HbA<Subscript>1c</Subscript> as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study

Aims/hypothesis  Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA_1c, a measure of glycaemia control, and HF risk. Methods  We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). Results  In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p<0.001). The adjusted HR of HF for each 1% higher HbA_1c was 1.17 (95% CI 1.11–1.25) for the non-CHD group and 1.20 (95% CI 1.04–1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11–1.29). Conclusions/interpretations  These data suggest HbA_1c is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.     

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.     

Effects of HbA1c and weight reduction on blood pressure in patients with type 2 diabetes mellitus treated with exenatide*

Aim: Treatment of patients with type 2 diabetes with glucagon‐like peptide‐1 (GLP‐1) receptor agonist exenatide has showed improvements in glycaemic control coupled with weight loss and lowered blood pressure (BP). We examined the synergy between improved glycaemia and weight loss on BP reduction in patients treated with either exenatide twice daily (BID) or once weekly (QW). Methods: Combining data from three controlled trials, 686 (53% male) patients [baseline mean ± SD: age 55 ± 10 years, weight 95 ± 20 kg, systolic blood pressure (SBP)/diastolic blood pressure (DBP) 130/79 ± 15/9 mmHg, HbA_1c 8.3 ± 1.1%] treated with exenatide QW (n = 541) or BID (n = 145) were observed over 26 weeks. Using weighted means (WMs) of the longitudinal measures of HbA_1c and weight, patients were subdivided into four groups at each visit by glycaemic and weight responses; patients who failed to reduce both HbA_1c and weight below WMs became the reference group (R). The other three groups corresponded to patients with HbA_1c reduction (A), weight reduction (W) and both HbA_1c and weight reduction (AW). Results: Compared with R, patients in AW, A and W groups had a significantly higher likelihood of improving SBP <130 mmHg by 88, 30 and 61%, respectively. Compared with R, patients in AW, A and W had 63, 13 and 45% higher likelihood of improving DBP <80 mmHg. Conclusion: Although the mechanism of BP‐lowering effect of exenatide is not established, it appears that the short‐term dynamics of BP is related to concomitant effects on glycaemia and body weight. These data offer a preliminary insight into the possible cardiometabolic effects of GLP‐1 receptor agonism.     

HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women

Aims/hypothesis Diabetes is known to increase mortality rate, but the degree to which mild hyperglycaemia may be associated with the risk of death is uncertain. We examined the association between HbA_1c measured in stored erythrocytes and mortality rate in women with and without diabetes. Methods We conducted a cohort study of 27,210 women ≥ 45 years old with no history of cardiovascular disease or cancer who participated in the Women’s Health Study, a randomised trial of vitamin E and aspirin. Results Over a median of 10 years of follow-up, 706 women died. Proportional hazards models adjusted for age, smoking, hypertension, blood lipids, exercise, postmenopausal hormone use, multivitamin use and C-reactive protein were used to estimate the relative risk of mortality. Among women without a diagnosis of diabetes and HbA_1c <5.60%, those in the top quintile (HbA_1c 5.19–5.59%) had a relative risk of mortality of 1.28 (95% CI 0.98–1.69, p value for linear trend = 0.14) compared with those with HbA_1c 2.27–4.79%. Women with HbA_1c 5.60–5.99% and no diagnosis of diabetes had a 54% increased risk of mortality (95% CI 1–136%) compared with those with HbA_1c 2.27–4.79%. HbA_1c was significantly associated with mortality across the range 4.50–7.00% (p value for linear trend = 0.02); a test of deviation from linearity was not statistically significant (p = 0.67). Diabetic women had more than twice the mortality risk of non-diabetic women. Conclusions/interpretation This study provides further evidence that chronic mild hyperglycaemia, even in the absence of diagnosed diabetes, is associated with increased risk of mortality. ClinicalTrials.gov ID no.: NCT00000479     

Impact of using a non-diabetes-specific risk calculator on eligibility for statin therapy in type 2 diabetes

Aims/hypothesis  The aim of this study was to investigate the impact of using a non-diabetes-specific cardiovascular disease (CVD) risk calculator to determine eligibility for statin therapy according to current UK National Institute for Health and Clinical Excellence (NICE) guidelines for those patients with type 2 diabetes who are at an increased risk of CVD (10 year risk ≥20%). Methods  The 10 year CVD risks were estimated using the UK Prospective Diabetes Study (UKPDS) Risk Engine and the Framingham equation for 4,025 patients enrolled in the Lipids in Diabetes Study who had established type 2 diabetes and LDL-cholesterol <4.1 mmol/l. Results  The mean (SD) age of the patients was 60.7 (8.6) years, blood pressure 141/83 (17/10) mmHg and the total cholesterol:HDL-cholesterol ratio was 3.9 (1.0). The median (interquartile range) diabetes duration was 6 (3–11) years and the HbA_1c level was 8.0% (7.2–9.0%). The cohort comprised 65% men, 91% whites, 4% Afro-Caribbeans, 5% Asian Indians and 15% current smokers. More patients were classified as being at high risk by the UKPDS Risk Engine (65%) than by the Framingham CVD equation (63%) (p < 0.0001). The Framingham CVD equation classified fewer men and people aged <50 years old as high risk (p < 0.0001). There was no difference between the UKPDS Risk Engine and Framingham classification of women at high risk (p = 0.834). Conclusions/interpretation  These results suggest that the use of Framingham-derived rather than UKPDS Risk Engine-derived CVD risk estimates would deny about one in 25 patients statin therapy when applying current NICE guidelines. Thus, under these guidelines the choice of CVD risk calculator is important when assessing CVD risk in patients with type 2 diabetes, particularly for the identification of the relatively small proportion of younger people who require statin therapy.     

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus

Aims/hypothesis The aim of this study was to assess the efficacy and safety of sitagliptin (MK-0431) as monotherapy in patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA_1c ≥7% and ≤10%) on exercise and diet.Methods A total of 521 patients aged 27–76 years with a mean baseline HbA_1c of 8.1% were randomised in a 1:2:2 ratio to treatment with placebo, sitagliptin 100 mg once daily, or sitagliptin 200 mg once daily, for 18 weeks. The efficacy analysis was based on an all-patients-treated population using an analysis of covariance, excluding data obtained after glycaemic rescue.Results After 18 weeks, HbA_1c was significantly reduced with sitagliptin 100 mg and 200 mg compared with placebo (placebo-subtracted HbA_1c reduction: −0.60% and −0.48%, respectively). Sitagliptin also significantly decreased fasting plasma glucose relative to placebo. Patients with higher baseline HbA_1c (≥9%) experienced greater placebo-subtracted HbA_1c reductions with sitagliptin (−1.20% for 100 mg and −1.04% for 200 mg) than those with HbA_1c <8% (−0.44% and −0.33%, respectively) or ≥8% to 8.9% (−0.61% and −0.39%, respectively). Homeostasis model assessment beta cell function index and fasting proinsulin:insulin ratio, markers of insulin secretion and beta cell function, were significantly improved with sitagliptin. The incidence of hypoglycaemia and gastrointestinal adverse experiences was not significantly different between sitagliptin and placebo. Sitagliptin had a neutral effect on body weight.Conclusions/interpretation Sitagliptin significantly improved glycaemic control and was well tolerated in patients with type 2 diabetes mellitus who had inadequate glycaemic control on exercise and diet. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.For the Sitagliptin Study 023 Group see electronic supplementary material for list of study investigators.     

Diabetes,glycaemic control and mortality risk in patients on haemodialysis: the Japan Dialysis Outcomes and Practice Pattern Study

Aims/hypothesis There are few data on the target level of glycaemic control among patients with diabetes on haemodialysis. We investigated the impact of glycaemic control on mortality risk among diabetic patients on haemodialysis. Subjects and methods Data were analysed from the Dialysis Outcomes Practice Pattern Study (DOPPS) for randomly selected patients on haemodialysis in Japan. The diagnosis of diabetes at baseline and information on clinical events during follow-up were abstracted from the medical records. A Cox proportional hazards model was used to evaluate the association between presence or absence of diabetes, glycaemic control (HbA_1c quintiles) and mortality risk. Results Data from 1,569 patients with and 3,342 patients without diabetes on haemodialysis were analysed. Among patients on haemodialysis, those with diabetes had a higher mortality risk than those without (multivariable hazard ratio 1.37, 95% CI 1.08–1.74). Compared with those in the bottom quintile of HbA_1c level, the multivariable-adjusted hazard ratio for mortality was not increased in the bottom second to fourth quintiles of HbA_1c (HbA_1c 5.0–5.5% to 6.2–7.2%), but was significantly increased to 2.36 (95% CI 1.02–5.47) in the fifth quintile (HbA_1c ≥ 7.3%). The effect of poor glycaemic control did not statistically correlate with baseline mortality risk (p = 0.27). Conclusions/interpretation Among dialysis patients, poorer glycaemic control in those with diabetes was associated with higher mortality risk. This suggests a strong effect of poor glycaemic control above an HbA_1c level of about 7.3% on mortality risk, and that this effect does not appear to be influenced by baseline comorbidity status.     

Changes in glycaemic control and risk of coronary artery disease in type 1 diabetes mellitus: findings from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC)

Aims/hypothesis To complete a comparative analysis of studies that have examined the relationship between glycaemia and cardiovascular disease (CVD)/coronary artery disease (CAD) and perform a prospective analysis of the effect of change in glycosylated Hb level on CAD risk in the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) of childhood-onset type 1 diabetes mellitus (n = 469) over 16 years of two yearly follow-up. Methods Measured values for HbA₁ and HbA_1c from the EDC were converted to the DCCT-standard HbA_1c for change analyses and the change in HbA_1c was calculated (final HbA_1c minus baseline HbA_1c). CAD was defined as EDC-diagnosed angina, myocardial infarction, ischaemia, revascularisation or fatal CAD after medical record review. Results The comparative analysis suggested that glycaemia may have a stronger effect on CAD in patients without, than in those with, albuminuria. In EDC, the change in HbA_1c differed significantly between CAD cases (+0.62 ± 1.8%) and non-cases (−0.09 ± 1.9%) and was an independent predictor of CAD. Conclusions/interpretation Discrepant study results regarding the relationship of glycaemia with CVD/CAD may, in part, be related to the prevalence of renal disease. Measures of HbA_1c change over time show a stronger association with CAD than baseline values.     

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.     

Short-term impact of HbA1c on morbidity and all-cause mortality in people with type 2 diabetes: a Danish population-based observational study

Aims/hypothesis  

In a population-based setting, we investigated whether diabetes-related morbidity and all-cause mortality within 2 years of HbA_1c measurement were associated with that HbA_1c level in individuals with type 2 diabetes. The main objective was to compare outcomes in those with HbA_1c ≥ and <7% (53 mmol/mol).     

Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes

Aims/hypothesis  The relationship between BP and microalbuminuria in young people with type 1 diabetes is not completely clear. As microalbuminuria is preceded by a gradual rise in albumin excretion within the normal range, we hypothesised that ambulatory BP (ABP) may be closely related to albumin excretion and progression to microalbuminuria. Methods  ABP monitoring (ABPM) was performed in 509 young people with type 1 diabetes (age median [range]: 15.7 [10.7–22.6] years) followed with annual assessments of three early morning urinary albumin:creatinine ratios (ACRs) and HbA_1c. Systolic BP (SBP) and diastolic BP (DBP) and the nocturnal fall in BP were analysed in relation to ACR. Results  All ABPM variables were significantly related to baseline log₁₀ ACR (p < 0.001). After the ABPM evaluation, 287 patients were followed for a median of 2.2 (1.0–5.5) years. ABP at baseline was independently related to mean ACR during follow-up. Nineteen initially normoalbuminuric patients developed microalbuminuria after 2.0 (0.2–4.0) years and their baseline daytime DBP was higher than in normoalbuminuric patients (p < 0.001). After adjusting for baseline ACR and HbA_1c, there was an 11% increased risk of microalbuminuria for each 1 mmHg increase in daytime DBP. Forty-eight per cent of patients were non-dippers for SBP and 60% for DBP; however, ACR was not different between dippers and non-dippers and there were no differences in the nocturnal fall in BP between normoalbuminuric and future microalbuminuric patients. Conclusions/interpretation  In this cohort of young people with type 1 diabetes, ABP was significantly related to ACR, and daytime DBP was independently associated with progression to microalbuminuria. Increasing albumin excretion, even in the normal range, may be associated with parallel rises in BP. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Elevated long-term glycated haemoglobin precedes proliferative retinopathy and nephropathy in Type 1 (insulin-dependent) diabetic patients

Summary The importance of glycaemic control for the development of proliferative retinopathy and nephropathy was assessed by monitoring glycated haemoglobin for 5 years or more before the diagnosis of these complications. The study comprised Type 1 (insulin-dependent) diabetic patients diagnosed at an age less than 31 years, and with diabetes duration 25 years or less. They were followed for an average of 7.9 years with 3.3 measurements per year. Of 172 patients screened for retinopathy 60 had no retinopathy, 104 had background retinopathy, and 8 had proliferative retinopathy. The mean HbA_1c (95% confidence intervals) of the groups was 6.4% (6.2–6.7%), 7.3% (7.1–7.5%) and 8.9% (8.1–9.6%), respectively (p<0.0001); the mean duration of diabetes was 12, 18, and 17 years. Of 186 patients 7 had nephropathy (albuminuria>200 mg/l). Mean HbA_1c in patients without nephropathy was 7.0% (6.8–7.1%) and in patients with nephropathy 8.8% (7.8–9.9%,p<0.001). Mean diabetes duration was 16 years in both groups. Multiple logistic regression including mean HbA₁₀, age at onset, duration, sex, and hypertension, was for both proliferative retinopathy and nephropathy significant only for mean HbA_1c. In all cases, proliferative retinopathy and nephropathy were preceded by poor glycaemic control over several years, suggesting that these complications are caused by poor glycaemic control.     

Markers of renal tubular dysfunction measured annually do not predict risk of microalbuminuria in the first few years after diagnosis of Type I diabetes

Aims/hypothesis. Early detection of risk of microalbuminuria could prevent early renal damage. We investigated whether urine retinol binding protein and N-acetyl-glucosaminidase could predict the risk of microalbuminuria in a large cohort of children followed from diagnosis of Type I (insulin-dependent) diabetes mellitus. Methods. Subjects under 16 years of age within a georaphically defined region were recruited at diagnosis of Type I (insulin-dependent) diabetes mellitus. Annually, albumin-, retinol binding protein- and N-acetyl-glucosaminidase- to creatinine ratios were each measured in 3 urine samples. Results. A total of 511 subjects were followed for a median of 6 years (range: 1–14). Microalbuminuria (males: ≥ 3.5 mg/mmol; females: ≥ 4.0 mg/mmol, in 2 out of 3 urines) developed in 78 subjects (36 male). The cumulative probability of microalbuminuria was 40 % after 12 years duration of diabetes. Retinol-binding-proteinuria (men: ≥ 21 μg/mmol; women ≥ 33 μg/mmol) developed in 217 subjects (152 men). The cumulative probability of retinol-binding-proteinuria was 67 % after 12 years duration of diabetes. The cumulative probability of retinol-binding-proteinuria was 40 % before the onset of microalbuminuria and 59 % in subjects who did not subsequently develop microalbuminuria. Retinol-binding-proteinuria developed at a higher rate with increasing HbA_{1 c} than microalbuminuria. N-acetyl-glucosaminidase-uria (males: ≥ 56 μmol-pnp · h^–1· mmol^–1; females: ≥ 46 μmol-pnp · h^–1· mmol^–1) developed in 477 subjects. The cumulative probability of N-acetyl-glucosaminidase-uria was 98 % after 10 years of diabetes duration. The cumulative probability of N-acetyl-glucosaminidase-uria was 73 % in the years before the onset of microalbuminuria and 97 % in subjects without microalbuminuria. The probability of N-acetyl-glucosaminidase-uria was 99 % with an HbA_{1 c} greater than or equal to 14.5 %. Conclusions/interpretation. Raised amounts of urine retinol binding protein and N-acetyl-glycosaminidase are related to HbA_{1 c} and the duration of diabetes. They occur in the majority of subjects and are not early markers for the risk of microalbuminuria. [Diabetologia (2001) 44: 224–229] Received: 25 July 2000 and in revised form: 29 September 2000     

Carotid artery stenosis is related to blood glucose level in an elderly Caucasian population: the Hoorn Study

Summary Cross-sectional associations between carotid artery stenosis (CAS) on the one hand, and parameters of glycaemia and specific insulin levels on the other, were investigated in an age, sex, and glucose tolerance stratified random sample from a 50–74-year-old Caucasian population. Subjects treated with insulin or oral hypoglycaemic agents were classified as having known diabetes mellitus (KDM) (n = 66). Using two oral glucose tolerance tests, and based on the World Health Organisation criteria, all other participants were classified as having a normal (NGT) (n = 287), an impaired (IGT) (n = 169) or a diabetic (NDM) (n = 106) glucose tolerance. CAS was defined haemodynamically using duplex scanning. The crude prevalences of only moderate (16–49 %) CAS were 6.6 %, 7.1 %, 5.7 % and 12.1 % in NGT, IGT, NDM and KDM subjects, respectively. For any severe ( ≥ 50 %) CAS, crude prevalences were 2.8 %, 4.7 %, 9.4 % and 7.6 %. The prevalence of any severe CAS was higher in NDM (p < 0.01) and KDM subjects (p = 0.07) than in NGT subjects. The prevalence of a history of stroke or transient ischaemic attack was 1.7 %, 1.8 %, 2.8 % and 1.5 % in NGT, IGT, NDM and KDM, respectively. In univariate logistic regression analysis, HbA_{1 c}, serum fructosamine, fasting and 2-h post-load glucose were significantly associated with any severe CAS. In multivariate analyses controlling for other risk factors, only HbA_{1 c} and 2-h post-load plasma glucose remained significantly associated (odds ratios: 1.29 per % and 1.09 per mmol/l, respectively) in separate models. No association could be shown between either fasting or 2-h post-load specific insulin and any severe CAS in either univariate or multivariate analyses. In conclusion, HbA_{1 c} and 2-h post-load plasma glucose are independently associated with any severe CAS, whereas specific insulin is not. [Diabetologia (1997) 40: 290–298] Received: 2 February 1996 and in final revised form: 22 November 1996     

Glycaemic control is associated with pre-eclampsia but not with pregnancy-induced hypertension in women with Type I diabetes mellitus

Aims/hypothesis. To investigate the association between glycaemic control and hypertensive pregnancy complications. Methods. From 1988 to 1997, we followed up 683 consecutive non-selected pregnancies in women with Type I (insulin-dependent) diabetes mellitus. Glycaemic control was assessed by assay of HbA_{1 c}. Pre-eclampsia was defined as diastolic blood pressure of 90 mmHg or more at the end of pregnancy after an increase of 15 mmHg or more, combined with proteinuria of 0.3 g or more for 24 h. Pregnancy-induced hypertension was defined similarly but without proteinuria. The same criteria were applied to a control group of 854 non-selected non-diabetic women. Results. Pre-eclampsia developed in 12.8 % of the women with diabetes (excluding those with nephropathy before pregnancy) and in 2.7 % of the control women (odds ratio 5.2; 95 % CI 3.3–8.4). In multiple logistic regression, glycaemic control, nulliparity, retinopathy and duration of diabetes emerged as statistically significant independent predictors of pre-eclampsia. The adjusted odds ratios for pre-eclampsia were 1.6 (95 % CI 1.3–2.0) for each 1 % increment in the HbA_{1 c} value at 4–14 (median 7) weeks of gestation and 0.6 (0.5–0.8) for each 1 % decrement achieved during the first half of pregnancy. Changes in glycaemic control during the second half of pregnancy did not significantly alter the risk of pre-eclampsia. Unlike pre-eclampsia, the risk of pregnancy-induced hypertension was not associated with glycaemic control. Conclusion/interpretation. In women with Type I diabetes, poor glycaemic control is associated with an increased risk of pre-eclampsia but not with a risk of pregnancy-induced hypertension. [Diabetologia (2000) 43: 1534–1539] Received: 23 June 2000 and in revised form: 9 August 2000     

Sex- and BMI-related differences in risk factors for coronary artery disease in patients with type 2 diabetes mellitus

There are contrasting data about the relationship between obesity and macrovascular complications in type 2 diabetes mellitus, and it is not known if risk factors for coronary artery disease are different in normal weight and overweight or obese patients. All 2113 patients with type 2 diabetes mellitus referring to the Diabetic Clinic of Asti were studied. Patients were divided into tertiles of body mass index, according to their sex (BMI < 26.9; ≥ 26.9 and < 31.4; ≥ 31.4 kg/m² for females and BMI < 25.7; ≥ 25.7 and < 28.8; ≥ 28.8 kg/m² for males). Age, BMI, duration of diabetes, blood pressure, HbA_1c total cholesterol, HDL-cholesterol, LDL-cholesterol, and prevalence of insulin treatment and hypertension were higher in females, whereas exercise, alcohol intake, smoking habits and prevalence of dyslipidemia were higher in males. An increase in BMI was associated with an increase in HbA_1c, number of cigarettes/day, blood pressure, triglycerides, C-peptide, prevalence of hypertension and dyslipidemia, and with a decrease in age, duration of diabetes and HDL-cholesterol values. In spite of an apparently worse cardiovascular risk profile, females showed a 50% lower prevalence of CAD than males and the prevalence of CAD was not significantly different in obese compared to other BMI categories. Multiple logistic regression showed that risk factors for CAD were different in males and females and similar in the lower tertiles of BMI, while different in the highest. In obese females, risk factors for CAD were age, reduced HDL-cholesterol and increased HbA_1c levels; in males they were years of smoking and duration of diabetes. These data suggest that in type 2 diabetes, risk factors for CAD are different in the two sexes and in patients with the highest BMI compared to the normal and overweight subjects; blood glucose control and duration of diabetes seem more important than conventional cardiovascular risk factors in obese patients. Received: 11 May 1998 / Accepted in revised form: 30 July 1999     

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.     

Reduced beta cell function in offspring of mothers with young-onset type 2 diabetes

Aims/hypothesis Animal models indicate that even exposure to mild maternal hyperglycaemia in utero is detrimental to the beta cell function of the offspring, but evidence of this in humans is limited. In Europids who are diagnosed with type 2 diabetes before the age of 50 years, the risk of diabetes in the offspring of the diabetic mothers is greatly increased compared with the risk in those born to diabetic fathers. We hypothesised that offspring born to mothers with young-onset type 2 diabetes would have been exposed to mild hyperglycaemia in utero, so we studied the impact of this on their beta cell function.Subjects and methods We measured beta cell function using early insulin response (EIR) after oral glucose; insulin resistance using HOMA; and HbA_1c in 568 non-diabetic adult offspring born to parents with type 2 diabetes (mean age 55.8 years), split according to which parent was affected (in 327 it was the mother) and parental age of diagnosis: <50 years (n=117) or ≥50 years. To reduce the impact of genetic susceptibility, the offspring of affected fathers were used as control subjects.Results Offspring of mothers with young-onset type 2 diabetes had lower EIR (log EIR 4.32, 95% CI [4.14–4.51] vs 4.63 [4.43–4.83] p=0.02) and higher HbA_1c (4.89% [4.79–4.99] vs 4.68% [4.57–4.79] p=0.02) than the offspring of fathers with young-onset type 2 diabetes. Insulin sensitivity was similar in the two groups. There were no differences in EIR or HbA_1c between the offspring born to mothers and fathers who were diagnosed after the age of 50 years.Conclusions/interpretation We conclude that the offspring of mothers with young-onset type 2 diabetes have a reduction in beta cell function. This is consistent with exposure to mild maternal hyperglycaemia programming beta cell function.     

Carotid intima-media thickness and stiffness in relation to type 2 diabetes in Chinese

We investigated carotid intima-media thickness (IMT) and quantitative carotid stiffness (QCS) index in relation to plasma glycosylated hemoglobin A_1C (HbA_1C) and duration of diabetes mellitus in 337 Chinese diabetic patients. In categorical analyses, carotid IMT was 710 μm in subjects with a duration of diabetes mellitus ≤2 years, 760 μm in subjects with a duration of diabetes mellitus more than two years and with plasma HbA_1C < 6.5% (P < 0.05), and 790 μm in subjects with a duration of diabetes mellitus more than two years but with plasma HbA_1C ≥ 6.5% (P < 0.01). The corresponding values for QCS values were 4.5, 4.6 and 5.1 (P < 0.05), respectively. In multiple stepwise regression analyses carotid IMT was significantly associated with the duration of diabetes mellitus, systolic blood pressure and serum concentration of total cholesterol, whereas QCS was significantly associated with age, HbA_1C, systolic and diastolic blood pressure (P < 0.05). In conclusion, carotid IMT as a structural measure of arterial wall is increased in patients with a longer history of diabetes mellitus, whereas QCS as functional index is mainly influenced by the quality of blood glucose control.     

Impaired Vibration Perception Threshold and Long-term Mean HbA1c in Patients with Type 1 Diabetes Mellitus

The impact of long-term glycaemic control, assessed as HbA_1c for 5 years or more, on vibration perception threshold (VPT) in Type 1 (insulin-dependent) diabetes was investigated. Patients with diabetes onset before 31 years of age and with a diabetes duration of <26 years were included. HbA_1c was on average monitored over 9.2 years with 32 measurements. VPT was measured with biothesiometry on the big toes, and compared to non-diabetic reference values standardized for age and height. The biothesiometry readings in the group of 207 patients were elevated. The median z score (z-transformation of ln (VPT)) was 1.4 in the diabetic population. Patients with HbA_1c >7.8 % (highest quartile) had a relative risk of 9.2 (95 % CI 3.5 < RR < 24.0) to be among the 10 % with the highest z score for VPT, compared to patients with HbA_1c < 7.8 %. Stepwise forward linear regression analysis with the log normal of the VPT as dependent variable included age, HbA_1c, height, body mass index, macroalbuminuria, and hypertension (>140/90 mmHg or antihypertensive treatment) as explaining variables. In conclusion, impaired VPT was strongly associated with high long-term HbA_1c.