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.     

The general use of glycated haemoglobin for the diagnosis of diabetes and other categories of glucose intolerance: still a long way to go

Glycated haemoglobin (HbA_1c) is considered the ‘gold standard’ for monitoring metabolic control in diabetes. An International Expert Committee recently recommended HbA_1c as a better method than measurement of glucose to use in the diagnosis of diabetes, based on its strong association with microvascular complications, a lower day-to-day variability and ease of use, not necessarily in the fasting state. These recommendations have been embraced by the American Diabetes Association (ADA), which stated in its Standards of Medical Care in Diabetes 2010 that “A_1c, fasting plasma glucose or the 2 h 75 g oral glucose tolerance test (OGTT) are appropriate for testing diabetes and assessing the risk of future diabetes,” and that “a confirmed A_1c ≥ 6.5% is diagnostic for diabetes.” Measuring HbA_1c has several advantages over glucose measurements, but its exclusive use should only be considered if the test is conducted under standardised conditions and its limitations are taken into due account. The impact of its use on the epidemiology of diabetes and other categories of glucose intolerance, as seen from recent reports, is also discussed.     

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.     

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.     

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)     

Insufficient sensitivity of hemoglobin A1C determination in diagnosis or screening of early diabetic states

An International Expert Committee made recommendations for using the hemoglobin A_1C (A1C) assay as the preferred method for the diagnosis of diabetes in nonpregnant individuals. A concentration of at least 6.5% was considered as diagnostic. It is the aim of this study to compare the sensitivity of A1C with that of plasma glucose concentrations in subjects with early diabetes or impaired glucose tolerance (IGT). We chose 2 groups of subjects who had A1C not exceeding 6.4%. The first group of 89 subjects had family histories of diabetes (MODY or type 2 diabetes mellitus) and had oral glucose tolerance test (OGTT) and A1C determinations. They included 36 subjects with diabetes or IGT and 53 with normal OGTT. The second group of 58 subjects was screened for diabetes in our Diabetes Clinic by fasting plasma glucose, 2-hour plasma glucose, or OGTT and A1C; and similar comparisons were made. Subjects with diabetes or IGT, including those with fasting hyperglycemia, had A1C ranging from 5.0% to 6.4% (mean, 5.8%). The subjects with normal OGTT had A1C of 4.2% to 6.3% (mean, 5.4%), or 5.5% for the 2 groups. The A1C may be in the normal range in subjects with diabetes or IGT, including those with fasting hyperglycemia. Approximately one third of subjects with early diabetes and IGT have A1C less than 5.7%, the cut point that the American Diabetes Association recommends as indicating the onset of risk of developing diabetes in the future. The results of our study are similar to those obtained by a large Dutch epidemiologic study. If our aim is to recognize early diabetic states to apply effective prophylactic procedures to prevent or delay progression to more severe diabetes, A1C is not sufficiently sensitive or reliable for diagnosis of diabetes or IGT. A combination of A1C and plasma glucose determinations, where necessary, is recommended for diagnosis or screening of diabetes or IGT.     

Efficacy and safety of patient‐directed titration of once‐daily pre‐dinner premixed biphasic insulin aspart 70/30 injection in Japanese type 2 diabetic patients with oral antidiabetic drug failure: STEP‐AKITA study

Aims/Introduction: To clarify clinical characteristics related to optimal glycemic control achieved after adding once‐daily pre‐dinner biphasic insulin aspart 70/30 (BIAsp 30) in Japanese type 2 diabetic (T2D) patients with oral antidiabetic drug (OAD) failure. Materials and Methods: Under this regimen, we evaluated changes in HbA_1c levels and daily self‐monitoring blood glucose (BG) profiles, as well as the incidences of hypoglycemia and retinopathy progression. The patients adjusted BIAsp 30 dosages themselves every 3–4 days according to a pre‐determined algorithm to achieve fasting BG levels of 101–120 mg/dL. HbA_1c levels were expressed as Japan Diabetes Society values. Results: Of 29 enrolled patients, 22 (HbA_1c levels, 8.5 ± 1.5% [mean ± SD]) and 20 patients completed the 16‐ and 24‐week follow‐up, respectively. At 16 weeks 68.2 and 45.5%, and at 24 weeks 80.0 and 35% of patients had achieved HbA_1c levels of <7.0 and <6.5%, respectively. The patients who had achieved optimal glycemic control, including daytime postprandial BG profiles after treatment, had lower post‐breakfast BG excursions at baseline, shorter diabetes durations and younger age. No severe hypoglycemic episodes were recorded. Progression of retinopathy was observed in 3 of the 29 enrolled patients. Conclusions: Lower post‐breakfast BG excursions, shorter diabetes duration and younger age in Japanese T2D patients with OAD failure might warrant optimal glycemic control with safety after adding once‐daily pre‐dinner BIAsp 30 initiating regimen. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00062.x, 2010)     

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.     

Glycated haemoglobin predicts progression to diabetes mellitus in Pima Indians with impaired glucose tolerance

Summary Glycated haemoglobin could offer several practical advantages over the OGTT for assessing glucose metabolism. Initial cross-sectional studies (1983–1985) on 381 subjects (mostly Pima Indians) described the relationship between HbA_1c (a specific glycated Hb) and the OGTT. We performed follow-up OGTTs and HbA_1c measurements on 257 of these same subjects 1.6–6.1 years later. Subjects were again grouped according to both the result of the OGTT (normal, IGT or diabetes, by WHO criteria) and HbA_1c result (normal or elevated based on mean ± 1.96 SD of normal). Of 66 subjects with IGT at baseline, 47 (71%) had normal HbA_1c and 19 (29%) had elevated HbA_1c. Twentysix (39%) of these subjects had diabetes at follow-up. Of these subjects with IGT, a significantly greater percentage of subjects with elevated HbA_1c at baseline (68%) showed worsening to diabetes than those with a normal HbA_1c (28%); (chi-square=7.8, df=1, p<0.01). Thus, in subjects with IGT, glycated Hb may be a useful predictor of progression to diabetes.Abbreviations OGTT Oral glucose tolerance test - WHO World Health Organisation - IGT impaired glucose tolerance     

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.     

Predictors of deterioration of glucose tolerance and effects of lifestyle intervention aimed at reducing visceral fat in normal glucose tolerance subjects with abdominal obesity

Aims/Introduction: The aim of the present study was to determine the predictors of deterioration of glucose tolerance in individuals with normal glucose tolerance (NGT) and abdominal obesity, and whether a lifestyle intervention to reduce visceral fat is effective in these individuals. Materials and Methods: The study subjects were 251 individuals who had abdominal obesity with certain risk factors (hypertension, high fasting plasma glucose (FPG), elevated hemoglobin A_1c (HbA_1c), dyslipidemia and hyperuricemia) and underwent oral glucose tolerance test (OGTT) in 2004 and 2005. Results: Using the area under the receiver operating characteristic curve, we found that PG at 0 min, 60 min, and area under the curve (AUC) of glucose from 0 to 120 min (AUC [glucose_0–120]) in OGTT were significant predictors of deterioration of glucose tolerance, with optimal cut‐off values of 95 mg/dL, 158 mg/dL and 271 mg h/dL, respectively. Although the rate of deterioration of glucose tolerance didn’t decrease with reductions in visceral fat area (VFA) over the 1‐year period in subjects with NGT, the rate tended to decrease with reductions in VFA in high‐risk NGT subjects (PG at 0 min > 95 or at 60 min > 158, or AUC [glucose_0–120] > 271). Conclusions: These results suggest that reduction of visceral fat over 1 year might not be beneficial in all subjects with NGT, but is beneficial in high‐risk NGT. We propose that individuals with values of the aforementioned predictors higher than the cut‐off levels, even those with NGT, should receive a lifestyle intervention program aimed at reducing visceral fat to prevent deterioration of glucose tolerance. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00080.x, 2011)     

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%.     

Addition of biphasic insulin aspart 30 to optimized metformin and pioglitazone treatment of type 2 diabetes mellitus: The ACTION Study (Achieving Control Through Insulin plus Oral ageNts)

Aim: Efficacy and safety of biphasic insulin aspart (BIAsp 30, 30% short‐acting and 70% intermediate‐acting insulin aspart) added to an optimized treatment of metformin and pioglitazone (met/pio) were compared with treatment with optimized met/pio in type 2 diabetes patients. Methods: This randomized, 34‐week, parallel‐group study enrolled insulin‐naive, type 2 diabetes patients (HbA_1c 7.5–12.0%) previously using two oral antidiabetic (OAD) agents. During an 8‐week run‐in period, treatment was changed to met/pio and doses were adjusted up to 2500 mg/day and 30 or 45 mg/day respectively. Subjects either continued met/pio alone or added BIAsp 30 initiated at 6 units twice daily and titrated to target plasma glucose (PG) (4.4–6.1 mmol/l). Results: At end‐of‐study, subjects treated with BIAsp 30+met/pio (n = 93) had a mean (±s.d.) HbA_1c reduction significantly greater than treatment with met/pio (n = 88) (1.5% ± 1.1 vs. 0.2% ± 0.9, p < 0.0001 between groups). Subjects treated with BIAsp 30+met/pio were more likely to reach The American Association of Clinical Endocrinologists and European Association for the Study of Diabetes/American Diabetes Association HbA_1c targets of ≤6.5 and <7.0%, respectively, than with met/pio only (HbA_1c≤6.5%: 59 vs. 12%; HbA_1c <7.0%: 76 vs. 24%). At end‐of‐study, self‐monitored glucose profile values at all eight daily time points were significantly less for the BIAsp 30+met/pio group compared with the met/pio group, and minor hypoglycaemia (defined as PG < 3.1 mmol/l) was more frequent (8.3 vs. 0.1 events/year, p < 0.001). Both groups gained weight during treatment (BIAsp 30+met/pio, 4.6 ± 4.3 kg; met/pio, 0.8 ± 3.2 kg; p < 0.001). Conclusion: Addition of insulin in type 2 patients treated with met/pio is an effective way to achieve glycaemic targets. Treatment with BIAsp 30+met/pio achieved significantly greater reduction in HbA_1c, as compared with met/pio alone. In patients with type 2 diabetes poorly controlled by 2 OADs, more achieved glycaemic targets using BIAsp 30+met/pio than using met/pio alone.     

Effects of colesevelam on glucose absorption and hepatic/peripheral insulin sensitivity in patients with type 2 diabetes mellitus

Aim: Colesevelam lowers glucose and low‐density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus. This study examined the mechanisms by which colesevelam might affect glucose control. Methods: In this 12‐week, randomized, double‐blind, placebo‐controlled study, subjects with type 2 diabetes and haemoglobin A_1c(HbA_1c) ≥7.5% on either stable diet and exercise or sulphonylurea therapy were randomized to colesevelam 3.75 g/day (n = 16) or placebo (n = 14). Hepatic/peripheral insulin sensitivity was evaluated at baseline and at week 12 by infusion of ³H‐labelled glucose followed by a 2‐step hyperinsulinemic–euglycemic clamp. Two 75‐g oral glucose tolerance tests (OGTTs) were conducted at baseline, one with and one without co‐administration of colesevelam. A final OGTT was conducted at week 12. HbA_1c and fasting plasma glucose (FPG) levels were evaluated pre‐ and post‐treatment. Results: Treatment with colesevelam, compared to placebo, had no significant effects on basal endogenous glucose output, response to insulin or on maximal steady‐state glucose disposal rate. At baseline, co‐administration of colesevelam with oral glucose reduced total area under the glucose curve (AUC_g) but not incremental AUC_g. At week 12, neither total AUC_g nor incremental AUC_g were changed from pre‐treatment values in either group. Post‐load insulin levels increased with colesevelam at 30 and 120 min, but these changes in total area under the insulin curve (AUC_i) and incremental AUC_i did not differ between groups. Both HbA_1c and FPG improved with colesevelam, but treatment differences were not significant. Conclusions: Colesevelam does not affect hepatic or peripheral insulin sensitivity and does not directly affect glucose absorption.     

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 .     

The prevalence of retinopathy in impaired glucose tolerance and recent‐onset diabetes in the Diabetes Prevention Program

Aims Retinopathy is considered the complication most closely associated with and characteristic of diabetes mellitus. Hyperglycaemia below levels diagnostic of diabetes, so called pre‐diabetes, is associated with a low prevalence of ‘diabetic’ retinopathy. However, few longitudinal studies of non‐diabetic populations have performed repeated measures of glycaemia and screened for retinopathy to determine its occurrence in the non‐diabetic population and the onset of retinopathy in new‐onset diabetic patients. We determined the prevalence of retinopathy characteristically seen in diabetes in persons with impaired glucose tolerance and in patients with new‐onset diabetes of known duration in the Diabetes Prevention Program (DPP) cohort. Methods The DPP recruited persons with elevated fasting glucose (5.3–6.9 mmol/l) and impaired glucose tolerance, and no history of diagnosed diabetes, other than gestational diabetes not persisting after pregnancy. Seven‐field, stereoscopic fundus photography was completed a mean of 3.1 years after the development of diabetes in 594 of 878 participants who had developed diabetes during the DPP, and in a random sample of 302 participants who remained non‐diabetic. Results Retinopathy consistent with diabetic retinopathy was detected in 12.6 and 7.9% of the diabetic and non‐diabetic participants, respectively (P = 0.03, comparing prevalence in the two groups). Systolic blood pressure and HbA_1c were higher at baseline in the diabetic participants who had retinopathy compared with the diabetic participants without retinopathy. Conclusions Retinopathy characteristic of diabetes is present in persons with elevated fasting glucose and impaired glucose tolerance and no known history of diabetes. The prevalence of retinopathy is significantly higher in persons who develop diabetes, even within 3 years of diagnosis.     

Predicting steady‐state HbA1c responses to sitagliptin in patients with type 2 diabetes mellitus*

Aims: To develop predictive formulas using short‐term changes in glycaemic parameters [haemoglobin A_1c (HbA_1c) and fasting plasma glucose (FPG)] with sitagliptin, a highly selective dipeptidyl peptidase‐4 inhibitor, to assess longer term steady‐state changes in HbA_1c. Methods: Results from two, 12‐week, double‐blind studies of sitagliptin in Japanese patients with type 2 diabetes mellitus receiving once‐daily sitagliptin 100 mg were used to construct linear models to develop predictive formulas based on study 1 (S1) and to validate them using study 2 (S2). HbA_1c and FPG were the primary and the key secondary end‐point for both studies and were both used to develop predictive formulas. Results: The predictive formulas using HbA_1c ± FPG results (slope of change) from week 0 to week 4 in S1 showed high correlations between fitted and observed week 12 HbA_1c: for HbA_1c alone R² = 0.76, for HbA_1c + FPG R² = 0.89. When using the sitagliptin 100 mg group of S2 data set to assess the validity of the predictive formulas, high correlations for HbA_1c alone (R² = 0.76) and for HbA_1c + FPG (R² = 0.77) were also observed. Data using a lower dose (25 mg once daily) of sitagliptin also demonstrated similar results. Conclusions: The early responses (over 4 weeks) in HbA_1c and FPG with sitagliptin can be used to accurately predict later responses (at week 12) in HbA_1c in Japanese patients with type 2 diabetes mellitus. Additional studies applying this approach to other agents with diverse mechanisms are important.     

Adherence to a Mediterranean diet and glycaemic control in Type 2 diabetes mellitus

Aims Mediterranean‐type diets reduce the risk of Type 2 diabetes. Whether a Mediterranean‐type diet improves glycaemic control in diabetes remains unknown. Methods We conducted a cross‐sectional analysis in 901 outpatients with Type 2 diabetes attending diabetes clinics located in Campania County, South Italy. We explored the relation between glycated haemoglobin (HbA_1c), measured centrally, self‐measured pre‐ and postprandial glucose levels and consumption of a Mediterranean‐type diet. Adherence to a Mediterranean‐type diet was assessed by a 9‐point scale that incorporated the salient characteristics of this diet (range of scores, 0–9, with higher scores indicating greater adherence). The study was conducted from 2001 to 2007. Results Diabetic patients with the highest scores (6–9) had lower body mass index and waist circumferences, a lower prevalence of the metabolic syndrome and lower HbA_1c and post‐meal glucose levels than diabetic patients with the lowest scores (0–3). In multivariate analysis, mean HbA_1c and 2‐h post‐meal glucose concentrations were significantly lower in diabetic patients with high adherence to a Mediterranean‐type diet than those with low adherence [difference: HbA_1c 0.9%, 95% confidence intervals (CI) 0.5–1.2%, P < 0.001; 2‐h glucose 2.2 mmol/l, 95% CI 0.8–2.9 mmol/l, P < 0.001]. Conclusions In Type 2 diabetes, greater adherence to a Mediterranean‐type diet is associated with lower HbA_1c and postprandial glucose levels.     

Children and young people with diabetes in Yorkshire: a population‐based clinical audit of patient data 2005/2006

Aims To provide a population‐based clinical audit of children and young people with diabetes, reporting outcomes, including glycaemic control, for named individual units. Methods Clinical audit data on care processes and glycated haemoglobin (HbA_1c) were collected for 1742 children and young people treated in 16 paediatric units in Yorkshire, from January 2005 to March 2006. The Yorkshire Register of Diabetes in Children and Young People provided information technology support and validation that enhanced data quality. Multi‐level linear regression modelling investigated factors affecting glycaemic control. Results An HbA_1c measure was recorded for 91.6% of patients. The National Institute for Clinical Excellence‐recommended target level for HbA_1c of < 7.5% was achieved for 14.7% of patients. HbA_1c was positively associated with duration of diabetes and later age at diagnosis. Patients living in deprived areas had significantly poorer control compared with those from affluent areas. Significant between‐unit variation in HbA_1c was not reflected by any association with unit size. Conclusions Our population‐based clinical audit of children with diabetes is the product of an effective collaboration between those who deliver care and health services researchers. High levels of recording the key care process measuring diabetes control, compared with national figures, suggests collaboration has translated into improved services. The interesting association between poor diabetes control and higher deprivation is noteworthy and requires further investigation. Future audits require recording of clinical management and clinic structures, in addition to resources to record, assemble and analyse data.