Use of HbA1C testing to diagnose pre-diabetes in high risk African American children: A comparison with fasting glucose and HOMA-IR

ObjectiveThis study aimed to compare the discriminating power of HbA_1C with other pre-diabetes diagnostic tests specifically in high-risk African American children.Research design and methodsA cross-sectional analysis was performed on a sample of 172 children (70 boys and 102 girls) aged 9–11 years with BMI's above the 85th percentile. Fasting glucose, insulin and HbA_1C were analyzed from the plasma samples.ResultsOf the 172 participants included in this analysis, 21 (12.2%) had HbA_1C concentrations above the cutoff of 5.7 used to identify pre-diabetes. None (0%) of these 21 participants, however, were observed to have a glucose concentration above the pre-diabetes cutoff of 110 mg/dl, and only 13 of 21 participants had HOMA-IR above the pre-diabetes cutoff of 2.5. When compared to the previously identified glucose cutoff of 110 mg/dl and HOMA-IR cutoff of 2.5 for pre-diabetes, HbA_1C showed high specificity (88 and 93%, respectively) but very low sensitivity (0 and 21%, respectively). Glucose, insulin and HOMA-IR were significantly interrelated, but HbA_1C was not significantly correlated with these biochemical prediabetes assessment variables, nor with anthropometric (BMIz, WC) risk factors.ConclusionOur results suggest that HbA_1C had poor discrimination power to identify prediabetes in overweight and obese 9- to 11-year-old African American children. Future studies are recommended to compare the feasibility, sensitivity and predictive power of different screening tests currently recommended to avoid inadequacy when screening for prediabetes and diabetes.     

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.     

Random Plasma Glucose in Serendipitous Screening for Glucose Intolerance: Screening for Impaired Glucose Tolerance Study 2

Background With positive results from diabetes prevention studies, there is interest in convenient ways to incorporate screening for glucose intolerance into routine care and to limit the need for fasting diagnostic tests. Objective The aim of this study is to determine whether random plasma glucose (RPG) could be used to screen for glucose intolerance. Design This is a cross-sectional study. Participants The participants of this study include a voluntary sample of 990 adults not known to have diabetes. Measurements RPG was measured, and each subject had a 75-g oral glucose tolerance test several weeks later. Glucose intolerance targets included diabetes, impaired glucose tolerance (IGT), and impaired fasting glucose₁₁₀ (IFG₁₁₀; fasting glucose, 110–125 mg/dl, and 2 h glucose < 140 mg/dl). Screening performance was measured by area under receiver operating characteristic curves (AROC). Results Mean age was 48 years, and body mass index (BMI) was 30.4 kg/m²; 66% were women, and 52% were black; 5.1% had previously unrecognized diabetes, and 24.0% had any “high-risk” glucose intolerance (diabetes or IGT or IFG₁₁₀). The AROC was 0.80 (95% CI 0.74–0.86) for RPG to identify diabetes and 0.72 (0.68–0.75) to identify any glucose intolerance, both highly significant (p < 0.001). Screening performance was generally consistent at different times of the day, regardless of meal status, and across a range of risk factors such as age, BMI, high density lipoprotein cholesterol, triglycerides, and blood pressure. Conclusions RPG values should be considered by health care providers to be an opportunistic initial screening test and used to prompt further evaluation of patients at risk of glucose intolerance. Such “serendipitous screening” could help to identify unrecognized diabetes and prediabetes.     

Capillary glucose determination in the screening of gestational diabetes

Paired capillary-venous blood samples were obtained from 418 pregnant women undergoing an oral glucose challenge test (GCT) for the screening of gestational diabetes (GD). The relationship between capillary and plasma glucose concentrations was investigated in order to establish a capillary GCT threshold. Plasma glucose was assayed by the glucose oxidase method and capillary glucose using Reflocheck Glucose strips and a Reflocheck reflectance meter. During GCT the capillary values exceeded plasma glucose values by a mean difference of 10-12 mg/dl fasting and 22-24 mg/dl after 1 h. A high correlation between the glucose values of the two techniques was found, particularly for those at 1 h, with corresponding capillary determinations being 20 mg/dl above plasma values. The sensitivity, specificity and predictive value of the various capillary thresholds investigated in detecting GD corresponded substantially to the accuracy of plasma thresholds 20 mg/dl lower. The receiver operator characteristic curves of the plasma and capillary thresholds were similar in shape and the optimal cut-off point for performing a diagnostic test was set at 135 and 155 mg/dl, respectively. These cut-off values should be reconsidered in the light of the costs and perinatal outcome.     

Diabetes primary prevention program: New insights from data analysis of recruitment period

Background

Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina.

Methods

People were recruited through population approach (house‐to‐house survey by FINDRISC in randomized areas) and opportunistic approach (FINDRISC completed by participants during consultations for nonrelated prediabetes/diabetes symptoms in public and private primary care centres of cities involved). In people with FINDRISC score ≥ 13 points, we evaluated blood concentrations of HbA_1c, creatinine, lipids, and an oral glucose tolerance test (OGTT).

Results

Approximately 3415 individuals completed the FINDRISC populational survey and 344 the opportunistic survey; 43% of the 2 groups scored over 13 points; 2.8 and 75.4% of them, respectively, took the prescribed OGTT. Approximately 53.7% of the OGTT showed normal values and 5.2% unknown T2D. The remaining cases showed 69.5% impaired fasting glucose, 13.6% impaired glucose tolerance, and 16.9% both impairments. HbA_1c values showed significant differences compared with normal glucose tolerance (4.96 ± 0.43%), prediabetes (5.28 ± 0.51%), and T2D (5.60 ± 0.51%). Participants with prediabetes and T2D showed a predominant increase in low‐density lipoprotein‐cholesterol values. In prediabetes, >50% showed insulin resistance.

Conclusions

People with prediabetes/T2D had dyslipidemia associated with insulin resistance, which promotes the development of T2D and cardiovascular disease. Thus, it merits its appropriate treatment.     

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.     

Lessons learned from the 1‐hour post‐load glucose level during OGTT: Current screening recommendations for dysglycaemia should be revised

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1‐hour post‐load glucose level during the 75‐g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1‐hour post‐load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β‐cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA_1c or 2‐hour post‐load glucose values. An elevated 1‐hour post‐load glucose level was a better predictor of type 2 diabetes than isolated 2‐hour post‐load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1‐hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2‐hour level was <140 mg/dl (7.8 mmol/L). The risk of myocardial infarction or fatal ischemic heart disease was also greater among subjects with elevated 1‐hour glucose levels as were risks of retinopathy and peripheral vascular complications in a Swedish cohort. The authors believe that the considerable evidence base supports redefining current screening and diagnostic recommendations with the 1‐hour post‐load level. Measurement of the 1‐hour PG level would increase the likelihood of identifying a larger, high‐risk group with the additional practical advantage of potentially replacing the conventional 2‐hour oral glucose tolerance test making it more acceptable in a clinical setting.     

Relationship between glycated haemoglobin levels and mean glucose levels over time

Aims/hypothesis HbA_1c, expressed as the percentage of adult haemoglobin that is glycated, is the most widely used measure of chronic glycaemia. Achieving near-normal HbA_1c levels has been shown to reduce long-term complications and the HbA_1c assay is recommended to determine whether treatment is adequate and to guide adjustments. However, daily adjustments of therapy are guided by capillary glucose levels (mmol/l). We determined the relationship between an accurate measure of mean glucose levels over time and the HbA_1c level, and whether HbA_1c can be expressed in the same units as self-monitoring results. Methods Twenty-two participants with diabetes and three non-diabetic participants were included in this longitudinal observational study. Mean glucose levels were measured by continuous glucose monitoring (CGM), which measures interstitial glucose levels every 5 min, for 12 weeks. Capillary measurements were obtained four times per day to confirm the accuracy of CGM. HbA_1c was measured at baseline and every 4 weeks. Results The HbA_1c results at weeks 8 and 12 correlated strongly (r = 0.90) with the CGM results during the preceding 8 and 12 weeks. A curvilinear (exponential) relationship and a linear regression captured the relationship with similarly high correlations, which allowed transformation of HbA_1c values to a calculated mean glucose level. Conclusions and interpretation HbA_1c correlates closely with a complete measure of average glycaemia over the preceding 8–12 weeks. The translation of HbA_1c to an average glucose level for reporting and management purposes is feasible.     

Comparison of triglyceride glucose index and HbA1C as a marker of prediabetes – A preliminary study

Background and aimsHbA₁C and HOMA-IR (Homeostatic model assessment for assessing insulin resistance) are established diagnostic markers of diabetes and insulin resistance respectively, but are relatively expensive. Triglyceride glucose (TyG) index is calculated based on fasting plasma glucose and fasting triglyceride levels which are available as routine laboratory parameters and is inexpensive. This is a preliminary study which aims to compare Triglyceride glucose (TyG) index with HbA₁C as a marker of prediabetes and also with HOMA-IR (Homeostatic model assessment for assessing insulin resistance) as a marker of insulin resistance.Methods100 diagnosed cases of prediabetes and 100 age and sex-matched normoglycemic controls were recruited in the study. Fasting plasma glucose, 2-hour OGTT, fasting triglycerides, fasting plasma insulin and HbA₁C were measured. Triglyceride glucose (TyG) index and HOMA-IR (Homeostatic model assessment for assessing insulin resistance) were calculated. Receiver operator curve was plotted and analysed between HbA₁C and Triglyceride glucose (TyG) index.ResultsOut of 100 subjects with prediabetes; 53 were female and 47 were male. In this study, there was higher mean Triglyceride glucose (TyG) index (4.942 ± 0.137 vs 4.661 ± 0.173) and HOMA-IR (Homeostatic model assessment for assessing insulin resistance) (2.424 ± 1.045 vs 1.03 ± 0.594) in individuals with prediabetes compared to normoglycemic individuals. The area under curve (AUC) for HbA1C (0.942) was more than Triglyceride glucose (TyG) index (0.898) for the diagnosis of prediabetes. But the difference was not statistically significant with p = 0.06.ConclusionsTriglyceride glucose (TyG) index is comparable to HbA1C as a marker for the diagnosis of prediabetes.     

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.     

Value of Risk Stratification to Increase the Predictive Validity of HbA1c in Screening for Undiagnosed Diabetes in the US Population

Background  Opportunistic screening using hemoglobin A1c (HbA1c) may improve detection of undiagnosed diabetes but remains controversial. Objective  To evaluate the predictive validity of HbA1c as a screening test for undiagnosed diabetes in a risk-stratified sample of the US population. Design  Weighted cross-sectional analysis of diabetes risk factors, HbA1c, and fasting plasma glucose (FPG) in National Health and Nutrition Examination Survey (NHANES), 1999–2004. Subjects  Six thousand seven hundred and twenty-three NHANES participants from morning examination session, aged ≥18 years and without prior physician-diagnosed diabetes. Measurements  HbA1c and undiagnosed diabetes defined by FPG ≥ 7.0 mmol/l (126 mg/dl). Results  The estimated prevalence of undiagnosed diabetes in the US population was 2.8% (5.5 million people). HbA1c had strong correlation with undiagnosed diabetes, with an area under the receiver-operating characteristic curve of 0.93. Independent predictors of undiagnosed diabetes were older age, male sex, black race, hypertension, elevated waist circumference, elevated triglycerides, and low high-density lipoprotein cholesterol. We derived a risk score for undiagnosed diabetes and stratified participants into low (0.44% prevalence), moderate (4.1% prevalence), and high (11.1% prevalence) risk subgroups. In moderate and high risk groups, a threshold HbA1c value ≥ 6.1% identified patients requiring confirmatory FPG; HbA1c ≤ 5.4% identified patients for whom diabetes could be reliably excluded. Intermediate HbA1c (5.5–6.0%) may exclude diabetes in moderate, but not high risk groups). Conclusions  Risk stratification improves the predictive validity of HbA1c in screening for undiagnosed diabetes in the US population. Although opportunistic screening with HbA1c would improve detection of undiagnosed diabetes, cost-effectiveness studies are needed before implementation of specific screening strategies using HbA1c.     

Prevalence of diabetes related vascular complications in subjects with normal glucose tolerance,prediabetes, newly detected diabetes and known diabetes

AimsVarying prevalence of individual diabetes related vascular complications in prediabetes has been reported. However, very few studies have looked at both macrovascular and microvascular complications in prediabetes.MethodsStudy subjects without any history of diabetes underwent oral glucose tolerance test (OGTT) and were classified as either normal glucose tolerance (NGT), prediabetes (PD), newly detected diabetes mellitus (NDDM) on the basis of American Diabetes Association (ADA) criteria. Age and sex matched known diabetes mellitus (KDM) patients were also recruited. All the participants were subsequently screened for both macrovascular (CAD, CVA,PVD) and microvascular (retinopathy, nephropathy and neuropathy)complications of diabetes.ResultsPrevalence of vascular complications among prediabetes subjects was 11.1% as compared to 1.4% among NGT subjects, 13.9% among NDDM subjects and 23.8% among KDM subjects. There was no significant between complication rates in prediabetes and NDDM group (p = 0.060). The prevalence of macrovascular and microvascular complications among prediabetes subjects was 4.2% and 6.9% while the same in NDDM was 4.2% and 9.7%.ConclusionsThe proportion of subjects with prediabetes and vascular complications was about half of those with known diabetes and almost similar to those with newly detected diabetes mellitus.     

Additive effects of glycaemia and blood pressure exposure on risk of complications in type 2 diabetes: a prospective observational study (UKPDS 75)

Aims/hypothesis The relative importance of glucose and blood pressure control in type 2 diabetes remains uncertain. We assessed interactive effects of glycaemia and systolic blood pressure (SBP) exposure on the risk of diabetic complications over time.Subjects, materials and methods HbA_1c and SBP, measured annually for a median of 10.4 years in 4,320 newly diagnosed type 2 diabetic patients from the UK Prospective Diabetes Study (UKPDS), were categorised as updated mean values <6.0, 6.0–6.9, 7.0–7.9 or ≥8.0%, and <130, 130–139, 140–149 or ≥150 mmHg, respectively. Clinical outcomes were UKPDS predefined composite endpoints.Results The incidence of the ‘any diabetes-related endpoint’ in the lowest (HbA_1c <6.0%, SBP <130 mmHg) and highest (HbA_1c ≥8%, SBP ≥150 mmHg) category combinations was 15 and 82 per 1,000 person-years, respectively, and 24 and 120 per 1,000 person-years in a Poisson model adjusted to white Caucasian male sex, age 50 to 54 years and diabetes duration of 7.5 to 12.5 years. Updated mean HbA_1c and SBP effects were additive in an adjusted proportional hazards model with risk reductions of 21% per 1% HbA_1c decrement and 11% per 10 mmHg SBP decrement. Endpoint rates obtained in the 887 patients randomised in both the glycaemia and hypertension intervention trial arms were consistent with the observational data. Those allocated to both intensive glucose and tight blood pressure control policies had fewer events than those allocated to either policy alone or to neither (p for trend 0.024).Conclusions/interpretation Risk of complications in type 2 diabetes is associated independently and additively with hyperglycaemia and hypertension. Intensive treatment of both these risk factors is required to minimise the incidence of complications.     

National Patterns in Diabetes Screening: Data from the National Health and Nutrition Examination Survey (NHANES) 2005–2012

BACKGROUND

There are few current population-based estimates of the patterns of diabetes screening in the United States. The American Diabetes Association (ADA) recommends universal screening of adults ≥ 45 years, and high-risk adults < 45 years, but there is no current assessment of ADA guideline performance in detecting diabetes and prediabetes. Furthermore, data on racial/ethnic patterns of screening are limited.

OBJECTIVE

Our aim was to estimate diabetes screening prevalence for the US adult population and specifically for those who meet ADA criteria; to report the prevalence of prediabetes and diabetes among these groups; and to determine if high-risk race/ethnicity was associated with reported screening.

DESIGN

This was a Cross-sectional survey.

PARTICIPANTS

Non-pregnant adults (≥ 21 years) without diabetes or prediabetes who participated in the National Health and Nutrition Examination Survey (NHANES) in 2005–2012 (n = 17,572) were included in the study. “Screening-recommended” participants, classified by ADA criteria, included (1) adults ≥ 45 years and (2) “high-risk” adults < 45 years. “Screening-not-recommended” participants were adults < 45 years who did not meet criteria.

MAIN MEASURES

Diabetes screening status was obtained by self-report. We used calibrated HbA_1c and/or fasting glucose levels to define undiagnosed diabetes and prediabetes.

KEY RESULTS

Seventy-six percent of the study population (approximately 136 million US adults) met ADA criteria. Among them, less than half (46.2 %) reported screening; undiagnosed diabetes affected 3.7 % (5 million individuals), and undiagnosed prediabetes affected 36.3 % (49 million people.) African Americans were more likely to report screening, both among adults ≥ 45 years and among “high risk” younger adults (OR 1.27 and 1.36, respectively.) Hispanic participants were also more likely to report screening (OR 1.31 for older adults, 1.42 for younger adults.) The screening rate among “screening-not-recommended” adults was 29.6 %; the prevalence of diabetes and prediabetes were 0.4 and 10.2 %, respectively.

CONCLUSIONS

In a nationally representative sample, 76 % of adults met ADA screening criteria, of whom fewer than half reported screening. Limitations include cross-sectional design and screening self-report.KEY WORDS: diabetes screening, prediabetes, NHANES, ADA, disparities     

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.     

Determinants of progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screened population: 3 year follow-up in the ADDITION study,Denmark

Aims/hypothesis We sought to identify determinants of progression from impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) to diabetes in high-risk screened individuals. Methods In general practices in Denmark, stepwise screening for type 2 diabetes mellitus in persons aged 40 to 69 years included a risk questionnaire, random blood glucose, HbA_1c, fasting blood glucose and an OGTT. The 1,821 individuals with IGT or isolated IFG (WHO 1999) were re-invited after 1 and 3 years. Follow-up data on glucose measurements were available in 1,510 individuals and additional clinical data in 1,002 collected at the 3-year visits. Regression models using interval censoring were used. Results Progression rates from IFG and IGT to diabetes over 3.5 years were 11.8 and 17.0 per 100 person-years, respectively and were particularly high in the first year. Baseline determinants of progression were: IFG: glucose measures, BMI [per kg/m², rate ratio (RR) 1.04 (95% CI, 1.01–1.08)] and triacylglycerol [per twofold increase, RR 2.19 (1.49–3.22)]; and IGT: glucose measures and known hypertension [RR 1.46 (1.11–1.93)]. Weight reduction and decreased triacylglycerol were inversely associated with development of diabetes in IFG individuals [per 1 kg/year, RR 0.81 (0.66–0.98) and per 1 mmol l⁻¹ year⁻¹, RR 0.08 (0.01–0.51), respectively], whereas in IGT participants only weight reduction was inversely associated [per 1 kg/year, RR 0.80 (0.67–0.96)]. Conclusions/interpretation Higher levels of glucose measures, larger BMI, known hypertension and hypertriacylglycerolaemia are significant determinants of progression in high-risk screened individuals. Weight loss of 1 kg/year or reduction of hypertriacylglycerolaemia markedly reduced the risk of diabetes.     

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.     

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.     

Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial

Aims/hypothesis  The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. Methods  An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0–40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided (‘patient-led’ use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA_1c level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4–10 mmol/l). Secondary outcomes were difference in HbA_1c, time in hypoglycaemic (≤3.9 mmol/l) and hyperglycaemic (≥10.1 mmol/l) ranges and glycaemic variability. Results  Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA_1c was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI −5.37 to 8.81), hypoglycaemic (0.54; 95% CI −3.48 to 4.55) or hyperglycaemic (−2.18; 95% CI −10.0 to 5.69) range or in glycaemic variability (−0.29; 95% CI −0.34 to 0.28). Within the intervention group, HbA_1c was 0.51% lower in participants with sensor use ≥70% compared with participants with sensor use <70% (95% CI −0.98 to −0.04, p = 0.04). Five episodes of device malfunction occurred. Conclusions/interpretation  Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (≥70%) was not universally acceptable. Trial registration: ACTRN12606000049572 Funding: Funding support and equipment were provided by Medtronic Australasia.