Intensive Treatment In People Research Articles

Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark.

To investigate the longitudinal development of neurofilament light chain (NfL) levels in type 2 diabetes with and without diabetic polyneuropathy (+/-DPN) and to explore the predictive potential of NfL as a biomarker for DPN. We performed retrospective longitudinal case-control analysis of data from 178 participants of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Denmark (ADDITION-Denmark) cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-ups were analyzed for serum NfL (s-NfL) using single-molecule array, and the results were compared with established reference material to obtain NfL z-scores. DPN was diagnosed according to Toronto criteria for confirmed DPN at the 10-year follow-up. s-NfL increased over time in +DPN (N = 39) and -DPN participants (N = 139) at levels above normal age-induced s-NfL increase. Longitudinal s-NfL change was greater in +DPN than in -DPN participants (17.4% [95% CI 4.3; 32.2] or 0.31 SD [95% CI 0.03; 0.60] higher s-NfL or NfL z-score increase in +DPN compared with -DPN). s-NfL at the 5-year follow-up was positively associated with nerve conduction studies at the 10-year follow-up (P = 0.02 to <0.001), but not with DPN risk. Areas under the curve (AUCs) for s-NfL were not inferior to AUCs for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated with higher DPN risk (odds ratio 1.36 [95% CI 1.08; 1.71] per 1 ng/L/year). Our findings suggest that preceding s-NfL trajectories differ slightly between those with and without DPN and imply a possible biomarker value of s-NfL trajectories in DPN.

Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus.

In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

Association of general health and lifestyle factors with the salivary microbiota - Lessons learned from the ADDITION-PRO cohort.

Previous research indicates that the salivary microbiota may be a biomarker of oral as well as systemic disease. However, clarifying the potential bias from general health status and lifestyle-associated factors is a prerequisite of using the salivary microbiota for screening. ADDDITION-PRO is a nationwide Danish cohort, nested within the Danish arm of the Anglo-Danish-Dutch Study of Intensive treatment in People with Screen-Detected Diabetes in Primary Care. Saliva samples from n=746 individuals from the ADDITION-PRO cohort were characterized using 16s rRNA sequencing. Alpha- and beta diversity as well as relative abundance of genera was examined in relation to general health and lifestyle-associated variables. Permutational multivariate analysis of variance (PERMANOVA) was performed on individual variables and all variables together. Classification models were created using sparse partial-least squares discriminant analysis (sPLSDA) for variables that showed statistically significant differences based on PERMANOVA analysis (p < 0.05). Glycemic status, hemoglobin-A1c (HbA1c) level, sex, smoking and weekly alcohol intake were found to be significantly associated with salivary microbial composition (individual variables PERMANOVA, p < 0.05). Collectively, these variables were associated with approximately 5.8% of the observed differences in the composition of the salivary microbiota. Smoking status was associated with 3.3% of observed difference, and smoking could be detected with good accuracy based on salivary microbial composition (AUC 0.95, correct classification rate 79.6%). Glycemic status, HbA1c level, sex, smoking and weekly alcohol intake were significantly associated with the composition of the salivary microbiota. Despite smoking only being associated with 3.3% of the difference in overall salivary microbial composition, it was possible to create a model for detection of smoking status with a high correct classification rate. However, the lack of information on the oral health status of participants serves as a limitation in the present study. Further studies in other cohorts are needed to validate the external validity of these findings.

Modification of cardiovascular disease risk by health behaviour change following type 2 diabetes diagnosis.

Among adults with type 2 diabetes (T2D), unhealthy behaviours are associated with increased risk of cardiovascular disease (CVD) events. To date, little research has considered whether healthy changes in behaviours following T2D diagnosis reduce CVD risk. A cohort of 867 adults with screen-detected T2D, participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial, were followed for 10years for incidence of CVD events. Diet, alcohol consumption, moderate/vigorous physical activity and smoking were assessed by questionnaire at the time of T2D screening and 1year later. We estimated associations between health behaviours and CVD using Cox regression. We assessed modification of the associations by behaviour change in the year following T2D diagnosis. Smoking [hazard ratio (HR): 1.73 (95% CI: 1.04, 2.87)] and high fat intake [HR: 1.70 (95% CI: 1.02, 2.85)] were associated with a higher hazard of CVD, while high plasma vitamin C [HR: 0.44 (95% CI: 0.22, 0.87)] and high fibre intake [HR: 0.60 (95% CI: 0.36, 0.99)] were associated with a lower hazard of CVD. Reduction in fat intake following T2D diagnosis modified associations with CVD. In particular, among those with the highest fat intake, decreasing intake attenuated the association with CVD [HR: 0.75 (95% CI: 0.36, 1.56)]. Following T2D diagnosis, decreasing fat intake was associated with lower long-term CVD risk. This evidence may raise concerns about low-carbohydrate, high-fat diets to achieve weight loss following T2D diagnosis. Further research considering the sources of fat is needed to inform dietary recommendations. This trial is registered as ISRCTN86769081. Retrospectively registered on 15 December 2006.

Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies.

Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death. We linked data from two Danish type 2 diabetes cohorts, the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) and the Danish Centre for Strategic Research in Type 2 Diabetes (DD2), to national health care registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios (IRRs) of CVD and all-cause mortality comparing MNSIq scores ≥4 with scores <4. Analyses were adjusted for a range of established CVD risk factors. In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores <4, MNSIq scores ≥4 were associated with higher incidence rate of CVD, with IRRs of 1.79 (95% CI 1.38-2.31) in ADDITION-Denmark, 1.57 (CI 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥4 did not associate with mortality; combined mortality rate ratio was 1.11 (CI 0.83-1.48). The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes with a high incidence rate of subsequent CVD. MNSIq scores ≥4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors.

Population-based screen-detected type 2 diabetes mellitus is associated with less need for insulin therapy after 10 years

IntroductionWith increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that early detection (eg, by...

Association Between Primary Care Practitioner Empathy and Risk of Cardiovascular Events and All-Cause Mortality Among Patients With Type 2 Diabetes: A Population-Based Prospective Cohort Study.

To examine the association between primary care practitioner (physician and nurse) empathy and incidence of cardiovascular disease (CVD) events and all-cause mortality among patients with type 2 diabetes. This was a population-based prospective cohort study of 49 general practices in East Anglia (United Kingdom). The study population included 867 individuals with screen-detected type 2 diabetes who were followed up for an average of 10 years until December 31, 2014 in the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen Detected Diabetes in Primary Care (ADDITION)-Cambridge trial. Twelve months after diagnosis, patients assessed practitioner empathy and their experiences of diabetes care during the preceding year using the consultation and relational empathy (CARE) measure questionnaire. CARE scores were grouped into tertiles. The main outcome measures were first recorded CVD event (a composite of myocardial infarction, revascularization, nontraumatic amputation, stroke, and fatal CVD event) and all-cause mortality, obtained from electronic searches of the general practitioner record, national registries, and hospital records. Hazard ratios (HRs) were estimated using Cox models adjusted for relevant confounders. The ADDITION-Cambridge trial is registered as ISRCTN86769081. Of the 628 participants with a completed CARE score, 120 (19%) experienced a CVD event, and 132 (21%) died during follow up. In the multivariable model, compared with the lowest tertile, higher empathy scores were associated with a lower risk of CVD events (although this did not achieve statistical significance) and a lower risk of all-cause mortality (HRs for the middle and highest tertiles, respectively: 0.49; 95% CI, 0.27-0.88, P = .01 and 0.60; 95% CI, 0.35-1.04, P = .05). Positive patient experiences of practitioner empathy in the year after diagnosis of type 2 diabetes may be associated with beneficial long-term clinical outcomes. Further work is needed to understand which aspects of patient perceptions of empathy might influence health outcomes and how to incorporate this understanding into the education and training of practitioners.

Moderate weight change following diabetes diagnosis and 10\xa0year incidence of cardiovascular disease and mortality

Aims/hypothesisAdults with type 2 diabetes are at high risk of developing cardiovascular disease (CVD). Evidence of the impact of weight loss on incidence of CVD events among adults with diabetes is sparse and conflicting. We assessed weight change in the year following diabetes diagnosis and estimated associations with 10 year incidence of CVD events and all-cause mortality.MethodsIn a cohort analysis among 725 adults with screen-detected diabetes enrolled in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)–Cambridge trial, we estimated HRs for weight change in the year following diabetes diagnosis and 10 year incidence of CVD (n = 99) and all-cause mortality (n = 95) using Cox proportional hazards regression. We used linear regression to estimate associations between weight loss and CVD risk factors. Models were adjusted for age, sex, baseline BMI, smoking, occupational socioeconomic status, cardio-protective medication use and treatment group.ResultsLoss of ≥5% body weight in the year following diabetes diagnosis was associated with improvements in HbA1c and blood lipids and a lower hazard of CVD at 10 years compared with maintaining weight (HR 0.52 [95% CI 0.32, 0.86]). The associations between weight gain vs weight maintenance and CVD (HR 0.41 [95% CI 0.15, 1.11]) and mortality (HR 1.63 [95% CI 0.83, 3.19]) were less clear.Conclusions/interpretationAmong adults with screen-detected diabetes, loss of ≥5% body weight during the year after diagnosis was associated with a lower hazard of CVD events compared with maintaining weight. These results support the hypothesis that moderate weight loss may yield substantial long-term CVD reduction, and may be an achievable target outside of specialist-led behavioural treatment programmes.

Risk Factors for the Presence and Progression of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes: ADDITION-Denmark.

To examine the course of cardiovascular autonomic neuropathy (CAN) and related cardiometabolic risk factors in patients with type 2 diabetes. CAN and cardiometabolic risk factors were assessed in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) at 6-year (n = 777) and 13-year (n = 443) follow-up examinations. Cardiovascular autonomic reflex tests (CARTs)-that is, lying to standing, deep breathing, and the Valsalva maneuver-and 2-min resting heart rate variability (HRV) indices were obtained as the main measures of CAN. Risk factors related to CAN status, as determined by CARTs, were studied by using multivariate logistic regressions. The effects of risk factors on continuous CARTs and HRV indices, and their changes over time, were estimated in linear mixed models. A progressive yet heterogeneous course of CAN occurred between the 6- and 13-year follow-ups. Higher HbA1c, weight, BMI, and triglycerides were associated with prevalent CAN. No significant effect of risk factors on CARTs was found when they were analyzed as continuous variables. CART indices decreased over time, and a trend of decreasing HRV indices was seen. Higher HbA1c and BMI were associated with lower HRV index values, but these differences diminished over time. These data confirm that hyperglycemia, obesity, and hypertriglyceridemia are negatively related to indices of CAN, although these effects diminish over time. The observed heterogeneous course of CAN may challenge the present clinical approach of categorically classifying CARTs to diagnose CAN and the notion of CAN being irreversible.

Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark

To study cardiometabolic risk-factor trajectories (in terms of levels and changes over time) preceding diabetic polyneuropathy (DPN) 13 years after a screen-detected diagnosis of type 2 diabetes. We clinically diagnosed DPN in a nested case-control study of 452 people in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION). By linear regression models, we estimated preceding risk-factor trajectories during 13 years. Risk of DPN was estimated by multivariate logistic regression models of each individual's risk-factor trajectory intercept and slope adjusting for sex, age, diabetes duration, height, and trial randomization group. Higher baseline levels of HbA1c (odds ratio [OR] 1.76 [95% CI 1.37; 2.27] and OR 1.68 [95% CI 1.33; 2.12] per 1% and 10 mmol/mol, respectively) and steeper increases in HbA1c over time (OR 1.66 [95% CI 1.21; 2.28] and OR 1.59 [95% CI 1.19; 2.12] per 1% and 10 mmol/mol increase during 10 years, respectively) were associated with DPN. Higher baseline levels of weight, waist circumference, and BMI were associated with DPN (OR 1.20 [95% CI 1.10; 1.31] per 5 kg, OR 1.27 [95% CI 1.13; 1.43] per 5 cm, and OR 1.24 [95% CI 1.12; 1.38] per 2 kg/m2, respectively). Both higher levels and slopes of HbA1c trajectories were associated with DPN after 13 years. Our findings indicate that the rate of HbA1c increase affects the development of DPN over and above the effect of the HbA1c level. Furthermore, this study supports obesity as a risk factor for DPN.

How good are GPs at adhering to a pragmatic trial protocol in primary care? Results from the ADDITION-Cambridge cluster-randomised pragmatic trial

ObjectiveTo assess the fidelity of general practitioners’ (GPs) adherence to a long-term pragmatic trial protocol.DesignRetrospective analyses of electronic primary care records of participants in the pragmatic cluster-randomised ADDITION (Anglo-Danish-Dutch Study...

Effect of screening for type 2 diabetes on healthcare costs: a register-based study among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009

Aims/hypothesisTrials have not demonstrated benefits to the population of screening for type 2 diabetes. However, there may be cost savings for those found to have diabetes. We therefore aimed to compare healthcare costs among individuals with incident type 2 diabetes in a screened group with those in an unscreened group.MethodsIn this register-based, non-randomised controlled trial, eligible individuals were men and women aged 40–69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk-score questionnaire. Individuals with a moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other practices in Denmark constituted the retrospectively constructed no-screening (control) group. In this post hoc analysis, we identified individuals from the screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 (n = 139,075). Using national registry data, we quantified the cost of healthcare services in these two groups between 2001 and 2012. From a healthcare sector perspective, we estimated the potential healthcare cost savings for individuals with diabetes that were attributable to the screening programme.ResultsIn the screening group, 27,177 of 153,107 individuals (18% of those sent a risk-score questionnaire) attended for screening, 1533 of whom were diagnosed with diabetes. Between 2001 and 2009, 13,992 people were newly diagnosed with diabetes in the screening group (including those diagnosed by screening) and 125,083 in the no-screening group. Healthcare costs were significantly lower in the screening group compared with the no-screening group (difference in mean total annual healthcare costs −€889 per individual with incident diabetes; 95% CI −€1196, −€581). The screening programme was associated with a cost saving per person with incident diabetes over a 5-year period of €2688 (95% CI €1421, €3995).Conclusions/interpretationHealthcare costs were lower among individuals with incident type 2 diabetes in the screened group compared with the unscreened group. The relatively modest cost of screening per person discovered to have developed diabetes was offset within 2 years by savings in the healthcare system.

Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults

Aims/hypothesisHealth check programmes for chronic disease have been introduced in a number of countries. However, there are few trials assessing the benefits and harms of these screening programmes at the population level. In a post hoc analysis, we evaluated the effect of population-based screening for type 2 diabetes and cardiovascular risk factors on mortality rates and cardiovascular events.MethodsThis register-based, non-randomised, controlled trial included men and women aged 40–69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk score questionnaire. Individuals at moderate-to-high risk were invited to visit their GP for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other general practices in Denmark constituted the retrospectively constructed no-screening (control) group. Outcomes were mortality rate and cardiovascular events (cardiovascular disease death, non-fatal ischaemic heart disease or stroke). The analysis was performed according to the intention-to-screen principle.ResultsAmong the screening group, 27,177 (18%) individuals attended for assessment of diabetes status and cardiovascular risk. Of these, 1,533 were diagnosed with diabetes. During a median follow-up of 9.5 years, there were 11,826 deaths in the screening group and 141,719 in the no-screening group (HR 0.99 [95% CI 0.96, 1.02], p = 0.66). There were 17,941 cardiovascular events in the screening group and 208,476 in the no-screening group (HR 0.99 [0.96, 1.02], p = 0.49).Conclusions/interpretationA population-based stepwise screening programme for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in rate of mortality or cardiovascular events between 2001 and 2012.

Effect of screening for type 2 diabetes on risk of cardiovascular disease and mortality: a controlled trial among 139,075 individuals diagnosed with diabetes in Denmark between 2001 and 2009

Aims/hypothesisThere is continuing debate about the net benefits of population screening for type 2 diabetes. We compared the risk of cardiovascular disease (CVD) and mortality among incident cases of type 2 diabetes in a screened group with those in an unscreened group.MethodsIn this register-based non-randomised controlled trial, eligible individuals were all men and women aged 40–69 years without known diabetes, registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes-risk-score questionnaire. Individuals at moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other practices in Denmark constituted the retrospectively constructed no-screening (control) group. In this post hoc analysis, we identified individuals from the screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 (n = 139,075), and compared risk of CVD and mortality in these groups between 2001 and 2012.ResultsIn the screening group, 27,177/153,107 (18%) individuals attended for screening, of whom 1533 were diagnosed with diabetes. Between 2001 and 2009, 13,992 people were newly diagnosed with diabetes in the screening group (including those diagnosed by screening) and 125,083 in the no-screening group. Between 2001 and 2012, the risks of CVD and mortality were lower among individuals with diabetes in the screening group compared with individuals with diabetes in the no-screening (control) group (CVD HR 0.84, 95% CI 0.80, 0.89; mortality HR 0.79, 95% CI 0.74, 0.84).Conclusions/interpretationA single round of diabetes screening and cardiovascular risk assessment in middle-aged Danish adults in general practice was associated with a significant reduction in risk of all-cause mortality and CVD events in those diagnosed with diabetes.

Incremental Costs and Cost Effectiveness of Intensive Treatment in Individuals with Type 2 Diabetes Detected by Screening in the ADDITION-UK Trial: An Update with Empirical Trial–Based Cost Data

BackgroundThere is uncertainty about the cost effectiveness of early intensive treatment versus routine care in individuals with type 2 diabetes detected by screening. ObjectivesTo derive a trial-informed estimate of the incremental costs of intensive treatment as delivered in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Europe (ADDITION) trial and to revisit the long-term cost-effectiveness analysis from the perspective of the UK National Health Service. MethodsWe analyzed the electronic primary care records of a subsample of the ADDITION-Cambridge trial cohort (n = 173). Unit costs of used primary care services were taken from the published literature. Incremental annual costs of intensive treatment versus routine care in years 1 to 5 after diagnosis were calculated using multilevel generalized linear models. We revisited the long-term cost-utility analyses for the ADDITION-UK trial cohort and reported results for ADDITION-Cambridge using the UK Prospective Diabetes Study Outcomes Model and the trial-informed cost estimates according to a previously developed evaluation framework. ResultsIncremental annual costs of intensive treatment over years 1 to 5 averaged £29.10 (standard error = £33.00) for consultations with general practitioners and nurses and £54.60 (standard error = £28.50) for metabolic and cardioprotective medication. For ADDITION-UK, over the 10-, 20-, and 30-year time horizon, adjusted incremental quality-adjusted life-years (QALYs) were 0.014, 0.043, and 0.048, and adjusted incremental costs were £1,021, £1,217, and £1,311, resulting in incremental cost-effectiveness ratios of £71,232/QALY, £28,444/QALY, and £27,549/QALY, respectively. Respective incremental cost-effectiveness ratios for ADDITION-Cambridge were slightly higher. ConclusionsThe incremental costs of intensive treatment as delivered in the ADDITION-Cambridge trial were lower than expected. Given UK willingness-to-pay thresholds in patients with screen-detected diabetes, intensive treatment is of borderline cost effectiveness over a time horizon of 20 years and more.

Associations Between Anthropometric Measurements and Cardiometabolic Risk Factors in White European and South Asian Adults in the United Kingdom

ObjectiveTo investigate the association of 4 anthropometric measurements with cardiometabolic risk factors in a UK biethnic sample of South Asians (SAs) and white Europeans (WEs). Patients and MethodsBaseline data were collected from adults of WE and SA origin participating in the Leicester arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION-Leicester) study between August 2004 and December 2007. Overall, 6268 WE and SA adults had measures of body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio assessed between June 18, 2004, and December 4, 2007. Hypertension, dyslipidemia, and dysglycemia were established from venous blood samples using standard definitions. Crude and adjusted (covariates used were age, sex, ethnicity, smoking, and alcohol consumption) odds ratios were calculated using multivariate logistic regression. Receiver operating characteristic curves and the area under the curve were used to calculate optimal cut points for the whole cohort and for both ethnic groups. ResultsIncreases in all anthropometric measurements resulted in a higher odds ratio for each of the risk factors in both the crude and adjusted models (P<.001). The adjusted odds ratios for dyslipidemia, hypertension, and dysglygemia ranged from 1.30 to 1.35, from 1.36 to 1.52, and from 1.62 to 1.75 (P<.001 for all), respectively, in WEs. The adjusted odds ratio for dyslipidemia, hypertension, and dysglygemia ranged from 1.50 to 1.65 (P<.01), from 1.40 to 1.60 (P<.01), and from 1.96 to 2.11 (P<.001 for all), respectively, in SAs. The areas under the receiver operating characteristic curves for all the anthropometric measurements had low accuracy (P<.70) for the whole cohort and when stratified by ethnicity and sex. ConclusionThere is insufficient evidence to recommend replacing body mass index with another anthropometric measurement for the ethnically diverse population in the United Kingdom. Trial Registrationclinicaltrials.gov Identifier: NCT00318032.

Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort.

Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus. This prospective study included 1014 individuals at high risk of type 2 diabetes mellitus participating in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment In PeOple with ScreeN-detected Diabetes in Primary Care (ADDITION-Europe trial) baseline examination in 2001-2006 and follow-up examination (ADDITION-Progression [ADDITION-PRO]) in 2009-2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2h glucose, fasting insulin, HOMA-IR and HOMA-β were assessed using a mixed-effects model. A doubling of sCD163 concentration was positively associated with changes in fasting insulin (β = 1.078 per year, 95% CI 0.454, 1.702) and HOMA-β (β = 1.313 per year, 95% CI 0.537, 2.089), and a doubling of CRP concentration was positively associated with HbA 1c (β = 0.004 per year, 95% CI 0.001, 0.007) and fasting insulin (β = 0.267 per year, 95% CI 0.029, 0.504) after adjustment for age and sex. A doubling of adiponectin was inversely associated with changes in fasting glucose (β = −0.017 per year, 95% CI −0.028, −0.005), 2 h glucose (β = −0.063 per year, 95% CI −0.107, −0.019), fasting insulin (β = −1.558 per year, 95% CI −2.020, −1.096), HOMA-IR (β = −0.040 per year, 95% CI −0.062, −0.019) and HOMA-β (β = −1.009 per year, 95% CI −1.589, −0.429) after adjustment for age and sex. The associations were robust to adjustment for baseline waist circumference and smoking. Adjustment for CRP did not change the associations for sCD163 or adiponectin. Our findings indicate that mechanisms related to inflammation, including macrophage activation and adipocyte metabolism, may play a role in changes in glucose homeostasis in individuals at high risk of type 2 diabetes mellitus.

A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.

Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain. To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes. Pragmatic, multicentre, cluster-randomised, parallel-group trial. Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK. Individuals aged 40-69 years with screen-detected diabetes. Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol. The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (©) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)]. We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient. Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted. ClinicalTrials.gov NCT00237549. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

Prevalence of Sexual Concerns and Sexual Dysfunction among Sexually Active and Inactive Men and Women with Screen-Detected Type 2 Diabetes.

IntroductionType 2 diabetes negatively impacts sexual health. Only limited information is available regarding sexual health among sexually inactive patients with type 2 diabetes.AimThe aim of this study was to examine the prevalence of sexual concerns among sexually active and sexually inactive men and women with type 2 diabetes and of sexual dysfunction (SD) among sexually active.MethodsData from the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen‐Detected Diabetes in Primary Care‐Denmark study was used. A total of 1,170 Danish patients with screen‐detected type 2 diabetes attended a health examination, including assessment of sexual concerns using self‐report questionnaires and of SD using the Female Sexual Function Index (FSFI‐R) and the International Index of Erectile Function (IIEF‐5) instruments.Main Outcome MeasuresThe main outcome measures used regarding sexual concerns are the following: prevalence of failure to fill sexual needs, of experiencing sexual distress, finding it important to have a good sexual life, and additionally, prevalence of SD.ResultsData regarding sexual activity status during the last 12 months were available among 583 men and 377 women. Seventeen percent of men and 47% of women reported to be sexually inactive, among whom 57% of men and 42% of women reported failure to fill sexual needs; 31% of men and 10% of women that it was important to have a good sexual life, and 32% of men and 11% of women that they were experiencing sexual distress. Around half of men and women were excluded from the SD analysis, mainly because of reporting lack of sexual intercourse during the last 4 weeks. Among those included, 54% of men and 12% of women were found to have SD.ConclusionsSexual inactivity is highly prevalent among middle‐aged and older men and women with early type 2 diabetes and these patients often have sexual concerns. The high exclusion rates when assessing SD using the FSFI‐R and IIEF‐5 instruments makes it difficult to draw conclusions regarding the prevalence. Sexual health should be broadly assessed in both sexually active and sexually inactive people with type 2 diabetes. Bjerggaard M, Charles M, Kristensen E, Lauritzen T, Sandbæk A, and Giraldi A. Prevalence of sexual concerns and sexual dysfunction among sexually active and inactive men and women with screen‐detected type 2 diabetes. Sex Med 2015;3:302–310.

Prospective associations between sedentary time, physical activity, fitness and cardiometabolic risk factors in people with type 2 diabetes

Aims/hypothesisThe aim of this study was to examine the prospective associations between objectively measured physical activity energy expenditure (PAEE), sedentary time, moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF) and cardiometabolic risk factors over 4 years in individuals with recently diagnosed diabetes.MethodsAmong 308 adults (mean age 61.0 [SD 7.2] years; 34% female) with type 2 diabetes from the Anglo–Danish–Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Plus study, we measured physical activity using individually calibrated combined heart rate and movement sensing. Multivariable linear regression models were constructed to examine the associations between baseline PAEE, sedentary time, MVPA, CRF and cardiometabolic risk factors and clustered cardiometabolic risk (CCMR) at follow-up, and change in these exposures and change in CCMR and its components over 4 years of follow-up.ResultsIndividuals who increased their PAEE between baseline and follow-up had a greater reduction in waist circumference (−2.84 cm, 95% CI −4.84, −0.85) and CCMR (−0.17, 95% CI −0.29, −0.04) compared with those who decreased their PAEE. Compared with individuals who decreased their sedentary time, those who increased their sedentary time had a greater increase in waist circumference (3.20 cm, 95% CI 0.84, 5.56). Increases in MVPA were associated with reductions in systolic blood pressure (−6.30 mmHg, 95% CI −11.58, −1.03), while increases in CRF were associated with reductions in CCMR (−0.23, 95% CI −0.40,−0.05) and waist circumference (−3.79 cm, 95% CI −6.62, −0.96). Baseline measures were generally not predictive of cardiometabolic risk at follow-up.Conclusions/interpretationEncouraging people with recently diagnosed diabetes to increase their physical activity and decrease their sedentary time may have beneficial effects on their waist circumference, blood pressure and CCMR.