Detecting undiagnosed diabetes using glycated haemoglobin: an automated screening test in hospitalised patients

The prevalence of diabetes is 7.4% in Australia.1 This continues to increase with an annual incidence of 0.8% in adult Australians.1 Diabetes is associated with excess mortality, major morbidities and substantial use of health care resources.2 The early phase of diabetes is usually asymptomatic and can remain undetected for many years, with about half of these patients unaware they have the condition.1,3 Treatment of diabetes, hypertension and dyslipidaemia reduces long-term complications.3-5 These factors favour early detection of diabetes by screening.6,7

The prevalence of diabetes among hospitalised patients is about three times the community prevalence.1,8,9 Furthermore, hospitalisation is a point of contact with the health care system. However, this opportunity for population screening is not currently recommended because glucose-based tests are confounded by stress hyperglycaemia.10

Screening for diabetes by measuring fasting plasma glucose (FPG) and/or using oral glucose tolerance tests (OGTTs) among high-risk individuals has been recommended since 1965.11 Glycated haemoglobin (HbA1c) testing was recently recommended by the International Expert Committee as the preferred test to diagnose diabetes and this has been adopted by the American Diabetes Association (ADA).6,12 Diabetes defined by HbA1c level predicts microvascular and macrovascular complications at least as well as diabetes defined by glucose testing.3,4,13-15 HbA1c testing is familiar to clinicians, as it is routinely used in clinical practice to guide treatment, and is the preferred biochemical marker of diabetes in clinical studies. HbA1c levels are less affected by acute illness than plasma glucose levels, and are therefore more likely to be reliable in the hospital setting.16 We hypothesised that HbA1c levels could be used as an automated screening test in hospitalised patients for the diagnosis of diabetes.

The primary aims of this study were to estimate the prevalence of undiagnosed diabetes in hospitalised patients, to assess the utility of HbA1c testing to screen hospitalised patients for diabetes, and to define the distribution of HbA1c levels among patients with undiagnosed diabetes. A further aim was to perform indicative cost analysis to explore the hypothesis that HbA1c testing at the time of hospitalisation is a cost-effective method to detect patients with undiagnosed diabetes.

HbA1c testing was conducted among 2672 patients. The study group was 93% white, comprised 48% women, and ranged in age from 18 to 102 years. The characteristics of the three groups classified by diabetes status are shown in Box 2. The prevalence of diabetes was 21.5% (95% CI, 19.9%–23.0%) among patients admitted to hospital with RPG ≥ 5.5 mmol/L. Diabetes was previously undiagnosed among 262/2360 patients (11.1%; 95% CI, 9.8%–12.4%). There were 312 patients with known diabetes (11.7%; 95% CI, 10.5%–12.9%). The prevalence of undiagnosed diabetes was highest in the 65–74-years age group (Box 3). In our study, the prevalence of diabetes among hospitalised patients was three times higher than the community prevalence. Among the younger patients (25–34 years), the hospital prevalence of diabetes was 24 times higher than the community prevalence (Box 3).

Older age (r = 0.08; P < 0.001), increased RPG (r = 0.41; P < 0.001) and decreased GFR (r = − 0.07; P = 0.003) correlated with undiagnosed diabetes. Sex and treating specialty did not correlate with undiagnosed diabetes. There was no significant difference in length of stay, number of admissions or discharge destination between those with and without undiagnosed diabetes. Among patients with known diabetes, the length of stay was longer compared with those with undiagnosed diabetes (P < 0.001).

We found that a high proportion of hospitalised patients with a RPG level ≥ 5.5 mmol/L had undiagnosed diabetes. The prevalences of known and undiagnosed diabetes were about threefold higher than in the Australian community.1,8,9 Among hospitalised patients younger than 55 years, the prevalence of diabetes was almost fivefold higher than in the community. We used the recent International Expert Committee recommended diagnostic threshold of HBA1c levels ≥ 6.5% to detect undiagnosed diabetes among hospitalised patients. A previous cohort study of unselected emergency admissions, which defined diabetes as an HbA1c level ≥ 6.2%, reported that 18% of patients had an HbA1c level above this value.8 In our study, 17% of patients had an HbA1c level ≥ 6.2%.

HbA1c monitoring can be used as an automated screening test in hospitalised patients using blood samples drawn during usual clinical care. Potential benefits of an automated HbA1c screening program include low implementation costs and extensive coverage of a high-risk group. In contrast, glucose-based automated screening processes are unreliable due to unknown fasting status and stress hyperglycaemia.8 Automated HbA1c testing was easily implemented using existing blood samples and was an inexpensive method to diagnose diabetes in this patient cohort.

Although RPG testing is not recommended for diagnosing diabetes, evidence suggests RPG testing is commonly used for reasons of convenience.5 In our study, RPG levels had low sensitivity in diagnosing diabetes; using the recommended RPG level of ≥ 11.1 mmol/L would have missed 188 patients with diabetes. Using lower thresholds improves sensitivity, but compromises specificity. This is consistent with many other studies.8,16,19

Other studies used FPG testing and/or OGTT to diagnose diabetes in hospitalised patients and reported rates of undiagnosed diabetes from 2.6% to 9%.20,21 The lower rates of diabetes in some studies may reflect the poor sensitivity of fasting glucose in this setting. We did not assess FPG levels in this study, but demonstrated that a post-discharge OGTT is unlikely to be an effective screening method. Despite a personal approach and two reminders, the completion rate of OGTTs was only 27%. Although other published studies have reported a higher completion rate (55%–58%), they have also noted poor compliance with this test.22,23

There is agreement about the need for screening and early intervention of diabetes. There is currently no recommendation to screen hospitalised patients in international guidelines.6,7,18 Existing Australian screening guidelines would have led to testing of only 25% of patients with unknown diabetes in our study. This is consistent with previous reports that established risk factors are poor predictors of diabetes or impaired glucose tolerance among hospitalised patients.19 Furthermore, 17% of patients with unknown diabetes in this study did not identify having a regular GP. This highlights the value of using hospitalisation as a point of contact with the health care system to screen patients who would otherwise be missed.

In any screening program, there is first-test bias and subsequent testing has lower yield. We estimated the likely ongoing yield from HbA1c testing from the annual incidence of diabetes, 0.8%. Consistent with ADA recommendation, our results suggest that the yield from screening patients under 45 years of age will be low. However, the prevalence of diabetes in hospitalised patients under 45 years in our study is sevenfold higher than in the community and there may be greater potential benefit of screening in this cohort. Based on our findings, we believe the most practical approach to screening hospitalised patients for diabetes is to test HbA1c level among all adult patients having blood tests on admission. For patients with known diabetes, this result is clinically important to guide discharge management. If local information technology systems permit, this could be further refined, for example, by excluding patients who have been tested within the past 12 months. We have shown HbA1c screening is feasible, and, on face value, the screening costs per new diagnosis do not appear excessive. Cost-effectiveness of specific programs tailored to local environments should be the subject of further research.

A limitation of our study is that the diagnoses of known diabetes and comorbidities were based on coding data, which are underestimates of the true prevalence. However, this limitation does not apply to the incidence estimates used in our analysis. In our study, patients who did not have blood tests on admission or with RPG level < 5.5 mmol/L were excluded. Of patients with an RPG level just above this threshold (5.5–5.9 mmol/L), only 4% (24/587) had undiagnosed diabetes. Although the excluded patients are likely to be healthier than the study participants, the prevalence of diabetes in this group is unknown. A conservative estimate of the hospital prevalence of undiagnosed diabetes is 7.4% (assuming all patients with RPG levels < 5.5 mmol/L do not have diabetes).

There are limitations to the use of HbA1c testing among hospitalised patients, particularly disorders of increased red cell turnover (eg, haemolytic disorders) and blood transfusion. However, these conditions are unlikely to be present in numbers that affect overall screening, and “first samples” are likely to be before transfusion.3

A hospital inpatient diagnosis of diabetes is only useful if patients receive adequate long-term management. Any automated laboratory-based screening program must be coupled to adequate resources to manage diabetes within the community. Further research into community integration should be conducted.

In summary, this study of 2672 patients with an RPG ≥ 5.5 mmol/L admitted to a tertiary hospital over 3 months found undia-gnosed diabetes in 11%. Automated HbA1c screening is easy to implement in a hospital setting using existing clinical blood samples. Screening hospitalised patients for HbA1c levels is an inexpensive method of detecting undiagnosed diabetes. If adopted as a screening tool it would need to be coupled with adequate resources for follow-up and management of diabetes in the community.

1 Enrolment of study participants

Age is presented in mean (SD) years. RPG = random plasma glucose.

3 Prevalence of diabetes among hospitalised patients, by age

The number in each group is shown within the columns.

4 Distribution of glycated haemoglobin (HbA1c) levels among patients with no or undiagnosed diabetes