculated as the percentage of days during baseline in which HbA1c was in individualized target ranges based on clinical characteristics and life expectancy, with higher HbA1c TIR viewed as more favorable. The association between HbA1c TIR and ADRD incidence was estimated. Additional models considered ADRD incidence in participants who were above or below HbA1c target ranges most of the time.ResultsThe study included 374 021 veterans with diabetes (mean [SD] age, 73.2 [5.8] years; 369 059 [99%] male). During follow-up of up to 10 years, 41 424 (11%) developed ADRD. Adjusted Cox proportional hazards regression models showed that lower HbA1c TIR was associated with increased risk of incident ADRD (HbA1c TIR of 0 to <20% compared with ≥80%: hazard ratio, 1.19; 95% CI, 1.16-1.23). Furthermore, the direction of out-of-range HbA1c levels was associated with incident ADRD. Having greater time below range (≥60%, compared with ≥60% TIR) was associated with significantly increased risk (hazard ratio, 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (ie, insulin and sulfonylureas) or with hypoglycemia events.Conclusions and relevanceIn this study of older adults with diabetes, increased HbA1c stability within patient-specific target ranges was associated with a lower risk of ADRD. Lower HbA1c TIR may identify patients at increased risk of ADRD.
| S-EPMC11297381 | biostudies-literature
Project description:IntroductionPosttransplantation diabetes mellitus (PTDM) is a common complication among kidney transplant recipients and is associated with a higher risk of cardiovascular events and poorer graft and patient survival. The association of pretransplantation hemoglobin A1c (HbA1c) with PTDM remains unclear. Identifying recipients at greatest risk for PTDM may help guide monitoring and treatment strategies to prevent or delay the onset of PTDM.MethodsWe analyzed data from 1499 nondiabetic primary kidney transplant recipients with available pretransplantation HbA1c values in the United States Renal Data System (USRDS) from 2005 to 2011. Recipients with pretransplantation diabetes diagnosis or HbA1c ≥ 6.5% were excluded. We assessed the association of pretransplantation HbA1c with PTDM using Cox proportional hazards models. Pretransplantation HbA1c level as a continuous variable was modeled using restricted cubic splines with knots at the 25th, 50th, and 75th percentiles. Based on results from this model, pretransplantation HbA1c was further modeled using a linear spline with a single knot at 5.4%.ResultsA total of 395 recipients (26.4%) developed PTDM over a median follow-up of 1.8 years. Pretransplantation HbA1c was not significantly associated with risk of PTDM below 5.4%, whereas each 1% higher HbA1c above 5.4% was associated with an adjusted hazard ratio of 1.84 (95% confidence interval = 1.28, 2.66; P for change in slope = 0.04).DiscussionHigher pretransplantation HbA1c above 5.4% is independently associated with greater risk of PTDM among kidney transplant recipients. A continuous relationship between pretransplantation HbA1c and risk of PTDM suggests that increased risk starts at HbA1c levels well below current thresholds for prediabetes.
| S-EPMC5733678 | biostudies-literature
Project description:ImportancePrepregnancy diabetes is associated with higher perinatal and maternal morbidity, especially if periconception glycemic control is suboptimal. It is not known whether improved glycemic control from preconception to early pregnancy and midpregnancy periods can reduce the risk of adverse perinatal and maternal outcomes.ObjectiveTo determine whether a net decline in glycated hemoglobin A1c (HbA1c) from preconception to the first half of pregnancy is associated with a lower risk of adverse outcomes for mother and child.Design, setting, and participantsThis population-based cohort study was completed in all of Ontario, Canada, from 2007 to 2018. Included were births among women with prepregnancy diabetes whose HbA1c was measured within 90 days preconception and again from conception through 21 weeks completed gestation (early pregnancy to midpregnancy). Statistical analysis was performed from July to September 2020.ExposuresNet decrease in HbA1c from preconception to early pregnancy and midpregnancy.Main outcomes and measuresThe main outcome was a congenital anomaly from birth to age 1 year. Other outcomes included preterm birth or perinatal mortality among offspring as well as severe maternal morbidity (SMM) or death among mothers. Adjusted relative risks (aRRs) were calculated per 0.5% absolute net decline in HbA1c from preconception up to early pregnancy and midpregnancy, adjusting for maternal age at conception, preconception HbA1c and hemoglobin concentration, and gestational age at HbA1c measurement.ResultsA total of 3459 births were included, with a mean (SD) maternal age of 32.6 (5.0) years at conception. Overall, the mean (SD) HbA1c decreased from 7.2% (1.6%) preconception to 6.4% (1.1%) in early pregnancy to midpregnancy. There were 497 pregnancies (14.4%) with a congenital anomaly, with an aRR of 0.94 (95% CI, 0.89-0.98) per 0.5% net decrease in HbA1c, including for cardiac anomalies (237 infants; aRR, 0.89; 95% CI, 0.84-0.95). The risk was also reduced for preterm birth (847 events; aRR, 0.89; 95% CI, 0.86-0.91). SMM or death occurred among 191 women (5.5%), with an aRR of 0.90 (95% CI, 0.84-0.96) per 0.5% net decrease in HbA1c.Conclusions and relevanceThese findings suggest that women with prepregnancy diabetes who achieve a reduction in HbA1c may have improved perinatal and maternal outcomes. Further study is recommended to determine the best combination of factors, such as lifestyle changes and/or glucose-lowering medications, that can influence periconception HbA1c reduction.
| S-EPMC7758806 | biostudies-literature
Project description:ImportanceWith the increase in prediabetes among adolescents with overweight and obesity, identifying those at highest risk for type 2 diabetes (T2D) can support prevention strategies.ObjectiveTo assess T2D risk by hemoglobin A1c (HbA1c) levels among adolescents with overweight and obesity.Design, setting, and participantsThis retrospective cohort study was conducted using data for January 1, 2010, to December 31, 2019, from a large California health care system. The study population comprised adolescents aged 10 to 17 years who had a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) at or above the 85th percentile, had HbA1c measured during 2010 to 2018, and did not have preexisting diabetes. Data abstraction and analyses were conducted from January 1, 2020, to November 16, 2023.ExposuresBaseline HbA1c, with covariates including BMI category (overweight: 85th to <95th percentile; moderate obesity: 100% to <120% of 95th percentile; or severe obesity: ≥120% of 95th percentile), age, sex, race and ethnicity, and Neighborhood Deprivation Index score.Main outcomes and measuresThe main outcome was incident T2D during follow-up through 2019, including cumulative incidence and multivariable hazard ratios (HRs) with 95% CIs using Cox proportional hazard regression analyses.ResultsThis study included 74 552 adolescents with a mean (SD) age of 13.4 (2.3) years. More than half (50.6%) were female; 26.9% of individuals had overweight, 42.3% had moderate obesity, and 30.8% had severe obesity. Individuals identified as Asian or Pacific Islander (17.6%), Black (11.1%), Hispanic (43.6%), White (21.6%), and other or unknown race or ethnicity (6.1%). During follow-up, 698 adolescents (0.9%) developed diabetes, and 626 (89.7%) had T2D; 72 individuals (10.3%) who had type 1, secondary, or other diabetes were censored. The overall T2D incidence was 2.1 (95% CI, 1.9-2.3) per 1000 person-years, with a 5-year cumulative incidence of 1.0% (95% CI, 0.9%-1.1%). Higher baseline HbA1c (from <5.5% to 5.5%-5.6%, 5.7%-5.8%, 5.9%-6.0%, 6.1%-6.2%, and 6.3-6.4%) was associated with higher 5-year cumulative T2D incidence (from 0.3% [95% CI, 0.2%-0.4%] to 0.5% [0.4%-0.7%], 1.1% [0.8%-1.3%], 3.8% [3.2%-4.7%], 11.0% [8.9%-13.7%], and 28.5% [21.9%-36.5%], respectively). In addition, higher baseline HbA1c was associated with greater T2D risk (reference [HbA1c <5.5%]: HR, 1.7 [95% CI, 1.3-2.2], 2.8 [2.1-3.6], 9.3 [7.2-12.1], 23.3 [17.4-31.3], and 71.9 [51.1-101.1], respectively). Higher BMI category, older age, female sex, and Asian or Pacific Islander race (HR, 1.7 [95% CI, 1.3-2.2]), but not Black race or Hispanic ethnicity (compared with White race), were also independent indicators of T2D. In stratified analyses, incremental risk associated with higher HbA1c was greater for Asian or Pacific Islander and White adolescents than for Black and Hispanic adolescents.Conclusions and relevanceIn this cohort study of adolescents with overweight and obesity, T2D risk increased substantially with baseline HbA1c above 6.0%. Risk varied by BMI, age, sex, and race and ethnicity. These findings suggest that diabetes surveillance in adolescents should be tailored to optimize identification among high-risk subgroups.
| S-EPMC10794942 | biostudies-literature