scenario, HbA1c_2). However, the clinical uncertainty associated with this conclusion is significant. Financial/budgetary impacts While HbA1c testing is proposed to replace currently available tests, accurate MBS utilisation data could not be retrieved for the FPG test, as the relevant item number also lists a number of other tests. In consequence, an epidemiological approach has been undertaken for estimation of the pre-diabetic and ‘high-risk’ population (who are recommended for FPG and OGT testing, if indicated). As women with a history of gestational diabetes or polycystic ovary syndrome are recommended for regular testing with the OGT test (; ), a market-share approach is used to estimate this population. The total cost savings to the MBS for the proposed use of diagnostic HbA1c testing, using a base-case set of assumptions, averages $39 million per year for the HbA1c_1 scenario and $25 million per year for HbA1c_2, when estimates include test accuracy data. When accuracy data is not included in the estimates, the average annual net cost savings to the MBS is $39 million for the HbA1c_1 and $37 million for the HbA1c_2 scenarios. However, a number of issues are present that contribute to uncertainty in the results of the financial Uncertainties relating to the estimated population likely to be tested include the proportion of pre-diabetic patients that are undiagnosed, the uptake rates of diabetes risk assessment (given that screening is recommended opportunistically), the patient uptake of testing, and the accuracy of the comparator and intervention tests. These issues are further compounded by recommendations for repeat testing in subsequent years. Additionally, the cost of the initial FPG test is uncertain (it varies depending on whether the test is ordered alone or with other tests listed in the same item number), leading to overall uncertainty in the costs that would be offset with the introduction of HbA1c testing. When financial impact estimates are varied from the base-case in sensitivity analyses (using plausible variable limits), the estimates range widely between annual cost savings of $40 million to net costs of $11 million. Given the multiple uncertainties in the estimated population eligible for testing and other testing parameters, the financial implications to the MBS cannot be confidently estimated.
Risk of developing diabetes complications in undiagnosed diabetes (base-case: 1.72) 1.52 $8,397.38 16.2370 $8,119.40 16.2131 –$277.98 –0.0239 $11,660 $8,464 As there are more cases of undiagnosed diabetes in the intervention, if risk of complications decreases, the incremental improves. However, this is outweighed by the increased incremental cost due to more complications: favours the comparator - 1.92 $8,447.18 16.2314 $8,318.07 16.1910 –$129.11 –0.0404 $3,196 - Decreased incremental costs outweigh the decrease in incremental effectiveness: favours the intervention Annual cost of diabetes (with complications) (base-case: $2,648) $1,836 $7,354.70 16.2340 $7,026.42 16.2015 –$328.28 –0.0326 $10,084 $7,897 As there are more cases of diabetes with complications in the intervention arm, incremental costs decrease: favours the intervention - $3,459 $9,490.74 16.2340 $9,419.53 16.2015 –$71.21 –0.0326 $2,187 - Increased incremental costs: favours the comparator Eff. = effectiveness; HbA1c = glycated haemoglobin; ICER = incremental cost-effectiveness; NGT = normal glucose tolerance
Appendix C Study profiles of included studies Table 57: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes with retinopathy as the reference standard Study and location Diagnostic level of evidence and study design Quality assessment Study population Inclusion/exclusion criteria Reference standard Index test Outcomes Massin ()Central Western France Level III-2 longitudinal cohort study, recruited in 1994–96 and followed up for 9–10 years; invited at 10 years to participate in microvascular examination. High risk of bias as it included people with treatment effect likely. No applicability concerns in terms of setting or population. N=733 people who were recruited into longitudinal study; n=237 had been treated for diabetes or had a diabetes-range FPG level during the 9-year study period; n=246 had IFG level at any time during study; n=249 with normal FPG level during study. Average age at baseline 52 years. No other descriptors provided. N=33 excluded because photographs not gradable; no other criteria described. Retinal photography by non-mydriatic retinal camera, all graded by same observer according to simplified Wisconsin protocol. HbA1c continuum FPG continuum ROC analysis, sensitivity and specificity, AUC, predefined and optimal cut-offs McCance () Gila River Indian community, Arizona, USA Level III-2 longitudinal cohort study that has been going since 1965; all community members over 5 years invited to participate. High risk of bias as it used HbA1 as measure for many subjects, and retinopathy diagnosed by direct ophthalmic examination; likely that quality of tests N=927 people but participation rates not reported. Included subjects not described, other than being 25 years of age or older. Baseline measures from Jan 1982 to Nov 1991, mean follow up of 4.5 years. Excluded subjects with retinopathy or receiving insulin or oral hypoglycaemics; also excluded those with missing blood glucose measures at baseline. Ophthalmoscopic exam by physician. HbA1c continuum FPG and 2hPG continuum ROC analysis, sensitivity, specificity, predefined and optimal cut-offs
has changed since this study was done. Limited applicability to Australian setting. Englegau () Cairo and rural surrounds, Egypt Level III-2 High-risk subgroup of randomly sampled population invited for further testing including OGT and retinal photographs; further testing appears concurrent. Low risk of bias in conduct of study, although likely that quality of tests has changed since this study was done. Limited applicability to Australia given Egyptian setting. N=1,018 people who had a random blood glucose measure of ≥5.6 mmol/L at baseline survey, plus random sample of those below; about 2/3 sample at high risk or with diabetes. Analysis conducted with and without people with diabetes. Description limited; mean age 45 years, 41% male. Analysis included subjects with all blood glucose and retinopathy measures; overall participation rate 50%. Retinal photo taken and graded by external staff using modified Airlie house classification. HbA1c continuum FPG and 2hPG continuum ROC analysis, only sensitivity and specificity reported Table 58: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes: studies included in meta-analysis Study and location Diagnostic level of evidence and study design Quality assessment Study population Inclusion/exclusion criteria HbA1c cut-off— HbA1c cut-off— diabetes Reference standard (FPG and/or OGT Reference standard cut-off(s): (FPG and/or OGT Outcomes
to timing. recruited into OGT test study. Overall, 79% of participants had original HbA1c ≥5.7% so considered high-risk. N=3476 participants, 51% male, age under 60 years 35%, age 60 years or older 65%. Alqahtani () Khamis Mushayt, Saudi Arabia Level III-2 Database review of participants who visited outpatient clinic of armed forces hospital and had tests on suspicion of diabetes. Low risk of bias in study design. Some concerns about applicability given very specific population; unlikely to be relevant to Australia. N=1,814 records of patients who had undergone concurrent OGT, FPG and HbA1c testing on suspicion of diabetes. N=622 males (34.3%), mean age 54.3 ± 13.6 years. Database review so the only inclusion criteria were having the test results available and ‘suspicion of diabetes’, but this not described. IFG: ≥6.5% IFG: FPG mmol/L; IGT: 2hPG mmol/L FPG ≥7.0 2hPG ≥11.1 3x3 table Baral () Dharan, Nepal Level III-2 Hospital-based study of patients referred for OGT testing. Risk of bias unclear overall. Reference standard differ from Australia, very little information about study design. Some concerns about applicability, N=920 subjects referred to hospital for OGT testing. Age range 30–65 years. No other details. Pregnant women excluded. No other details. Not reported ≥6.0% FPG mmol/L; 2hPG mmol/L FPG ≥7.0 2hPG ≥11.1 2x3 table 11.1 6.4%
no information on patient selection, Nepalese population unlikely to be relevant to Australia. Cosson () Bondy, France Level III-2 Hospital-based study of patients referred for weight management. Low risk of bias. Applicable to Australian setting. Relevant points. N=1,157 consecutive patients referred to hospital clinic who fitted ADA risk criteria for diabetes and underwent diabetes tests; 17% male, mean age 41 ± 13 years. Exclusions not detailed. 5.7%≥ HbA1c <6.5% ≥6.5% 5.5 mmol/L≥ FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L FPG ≥7.0 2hPG ≥11.1 3x3 table, ROC analysis Du () Wuhan, China Level III-2 Patients referred to diabetes outpatient clinic of hospital in China. Low risk of bias. Applicability to Australian setting unclear as Chinese study. Relevant points. N=2,856 in sample, n=2,318 recruited patients referred to hospital outpatient clinic on suspicion of diabetes; age years, mean 47.5 years. Exclusions were chronic disease (n=45), blood disorder (n=13), pregnancy (n=112), other medical reason (n=10), currently have diabetes (n=157), rejection of blood collection (n=103) and no information on tests (n=98), leaving total sample of n=2,318. 5.7%≥ HbA1c <6.5% ≥6.5% 100 mmol/L≥ FPG <126 mg/dL FPG ≥126 2x2 table, ROC analysis Lee, H () 10 sites in South Korea Level III-2 10 hospital outpatient clinics in South Korea, each participant had OGT and HbA1c as part of battery of Low risk of bias. Applicability to Australian setting unclear as Korean study. Relevant points. N=4,616 patients who were referred to or voluntarily attended hospital clinic for diabetes diagnosis; 55% male, mean age 50 ± 13 years. Excluded patients with known diabetes, renal impairment, conditions, conditions known to impact on glucose tolerance. Numbers excluded not given. Not reported ≥6.1% FPG ≥7.0 2hPG ≥11.1 2x2 table, ROC analysis L
the same study. concern. Applicable to population in question; high-risk population in Italy. 33% male; 2012b: n=780, mean age 45 ± years, 42% male (exclusions not described). disease, chronic gastrointestinal disease, history of alcohol or drug abuse (n=91); n=330 excluded due to missing data. Total n=1,019. Also excluded if positive to hepatitis C or B, or if anaemic, but numbers not provided. Study on pre-diabetes excluded people found to have diabetes from analysis. Cavagnolli () Porto Alegre, Brazil Level III-2 Study of subjects referred to hospital clinical pathology department for OGT tests. Low risk of bias. Few applicability concerns; Brazilian study but majority of subjects of European descent. Cut-offs appropriate. Patients with high risk of diabetes referred (unclear where from) for OGT tests, all Brazilians with 84% white, 39% males. Included patients with hypertension, family history of hypertension, diabetes or cardiovascular disease. Excluded participants with conditions known to interfere with HbA1c results (e.g. anaemia, variant haemoglobin). 6.0%≥ HbA1c <6.5% ≥6.5% 5.6 mmol/L≥ FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L FPG ≥7.0 2hPG ≥11.1 3x3 table, ROC analysis Table 59: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes: studies not included in meta-analysis but providing diagnostic accuracy data Study and location Diagnostic level of evidence and study design Quality assessment Study population Inclusion/exclusion criteria HbA1c cut-off— HbA1c cut-off— diabetes Reference standard (FPG and/or OGT Reference standard cut-off(s): (FPG and/or OGT Outcomes
Colagiuri () Australia Level III-2 Subgroup analysis of participants in study of diabetes prevalence. Risk of bias unclear; study, results given on a subgroup with at least one risk factor. High applicability as Australian setting. Different to current Subgroup of AusDiab study, study of diabetes prevalence. Subgroup determined by presence of at least one risk factor, but subgroup not described at all. Subgroup not described. Larger population study recruited from stratified random sample. ≥5.3% ≥5.3% 6.1 mmol/L≥ FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L FPG ≥7.0 2hPG ≥11.0 ROC analysis for people with HbA1c ≥5.3% Cosson () Paris, France Cohort also reported in meta-analysis (Cosson ) Level III-2 Inpatients without known diabetes referred for OGT testing as part of battery of tests. Low risk of bias. Applicable to Australian setting. Appropriate cut-offs. Patients referred to hospital clinic for treatment of overweight or obesity, free of any acute disease but likely to be at high risk. N=1,287, 82% female, mean age 39 ± 14 years, range 16–76 years. Excluded patients with known diabetes. Included patients with comorbidities but no acute disease. Not reported Not reported 6.0 mmol/L> FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L FPG ≥7.0 2hPG ≥11.1 Sensitivity and specificity Gomyo () Various locations, Japan Level III-2 Patients identified with pre-diabetes after initial screening for an RCT of Low risk of bias. Applicability uncertain as population not well described; Population not well described; n=997. Exclusions not reported. To have OGT test, patients had to have: (1) 100 mg/dL≤ FPG <126 mg/dL; (2) 140 mg/dL≤ casual plasma glucose (CPG) <200 mg/dL (less than Not reported Not reported IGT: FPG <126 mg/dL; 140 mg/dL≥ 2hPG <200 mg/dL; IFG: FPG ≥126 2hPG ≥200 ROC analysis
interventions for diabetes prevention; subjects recruited to have OGT test. Japanese population. Cut-offs different to current criteria. 2 hours after a meal); (3) 110 mg/dL≤ CPG <140 mg/dL (more than 2 hours after a meal); (4) IGT by 75 g OGT at original screen for recruitment to the RCT. 110 mg/dL≥ FPG <126 mg/dL; 2hPG <140 mg/dL Hajat () Abu Dhabi, United Arab Emirates Level III-2 Patients recruited from screening program in community setting in Abu Dhabi; after initial screen, patients with possible diabetes recalled for further testing including OGT. Risk of bias unclear as only patients with HbA1c >6.1%, random glucose ≥11.1 mmol/L or missing data recalled for OGT test. Middle Eastern population, so some concerns about applicability. Appropriate cut-offs. N=1,028 people 18 years of age or older included, but not described. Not reported. Unknown how many were recalled for OGT test and how many actually had tests. Not reported Not reported Not reported FPG ≥7.0 2hPG ≥11.1 ROC analysis Hu () Shanghai, China Level III-2 Participants with at least one risk factor for diabetes were identified from medical examination database and invited to attend for diabetes Low risk of bias in study design. Some concerns with applicability to Australian setting as Chinese population. Cut-offs appropriate. N=2,298 participants, 42% male, mean age 52.4 years (SD 13.3). Participants had at least one of: family history of diabetes, history of gestational diabetes, obesity or history of IGT. Excluded subjects with previously diagnosed diabetes, receiving medication for diabetes or who were pregnant. Not reported Not reported IGT: FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L; IFG: 6.1 mmol/L≥ FPG <7.0 mmol/L; 2hPG FPG ≥7.0 or 2hPG ≥11.1 ROC analysis
a diabetes intervention program, from primary care family practices in England. although conduct of study has low level of bias. Applicable to Australian setting as culturally similar and general practice setting. Appropriate cut-offs. 2009 and April 2010. N=3,921, age years. No further details reported. disease, history of gestational diabetes). Excluded n=15 patients but no reasons given. Santos-Rey () Seville, Spain Level III-2 Study of patients from a cardiovascular risk clinic in a Spanish Hospital; study primarily concerned with diagnosing IGT. Low risk of bias in study design. population applicable to population in question, although Spanish. Appropriate cut-offs. Consecutive patients aged 18–70 years with at least two risk factors recruited between March 2005 and Nov 2008 from a cardiovascular risk clinic. N=713, mean age 51 ± 12 years, 50% male, 98% Caucasian. Patients with two or more risk factors: obesity, dyslipidaemia, hypertension, previous IGT or family history of diabetes) were included. Patients aged less than 18 years or 70 years or older were excluded. Only patients with FPG <7.0 mmol/L had OGT tests and are included in ROC analysis. Not reported Not reported FPG: 5.6 mmol/L≥ FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG <11.1 mmol/L Not reported ROC analysis for IGT Snehalatha () Chennai, India Level III-2 Study of patients who underwent diabetes testing in a hospital diabetes clinic in India. Risk of bias unclear due to inadequate description of population. Questionable applicability to Australia as Indian population. Appropriate cut-offs. Patients recruited from diabetes clinic between July and Dec 1998, but recruitment not described. N=1,261 participants, mean age 40 ± 12 years, 67% male. Many had strong family history of diabetes or other risk factors, but not described. Patients had no known history of diabetes. No other criteria described. Not reported Not reported Not reported FPG >125 2hPG ≥200 ROC analysis
Tanaka () Tokyo, Japan Level III-2 Study of patients suspected of having diabetes, assessment at two hospitals in Tokyo. Risk of bias and applicability unclear due to inadequate description of population. Study in Japan so questionable applicability to Australian population. Appropriate cut-offs. Patients suspected of having diabetes and undergoing OGT testing as part of a battery of tests in hospitals in Japan, June 1995 – April 1999. N=866 enrolled, 66% male, mean age 56 ± 0.4 years, range 20–82 years. Patients with anaemia, renal or hepatic dysfunction excluded. Not reported 6.5% IGT: 7.8 mmol/L≥ 2hPG <11.1 mmol/L FPG ≥7.0 2hPG ≥11.1 ROC analysis Tankova () Sofia, Bulgaria Level III-2 Study of diabetes diagnosis in people who were doctor- or self-referred to the study conducted in a university hospital department. Risk of bias in conduct of study low. Few applicability population. Cut-offs differ from Australian guidelines. N=2,231 patients with at least one risk factor for diabetes, referred by doctor or to screening program from April 2006 – Oct 2010; mean age 50.3 ± 13.9 years, 41% male. Patients had at least one of: relative with diabetes, overweight or central obesity, history of gestational diabetes, had baby over 4 kg, history of IFG or IGT, hypertension, lipid abnormalities or atherosclerotic vascular disease. Exclusions not described. Not reported Not reported 6.1 mmol/L≥ FPG <7.0 mmol/L; 7.8 mmol/L≥ 2hPG< 11.1 mmol/L FPG ≥7.0 2hPG ≥11.1 ROC analysis Table 60: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes in older adults Study and location Diagnostic level of evidence and study design Quality assessment Study population Inclusion/exclusion criteria HbA1c HbA1c cut-off— diabetes Reference standard (FPG and/or OGT Reference standard cut-off(s): (FPG and/or OGT Outcomes
Rathmann () Augsburg, Germany Level III-2 Elderly subgroup of participants recruited as part of health survey, selected using random sampling. Low risk of bias. No applicability concerns. Cut-offs appropriate. Patients who formed part of a cohort study: subjects who were aged 61–75 years without pre-existing diabetes underwent OGT testing. N=896, males 51.5%, mean age 67 ± 3.7 years. Included patients without diabetes aged 61–75 years. Excluded patients with acute illness who could not undergo OGT testing, and people whose data was incomplete. 5.7%≥ HbA1c <6.5% ≥6.5% IFG: 6.1 mmol/L≥ FPG <7.0 mmol/L; 2hPG <7.8 mmol/L; IGT: 7.8 mmol/L≥ 2hPG <11.1 mmol/L; FPG <6.1 mmol/L FPG ≥7.0 2hPG ≥7.8 3x3 table, ROC analysis Kramer () San Diego, USA Level III-3 Cross-sectional study of older adults; subgroup analysis of larger cohort. Unclear level of bias in study as population selection, and study flow and timing, not well described. Applicability unclear as difficult to ascertain if relevant population; however, likely to be similar to Australia. Older participants in a cross-sectional study who underwent concurrent OGT and HbA1c tests between 1984 and 1987; selection and recruitment not described. N=2,107 subjects, 43% males, mean age 69.4 ± 11 years. Included patients without known diabetes; no other inclusion or exclusion criteria described. Not reported Not reported Not reported Not reported ROC analysis Table 61: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes in ethnic minorities Study and location Diagnostic level of evidence and Quality assessment Study population Inclusion/exclusion criteria HbA1c HbA1c Reference standard Reference standard Outcomes
study design (FPG and/or OGT cut-off(s): (FPG and/ or OGT Araneta () California and Hawaii, USA Level III-2 Cross-sectional study of ethnic minorities recruited from community. Risk of bias unclear due to poor reporting. Limited applicability due to ethnic minorities not applicable to Australia. Appropriate cut-off points. N=933 Japanese-Americans, native Hawaiians; mean age 54.2 years, 27% male. Excluded individuals with known diabetes. Wang, H () and Wang, W () Four states of USA Level III-2 Baseline and follow-up measures of subjects in large cohort study of heard disease. Risk of bias unclear as selection of population not described and people with CVD excluded. Limited applicability due to ethnic minority, not relevant to Australia. Appropriate cut-off points. American Indians from Arizona, Oklahoma, North and South Dakota. Baseline n=3850, follow-up n=1670. Age range years. Excluded people with CVD; at follow up, excluded people with diabetes diagnosed at baseline. 5.5%≥ HbA1c <6.5% 6.0%≥ HbA1c <6.5% HbA1c ≥6.5% 5.6 mmol/L≥ FPG <7.0 mmol/L FPG ≥7.0 3x3 table Exebio () Florida, USA Level III-2 Cross-sectional analysis of control arm of patients Risk of bias unclear as patient recruitment Patients of Haitian origin (2 Haitian parents), n=128, all aged 35 years or Excluded people less than 35 years of age, and pregnant and breastfeeding women, n=1 who had missing HbA1c value. Not reported Not reported Not reported FPG ≥7.0 ROC analysis Americans,
over that time. Methodology not well described. Limited applicability to Australian setting due to Japanese subjects. male: female ratio 1:1.1. Sharma () California, USA Level III-2 Baseline analysis of participants in a community-based lifestyle modification program to reduce risk of type 2 diabetes. Some likelihood of bias as participants recruited through community, not from referral. Limited applicability to Australian setting as all children. Subjects were African-American children with BMI at or above 85th percentile; n= 172 children, mean age boys 9.96 years, girls 9.80 years; 41% males. Inclusion criteria were aged years, BMI at or above 85th percentile; exclusion criteria FPG ≥120 mg/dL, other metabolic disease or taking medications known to affect study outcomes. 5.7%≥ HbA1c ≤6.4% HbA1c ≥6.5% 5.6 mmol/L≥ FPG <7.0 mmol/L FPG ≥7.0 mmol/L Limited 3x3 table Yesiltepe Mutlu () Kocaeli, Turkey Level III-2 Chart review of children who underwent OGT testing between Feb 2010 and Feb 2011. Level of bias and applicability unclear as population and other methodology not well described. N=106 obese or overweight children who underwent OGT testing; mean age 13.4 ± 2.6 years, range 7–18 years, 33% male. No inclusion or exclusion criteria described. HbA1c ≥5.5% Not reported 100 mg/dL≥ FPG <126 mg/dL; 140 mg/dL≥ 2hPG <200 mg/dL FPG ≥126 mg/dL; 2hPG ≥200 mg/dL ROC analysis
Table 63: Study profiles of included studies on diagnostic accuracy of HbA1c testing for diagnosing diabetes in people with CVD Study and location Diagnostic level of evidence and study design Quality assessment Study population Inclusion/exclusion criteria HbA1c HbA1c cut-off— diabetes Reference standard (FPG and/or OGT Reference standard (FPG and/or OGT test)—diabetes Outcomes Doerr () Germany Level III-2 Study of test accuracy against reference standard. Low risk of bias. No applicability concerns. N=1,015 patients; 69% male. Mean age 68.2 ± 9.0 years. Included patients 54 years of age or older admitted for acute (n=146) or elective (n=866) coronary angiography. Excluded patients with known diabetes or history of taking glucose-lowering agents, or with pancreatic, hepatic or kidney disease, or presence of endocrine diseases or treatment with steroid medication. 5.7–6.4% ≥6.5% IGT: FPG <126 mg/dL and OGT test ≥140 mg/dL; IFG: FPG ≥100 mg/dL and <126 mg/dL FPG ≥126 mg/dL and/or OGT test ≥200 mg/dL Sensitivity, specificity Gianchandani () Unites States Level III-2 Study of test accuracy against reference standard. Low risk of bias. No applicability concerns. N=92/116 patients (12 excluded to rescheduled surgery, 10 declined, 1 withdrew, 1 did not meet criteria). Mean age years. Included patients participating in ongoing study following cardiothoracic surgery procedures. Excluded patients with history of diabetes or of taking medication that interferes with glucose metabolism (glucocorticoids, immunosuppressive 5.7–6.4% ≥6.5% IFG: FPG mg/dL; IGT: OGT test mg/dL FPG ≥126 mg/dL and/or OGT test ≥200 mg/dL Sensitivity/ specificity (2x2)
6.2 mmol/L) N=2 HbS non-diabetic (mean FPG = 5.3 mmol/L) Schnedl () Austria N=2 Hb Graz diabetic (mean FPG = 13.7 mmol/L) N=2 Hb Graz (mean FPG = 4.8 mmol/L) N=1 Hb Sherwood Forest (mean FPG = 5.2 mmol/L) N=1 HbD diabetic (mean FPG = 5.9 mmol/L) N=1 HbO-Padova diabetic (mean FPG = 5.9 mmol/L) N=1 HbO-Padova normal (mean FPG = 6.1 mmol/L) Enzymatic BA-HPLC Arkray Primus 8.7 8.55 5.2 5.35 5.1 4.8 5.1 5.4 7.3 7.6 5.9 5.3 IE-HPLC analysers HA8160 HLC-723 No result No result No result No result No result 2.8 4.1 3.5 5.9 7.6 3.8 5.4 Immunoassays DCA Tina Unimate Rapida 5.85 5.8 5.9 5.15 4.05 4.35 4.05 2.6 4.7 5.2 5.1 4.4 6.2 5.7 5.9 5.7 7.8 7.6 8.0 8.3 5.8 5.4 5.7 5.6 The enzymatic and boronate affinity HPLC method did not interfere with any of the variants evaluated. Hb Graz interfered with all immunoassay and ion-exchange HPLC methods evaluated. The Tosoh ion-exchange HPLC method did not detect the late migrating in the chromatogram, but this haemoglobin variant still interfered, causing artificially low HbA1c results.