Hemoglobin A1c,comorbid conditions and all-cause mortality in older patients with diabetes: A retrospective 9-year cohort study

AimsTo examine whether hemoglobin A_1c levels and comorbid conditions are related to all-cause mortality in a cohort of patients with type 1 or 2 diabetes receiving continuous care for 9 years. In patients with comorbid congestive heart failure (CHF), we test for ‘reverse epidemiology,’ or whether greater HbA_1c values are associated with lower risk of mortality.MethodsThe population for this longitudinal cohort study was 8820 Group Health enrollees in the Seattle area with type 1 or 2 diabetes in 1997 and enrolled continuously from 1997 to 2006. Comorbid conditions were hypertension, coronary artery disease, congestive heart failure, depression, and chronic pulmonary disease. Mistimed HbA_1c scores were addressed by multiple imputation, and Cox proportional hazards models estimated associations controlling for other risk factors.ResultsAbout 30% of the enrollees died in 1998–2006. CHF had the strongest association with all-cause mortality. Compared to enrollees with HbA_1c ≥ 7.1% (54 mmol/mol) and <7.5% (58 mmol/mol; 5th decile), enrollees with HbA_1c < 6.4% (46 mmol/mol) had a significantly greater risk of death (HR range: 1.28–2.26). HbA_1c > 7.5% had HR < 1.0 but were not significant. For enrollees with diabetes and CHF at baseline, HbA_1c scores ≥ 8.7% (72 mmol/mol) had a significantly lower risk of death (HR range: 0.64–0.69).ConclusionsIn our patient population, HbA_1c scores < 6.4% have significantly higher all-cause mortality. CHF is a major determinant of all-cause mortality. Adults with comorbid CHF and high HbA_1c scores have lower all-cause mortality.     

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly

Background and aimsGlycosylated hemoglobin (HbA_1c) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA_1c may be associated with an increased risk of death and cardiovascular mortality in older adults.Methods and resultsWe evaluated the association between HbA_1c with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals ≥65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA_1c and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA_1c groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (≤5.6%), tertile 2 (5.61–6.20%) and tertile 3 (≥6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA_1c was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91–1.47] and hazard ratio: 1.31 [95% confidence interval 0.90–1.93], respectively for the highest HbA_1c tertile compared with the lowest).ConclusionThese results suggest that HbA_1c does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.     

Glycated haemoglobin and cardiovascular outcomes in people with Type 2 diabetes: a large prospective cohort study

Aims To investigate the association between long‐term glycaemic control, measured by glycated haemoglobin (HbA_1c), and time to first cardiovascular disease (CVD) event for people with Type 2 diabetes in New Zealand. Methods A prospective cohort study including people with Type 2 diabetes but no previous CVD. The primary outcome measure was time to first recorded fatal or non‐fatal CVD event (ischaemic heart disease, cerebrovascular accident, transient ischaemic attack or peripheral vascular disease) as identified from linked primary care, hospital and mortality records between January 2000 and December 2005. A Cox proportional hazards model was used to examine the association between HbA_1c and time to CVD event, adjusting for age at diagnosis, duration of diabetes, gender, ethnicity, socio‐economic status, smoking, blood pressure (BP), serum total cholesterol : high‐density lipoprotein ratio, body mass index (BMI) and urine albumin : creatinine ratio. Results Participants included 48 444 people with Type 2 diabetes. Fifty‐one per cent (n = 24 721) were women, median age 60 years. Median duration of diabetes was 3 years, median BMI 31 kg/m², median HbA_1c 7.1% and mean BP was 138/81 mmHg. During the study period (median follow‐up 2.4 years), there were 5667 first CVD events (11.7% of cohort). Each 1% increase in HbA_1c was associated with an increase in hazard ratio (HR) for CVD of 1.08 (95% confidence interval 1.06–1.10, P < 0.001), myocardial infarction [HR 1.08 (1.04, 1.11)] and stroke [HR 1.09 (1.04, 1.13)]. Conclusion This study has confirmed in a large prospective cohort that increased HbA_1c is an independent risk factor for cardiovascular disease after controlling for traditional risk factors.     

The joint association of physical activity and glycaemic control in predicting cardiovascular death and all-cause mortality in the US population

Aims/hypothesis  

The aim of this study was to examine the joint association of physical activity and glycaemic control as measured by HbA_1c on all-cause and cardiovascular disease (CVD) mortality risk.     

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.     

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).     

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     

Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study

Aims/hypothesis  

We aimed to examine whether sex differences in fasting plasma glucose (FPG), 2 h post-OGTT plasma glucose (2hPG) and HbA_1c could be explained by differences in body size and/or body composition between men and women in a general non-diabetic Danish population. Moreover, we aimed to study to what degree the newly suggested high-risk HbA_1c criteria overlapped with the current OGTT-based criteria of glucose intolerance.     

Size and shape of the associations of glucose,HbA<Subscript>1c</Subscript>, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study

Aims/hypothesis

Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA_1c, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus.

Methods

The study population included 1349 participants aged 50–75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations.

Results

After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA_1c, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA_1c with incident diabetes were non-linear, rising more steeply at higher values.

Conclusions/interpretation

FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA_1c, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

     

QT<Subscript>c</Subscript> interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

Aims/hypothesis We evaluated the association of QT interval corrected for heart rate (QT_c) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes. Methods We followed 523 diabetic patients (221 with type 1 diabetes, 302 with type 2 diabetes) who were recruited between 1974 and 1977 in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes. Duration of follow-up was 22.6 ± 0.6 years. Causes of death were obtained from death certificates, hospital records, post-mortem reports, and additional information given by treating physicians. Results In subjects with type 1 diabetes QT_c, but not rHR, was associated with an increased risk of: (1) all-cause mortality (hazard ratio [HR] 1.10 per 10 ms increase in QT_c, 95% CI 1.02–1.20, p = 0.011); (2) mortality due to cardiovascular (HR 1.15, 1.02–1.31, p = 0.024); and (3) mortality due to cardiac disease (HR 1.19, 1.03–1.36, p = 0.016). Findings for subjects with type 2 diabetes were different: rHR, but not QT_c was associated with mortality due to: (1) all causes (HR 1.31 per 10 beats per min, 95% CI 1.15–1.50, p < 0.001); (2) cardiovascular disease (HR 1.43, 1.18–1.73, p < 0.001); (3) cardiac disease (HR 1.45, 1.19–1.76, p < 0.001); and (4) ischaemic heart disease (HR 1.52, 1.21–1.90, p < 0.001). Effect modification of QT_c by type 1 and rHR by type 2 diabetes was statistically significant (p < 0.05 for all terms of interaction). Conclusions/interpretation QT_c is associated with long-term mortality in subjects with type 1 diabetes, whereas rHR is related to increased mortality risk in subjects with type 2 diabetes.     

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.     

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.     

Limited benefit of haemoglobin glycation index as risk factor for cardiovascular disease in type 2 diabetes patients

BackgroundThe haemoglobin glycation index (HGI) has been proposed as a marker of interindividual differences in haemoglobin glycosylation. Previous studies have shown a relationship between high HGI and risk of cardiovascular disease (CVD) in patients with diabetes. However, no studies have investigated the role of previous CVD in this association.MethodsThe study cohort comprised patients with type 2 diabetes mellitus (T2DM; n = 1910) included in the Second Manifestations of Arterial Disease (SMART) study. The relationship between either HGI or HbA_1c and a composite of cardiovascular events as the primary outcome, and mortality, cardiovascular mortality, myocardial infarction and stroke as secondary outcomes, was investigated using Cox proportional-hazards models. Similar analyses were performed after stratification according to previous CVD.ResultsA 1-unit higher HGI was associated with a 29% greater risk of a composite of cardiovascular events (HR: 1.29, 95% CI: 1.06–1.57) in patients without previous CVD, whereas no such relationship was seen in patients with previous CVD (HR: 0.96, 95% CI: 0.86–1.08). The direction and magnitude of the hazard ratios (HRs) of HGI and HbA_1c in relation to outcomes were similar. Additional adjustment for HbA_1c in the association between HGI and outcomes lowered the HRs.ConclusionSimilar to HbA_1c, higher HGI is related to higher risk of cardiovascular events in patients with T2DM without CVD. As HbA_1c has proved to be a comparable risk factor, and obtaining and interpreting the HGI is complicated, any additional benefit of applying the HGI in clinical settings is likely to be limited.     

Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study

Aims/hypothesis. The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA_{1 c} in a population-based cohort of 2363 older (50–75 years) subjects, without known diabetes. Methods. Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. Results. During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA_{1 c} values were, even within the non-diabetic range, associated with an increased risk (p for linear trend < 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p < 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p < 0.05). Conclusion/interpretation. High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA_{1 c} values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes. [Diabetologia (1999) 42: 926–931] Received: 18 January 1999 and in revised form: 22 April 1999     

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.     

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)     

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.     

A Body Shape Index is positively associated with all-cause and cardiovascular disease mortality in the Chinese population with normal weight: A prospective cohort study

Background and aimA body shape index (ABSI) is a valuable predictor of mortality in the Western population, but similar evidence in the general Chinese population is limited. This study aims to evaluate the association between the ABSI and all-cause and cardiovascular disease (CVD) mortality in the Chinese population with normal weight.Methods and results9046 participants with normal BMI (18.5–24.9 kg/m²) from the China Hypertension Survey were enrolled. The baseline ABSI was calculated as waist circumference/(BMI^2/3height^1/2). Cox proportional hazards regression was performed to evaluate the association of the ABSI with all-cause and CVD mortality. Over an average follow-up of 5.4 years, 686 all-cause and 215 CVD deaths occurred. A 0.01-unit increment in the ABSI was associated with a 31% greater risk of all-cause mortality (hazard ratio [HR], 1.31; 95% CI: 1.12, 1.48) and CVD mortality (HR, 1.30; 95% CI: 1.08, 1.58). Compared with quartile 1 of the ABSI, the adjusted HRs of all-cause mortality for quartiles 2–4 were, respectively, 1.25 (95% CI: 0.98, 1.59), 1.28 (95% CI: 0.99, 1.67), and 1.54 (95% CI: 1.17, 2.03) (P_trend = 0.004), and those of CVD mortality for quartiles 2–4 were, respectively, 1.28 (95% CI: 0.88, 1.83), 1.42 (95% CI: 0.97, 2.08), and 1.45 (95% CI: 0.98, 2.170) (P_trend = 0.043). The dose–response analysis showed a linear positive association of the ABSI with all-cause (P_nonlinearity = 0.158) and CVD mortality (P_nonlinearity = 0.213).ConclusionThe ABSI was positively associated with all-cause and CVD mortality among the general Chinese population with normal BMI. The data suggest that the ABSI may be an effective tool for central fatness for mortality risk assessment.     

Fresh fruit consumption,physical activity,and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study

Background and aimsWe explored the associations among fruit consumption, physical activity, and their dose–response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients.Methods and resultsWe prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21–94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose–response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64–0.88), CVD mortality (HR 0.69, 0.51–0.94) and stroke mortality (HR 0.57, 0.36–0.89), but not with heart disease mortality (HR 0.93, 0.56–1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37–0.53) for all-cause mortality, 0.46 (0.33–0.64) for CVD mortality, 0.46 (0.29–0.74) for stroke mortality and 0.51 (0.29–0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease.ConclusionsFruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.     

Effect of time of day and fasting duration on measures of glycaemia: analysis from the Whitehall II Study

Aims/hypothesis

We aimed to study diurnal variation in glucose regulation by examining the effects of time of day and fasting duration on fasting plasma glucose (FPG), 2 h post-load plasma glucose (2hPG) and HbA_1c levels.

Methods

We analysed data from 5,978 non-diabetic white men and women from the prospective Whitehall II Study. All studied participants fasted for at least 8 h before a clinical examination, which included an OGTT and anthropometric measurements. We fitted mixed-effects models for FPG, 2hPG and HbA_1c as outcome variables, and time of day and/or fasting duration as explanatory variables. Models were adjusted for age, BMI and study phase.

Results

Time of day and fasting duration were associated inversely with FPG and positively with 2hPG. The mean difference between measures at 08:00 and 15:00 hours in men/women was ?0.46 (95% CI ?0.50, ?0.42) mmol/l/?0.39 (95% CI ?0.46, ?0.31) mmol/l and 1.39 (95% CI 1.25, 1.52) mmol/l/1.19 (95% CI 0.96, 1.42) mmol/l for FPG and 2hPG, respectively. HbA_1c levels were independent of either time. Time of day and fasting duration were independently associated with 2hPG. In contrast, the effect of fasting duration on FPG was markedly attenuated with adjustment for time of day. Ageing, but not obesity, was associated with increased diurnal variation in glucose tolerance.

Conclusions/interpretation

Both time of day and fasting duration should be considered in clinical practice and epidemiological studies, since they have clinically relevant effects on FPG and 2hPG levels. As biochemically expected, HbA_1c levels are independent of time of blood sampling and fasting duration.