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.     

Diagnostic value of glycated haemoglobin (HbA1c) for the early detection of diabetes in high‐risk subjects

Objective The aim of this study was to assess the validity of fasting plasma glucose (FPG) and/or glycated haemoglobin (HbA_1c) as screening tests for the early detection of diabetes in high‐risk subjects. Methods A total of 392 subjects (149 male and 243 female) with risk factors for diabetes were included. All subjects underwent a 75‐g oral glucose tolerance test and HbA_1c measurement. Receiver operating characteristic curve analysis was used to examine the sensitivity and specificity of FPG and HbA_1c for detecting diabetes, which was defined as a FPG ≥ 7.0 mmol/l or a post‐challenge 2‐h plasma glucose ≥ 11.1 mmol/l. Results The prevalence of newly diagnosed diabetes was 22.4% (n = 88). The current guideline of FPG ≥ 7.0 mmol/l for diabetes screening detected only 55.7% of diabetic subjects. The optimal cut‐off points of HbA_1c and FPG for the diagnosis of diabetes were 6.1% (sensitivity 81.8%, specificity 84.9%) and 6.1 mmol/l (sensitivity 85.2%, specificity 88.5%), respectively. The screening model using FPG ≥ 6.1 mmol/l and/or HbA_1c ≥ 6.1% had sensitivities of 71.6–95.5% and specificities of 77.6–95.7% for detecting undiagnosed diabetes. Conclusions The current American Diabetes Association diagnostic criteria, based only on FPG, are relatively insensitive in the detection of diabetes in high‐risk subjects. The simultaneous measurement of FPG and HbA_1c might be a more sensitive screening tool for identifying high‐risk individuals with diabetes at an early stage.     

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.     

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.     

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.     

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.     

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%.     

Progression rates from HbA1c 6.0–6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis

Aims/hypothesis

Precise estimates of progression rates from ‘prediabetes’ to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA_1c-defined prediabetes ranges, with some favouring 6.0–6.4% (42–46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories.

Methods

Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6–6.9 mmol/l], WHO-defined IFG [6.1–6.9 mmol/l], IGT (7.8–11.0 mmol/l) or raised HbA_1c [6.0–6.4%/42–46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models.

Results

Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA_1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes.

Conclusions/interpretation

This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA_1c 6.0–6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.     

Oral glucose tolerance test and HbA1c for diagnosis of diabetes in patients undergoing coronary angiography the Silent Diabetes Study

Aims/hypothesis

The primary aim of this study was to compare the results of HbA_1c measurements with those of an OGTT for early diagnosis of ??silent diabetes?? in patients with coronary artery disease (CAD) undergoing angiography without prediagnosed diabetes. A secondary aim was to investigate the correlation between the extent of CAD and the glycaemic status of the patient.

Methods

Data from 1,015 patients admitted for acute (n?=?149) or elective (n?=?866) coronary angiography were analysed. Patients with known diabetes were excluded from the study. Using the OGTT results, patients were classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. According to the results of the HbA_1c measurements, patients were classified into three groups: normal (HbA_1c <5.7% [<39?mmol/mol]), borderline (HbA_1c 5.7?C6.4% [39?C47?mmol/mol]) and diabetes (HbA_1c ??6.5% [??48?mmol/mol]).

Results

Based on the OGTT, 513 patients (51%) were classified with NGT, 10 (1%) with IFG, 349 (34%) with IGT and 149 (14%) were diagnosed with diabetes. According to HbA_1c measurements, 588 patients (58%) were classified as normal, 385 (38%) as borderline and 42 (4%) were diagnosed with diabetes. The proportion of patients with IGT and diabetes increased with the extent of CAD (IGT ???=?0.14, p?p?=?0.01). No differences in HbA_1c were seen among the groups with different extents of CAD (p?=?0.652).

Conclusions/interpretation

An OGTT should be performed routinely for diagnosis of diabetes in patients with CAD undergoing coronary angiography, since HbA_1c measurement alone appears to miss a substantial proportion of patients with silent diabetes. A limitation of the study is that the OGTT was not performed before the angiography.     

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.     

Cardiovascular risk profile assessment in glucose‐intolerant Asian individuals—an evaluation of the World Health Organization two‐step strategy: the DECODA Study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia)

Aims To assess the cardiovascular (CVD) risk factor profile in individuals with diabetes and impaired glucose tolerance (IGT) identified by a one‐step (fasting plasma glucose (FPG)) or a two‐step strategy (including an oral glucose tolerance test (OGTT) in subjects with impaired fasting glucose (IFG)) as recommended by the World Health Organization (WHO). Methods Twelve population‐based studies in six countries (17 512 subjects, age 30–89 years, without known diabetes, with OGTT (fasting and 2‐h plasma glucose (2‐h PG))). Age, gender, and centre‐adjusted means of CVD risk factors were compared according to the level of glucose intolerance. Results Diabetes was found in 1270 individuals and IFG or IGT in 3158. In the diabetic group 55.1% had a FPG ≥ 7.0 mmol/l (range between countries 36.2–67.0%), 20.5% were identified through the stepwise strategy (range 0–32%), while 24.4% would remain undiagnosed (FPG < 6.1 mmol/l) (range 9.0–40.0%). The two‐step strategy identified 60–91% of all newly diagnosed diabetic subjects with 5–12% of the population requiring an OGTT. Mean body mass index (BMI), blood pressure, and total cholesterol did not differ between diabetic individuals diagnosed by FPG or OGTT. The step‐wise strategy identified < 50% of the subjects with impaired glucose regulation, and the cardiovascular risk profile (BMI, blood pressure, and cholesterol) did not differ between those identified and those not identified in the screening process. Conclusions Applying an OGTT in subjects with IFG will fail to detect every fourth diabetic individual and every second individual with impaired glucose regulation. Individuals not diagnosed had a cardiovascular risk profile identical to those identified in the diagnostic process. Lower thresholds for an OGTT may be necessary in Asian populations. Diabet. Med. 19, 549–557 (2002)     

Haemoglobin glycation may partly explain the discordance between HbA1c measurement and oral glucose tolerance test to diagnose dysglycaemia in overweight/obese subjects

AimThis study assessed whether the poor correlation between HbA_1c and oral glucose tolerance test (OGTT) for dysglycaemia diagnosis may be explained by haemoglobin glycation (HbG).MethodsA total of 1033 consecutive overweight or obese patients with no known diabetes underwent OGTT and measurement of HbA_1c to diagnose diabetes and dysglycaemia (American Diabetes Association criteria). For each OGTT result category, low, medium and high HbG was defined according to the mean HbA_1c/fructosamine ratio and mean fructosamine. High HbG was defined as values greater than mean values in each OGTT category for both HbA_1c/fructosamine ratio and fructosamine levels, and low HbG was defined as lower values of both. The remaining patients were considered medium HbG.ResultsBased on OGTT and HbA_1c values, 267 (25.8%) and 443 (42.8%) patients had intermediate hyperglycaemia, and 66 (6.4%) and 95 (9.2%) patients had diabetes, respectively. The results were discordant for intermediate hyperglycaemia or diabetes diagnosis in 41.7% and for diabetes diagnosis in 10.0% of the patients. The proportion of patients with HbA_1c ≥ 6.5%, but without OGTT-diagnosed diabetes, was 0%, 3.8% and 32.8% in the low-HbG, medium-HbG and high-HbG groups, respectively. In contrast, the proportion of patients with HbA_1c < 5.7%, but with an abnormal OGTT, was 30.4%, 11.1% and 0%, respectively. The AUROC of HbA_1c to detect OGTT-diagnosed diabetes was better in the medium-HbG group [0.874 (0.816–0.931)] than in those with low or high HbG [0.628 (0.489–0.768); P < 0.01]. Only age was independently associated with high-HbG status [10-year OR: 1.3 (1.1–1.5); P < 0.0001].ConclusionHaemoglobin glycation may explain many of the discordant results between HbA_1c and OGTT when used for dysglycaemia diagnosis.     

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.     

Undiagnosed Diabetes in Kidney Transplant Candidates: A Case-Finding Strategy

Background and objectives: Guidelines recommend that candidates for kidney transplantation (KTx) who do not have diabetes perform a pretransplantation oral glucose tolerance test (OGTT) when fasting plasma glucose (FPG) is <110 mg/dl (<6.1 mmol/L); however, the OGTT is potentially costly and cumbersome. We studied the role of the OGTT for diagnosing diabetes and the accuracy of FPG and glycated hemoglobin (HbA_1c) for predicting a diabetic OGTT before KTx.Design, setting, participants, & measurements: In this cross-sectional study, 889 first single-kidney transplant candidates without diabetes, mainly white, performed an OGTT during the transplantation workup. Results were studied using receiver operating characteristic analysis.Results: Of 72 (8.1%) patients with undiagnosed diabetes, only 16 (22%) had a diabetic FPG (≥126 mg/dl [≥7.0 mmol/L]). In patients with a nondiabetic FPG, diabetes (2-hour plasma glucose [2h-PG] ≥200 mg/dl [≥11.1 mmol/L]) was predicted by FPG but not by HbA_1c. Performing the OGTT in patients with FPG 92 to 125 mg/dl (5.1 to 6.9 mmol/L) identified 65 (90%) patients with diabetes (16 by FPG, 49 by 2h-PG) and required seven OGTTs per patient identified. Subjecting all patients with FPG <110 mg/dl (<6.1 mmol/L) to the OGTT identified 60 (83%) patients with diabetes (16 by FPG, 44 by 2h-PG) but required 14 OGTTs per patient.Conclusions: The OGTT was paramount in finding most cases of undiagnosed diabetes before KTx. FPG but not HbA_1c predicted a diabetic OGTT. We suggest that white KTx candidates without diabetes perform a pretransplantation OGTT when FPG is 92 to 125 mg/dl (5.1 to 6.9 mmol/L).Assessment of glycemic status before kidney transplantation (KTx) is important to enable patients with undiagnosed diabetes to be identified. In Norway, these patients have been prescribed cyclosporine rather than tacrolimus after KTx. The underlying rationale has been to lower the risk for posttransplantation hyperglycemia while maintaining short- and long-term outcomes for the kidney graft (1). In addition to undiagnosed diabetes, even nondiabetic glucose abnormalities can be important. They may threaten patient survival before KTx (2) and seem to predict new-onset diabetes after KTx (NODAT) (3–6). NODAT is associated with increased cardiovascular morbidity and reduced patient and graft survival (7–9).According to available guidelines, the pretransplantation workup of KTx candidates seemingly without diabetes should include an oral glucose tolerance test (OGTT) when fasting plasma glucose (FPG) is <110 mg/dl (<6.1 mmol/L) (10); however, no clear explanation is provided to substantiate this recommendation. Specifically, it is unclear why patients with FPG 110 to 125 mg/dl (6.1 to 6.9 mmol/L) are not entailed. The recommended approach also suggests performing the OGTT in a large number of patients, making it time-consuming and costly in clinical practice. To select patients for a diagnostic OGTT, screening strategies based on FPG or glycated hemoglobin (HbA_1c) have been proposed for patients who have undergone transplantation (11–13) and the general population (14); no such approach has been explored in KTx candidates.Using common glycemic tests, this study aimed to identify a simple and effective strategy for detecting undiagnosed diabetes in KTx candidates. The need for an OGTT was examined, along with the accuracy of FPG and HbA_1c for predicting a diabetic OGTT. FPG and HbA_1c cutoffs were studied to help select patients who should proceed to a diagnostic OGTT. To these ends, pretransplantation OGTT data were studied in all patients who had ESRD but not diabetes and were referred for a first single KTx in Norway during the previous 7 yr.     

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.     

不同空腹血糖受损下限切点对重庆地区人群代谢状态的影响

目的寻找预测2型糖尿病（T2DM）和糖耐量减低（IGT）发生的最佳空腹血糖受损（IFG）下限切点及其对代谢状态的影响。方法采用横断面调查的方法对重庆局部地区3189例既往无糖尿病史的自然人群的空腹血糖（FPG）进行ROC分析，绘制ROC曲线，并进行糖脂代谢调查和分析。结果预测T2DM和IGT发生的最佳IFG下限切点ROC曲线下面积分别为0．899和0．728。用FPG来预测T2DM和IGT，其灵敏度及特异度均较好的点分别为5．6mmol／L和5．2mmol／L。在负荷后2h血糖（2hPG）〈7．8mmol／L人群中，与FPG〈5．6mmol／L亚组比较，FPG5．6～6．1mmol／L亚组肥胖、高血压、代谢综合征和胰岛素抵抗的发生率分别增加了53％、54％、60％和126％。IFG下限切点下调前后，糖调节受损（IGR）各亚组组分的代谢特征不改变。结论将5．6mmol／L作为IFG的下限值适用于中国人群。     

空腹血糖受损诊断标准下调的合理性分析

目的　探讨空腹血糖受损 (IFG)诊断点从 6.1mmol/L下调至 5 .6mmol/L的合理性。方法对1986年入选的 468名非糖尿病人群〔3 41例正常糖耐量 (NGT) ,12 7例糖耐量受损 (IGT)〕在 1988年 ,1990年和 1992年分别进行OGTT复查 ,测定空腹血糖 (FPG)及 2h血糖 (2hPG)。以COX模型分析不同基线血糖水平增加糖尿病的风险。结果　 (1) 10 9例 6年后发生糖尿病。COX成比例风险模型分析校正年龄、性别、体重指数 (BMI)影响后发现FPG与 2型糖尿病发病显著相关 (P =0 .0 0 0 1)。基线FPG 5 .6～ 6.0mmol/L组糖尿病发病危险性比FPG <5 .6mmol/L组已显著增加 ,RR为 3 .3 (95 %CI 2 .0～ 5 .3 ,P =0 .0 0 0 1)。 (2 )受试者工作特征 (ROC)曲线分析FPG预测糖尿病发病的最佳阈值是 5 .6mmol/L ,以FPG 5 .6mmol/L为诊断点IFG预报糖尿病发病的灵敏度、特异度、阳性预测值分别为 45 .0 % ,92 .8%和 65 .3 %。 (3 )NGT个体中COX成比例风险模型校正年龄、性别、BMI后显示 ,FPG分组 (5 .0～ 6.0mmol/L与 <5 .0mmol/L)与糖调节受损 (IGR ,包括IFG或IGT)发生显著正相关 (P =0 .0 0 7)。ROC曲线显示 ,FPG预测糖耐量恶化而进展为DM或IGR的最佳阈值为 5 .3mmol/L。结论　 (1)本组非糖尿病人群中FPG预测糖尿病发病的最佳阈值为 5 .6mmol/L     

Relationship between mean blood glucose and glycated haemoglobin in Type 2 diabetic patients

Aims To correlate the values of MBG to HbA_1c in Greek patients with Type 2 diabetes and/or metabolic syndrome. Methods We followed up 140 Greek adult patients: 92 patients with Type 2 diabetes treated with insulin or oral glucose‐lowering medication, and 48 patients with newly diagnosed Type 2 diabetes or metabolic syndrome not receiving any treatment. MBG was calculated for each patient from self‐measurements of blood glucose using a portable glucometer, made six times a day (before eating and 2 h after a meal), three times a week for 1 month. HbA_1c was determined by HPLC at 0 and 12 weeks. Results HbA_1c at 0 (x) and 12 weeks (y) correlated strongly (y = 0.790x + 1.115, r = 0.92), confirming that the patient's glycaemic status remained stable during the whole period of follow‐up. Linear regression was performed on MBG values; HbA_1c at 12 weeks, sex, age, body mass index (BMI) and patient status (Type 2 diabetes treated or not) were used as independent variables. None of the independent variables reached statistical significance in the model, with the exception of HbA_1c at 12 weeks. The final model was: MBG (mg/dl) = (34.74 × HbA_1c) – 79.21, r = 0.93; or MBG (mmol/l) = 1.91 × HbA_1c – 4.36, r = 0.93. Conclusions Our results establish for the first time a strong correlation between MBG and HbA_1c in Type 2 diabetic patients and support the idea of expressing HbA_1c results as MBG. This will help patients to gain a clearer interpretation of the result, with less confusion. This simplification will allow every person with diabetes using home glucose‐monitoring to understand his or her own target level.     

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.     

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.