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.     

Comparison of Hemoglobin A1c and Fasting Glucose Criteria to Diagnose Diabetes Among People With Metabolic Syndrome and Fasting Glucose Above 100 mg/dL (5.5 mmol/L)

J Clin Hypertens(Greenwich). 2010;12:543–548. © 2010 Wiley Periodicals, Inc. The aim of this study was to compare hemoglobin A_1c (HbA_1c) and fasting glucose for the diagnosis of diabetes among people with metabolic syndrome and fasting glucose >100 mg/dL (5.5 mmol/L). Consecutive individuals (N=142) with metabolic syndrome and fasting glucose >100 mg/dL (5.5 mmol/L) but without a self-reported history of diabetes who visited the outpatient lipid and obesity clinic of the University Hospital of Ioannina, Greece from January through September 2009 were included. HbA_1c≥6.5% and fasting glucose ≥126 mg/dL (7 mmol/L) were used separately to define diabetes. Overall, 29.5% of patients had both HbA_1c≥6.5% and fasting glucose ≥126 mg/dL (7 mmol/L), 25.3% had HbA_1c≥6.5% but fasting glucose <126 mg/dL (7 mmol/L), and 9.1% had HbA_1c <6.5% but fasting glucose ≥126 mg/dL (7 mmol/L). A greater proportion of patients reached a diagnosis of diabetes based on the HbA_1c criterion (n=78, 54.9%) compared with the fasting glucose criterion (n=55, 38.7%, P=.000). A large proportion of patients (44.8%) with impaired fasting glucose (fasting glucose 100–125 mg/dL; 5.6–6.9 mmol/L) would be classified as diabetics using the HbA_1c criterion. Implication of the HbA_1c criterion may increase the rate of diabetes diagnosis among people with metabolic syndrome and fasting glucose >100 mg/dL (5.5 mmol/L).     

Risks of Diabetic Nephropathy with Variation in Hemoglobin A1c and Fasting Plasma Glucose

Background

This study examined whether annual variation in glycosylated hemoglobin A_1c (HbA_1c) and fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), can predict diabetic nephropathy independently of mean FPG, mean HbA_1c, and other risk factors in patients with type 2 diabetes.

Methods

A computerized database of patients with type 2 diabetes aged ≥30 years and free of diabetic nephropathy (n = 3220) who were enrolled in the Diabetes Care Management Program of China Medical University Hospital before 2007 was used in a time-dependent Cox proportional hazards regression model.

Results

The incidence rates of diabetic nephropathy were 16.11, 22.95, and 28.86 per 1000 person-years in the first, second, and third tertiles of baseline HbA_1c-CV, respectively; the corresponding incidence rates for FPG-CV were 9.46, 21.23, and 37.51 per 1000 person-years, respectively. After multivariate adjustment, the corresponding hazard ratios for the second and third tertiles versus the first tertile of annual HbA_1c-CV were 1.18 (95% confidence interval [CI], 0.88-1.58) and 1.58 (95% CI, 1.19-2.11), respectively, and 1.55 (95% CI, 0.99-2.41) and 4.75 (95% CI, 3.22-7.01) for FPG-CV, respectively. The risks of diabetic nephropathy for HbA_1c-CV and FPG-CV stratified according to age, gender, renal function, and hypertension status were provided.

Conclusions

Annual FPG and HbA_1c variations have a strong association with diabetic nephropathy in patients with type 2 diabetes. Whether intervention for reducing glucose variation should be administered needs to be examined in a future study.     

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.     

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.     

Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetes

Aims/hypothesis The main disadvantage of intensive treatment in the Diabetes Control and Complications Trial (DCCT) was an increased risk of hypoglycaemia that was not explained by the difference in HbA_1c values alone. This study re-analysed DCCT data to establish whether mean blood glucose (MBG) and/or glucose variability add to the predictive value of HbA_1c for hypoglycaemia risk in type 1 diabetes. Methods The times to first and subsequent severe hypoglycaemic events were compared with MBG, HbA_1c and within-day SD of blood glucose using Cox regression after adjusting for other known risk factors for hypoglycaemia. Results On its own, the incidence of time to first hypoglycaemic event increased 1.05-fold for each 1 mmol/l decrease in MBG and 1.07-fold for every 1 mmol/l increase in glucose SD. MBG and SD of blood glucose also both added to the ability of HbA_1c to predict repeated hypoglycaemic events: after adjusting for HbA_1c, a 1 mmol/l increase in SD was associated with a 1.09-fold increased risk of a first event, increasing to a 1.12-fold risk of a fifth event. A 1 mmol/l fall in MBG added a constant 1.02–1.03-fold risk of repeated events. Daytime events were predicted more accurately than nocturnal episodes. Conclusions/interpretation This study has established that HbA_1c, MBG and glucose variability measurements each have an independent role in determining an individual’s risk of hypoglycaemia in type 1 diabetes. All three aspects of glycaemic assessment should thus be considered in patients in whom hypoglycaemia is a real or potential problem.     

Non-diabetic hyperglycaemia correlates with angiographic coronary artery disease prevalence and severity

AimThe role of glycaemia as a coronary artery disease (CAD) risk factor is controversial, and the optimal glucose level is still a matter of debate. For this reason, we assessed the prevalence and severity of angiographic CAD across hyperglycaemia categories and in relation to haemoglobin A_1c (HbA_1c) levels.MethodsWe studied 273 consecutive patients without prior revascularization undergoing coronary angiography for suspected ischaemic pain. CAD severity was assessed using three angiographic scores: the Gensini's score; extent score; and arbitrary index. Patients were grouped, according to 2003 American Diabetes Association criteria, into those with normal fasting glucose (NFG), impaired fasting glucose (IFG) and diabetes mellitus (DM).ResultsCAD prevalence was 2.5-fold higher in both the IFG and DM groups compared with the NFG group. Deterioration of glycaemic profile was a multivariate predictor of angiographic CAD severity (extent score: P = 0.027; arbitrary index: P = 0.007). HbA_1c levels were significantly higher among CAD patients (P = 0.016) and in those with two or more diseased vessels (P = 0.023) compared with the non-CAD group. HbA_1c levels remained predictive of CAD prevalence even after adjusting for conventional risk factors, including DM (adjusted OR: 1.853; 95% CI: 1.269–2.704).ConclusionNon-diabetic hyperglycaemia, assessed either categorically by fasting glucose categories or continuously by HbA_1c levels, correlates with the poorest angiographic outcomes.     

Genetic Determinants of Variability in Glycated Hemoglobin (HbA<Subscript>1c</Subscript>) in Humans: Review of Recent Progress and Prospects for Use in Diabetes Care

Glycated hemoglobin A_1c (HbA_1c) indicates the percentage of total hemoglobin that is bound by glucose, produced from the nonenzymatic chemical modification by glucose of hemoglobin molecules carried in erythrocytes. HbA_1c represents a surrogate marker of average blood glucose concentration over the previous 8 to 12 weeks, or the average lifespan of the erythrocyte, and thus represents a more stable indicator of glycemic status compared with fasting glucose. HbA_1c levels are genetically determined, with heritability of 47% to 59%. Over the past few years, inroads into understanding genetic predisposition by glycemic and nonglycemic factors have been achieved through genome-wide analyses. Here I review current research aimed at discovering genetic determinants of HbA_1c levels, discussing insights into biologic factors influencing variability in the general and diabetic population, and across different ethnicities. Furthermore, I discuss briefly the relevance of findings for diabetes monitoring and diagnosis.     

Mean blood glucose compared with HbA<Subscript>1c</Subscript> in the prediction of cardiovascular disease in patients with type 1 diabetes

Aims/hypothesis It is not known whether mean blood glucose (MBG) predicts the risk of macrovascular complications in diabetes any differently from HbA_1c. In this study we therefore analysed data from the Diabetes Control and Complications Trial (DCCT) to assess the relationship between MBG, HbA_1c and glucose variability with regard to the risk of cardiovascular disease in patients with type 1 diabetes. Methods Pre- and postprandial seven-point glucose profiles were collected quarterly during the DCCT in 1441 individuals. The relationship between time to first cardiovascular event and MBG, HbA_1c and daily SD of blood glucose was assessed by Cox regression after adjusting for the known risk factors of macrovascular disease and the treatment groups of the patients. Results Cox regression showed MBG to be predictive of a cardiovascular event (p = 0.019), but not HbA_1c (p = 0.858). A rise of 1 mmol/l in MBG was associated with an 11% rise in cardiovascular risk. MBG remained highly predictive (p = 0.015) even after adjustment for HbA_1c values and glucose variability. Conclusions/interpretation This study has shown that during the DCCT MBG was a better predictor of the macrovascular complications of type 1 diabetes than HbA_1c. It indicates that the cardiovascular risk associated with hyperglycaemia appeared within the time period of the study and that blood glucose rather than HbA_1c may be the preferred means of assessing this risk.     

International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations

Diabetes is a significant and growing concern, with over 246 million people around the world living with the disease and another 308 million with impaired glucose tolerance. Depending on the resources of different nations, intervention has generally focused on optimizing overall glycaemic control as assessed by glycated haemoglobin (HbA_1c) and fasting plasma glucose (FPG) values. Nevertheless, increasing evidence supports the importance of controlling all three members of the glucose triad, namely HbA_1c, FPG and postmeal glucose (PMG) in order to improve outcome in diabetes. As part of its global mission to promote diabetes care and prevention and to find a cure, the International Diabetes Federation (IDF) recently developed a guideline that reviews evidence to date on PMG and the development of diabetic complications. Based on an extensive database search of the literature, and guided by a Steering and Development Committee including experts from around the world, the IDF Guideline for Management of Postmeal Glucose offers recommendations for appropriate clinical management of PMG. These recommendations are intended to help clinicians and organizations in developing strategies for effective management of PMG in individuals with Type 1 and Type 2 diabetes. The following review highlights the recommendations of the guideline, the supporting evidence provided and the major conclusions drawn. The full guideline is available for download at http://www.idf.org .     

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.     

Epidemiological features of glycated haemoglobin A1c-distribution in a healthy population

Summary HbA_1c was measured in 3240 healthy non-diabetic adult individuals in a working population. There was no difference in HbA_1c between sexes. The distribution of HbA_1c was approximately normal with a slight difference between mean and median values at all ages in both sexes. HbA_1c increased with deterioration of glucose tolerance and with all the known risk factors for diabetes (age, obesity, family history of diabetes, history of a large newborn delivery); age but not body mass index appeared as a factor influencing HbA_1c independently. In women, HbA_1c levels rose particularly at the age of menopause but the use of oral contraceptives or oestrogens made no difference. In both sexes, HbA_1c was higher in smokers than in non-smokers. No consistent seasonal variation was observed. Haematologic factors had a negligible influence on HbA_1c level. HbA_1c was more highly correlated with fasting plasma glucose than with 2 h-plasma/glucose (r=0.20 vs 0.11). In a stepwise multiple regression analysis, age followed by fasting plasma glucose were the only two significant factors associated with the level of HbA_1c. These data indicate that HbA_1c is influenced only by factors closely linked to diabetes.     

Accuracy of glycated haemoglobin in screening for pre‐diabetes in Asian Indians—a community survey: the Chandigarh Urban Diabetes Study (CUDS)

Aim To compare American Diabetes Association and International Expert Committee recommended cut‐off values of HbA_1c for detecting the presence of pre‐diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. Methods A cross‐sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA_1c was measured on a Bio‐Rad 10 system in 1972 subjects. Results Of the 1972 subjects studied, 329 were detected to have pre‐diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA_1c cut‐off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre‐diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA_1c cut‐off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA_1c cut‐offs underdiagnosed the presence of pre‐diabetes in 38 and 64% of these subjects, respectively. Conclusions The American Diabetes Association and the International Expert Committee recommended HbA_1c cut‐off values and oral glucose tolerance tests identify different pre‐diabetes cohorts. Long‐term prospective studies are required to define the usefulness of one over the other.     

Glucose challenge test screening for prediabetes and undiagnosed diabetes

Aims/hypothesis  Diabetes prevention and care are limited by lack of screening. We hypothesised that screening could be done with a strategy similar to that used near-universally for gestational diabetes, i.e. a 50 g oral glucose challenge test (GCT) performed at any time of day, regardless of meal status, with one 1 h sample. Methods  At a first visit, participants had random plasma and capillary glucose measured, followed by the GCT with plasma and capillary glucose (GCTplasma and GCTcap, respectively). At a second visit, participants had HbA_1c measured and a diagnostic 75 g OGTT. Results  The 1,573 participants had mean age of 48 years, BMI 30.3 kg/m² and 58% were women and 58% were black. Diabetes (defined by WHO) was present in 4.6% and prediabetes (defined as impaired glucose tolerance [2 h glucose 7.8–11.1 (140–199 mg/dl) with fasting glucose ≤6.9 (125 mg/dl)] and/or impaired fasting glucose with plasma glucose 6.1–6.9 mmol/l [110–125 mg/dl]) in 18.7%. The GCTplasma provided areas under the receiver-operating-characteristic curves of 0.90, 0.82 and 0.79 for detection of diabetes, diabetes or prediabetes, and prediabetes, respectively, all of which were higher than GCTcap, random and capillary glucose, and HbA_1c (p < 0.02 for all). The performance of GCTplasma was unaffected by time after meals or time of day, and was better in blacks than whites, but otherwise comparable in men and women, and in groups with differing prevalence of glucose intolerance. GCTplasma screening would cost approximately US$84 to identify one person with previously unrecognised diabetes or prediabetes. Conclusions/interpretation  GCT screening for prediabetes and previously unrecognised diabetes would be accurate, convenient and inexpensive. Widespread use of GCT screening could help improve disease management by permitting early initiation of therapy aimed at preventing or delaying the development of diabetes and its complications. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

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.     

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.     

Thiazolidinediones reduce the risk of hepatocellular carcinoma and hepatic events in diabetic patients with chronic hepatitis B

Thiazolidinediones (TZDs) improve glycaemic control and ameliorate liver steatosis, inflammation and fibrosis in patients with fatty liver disease. We aimed to study the impact of TZD and glycaemic control on the risk of hepatocellular carcinoma (HCC) and hepatic events in diabetic patients with chronic hepatitis B (CHB). We performed a retrospective cohort study on diabetic patients with CHB in 2000‐2017 using a territory‐wide electronic healthcare database in Hong Kong. Diabetes mellitus was identified by use of any antidiabetic medication, haemoglobin A_1c (HbA_1c) ≥6.5%, fasting glucose ≥7 mmol/L in two measurements or ≥11.1 mmol/L in one measurement and/or diagnosis codes. Use of antidiabetic medications was modelled as time‐dependent covariates. Of 28 999 diabetic patients with CHB, 3963 (13.7%) developed liver‐related events (a composite endpoint of HCC and hepatic events) at a median (interquartile range) follow‐up of 7.1 (3.7‐11.8) years; 1153 patients received TZD during follow‐up. After adjusted for important confounders, TZD use was associated with a reduced risk of liver‐related events (adjusted hazard ratio [aHR] 0.46, 95% confidence interval [CI] 0.24‐0.88; P = .019). Similar trends were observed in HCC (aHR 0.57) and hepatic events (aHR 0.35) separately. Compared to HbA_1c of 6.5% at baseline, patients with HbA_1c ≥7% had an increased risk of liver‐related events; the risk further increased in 5795 (20.0%) patients with HbA_1c ≥9% at baseline (aHR 1.14, 95% CI 1.04‐1.26; P = .006). TZD use is associated with a lower risk of liver‐related events in diabetic patients with CHB. Liver‐related events are more common in patients with high HbA_1c levels.     

Targeting prandial hyperglycemia: How important is it and how best to do this?

The contribution of postprandial glucose (PPG) excursions to the overall hyperglycemia of patients with type 2 diabetes depends on the degree of diabetic control. PPG is a major contributor in patients with hemoglobin A_1c (HbA_1c) levels below 7.3%, whereas the contribution of fasting plasma glucose (FPG) is preponderant in poorly controlled patients. In addition, the loss of postprandial glycemic control precedes stepwise degradation of fasting with worsening diabetes. As a consequence, monitoring after meals is particularly important in patients with HbA_1c levels ranging from 6.5% to 8%. In such patients, targeting PPG below 140 mg/dL should be one of the main objectives to achieve HbA_1c less than 6.5%. The new hypoglycemic agents, such as the glucagon-like peptide-1 analogues and the dipeptidyl peptidase-4 inhibitors which have a gluco-dependent insulinotropic effect, should normally reinforce our therapeutic armamentarium for achieving the glycemic targets that should include the three components of the glucose triad: HbA_1c, FPG, and PPG.     

Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: the Hisayama Study

Aims/hypothesis The aims of this study were to compare the ability of tests measuring fasting plasma glucose, 2-h plasma glucose and HbA₁c levels in predicting specific diabetic retinopathy, and to determine the cut-off level of each measurement for diagnosing diabetes in a Japanese population.Methods In a total of 1637 subjects, fasting plasma glucose, 2-h plasma glucose and HbA₁c levels were measured in a 75-g oral glucose tolerance test, and diabetic retinopathy was assessed by ophthalmic examination. We calculated receiver operating characteristic (ROC) curves as well as the prevalence of diabetic retinopathy by deciles of the distribution of these glycaemic measurements.Results Of the subjects, 37 (2.3%) had diabetic retinopathy. The prevalence of retinopathy dramatically increased in the tenth decile of each variable. Analysis with ROC curves showed that the optimal cut-off levels for diagnosis of diabetes were 6.4 mmol/l for fasting plasma glucose, 11.1 mmol/l for 2-h plasma glucose, and 5.7% for HbA₁c. The sensitivities for the cut-off point of the three measurements were identical (86.5%), and the specificities were similar (fasting plasma glucose 87.3%; 2-h plasma glucose 89.6%; HbA₁c 90.1%). The area under the ROC curve for 2-h plasma glucose (96.1%) was slightly but not significantly larger than that for fasting plasma glucose (90.0%) and that for HbA₁c (94.5%).Conclusions/interpretation Our findings suggest that measuring fasting plasma glucose or HbA₁c is just as useful as measuring 2-h plasma glucose for the diagnosis of diabetes, and that the cut-off point for diagnostic fasting plasma glucose level is lower than that of the current diagnostic criteria.Abbreviations ADA American Diabetes Association - FPG fasting plasma glucose - 2-h PG 2-hour post-load plasma glucose - NHANES III the Third National Health and Nutrition Examination Survey - ROC receiver operating characteristic     

Patients newly diagnosed with clinical type 2 diabetes mellitus but presenting with HbA1c within normal range: 19-Year mortality and clinical outcomes

AimsTo investigate whether long-term mortality or clinical outcomes differed between patients diagnosed with type 2 diabetes mellitus and presenting with HbA_1c within or above normal range at time of diagnosis.MethodsData were from a population-based sample of 1136 individuals with newly diagnosed type 2 diabetes mellitus. The diagnosis was confirmed with a single fasting whole blood/plasma glucose ≥7.0/8.0 mmol/l. The median time from day of diagnosis until end of follow up was 18.8 years. Patients were grouped according to normal HbA_1c and elevated HbA_1c at diagnosis. The effect of elevated HbA_1c on a number of clinical outcomes and all-cause mortality was assessed in Cox regression models.ResultsAt diagnosis, 97 patients (8.5%) had an HbA_1c level within normal range. Age (mean (SD)) at diagnosis was 64.5 (11.5) years. Both unadjusted and adjusted hazard ratios for the effect of HbA_1c on mortality and other outcomes were not statistically significant.ConclusionsPatients who are diagnosed with type 2 diabetes mellitus by means of elevated fasting whole blood/plasma glucose but have HbA_1c within reference range at diagnosis do not seem to have a relatively benign long-term clinical course. Therefore new diagnostic procedures should preferably be able to identify these individuals.