Diagnostic HbA1c Research Articles

Using nephropathy as an outcome to determine the HbA1c diagnostic threshold for type 2 diabetes

ObjectiveThe hemoglobin A1c (HbA1c) diagnostic threshold for type 2 diabetes (T2D) of 6.5 % (48 mmol/mol) was based on the prevalence of retinopathy found in populations not known to have T2D. It is unclear if nephropathy has a similar HbA1c threshold, partly because it is a rarer complication of early diabetes. This cohort study investigated a very high diabetes prevalence population to determine if a better diagnostic HbA1c value can be established for predicting nephropathy rather than retinopathy in subjects without T2D. MethodsThe urine albumin:creatinine ratios (UACRs) of 2920 healthy individuals from the Qatar Biobank who had an HbA1c ≥ 5.6 %. were studied. Nephropathy was defined as a UACR≥30 mg/g and its prediction by HbA1c was assessed using cut-points ranging from 5.7 to 7.0 % to dichotomize high from low HbA1c. ResultsAlthough there was a significant trend for an increased prevalence of abnormal UACR as the HbA1c threshold increased (p < 0.01), significance was due mostly to subjects with HbA1c ≥ 7.0 % (53 mmol/mol). The odds ratios for abnormal UACR were similar over the 5.7–6.9 % HbA1c threshold range, with a narrow odds ratio range of 1.2–1.6. Utilizing area-under-receiver-operating characteristic curves, no HbA1c threshold <7.0 % was identified as the best predictor of nephropathy. ConclusionEven in a population with a high prevalence of known and unknown diabetes, no HbA1c threshold <7.0 % could be found predicting an increased prevalence of nephropathy. This means there is not a requirement to change the existing retinopathy-based HbA1c threshold of 6.5 % to also accommodate diabetes nephropathy risk.

QLTI-05. HBA1C AND INSULIN COVERAGE FOR NEWLY DIAGNOSED HGG PATIENTS IN THE HOSPITAL

Abstract Corticosteroids are used in the management of patients with high-grade gliomas (HGG). Corticosteroids lead to elevated serum glucose levels, necessitating sliding-scale insulin. A hemoglobin A1c (HbA1c) reflects historical serum glucose levels but it’s unclear if it predicts corticosteroid-induced hyperglycemia. We retrospectively reviewed all newly diagnosed HGG patients who were admitted between Jan 2019 to July 2021 who had an HbA1c performed at the time of their diagnosis. HbA1c is classified into: normal (&amp;lt; 5.6%), elevated (5.7 – 6.4%) and diagnostic (&amp;gt; 6.5%). We identified 86 patients of whom 29 and 16 had elevated and diagnostic HbA1c, respectively. These patients were more likely to require sliding scale insulin at least twice during their hospitalization, 64% vs 13% of those with a normal HbA1c. Only 28% of patients had a history of diabetes. There was no correlation between elevated HbA1c and the likelihood of initiating post-operative therapy, surgical complications, or BMI results. When reviewing age, 39 patients were less than 65, of which 34% had at least an elevated HbA1c. Of those older than 65, 65% had at least an elevated HbA1c. Our analysis suggests there is a predictive value of HbA1c and the need for sliding-scale insulin while receiving corticosteroids in the HGG population, especially in the older population. We recommend screening all new HGG patients with an HbA1c at the time of diagnosis, regardless if they have a history of diabetes. We also recommend monitoring serum glucose less frequently with those who have a normal HbA1c. If the HbA1c is elevated or diagnostic, they should have monitored serum glucose levels with available sliding-scale insulin. If the patient is &amp;gt; 65 years of age, they should be considered a higher risk for having hyperglycemia and HbA1c should be reviewed. Further analysis is being conducted and will be reviewed at a later date.

Risk of Macrovascular and Microvascular Disease in Diabetes Diagnosed Using Oral Glucose Tolerance Test With and Without Confirmation by Hemoglobin A1c: The Whitehall II Cohort Study.

Background:It is unclear whether replacing oral glucose tolerance test (OGTT) with hemoglobin A1c (HbA1c) measurement for diagnosing diabetes is justified. We aimed to assess the proportion of OGTT-diagnosed diabetes cases that can be confirmed by HbA1c and to examine whether individuals with OGTT diagnosis but nondiagnostic HbA1c are at higher risk of macrovascular and microvascular disease.Methods:Participants were 5773 men and women from the population-based Whitehall II prospective cohort study in the United Kingdom. New OGTT diabetes cases diagnosed in clinical examinations in 2002 to 2004 and 2007 to 2009 were assessed for HbA1c confirmation (≥6.5%) in these and subsequent clinical examinations in 2012 to 2013 and 2015 to 2016. All participants were followed up for major cardiovascular events through linkage to electronic health records until 2017 and for incident chronic kidney disease (estimated glomerular filtration rate <60 mL·min−1·1.73 m−2) until the last clinical examination. In analysis of vascular disease risk, new OGTT-diagnosed diabetes cases with and without diagnostic HbA1c and preexisting diabetes cases were compared with diabetes-free participants.Results:Of the 378 (59.3%) participants with OGTT-diagnosed diabetes, 224 were confirmed by HbA1c during 4.1 years (SD, 4.1 years) of follow-up. We recorded 942 cardiovascular events over 12.1 years. After adjustment for nonmodifiable risk factors and compared with the 4997 diabetes-free participants, 371 participants with new HbA1c-confirmed diabetes and 405 participants with preexisting diabetes had increased risk of cardiovascular disease (hazard ratio, 1.53 [95% CI, 1.12–2.10] and 1.85 [95% CI, 1.50–2.28], respectively). The corresponding hazard ratios in the analysis of incident chronic kidney disease (487 cases; follow-up, 6.6 years) were 1.69 (95% CI, 1.09–2.62) for 282 participants with new HbA1c-confirmed diabetes and 1.67 (95% CI, 1.22–2.28) for 276 participants with preexisting diabetes. In both analyses, OGTT cases with nondiagnostic HbA1c (n=149 and 107) had a risk (hazard ratio, 0.99–1.07) similar to that of the diabetes-free population.Conclusions:More than 40% of OGTT-diagnosed diabetes cases were not confirmed by HbA1c during an extended follow-up. However, because these individuals have a risk of cardiovascular disease and chronic kidney disease similar to that of the diabetes-free population, replacement of OGTT with HbA1c-based diagnosis appears justified.

Assessment of glycaemic status in adult hospital patients for the detection of undiagnosed diabetes mellitus: A systematic review.

AimIn‐hospital blood glucose testing is commonplace, particularly in acute care. In‐hospital screening for hyperglycaemia may present a valuable opportunity for early diabetes diagnosis by identifying at‐risk individuals. This systematic review investigates the extent to which random blood glucose testing in acute and inpatient hospital settings predicts undiagnosed diabetes.MethodsTwo databases were systematically searched for studies in which adult patients received an in‐hospital random blood glucose test, followed by a diagnostic HbA1c test. The primary outcome was the proportion of hyperglycaemic individuals diagnosed with diabetes by HbA1c.ResultsA total of 3245 unique citations were identified, and 12 were eligible for inclusion. Ten different blood glucose thresholds, ranging from 5.5 to 11.1 mmol/L, were used to detect hyperglycaemia, indicating that there is no consistent clinical definition for hyperglycaemia. The proportion of participants with hyperglycaemia in each study ranged from 3.3% to 62.1%, with a median (Q1, Q3) of 34.5% (5.95%, 61.1%). The proportion of hyperglycaemic participants found to have a diabetes‐range HbA1c varied from 4.1% to 90%, with a median (Q1, Q3) of 18.9% (11.5%, 61.1%). Meta‐analysis was not possible due to substantial heterogeneity between study protocols.ConclusionsAll studies consistently identified a proportion of hyperglycaemic hospital patients as having a diabetes‐range HbA1c, showing that in‐hospital blood glucose screening can facilitate diabetes diagnosis. The proportion of hyperglycaemic participants with undiagnosed diabetes varied substantially, indicating a need for further research and consistency in defining in‐hospital hyperglycaemia. This may aid the development of a standardised screening protocol to identify people with possible undiagnosed diabetes.

Glycemic control in youth-onset type 2 diabetes correlates with weight loss.

To identify risk factors for glycemic failure in youth with type 2 diabetes (T2D). A retrospective review of HbA1c, anthropomorphic measures, medication records, and laboratory studies was performed using registry data from a dedicated pediatric T2D clinic. Latent profile analysis (LPA) was performed to model longitudinal trajectory of HbA1c over 5 years. The registry includes 229 youth with T2D, of whom 80% self-identify as Latinx. The odds ratio (OR) for uncontrolled diabetes 5 years after diagnosis correlated with diagnostic HbA1c, with OR of 2.41 if HbA1c at diagnosis >8.5% (sensitivity 68%, specificity 54%, P = .015). LPA modeling identified three HbA1c profiles: (a) mean HbA1c <8% throughout the 5 years, (b) persistent elevation of mean HbA1c >9%, and (c) mean HbA1c of 12% at diagnosis, rapid decline to 6.4% by 4 to 6 months, and increase to 11% by 18 months. Our analysis of medication regimen showed that, amongst patients treated with metformin, the addition of multiple daily injections (MDI) did not improve HbA1c compared to those on basal insulin. Finally, weight loss over the 1 year after diagnosis correlated with improvement in HbA1c in both subjects prescribed metformin monotherapy, as well as insulin-containing regimen. Youth with T2D exhibit distinct HbA1c profiles. Patients with diagnostic HbA1c >8.5% are at high risk for glycemic failure, irrespective of short-term improvement in HbA1c. Weight management has the potential to improve short-term HbA1c outcome in youth with T2D. Additional studies are needed to determine the role of medication adherence on glycemic control.

1270-P: Glycemic Control in Youth with Type 2 Diabetes Correlates with Weight Loss and Markers of Beta-Cell Function, but Not Intense Insulin Regimen

Background: Youth with type 2 diabetes develop early treatment failure to metformin and diabetes-related comorbidities. Objective: To identify risk factors for glycemic failure in youth with type 2 diabetes. Methods: Anthropomorphic measures, medication records, and laboratory studies were collected from patients attending a dedicated type 2 diabetes clinic. Repeat measures of HbA1c were averaged to prevent errors from unbalanced data points. Latent profile analysis (LPA) was performed to model longitudinal trajectory of HbA1c over 5 years. Results: The registry includes 226 patients, of which 80% are Latinx. Analysis of the glycemic outcomes showed that the odds ratio (OR) for uncontrolled diabetes 5 years after diagnosis (HbA1c&amp;gt;8%) is proportional to baseline HbA1c, with OR of 2.41 when diagnostic HbA1c &amp;gt;8.5% (sensitivity 68%, specificity 54%, P=0.015). LPA modeling identified three HbA1c profiles, all demonstrating some improvement in HbA1c at 4-6 months: (A) HbA1c &amp;lt;8% throughout the 5 years, (B) persistent elevation of HbA1c &amp;gt;9%, and (C) mean HbA1c of 12% at diagnosis, rapid decline to 6.4% by 4-6 months, but rose to 11% by 18 months. At diagnosis, group A had lower HbA1c and higher fasting c-peptide levels than B and C, suggesting that baseline beta-cell function is a dominant variable in long-term glycemic control. Our analysis of medication regimen showed that amongst patients treated with metformin, the addition of multiple daily injections (MDI) did not improve HbA1c compared to those on basal insulin. Finally, weight loss correlated with improved HbA1c outcome in patients on metformin monotherapy, but not in patients prescribed insulin. Conclusion: Patients with baseline HbA1c &amp;gt;8.5% are at high risk for glycemic failure, irrespective of short-term improvement in HbA1c. Additional studies are needed to decipher if medication omission accounts for the comparable HbA1c outcome between patients on MDI and basal insulin. Disclosure L. Chao: None. M. Yeh: None. J. Raymond: None. J. Ryoo: None. N.T. Chang: None. Funding Good Hope Foundation; Saban Research Institute

Use of the Burden of Diabetes Mellitus Score for Cardiovascular Disease Risk Assessment

Uncontrolled type II diabetes mellitus (DM) using single point hemoglobin A1c levels has been associated with poor cardiovascular outcomes. However, methods to quantify the effect of uncontrolled DM over time have been inconsistent. To quantify hyperglycemia over time and assess its cardiovascular effects we developed and tested a DM burden score which accounts for time in years prior to DM diagnosis, diagnostic HbA1c, and aggregate HbA1c levels thereafter. A retrospective cohort study was performed with patients (n = 188) from a single academic center with type II DM and no prior cardiac disease history. Patient scores were calculated from diagnosis until the year 2015 and were grouped into low (<5.3%; n = 55), moderate (5.3% to 5.5%; n = 80), and high (>5.5%; n = 53) DM burden score cohorts. At 48 months, the cohort with high DM burden scores correlated with significantly worse major adverse cardiovascular events (hazard ratio [HR] 3.07, p = 0.012), myocardial infarction (HR 12.78, p = 0.015), coronary revascularization (HR 4.53, p = 0.019), cardiovascular hospitalizations (HR 4.20, p = 0.005), and all-cause hospitalizations (HR 2.57, p = 0.01). Cardiovascular and all-cause mortality showed significant difference between groups in log-rank testing. Also, a multivariate regression model showed DM burden score (p = 0.045) to be an independent predictor of major adverse cardiovascular events (HR 9.38, p = 0.045). In conclusion, this study provides evidence that DM control over time impacts cardiovascular outcomes.

Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults.

The metabolic serum marker HbA1c has been associated with both impaired cognitive performance and altered white matter integrity in patients suffering from diabetes mellitus. However, it remains unclear if higher levels of HbA1c might also affect brain structure and function in healthy subjects. With the present study we therefore aimed to investigate the relationship between HbA1c levels and cognitive performance as well as white matter microstructure in healthy, young adults. To address this question, associations between HbA1c and cognitive measures (NIH Cognition Toolbox) as well as DTI-derived imaging measures of white matter microstructure were investigated in a publicly available sample of healthy, young adults as part of the Humane Connectome Project (n = 1206, mean age = 28.8 years, 45.5% male). We found that HbA1c levels (range 4.1-6.3%) were significantly inversely correlated with measures of cognitive performance. Higher HbA1c levels were associated with significant and widespread reductions in fractional anisotropy (FA) controlling for age, sex, body mass index, ethnicity, and education. FA reductions were furthermore found to covary with measures of cognitive performance. The same pattern of results could be observed in analyses restricted to participants with HBA1c levels below 5.7%. The present study demonstrates that low-grade HbA1c variation below diagnostic threshold for diabetes is related to both cognitive performance and white matter integrity in healthy, young adults. These findings highlight the detrimental impact of metabolic risk factors on brain physiology and underscore the importance of intensified preventive measures independent of the currently applied diagnostic HbA1c cutoff scores.

Limitations of hemoglobin A1c for the diagnosis of posttransplant diabetes mellitus.

Posttransplant diabetes mellitus (PTDM) is usually detected 2 to 3 months after transplantation by fasting plasma glucose (fPG) ≥ 7.0 mmol/L (≥ 126 mg/dL) and/or 2 hr post-challenge plasma glucose ≥ 11.1 mmol/L (≥ 200 mg/dL) during an oral glucose tolerance test (OGTT). Recently, glycosylated hemoglobin (HbA1c) of 6.5% or higher (≥ 47.5 mmol/mol) has been proposed as an alternative diagnostic criterion (the HbA1c criterion). We aimed to assess the sensitivity of applying the HbA1c criterion alone or in combination with a single measurement of fPG of 7.0 mmol/L or higher (≥ 126 mg/dL) at 10 weeks after transplantation as screening tests for the diagnosis of PTDM. From 1999 to 2011, measurements of fPG, HbA1c, and OGTT were performed in 1,619 nondiabetic renal transplant recipients. The HbA1c criterion detected 38.0% of patients with PTDM diagnosed with the standard diagnostic criteria. The specificity was 86.3%. When the HbA1c threshold value was lowered to 6.2% (44.3 mmol/mol), sensitivity increased to 57.8% with a corresponding reduced specificity of 80.4%. A combination of the HbA1c criterion and fPG of 7.0 mmol/L or higher (126 mg/dL) at 10 weeks after transplantation improved diagnostic precision with a sensitivity of 77.7% and a specificity of 96.1%. The proposed diagnostic HbA1c criterion failed to detect most cases of PTDM, and one of four cases of PTDM was detected by OGTT alone. This indicates that the HbA1c threshold value likely needs to be lowered for renal transplant recipients and supports continued use of OGTT as a diagnostic tool for detection of PTDM.

Diabetes Complications at Presentation and One Year by Glycated Haemoglobin at Diagnosis in a Multiethnic and Diverse Socioeconomic Population: Results from the South London Diabetes Study.

Background. WHO's recommendation of HbA1c ≥ 48 mmol/mol (6.5%) as diagnostic for type 2 diabetes mellitus (T2DM) was adopted by three UK London boroughs in May 2012. The South London Diabetes (SOUL-D) study has recruited people with newly diagnosed T2DM since 2008. We compared participants diagnosed before May 2012 with HbA1c < 48 mmol/mol to those with diagnostic HbA1c ≥ 48 mmol/mol. Methods. A prospective cohort study of newly diagnosed T2DM participants from 96 primary care practices, comparing demographic and biomedical variables between those with diagnostic HbA1c < 48 mmol/mol or HbA1c ≥ 48 mmol/mol at recruitment and after one year. Results. Of 1488 participants, 22.8% had diagnostic HbA1c < 48 mmol/mol. They were older and more likely to be white (p < 0.05). At recruitment and one year, there were no between-group differences in the prevalence of diabetic complications, except that those diagnosed with HbA1c < 48 mmol/mol had more sensory neuropathy at recruitment (p = 0.039) and, at one year, had new myocardial infarction (p = 0.012) but less microalbuminuria (p = 0.012). Conclusions. Use of HbA1c ≥ 48 mmol/mol as the sole T2DM diagnostic criterion may miss almost a quarter of those previously diagnosed in South London yet HbA1c < 48 mmol/mol may not exclude clinically important diabetes.

Relationship between insulin resistance and β-cell dysfunction in subphenotypes of prediabetes and type 2 diabetes.

There is little overlap between diabetes diagnosed by glycated hemoglobin (HbA1c) and blood glucose, and it is unclear which pathophysiological defects are captured when using HbA1c for diagnosis. We examined and compared the relationship between insulin sensitivity and β-cell function in different subphenotypes of prediabetes and type 2 diabetes (T2D). A cross-sectional analysis of the Danish ADDITION-PRO study was performed (n = 1713). Participants without known diabetes were classified into subgroups of prediabetes and T2D based on fasting or 2-hour glucose criteria or HbA1c. Insulin sensitivity and insulin release were determined from glucose and insulin concentrations during the oral glucose tolerance test, and disposition indices were calculated. Individuals with prediabetes or T2D diagnosed by fasting glucose had lower absolute insulin release (P ≤ .01) and higher insulin sensitivity in response to glucose intake (P ≤ .01) but a similar disposition index (P ≥ .36), compared with individuals with elevated 2-hour glucose concentrations. Individuals with HbA1c-defined T2D or prediabetes had a mixture of the pathophysiological defects observed in the glucose-defined subgroups, and individuals with normoglycemia by HbA1c had worse pathophysiological abnormalities than individuals with normoglycemia by the glucose criteria. On average, the diagnostic HbA1c criteria for diabetes and prediabetes identified individuals with a mixture of the pathophysiological characteristics found when using the glucose criteria, but the diversity and pathophysiology captured by the oral glucose tolerance test cannot be captured when applying the more simple HbA1c criteria. Whether the disease progression and prognosis will differ in individuals diagnosed by fasting glucose, 2-hour glucose, or HbA1c should be examined in longitudinal studies.

Changes in levels of haemoglobin A1c during the first 6 years after diagnosis of clinical type 2 diabetes

Objective: To assess the variability in levels of glycosylated haemoglobin (HbA1c) during the first six years after diagnosis of clinical type 2 diabetes in relation to possible predictors. Material and methods: Data were from a population-based sample from general practice of 581 newly diagnosed diabetic patients aged 40 or over. Estimation of HbA1c was centralized. The changes in levels of HbA1c were described by HbA1c at diagnosis and a regression line fitted to the HbA1c measurements after 1-year follow-up for each patient. The predictive effect of patient characteristics for changes in HbA1c was investigated in a multivariate mixed model. Results: During the first year after diabetes diagnosis, HbA1c dropped to near normal average level and then started rising almost linearly. A sharp rise in long-term glycaemic level was observed in approximately a quarter of the patients, especially the relatively young. Of 581 patients, 156 (26.9%) patients, however, experienced a fall in HbA1c after 1-year follow-up and another quarter showed constant or only slowly rising HbA1c. The changes in levels of HbA1c were only predicted by diagnostic HbA1c and age. Conclusions: During the first 6 years after the diagnosis of clinical type 2 diabetes, changes in levels of HbA1c show considerable inter-individual variability with age as the only long-term predictor. The results indicate that it is important to monitor changes in HbA1c more closely and intensify treatment of those often relatively young patients who actually experience the beginning of an apparently relentless deterioration of their glycaemic control.