Diagnostic performance of using one- or two-HbA1c cut-point strategies to detect undiagnosed type 2 diabetes and impaired glucose regulation within a multi-ethnic population

Abstract

Introduction:We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis. Materials and methods:We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing. Results: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c ≥ 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c ≤ 5.8% (rule-in, 40 mmol/mol) and HbA1c ≥ 6.8% (rule-out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c≥ 6.5% of £38.53 (1.89 to 86.81) per case, but was more expensive in SA by £84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became £63.33 (23.33 to 113.26) in WE and £69.21 (55.60 to 82.41) in SA. Conclusion: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests.

Screening South Asians for type 2 diabetes and prediabetes: (1) comparing oral glucose tolerance and haemoglobin A1c test results and (2) comparing the two sets of metabolic profiles of individuals diagnosed with these two tests

“…Although the AUROC in our study was high, the low sensitivity of HbA1c for OGTT-defined diabetes and prediabetes was in line with previous studies in various ethnic groups [8,10,11,21-23]. For instance, a recent cost analysis in a South Asian population aged 40–75 years in the UK reports low sensitivity of HbA1c (at >6.5%) for diabetes [23].…”

“…For instance, a recent cost analysis in a South Asian population aged 40–75 years in the UK reports low sensitivity of HbA1c (at >6.5%) for diabetes [23]. Although many studies have reported a relatively high specificity, a study in India – similarly to our study – found low specificity of HbA1c, particularly for prediabetes [8,10,11,21-23]. The lower optimal HbA1c threshold for prediabetes in our population was in line with the threshold that the Indian study recommended [10].…”

Prevalence of moderately increased albuminuria among individuals with normal HbA1c level but impaired glucose tolerance: Results from the LIFE‐Adult‐Study

“…TA B L E 3 Prevalence of moderately increased albuminuria and UACR values by diabetes status according to HbA1c and FPG/2 h-PGFirst, the cross-sectional approach does not allow proving a causal relationship between the increased FPG/2 h-PG levels among individuals with normal HbA1c levels and the increased prevalence of moderately increased albuminuria, which would require longterm longitudinal follow-up studies. Thus, our results might not be applicable to populations with other ethnicities, since it has been shown that results may vary depending on ethnicity and race 15. The solid curve shows the remaining discriminative performance of the HbA1c levels.…”

“…6,7 Some guidelines, including those of the German Diabetes Association, recommend a stepwise diagnostic approach using HbA1c as a first screening test with two different cut-off values for the diagnostic decision, of which the lower cutoff is used to rule out diabetes and the higher cut-off is used to diagnose diabetes without measuring FPG and/or two-hour postload glucose levels (2 h-PG). [11][12][13][14][15][16][17][18][19][20][21][22][23][24] Importantly, stepwise diabetes screening strategies using only HbA1c as first-instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications despite HbA1c levels below the "rule-out" cut-off. [8][9][10] Despite the advantages of HbA1c-based diabetes screening, there is an ongoing debate about the usefulness of this marker to detect individuals with diabetes and prediabetes.…”

“…A large number of studies have addressed this question in different populations, however resulting in ambiguous results and conclusions particularly with regard to optimal cut-off values for diagnostic decisions. [11][12][13][14][15][16][17][18][19][20][21][22][23][24] Importantly, stepwise diabetes screening strategies using only HbA1c as first-instance diagnostic parameter may cause failure to detect individuals with abnormal glucose regulation and possible signs of microvascular complications despite HbA1c levels below the "rule-out" cut-off. In this study, we analysed the diagnostic performance of HbA1c compared to FPG and 2 h-PG in a representative sample of adult individuals taken from an urban general population, who were not yet diagnosed with diabetes.…”