Validation of an algorithm combining haemoglobin A1c and fasting plasma glucose for diagnosis of diabetes mellitus in UK and Australian populations

Aim To determine whether glycated haemoglobin (HbA_1c) can be used in combination with fasting plasma glucose (FPG) for the diagnosis of diabetes in patients with impaired fasting glucose (IFG) and in a broader spectrum of patients. Methods An algorithm was derived from oral glucose tolerance test (OGTT) capillary samples in 500 consecutive UK patients with IFG by World Health Organization criteria. It was validated in a further 500 UK patients and, with venous specimens, in 1175 unselected Australian patients. Results The derivation cohort was aged 61 years (50–69 years) (median IQ range) with 52% male and 12% South Asian. Diabetes Control and Complications Trial‐aligned HbA_1c was 6.2% (5.8–6.6%) (reference interval < 6.0%) and FPG 6.7 mmol/l (6.3–7.2 mmol/l). FPG was in the diabetes range in 36% of patients, with an OGTT identifying a further 12% with diabetes. The derived algorithm, (HbA_1c ≥ 6.0% with FPG < 7.0 mmol/l) identified those patients requiring an OGTT to diagnose diabetes. When applied to the UK validation cohort, sensitivity was 97% and specificity 100%. The algorithm was equally effective in the unselected group, aged 59 years (49–68 years) and 54% male, with sensitivity 93% and specificity 100%. HbA_1c was 6.0% (5.6–6.6%) and FPG 6.0 mmol/l (5.3–6.8 mmol/l), with 26% having IFG. Use of the algorithm would reduce the number of OGTTs performed in the UK validation cohort by 33% and by 66% in the Australian patients studied. Conclusions Use of this algorithm would simplify procedures for diagnosis of diabetes and could also be used for monitoring pre‐diabetes. Validation is now required in other populations and patient groups.     

Fasting plasma glucose and HbA1c as risk factors for Type 2 diabetes

Aims We examined the value of combining fasting plasma glucose (FPG) and glycated haemoglobin (HbA_1c) as a predictor of diabetes, using the new American Diabetes Association (ADA) criteria of FPG and lower cut‐off point of HbA_1c. Methods A retrospective cohort study was conducted from 1998 to 2006, inclusive, in 10 042 persons (55 884 person‐years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes (defined either as an FPG ≥ 7.0 mmol/l or as clinically diagnosed diabetes) was measured. Results The cumulative incidence and incidence density of diabetes were 3.7% (368 cases) and 6.6/1000 person‐years over a mean follow‐up period of 5.5 years. The cumulative incidence of diabetes in subjects with impaired fasting glucose (IFG) and HbA_1c 5.5–6.4% was 24.8% (172/694 persons) compared with 0.4% (25/6698 persons), 2.5% (15/605 persons), 7.6% (156/2045 persons) in those with normal fasting glucose (NFG) and HbA_1c < 5.5%, NFG and HbA_1c 5.5–6.4% and IFG and HbA_1c < 5.5%, respectively. The hazard ratio for diabetes, adjusted for possible confounders, was 7.4 (95% confidence interval, 4.70 to 11.74) for those with NFG and HbA_1c 5.5–6.4%, 14.4 (11.93 to 27.79) for those with IFG and HbA_1c < 5.5% and 38.4 (24.63 to 59.88) for those with IFG and HbA_1c 5.5–6.4%. Conclusions The combination of FPG and HbA_1c identifies individuals who are at risk of progression to Type 2 diabetes at the new ADA criteria of FPG and a lower cut‐off point of HbA_1c than previous studies.     

Fasting plasma glucose and glycated haemoglobin in the screening of diabetes and impaired glucose tolerance

Abstract. The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA_1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA_1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG 7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA_1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA_1C is effective in the screening of IGT; although combined FPG and HbA_1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.     

Effect of HbA1c combined FPG on screening diabetes in health check-up

ObjectiveTo appraise the effectiveness of HbA_1c and fasting plasma glucose (FPG) on screening diabetes in health check-up.MethodsA total of 1 337 individuals (male 850, female 487), aged 27 to 91 years with HbA_1c test were included. Participates with HbA_1c ?6.0% or FPG?6.1 mmol/L underwent oral glucose tolerance test (OGTT). Diabetes mellitus was diagnosed according to the criteria of WHO in 1999, FPG?7.0 mmol/L and/or OGTT 2 h-postload plasm glucose (2 h-PG)?11.1 mmol/L. The sensitivity and specificity of HbA_1c thresholds and FPG or combination test on screening of diabetes were analyzed.ResultsA total of 842 subjects had HbA_1c <6.0%, in which 32 had isolated FPG?6.1 mmol/L, of 495 had HbA_1c?6.0%. Subjects with HbA_1c?6.0% had significant increased disorder indexes than those with HbA_1c<6.0%. 527 subjects who had HbA_1c?6.0% or FPG?6.1 mmol/L underwent OGTT. A total of 234 subjects were newly diagnosed diabetes, including 123 (123/234, 52.56%) with FPG?7.0 mmol/L, and 111 subjects (111/234, 47.43%) with isolated 2 h-PG?11.1 mmol/L. Among 234 new diabetes, 91.88% (215 subjects) had HbA_1c?6.3%, and 77.40% (181 subjects) had HbA_1c?6.5%. HbA_1c?6.3% combined FPG ?7.0 mmol/L increased the positive rate of newly diagnosed diabetes from 91.88% to 96.58%.ConclusionsHbA_1c is a practical and convenient tool for screening undiagnosed diabetes in routine health check-up of a large population. Combined use of HbA_1c?6.3% and/or FPG?7.0 mmol/L is efficient for early detection of diabetes.     

Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets - the TITRATETM study

Aims: To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4–6.1 mmol/l (80–110 mg/dl) and 3.9–5.0 mmol/l (70–90 mg/dl)] using a patient‐directed, treat‐to‐target algorithm for once‐daily basal insulin in insulin‐naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs). Methods: In this 20‐week, randomized, controlled, open‐label, multicentre, treat‐to‐target study, 244 insulin‐naïve subjects with type 2 diabetes, HbA_1c≥7.0 and ≤9.0% on OAD treatment, were randomized (1 : 1) to one of two treatment arms using 3.9–5.0 or 4.4–6.1 mmol/l FPG as titration targets. Once‐daily insulin detemir doses were adjusted using algorithm‐guided patient‐directed titration to achieve target FPG values. Results: Overall, the combined treatment groups achieved a mean HbA_1c level of 6.9% at the end of the study. Substantial reductions in HbA_1c were seen in both treatment groups, with the majority of subjects in both titration groups at the end of the study achieving the American Diabetes Association (ADA)‐recommended HbA_1c level of <7%. In the 3.9–5.0 mmol/l FPG target treatment group, HbA_1c values decreased from a baseline mean of 8.0% to 6.8% at 20 weeks. In the 4.4–6.1 mmol/l FPG target group, HbA_1c values decreased from 7.9% at baseline to 7.0% at 20 weeks (Intention to treat ‐ last observation carried forward data set). These decreases were significantly different between the two treatment groups (Least squares mean difference = ?0.271, 95% CI ?0.441 to ?0.101, p = 0.0019), favouring the FPG target of 3.9–5.0 mmol/l vs. the 4.4–6.1 mmol/l target. At the end of the study period, 64.3% of subjects in the 3.9–5.0 mmol/l treatment group achieved HbA_1c levels <7% compared with 54.5% of subjects in the 4.4–6.1 mmol/l group (95% CI 1.03–3.37, odds ratio 1.86, p = 0.04). Insulin detemir dosing patterns were similar between treatment groups, with the 3.9–5.0 mmol/l group using slightly greater doses throughout the study period (0.57 U/kg vs. 0.51 U/kg at the end of the study). Overall rates of hypoglycaemia episodes were low and were comparable between treatment groups (7.73 and 5.27 events/subject/year for the 3.9–5.0 and 4.4–6.1 mmol/l groups, respectively). A single event of major hypoglycaemia was reported in the 3.9–5.0 mmol/l group. Mean weight changes from baseline to the end of the study were small and did not differ significantly between treatment groups. Conclusions: The 3.9–5.0 mmol/l FPG target showed superior efficacy compared with the 4.4–6.1 mmol/l target, although both FPG titration targets resulted in substantial reductions of HbA_1c in patients with type 2 diabetes using a patient‐directed insulin titration algorithm. A majority of subjects in both titration groups achieved the ADA‐recommended guideline of <7% HbA_1c at the end of the study with low rates of hypoglycaemia. These data indicate that lowering the fasting glucose target using a self‐directed titration algorithm with once‐daily detemir is safe and increases the likelihood of achieving the target level of HbA_1c. Indeed, using this approach, a majority of patients can achieve an HbA_1c of <7%.     

Combined use of fasting plasma glucose and glycated hemoglobin A1c in the screening of diabetes and impaired glucose tolerance

The aim of this study is to assess the validity of combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) as screening tests for diabetes and impaired glucose tolerance (IGT) in high-risk subjects. A total of 2,298 subjects were included. All subjects underwent a 75-g oral glucose tolerance test (OGTT) and HbA1c measurement. Receiver operating characteristic curve (ROC curve) analysis was used to examine the sensitivity and specificity of FPG and HbA1c for detecting diabetes and IGT, which was defined according to the 1999 World Health Organization (WHO) criteria. (1) Based on the ROC curve, the optimal cut point of FPG related to diabetes diagnosed by OGTT was 6.1 mmol/l that was associated with a sensitivity and specificity of 81.5 and 81.0%, respectively; The optimal cut point of HbA1c related to diabetes diagnosed by OGTT was 6.1%, which was associated with a sensitivity and specificity of 81.0 and 81.0%, respectively; The screening model using FPG ≥ 6.1 mmol/l or HbA1c ≥ 6.1% had sensitivity of 96.5% for detecting undiagnosed diabetes; the screening model using FPG ≥ 6.1 mmol/l and HbA1c ≥ 6.1% had specificity of 96.3% for detecting undiagnosed diabetes. (2) Based on the ROC curve, the optimal cut point of FPG related to IGT diagnosed by OGTT was 5.6 mmol/l that was associated with a sensitivity and specificity of 64.1 and 65.4%, respectively; The optimal cut point of HbA1c related to IGT diagnosed by OGTT was 5.6%, which was associated with a sensitivity and specificity of 66.2 and 51.0%, respectively; The screening model using FPG ≥ 5.6 mmol/l or HbA1c ≥ 5.6% had sensitivity of 87.9% for detecting undiagnosed IGT; The screening model using FPG ≥ 5.6 mmol/l and HbA1c ≥ 5.6% had specificity of 82.4% for detecting undiagnosed IGT. Compared with FPG or HbA1c alone, the simultaneous measurement of FPG and HbA1c (FPG and/or HbA1C) might be a more sensitive and specific screening tool for identifying high-risk individuals with diabetes and IGT at an early stage.     

Development of a new scoring system for predicting the 5?year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6)

Aims/hypothesis

The aims of this study were to assess the clinical significance of introducing HbA_1c into a risk score for diabetes and to develop a scoring system to predict the 5?year incidence of diabetes in Japanese individuals.

Methods

The study included 7,654 non-diabetic individuals aged 40–75?years. Incident diabetes was defined as fasting plasma glucose (FPG) ≥7.0?mmol/l, HbA_1c ≥6.5% (48?mmol/mol) or self-reported clinician-diagnosed diabetes. We constructed a risk score using non-laboratory assessments (NLA) and evaluated improvements in risk prediction by adding elevated FPG, elevated HbA_1c or both to NLA.

Results

The discriminative ability of the NLA score (age, sex, family history of diabetes, current smoking and BMI) was 0.708. The difference in discrimination between the NLA + FPG and NLA + HbA_1c scores was non-significant (0.836 vs 0.837; p?=?0.898). A risk score including family history of diabetes, smoking, obesity and both FPG and HbA_1c had the highest discrimination (0.887, 95% CI 0.871, 0.903). At an optimal cut-off point, sensitivity and specificity were high at 83.7% and 79.0%, respectively. After initial screening using NLA scores, subsequent information on either FPG or HbA_1c resulted in a net reclassification improvement of 42.7% or 52.3%, respectively (p?<?0.0001). When both were available, net reclassification improvement and integrated discrimination improvement were further improved at 56.7% (95% CI 47.3%, 66.1%) and 10.9% (9.7%, 12.1%), respectively.

Conclusions/interpretation

Information on HbA_1c or FPG levels after initial screening by NLA can precisely refine diabetes risk reclassification.     

Continuous relationships between non-diabetic hyperglycaemia and both cardiovascular disease and all-cause mortality: the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study

Aims/hypothesis  Hyperglycaemia is a risk factor for cardiovascular disease (CVD) and all-cause mortality in individuals without diabetes. We investigated: (1) whether the risk of all-cause and CVD mortality extended continuously throughout the range of fasting plasma glucose (FPG), 2 h plasma glucose (2hPG) and HbA_1c values; and (2) the ability of these measures to improve risk prediction for mortality. Methods  Data on 10,026 people aged ≥25 years without diagnosed diabetes were obtained from the population-based Australian Diabetes, Obesity and Lifestyle study. Between 1999 and 2000, FPG, 2hPG and HbA_1c were assessed and all-cause (332 deaths) and CVD (88 deaths) mortality were obtained after 7 years. Results  Both 2hPG and HbA_1c exhibited linear relationships with all-cause and CVD mortality, whereas FPG showed J-shaped relationships. The adjusted HR (95% CI) for all-cause mortality per SD increase was 1.2 (1.1–1.3) for 2hPG and 1.1 (1.0–1.2) for HbA_1c. The HR for FPG <5.1 mmol/l (per SD decrease) was 2.0 (1.3–3.0); for FPG ≥5.1 mmol/l (per SD increase) the HR was 1.1 (1.0–1.2). Corresponding HRs for CVD mortality were 1.2 (1.0–1.4), 1.2 (1.0–1.3), 4.0 (2.1–7.6) and 1.3 (1.1–1.4). The discriminative ability of each measure was similar; no measure substantially improved individual risk identification over traditional risk factors. Conclusions/interpretation  In individuals without diagnosed diabetes, 2hPG and FPG, but not HbA_1c were significant predictors of all-cause mortality, whereas all measures were significant predictors of CVD mortality. However, these glucose measures did not substantially improve individual risk identification.     

Comparison of nateglinide and gliclazide in combination with metformin,for treatment of patients with Type 2 diabetes mellitus inadequately controlled on maximum doses of metformin alone

Aims To compare the effects of nateglinide plus metformin with gliclazide plus metformin on glycaemic control in patients with Type 2 diabetes. Methods Double‐blind, double‐dummy, parallel group, randomized, multicentre study over 24 weeks. Patients with inadequate glucose control on maximal doses of metformin were randomized to additionally receive nateglinide (n = 133) or gliclazide (n = 129). Changes from baseline in HbA_1c, fasting plasma glucose (FPG) and mealtime glucose and insulin excursions were examined. Results HbA_1c was significantly (P < 0.001) decreased from baseline in both treatment groups (mean changes: nateglinide ?0.41%, gliclazide ?0.57%), but with no significant difference between treatments. Proportions of patients achieving a reduction of HbA_1c ≥ 0.5% or an end point HbA_1c < 7% were also similar (nateglinide 58.1%, gliclazide 60.2%). Changes from baseline in FPG were similarly significant in both treatment groups (nateglinide ?0.63, gliclazide ?0.82 mmol/l). Reduction from baseline in maximum postprandial glucose excursion were significant in the nateglinide group only (nateglinide ?0.71, gliclazide ?0.10 mmol/l; P = 0.037 for difference). Postprandial insulin levels were significantly higher with nateglinide compared with gliclazide. The overall rate of hypoglycaemia events was similar in the nateglinide group compared with the gliclazide group. Conclusions No significant difference was seen between nateglinide plus metformin and gliclazide plus metformin in terms of HbA_1c. However, the nateglinide combination demonstrated better postprandial glucose control.     

Impaired glucose regulation,elevated glycated haemoglobin and cardiac ischaemic events in vascular surgery patients

Aims Cardiac morbidity and mortality is high in patients undergoing high‐risk surgery. This study investigated whether impaired glucose regulation and elevated glycated haemoglobin (HbA_1c) levels are associated with increased cardiac ischaemic events in vascular surgery patients. Methods Baseline glucose and HbA_1c were measured in 401 vascular surgery patients. Glucose < 5.6 mmol/l was defined as normal. Fasting glucose 5.6–7.0 mmol/l or random glucose 5.6–11.1 mmol/l was defined as impaired glucose regulation. Fasting glucose ≥ 7.0 or random glucose ≥ 11.1 mmol/l was defined as diabetes. Perioperative ischaemia was identified by 72‐h Holter monitoring. Troponin T was measured on days 1, 3 and 7 and before discharge. Cardiac death or Q‐wave myocardial infarction was noted at 30‐day and longer‐term follow‐up (mean 2.5 years). Results Mean (± sd ) level for glucose was 6.3 ± 2.3 mmol/l and for HbA_1c 6.2 ± 1.3%. Ischaemia, troponin release, 30‐day and long‐term cardiac events occurred in 27, 22, 6 and 17%, respectively. Using subjects with normal glucose levels as the reference category, multivariate analysis revealed that patients with impaired glucose regulation and diabetes were at 2.2‐ and 2.6‐fold increased risk of ischaemia, 3.8‐ and 3.9‐fold for troponin release, 4.3‐ and 4.8‐fold for 30‐day cardiac events and 1.9‐ and 3.1‐fold for long‐term cardiac events. Patients with HbA_1c > 7.0% (n = 63, 16%) were at 2.8‐fold, 2.1‐fold, 5.3‐fold and 5.6‐fold increased risk for ischaemia, troponin release, 30‐day and long‐term cardiac events, respectively. Conclusions Impaired glucose regulation and elevated HbA_1c are risk factors for cardiac ischaemic events in vascular surgery patients.     

The relative merits of haemoglobin A1c and fasting plasma glucose as first-line diagnostic tests for diabetes mellitus in non-pregnant subjects

HbA_1c was measured by high-performance ion-exchange chromatography in 401 non-pregnant patients undergoing oral glucose tolerance tests (OGTT). All those with HbA_1c>6.2 % (reference range 3.8–5.5 %) had diabetic OGTT (sensitivity 41 %, specificity 100 %). Although a fasting plasma glucose (FPG) cut-off ≥7.0 mmol l⁻¹, as recommended by the American Diabetes Association (ADA), had greater sensitivity (78 %), false positives (12 %) limited its usefulness, so more diagnostic confidence could be placed in a positive HbA_1c. In agreement with the ADA, we found FPG gave only slightly lower diabetes prevalence than the OGTT, but this masked a significant number of individual discrepancies (false positives and negatives) cancelling out each other. The new ADA category of impaired fasting glucose did not correlate well with impaired glucose tolerance. HbA_1c is insufficiently sensitive as a direct substitute for the OGTT. A third of subjects diabetic on OGTT had normal HbA_1c values, so it cannot exclude diabetes as currently defined, but HbA_1c screening could make sufficient positive diagnoses to reduce our non-pregnant OGTTs by one-fifth. If a ‘risk threshold’ for diabetic complications could be applied to HbA_1c, it could replace the OGTT as a more pragmatic diagnostic/prognostic test. © 1998 John Wiley & Sons, Ltd.     

Associations of HbA1c and educational level with risk of cardiovascular events in 32 871 drug‐treated patients with Type 2 diabetes: a cohort study in primary care

Aims

To explore the association of HbA_1c and educational level with risk of cardiovascular events and mortality in patients with Type 2 diabetes.

Methods

A cohort of 32 871 patients with Type 2 diabetes aged 35 years and older identified by extracting data from electronic patient records for all patients who had a diagnosis of Type 2 diabetes and had glucose‐lowering agents prescribed between 1999 and 2009 at 84 primary care centres in Sweden. Associations of mean HbA_1c levels and educational level with risks of cardiovascular events and all‐cause mortality were analysed.

Results

The associations of HbA_1c with risk of all‐cause and cardiovascular mortality were J‐shaped, with the lowest risk observed for cardiovascular mortality at an HbA_1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin‐treated patients. The lowest risk observed for all‐cause mortality was at an HbA_1c level of 51 mmol/mol (6.8%) for subjects on oral agents and 56 mmol/mol (7.3%) in insulin‐treated patients. There was an increased risk for cardiovascular death [hazard ratio 1.6 (1.2–2.1), P = 0.0008] at the lowest HbA_1c decile for subjects in the low education category. For subjects with higher education there was no evident J curve for cardiovascular death [hazard ratio 1.2 (0.8–1.6), P = 0.3873].

Conclusions

Our results lend support to the recent American Diabetes Association/ European Association for the Study of Diabetes position statement that emphasizes the importance of additional factors, including the propensity for hypoglycaemia, which should influence HbA_1c targets and treatment choices for individual patients. (Clinical Trials Registry No; NCT 01121315)     

Modelling incremental benefits on complications rates when targeting lower HbA1c levels in people with Type 2 diabetes and cardiovascular disease

Aim

Glucose‐lowering interventions in Type 2 diabetes mellitus have demonstrated reductions in microvascular complications and modest reductions in macrovascular complications. However, the degree to which targeting different HbA_1c reductions might reduce risk is unclear.

Methods

Participant‐level data for Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) participants with established cardiovascular disease were used in a Type 2 diabetes‐specific simulation model to quantify the likely impact of different HbA_1c decrements on complication rates. Ten‐year micro‐ and macrovascular rates were estimated with HbA_1c levels fixed at 86, 75, 64, 53 and 42 mmol/mol (10%, 9%, 8%, 7% and 6%) while holding other risk factors constant at their baseline levels. Cumulative relative risk reductions for each outcome were derived for each HbA_1c decrement.

Results

Of 5717 participants studied, 72.0% were men and 74.2% White European, with a mean (sd ) age of 66.2 (7.9) years, systolic blood pressure 134 (16.9) mmHg, LDL‐cholesterol 2.3 (0.9) mmol/l, HDL‐cholesterol 1.13 (0.3) mmol/l and median Type 2 diabetes duration 9.6 (5.1–15.6) years. Ten‐year cumulative relative risk reductions for modelled HbA_1c values of 75, 64, 53 and 42 mmol/mol, relative to 86 mmol/mol, were 4.6%, 9.3%, 15.1% and 20.2% for myocardial infarction; 6.0%, 12.8%, 19.6% and 25.8% for stroke; 14.4%, 26.6%, 37.1% and 46.4% for diabetes‐related ulcer; 21.5%, 39.0%, 52.3% and 63.1% for amputation; and 13.6%, 25.4%, 36.0% and 44.7 for single‐eye blindness.

Conclusions

These simulated complication rates might help inform the degree to which complications might be reduced by targeting particular HbA_1c reductions in Type 2 diabetes.     

Hemoglobin A1c as a marker for identifying diabetes and cardiovascular risk factors: the China Health and Nutrition Survey 2009

Hemoglobin A_1c (HbA_1c) has been recommended as an optional method for diagnosing diabetes. The impact of HbA_1c on the diagnosis of diabetes has not been evaluated in China, a country with the greatest number of people with diabetes in the world. Hence, we aim to examine how well HbA_1c performs as compared with fasting plasma glucose (FPG) for diagnosing diabetes in Chinese population. We conducted a cross-sectional analysis of 7,641 Chinese men and women aged ≥18 years using data from the China Health and Nutrition Survey 2009 in which FPG and standardized HbA_1c were measured. HbA_1c was measured with high-performance liquid chromatography system. Diabetes is defined as having FPG ≥7 mmol/l or HbA_1c ≥6.5 %. Overall, 5.0 and 5.8 % had undiagnosed diabetes by FPG ≥7 mmol/l and HbA_1c ≥6.5 %, respectively. Overlap between HbA_1c- and FPG-based diagnosis of diabetes was limited (n = 214, 34.9 %). Similar trends were noted in both genders, all age groups, urban/rural settings, regions, body mass index (BMI) categories, waist circumference (WC) groups, and blood pressure status. Solely HbA_1c-defined individuals exhibited higher levels of BMI, WC, total cholesterol, and hypersensitive C-reactive protein and lower levels of homeostasis model assessment of insulin resistance. We note limited overlap between FPG- and HbA_1c-based diagnosis of diabetes. The limited overlap between FPG- and HbA_1c-based diagnosis of diabetes persisted in each evaluated subgroup. HbA_1c criterion for the diagnosis of diabetes identifies individuals with a worse cardiovascular risk profile compared with FPG.     

Performance of HbA1c for detecting newly diagnosed diabetes and pre‐diabetes in Chinese communities living in Beijing

Aim To determine the performance of glycated haemoglobin (HbA_1c) as a screening tool for detecting newly diagnosed diabetes (NDM) and pre‐diabetes. Methods A diabetes survey was conducted in Beijing among community dwellers who were willing to participate in the survey. Included in the survey were 903 individuals aged 21–79 years without previously diagnosed diabetes and in whom HbA_1c and other required covariates had been measured. NDM and pre‐diabetes (impaired glucose tolerance + impaired fasting glucose) were defined according to the World Health Organization 1999 criteria based on 75‐g oral glucose tolerance test. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA_1c. Results The prevalence of NDM and pre‐diabetes was 11.1% and 22.4%, respectively. At an optimal HbA_1c cut‐off point of ≥ 6.0%, the test gave a sensitivity of 80.0% and a specificity of 89.8% for diagnosing NDM; at an optimal cut‐off point of ≥ 5.7%, the sensitivity was 59.4% and specificity 73.9% for diagnosing pre‐diabetes. Individuals with HbA_1c≥ 6.0% tended to be more obese than those with HbA_1c < 6.0%, but blood pressure and lipid profiles did not differ between the two groups. Conclusions HbA_1c as a single screening test is adequate to detect newly diagnosed diabetes but is not able to identify pre‐diabetes in this obese Chinese population.     

Assessing the economic value of maintained improvements in Type 1 diabetes management,in terms of HbA1c,weight and hypoglycaemic event incidence

Aims

Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA_1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.

Methods

The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA_1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.

Results

Modelled subjects with an HbA_1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA_1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA_1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event.

Conclusions

Maintained reductions in HbA_1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.     

Fasting plasma glucose and HbA1c in cardiovascular risk prediction: a sex-specific comparison in individuals without diabetes mellitus

Aims/hypothesis

This study aimed to assess the cardiovascular risk of individuals with fasting plasma glucose (FPG)- and/or HbA_1c-defined prediabetes (5.6–6.9 mmol/l and 39–47 mmol/mol [5.7–6.4%], respectively) or manifest diabetes mellitus and to evaluate whether FPG or HbA_1c can improve risk prediction beyond that estimated by the Systematic Coronary Risk Evaluation (SCORE) chart in individuals without diabetes mellitus.

Methods

Cox regression was employed to estimate HRs for primary incident cardiovascular events (CVEs) in a cohort of 8,365 individuals aged 50–74 years. Furthermore, HbA_1c and FPG were added individually to the variables of the SCORE and measures of model discrimination and reclassification were assessed.

Results

During 8 years of follow-up, 702 individuals had a primary CVE. After adjusting for conventional cardiovascular risk factors, HRs were attenuated close to one for the prediabetes groups (especially for women), whereas a 1.7- and a 1.9-fold increased risk persisted for men and women with diabetes, respectively. Extension of the SCORE variables by either FPG or HbA_1c did not improve its predictive abilities in individuals without diabetes. There was a non-significant net reclassification improvement for men when HbA_1c was added (2.2%, p?=?0.16).

Conclusions/interpretation

The increased cardiovascular risk of individuals with FPG- or HbA_1c-defined prediabetes can mainly be explained by other cardiovascular risk factors. Adding FPG or HbA_1c did not significantly improve CVE risk prediction by the SCORE variables in individuals without diabetes mellitus.     

Longitudinal screening of serum lipids in children and adolescents with Type 1 diabetes in a UK clinic population

Aims To determine the prevalence of abnormal lipid levels in a large group of children and adolescents with Type 1 diabetes and to examine the changes longitudinally. In addition, to study the relationships of any lipid abnormalities to glycaemic control, age and duration of diabetes. Methods Non‐fasting blood samples were taken annually from all the patients in the Oxford Children's diabetes clinic and total cholesterol (TC), high‐density lipoprotein (HDL) cholesterol, triglycerides (TG) and glycated haemoglobin (HbA_1c) measured over a period of 8 years. Low‐density lipoprotein (LDL) cholesterol and non‐HDL were calculated from these values and compared. Tests performed less than 4 months after diagnosis were excluded. Results A total of 229 children had complete data from more than 1 year and 798 sets of data were examined. TC was lower in males and increased with duration of diabetes and with increasing HbA_1c. HDL cholesterol fell with increasing age, but independently increased with duration, and was not related to HbA_1c. LDL cholesterol and non‐HDL cholesterol were highly correlated (r = 0.9). Both were lower in males and increased with duration of diabetes. Non‐HDL cholesterol increased with HbA_1c. A total of 23.7% had HDL cholesterol < 1.1 mmol/l and 22.5% had TC > 5.2 mmol/l. Thirty‐eight per cent had LDL cholesterol > 2.6 mmol/l and 10.8% > 3.4 mmol/l, the thresholds for lifestyle and drug intervention respectively. Conclusions Abnormalities in plasma lipid levels are common in this age group and the prevalence increases with poor glycaemic control and with duration of diabetes. Around 10% of adolescents would fit criteria for lipid‐lowering medication in adults, but further study is needed to examine the risks and benefits in this age group.     

A large proportion of prediabetes and diabetes goes undiagnosed when only fasting plasma glucose and/or HbA1c are measured in overweight or obese patients

AimsThe purposes of the study were to determine the prevalence of unrecognized dysglycaemia in overweight (body mass index [BMI] 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²) patients, to assess the extent to which measures of fasting plasma glucose (FPG) and/or HbA_1c, compared with oral glucose tolerance tests (OGTTs), misdiagnose dysglycaemia, and to determine the factors associated with an isolated abnormal post-OGTT glucose value.MethodsOGTT was performed and HbA_1c was measured in 1283 inpatients with BMI scores ≥25 kg/m² and no history of dysglycaemia.ResultsPrediabetes was found in 257 (20.0%) subjects (197 with impaired glucose tolerance, 29 with impaired fasting glucose, 31 with both) and diabetes in 77 (6.0%), including 22 with FPG ≥7 mmol/L (WHO definition). The sensitivity of FPG >6 mmol/L, FPG >5.5 mmol/L, HbA_1c ≥6% and the recommendations of the French National Agency of Accreditation and Evaluation in Health Care (ANAES) to identify patients with abnormal OGTTs was 29.9, 41.3, 36.8 and 15.6%, respectively. The factors that were independently associated with diabetes in obese women with FPG <7 mmol/L were age (per 10 years: OR 1.54 [1.00–2.11]; P = 0.049) and FPG (OR 6.1 [1.4–30.0]; P = 0.014), whereas age (OR 1.26 [1.09–1.44]; P < 0.01) and waist circumference (per 10 cm: OR 1.17 [1.01–1.33]; P < 0.05) were independently associated with dysglycaemia in obese women with FPG <6.1 mmol/L.ConclusionIn overweight and obese patients: dysglycaemia is commonly seen; FPG alone, compared with OGTT, failed to diagnose 70% of dysglycaemia cases; FPG >5.5 mmol/L and HbA_1c ≥6.0% are not necessarily substitutes for OGTT; and older age and larger waist circumference should be used to select those obese women with normal FPG who might further benefit from OGTTs to diagnose dysglycaemia.     

Hemoglobin A1c,comorbid conditions and all-cause mortality in older patients with diabetes: A retrospective 9-year cohort study

AimsTo examine whether hemoglobin A_1c levels and comorbid conditions are related to all-cause mortality in a cohort of patients with type 1 or 2 diabetes receiving continuous care for 9 years. In patients with comorbid congestive heart failure (CHF), we test for ‘reverse epidemiology,’ or whether greater HbA_1c values are associated with lower risk of mortality.MethodsThe population for this longitudinal cohort study was 8820 Group Health enrollees in the Seattle area with type 1 or 2 diabetes in 1997 and enrolled continuously from 1997 to 2006. Comorbid conditions were hypertension, coronary artery disease, congestive heart failure, depression, and chronic pulmonary disease. Mistimed HbA_1c scores were addressed by multiple imputation, and Cox proportional hazards models estimated associations controlling for other risk factors.ResultsAbout 30% of the enrollees died in 1998–2006. CHF had the strongest association with all-cause mortality. Compared to enrollees with HbA_1c ≥ 7.1% (54 mmol/mol) and <7.5% (58 mmol/mol; 5th decile), enrollees with HbA_1c < 6.4% (46 mmol/mol) had a significantly greater risk of death (HR range: 1.28–2.26). HbA_1c > 7.5% had HR < 1.0 but were not significant. For enrollees with diabetes and CHF at baseline, HbA_1c scores ≥ 8.7% (72 mmol/mol) had a significantly lower risk of death (HR range: 0.64–0.69).ConclusionsIn our patient population, HbA_1c scores < 6.4% have significantly higher all-cause mortality. CHF is a major determinant of all-cause mortality. Adults with comorbid CHF and high HbA_1c scores have lower all-cause mortality.