Screen-detected Type Research Articles

Investigating the altered expression of miR-486-5p and miR-novel-chr1_40444 in dysglycemia in a South African population.

This study aims to investigate miR-486-5p and miR-novel-chr1_40444 expressions in dysglycemic individuals. Validating RNA-sequencing findings in a larger sample via reverse transcription qPCR (RT-qPCR), we aim to address global diagnostic and screening limitations, using an African cohort as an example. This cross-sectional study involved 1,271 individuals [normoglycemic (n = 974), prediabetic (n = 206), screen-detected type 2 diabetes (n = 91)] from the ongoing Vascular and Metabolic Health (VMH) study in Cape Town, South Africa. Whole blood miRNA expression was assessed using TaqMan-based RT-qPCR, with data normalized to an endogenous control (miR-16-5p). Significant underexpression was observed in prediabetes vs normoglycemia for miR-486-5p (P = 0.038), whilst both miRNAs demonstrated significant upregulation in screen-detected type 2 diabetes vs normoglycemia (miR-486-5p, P = 0.009; miR-novel-chr1_40444, P < 0.001), and screen-detected type 2 diabetes in comparison with prediabetes (miR-486-5p, P < 0.001; miR-novel-chr1_40444, P < 0.001). Multivariable regression analyses revealed pronounced interrelations between miR-novel-chr1_40444 and screen-detected type 2 diabetes in unadjusted and adjusted models (Model 1: P < 0.001, Model 2: P < 0.001, Model 3: P = 0.030). Moreover, receiver operating characteristic (ROC) curves revealed significantly enhanced diagnostic capabilities for screen-detected type 2 diabetes vs either normoglycemia (AUC = 0.971, P < 0.001), non-diabetes (AUC = 0.959, P < 0.001), or prediabetes (AUC = 0.902, P < 0.001) when combining the miRNAs with 2 h postprandial glucose. This study demonstrated the enhanced power of incorporating miRNAs with traditional markers in distinguishing screen-detected type 2 diabetes, warranting further investigations on their unique role in the development of type 2 diabetes.

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.

Serum neurofilament light chain – A potential biomarker for polyneuropathy in type 2 diabetes?

AimsTo investigate the relationship between neurofilament light chain (NfL) and the presence and severity of diabetic polyneuropathy (DPN). MethodsWe performed cross-sectional analysis of data from 178 participants of the ADDITION-Denmark cohort of people with screen-detected type 2 diabetes and 32 healthy controls. Biobank serum samples were analyzed for NfL using single-molecule array. DPN was defined by Toronto criteria for confirmed DPN. Original and axonal nerve conduction study (NCS) sum z-scores were used as indicators of the severity of DPN and peripheral nerve damage. Results39 (21.9%) participants had DPN. Serum NfL (s-NfL) was significantly higher in participants with DPN (18.8 ng/L [IQR 14.4; 27.9]) than in participants without DPN (15.4 ng/L [IQR 11.7; 20.1]). There were no unadjusted s-NfL differences between controls (17.6 ng/L [IQR 12.7; 19.8]) and participants with or without DPN. Higher original and axonal NCS sum z-scores were associated with 10% higher s-NfL (10.2 and 12.1% [95% CI’s 4.0; 16.8 and 6.6; 17.9] per 1 SD). The AUC of s-NfL for DPN was 0.63 (95% CI 0.52; 0.73). ConclusionsS-NfL is unlikely to be a reliable biomarker for the presence of DPN. S-NfL is however associated tothe severity of the nerve damage underlying DPN.

Long-term effects of intensive multifactorial treatment on aortic stiffness and central hemodynamics after 13 years with screen-detected type 2 diabetes: the ADDITION-Denmark trial

BackgroundPeripheral and central hemodynamic indices are modifiable by lifestyle and medical intervention. We aimed to determine the long-term effect of intensive multifactorial treatment on peripheral and central hemodynamic indices among people with screen-detected diabetes.MethodsBetween 2001 and 2006, people with screen-detected type 2 diabetes were included in the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION) trial (NCT00237549, ClinicalTrials.gov). In the Danish arm, participants were invited to a clinical examination in 2015–2016, 13 years after inclusion and 8 years after trial-end. Out of 586 eligible participants who attended the clinical examination, 411 had a valid examination of central and peripheral hemodynamic indices (242 received intensive treatment and 169 received routine care). Carotid-femoral pulse wave velocity (cfPWV), central blood pressure and augmentation index were assessed by applanation tonometry. We used mixed-effect models to examine the intervention effect adjusting for cluster randomization and heart rate.ResultsRandomization to intensive treatment during the trial-period was associated with a 0.58 m/s lower cfPWV (95% CI − 1.09 to − 0.06) at follow-up. Adjustment for blood pressure attenuated the association. Differences between intervention groups for central augmentation index were − 1.25% (95% CI: − 3.28 to 0.78), central pulse pressure − 1.74 mmHg (95% CI − 4.79 to 1.31), central systolic blood pressure − 3.06 mmHg (− 7.08 to 0.96), and central diastolic blood pressure − 1.70 mmHg (− 3.74 to 0.34).ConclusionsIntensive multifactorial treatment of screen-detected type 2 diabetes has a sustained positive effect on aortic stiffness measured by cfPWV. Although all estimates pointed in favor of intensive treatment, we observed no clear beneficial effect on other hemodynamic indices.

Effects of the Norfolk diabetes prevention lifestyle intervention (NDPS) on glycaemic control in screen-detected type 2 diabetes: a randomised controlled trial

BackgroundThe purpose of this trial was to test if the Norfolk Diabetes Prevention Study (NDPS) lifestyle intervention, recently shown to reduce the incidence of type 2 diabetes in high-risk groups, also improved glycaemic control in people with newly diagnosed screen-detected type 2 diabetes.MethodsWe screened 12,778 participants at high risk of type 2 diabetes using a fasting plasma glucose and glycosylated haemoglobin (HbA1c). People with screen-detected type 2 diabetes were randomised in a parallel, three-arm, controlled trial with up to 46 months of follow-up, with a control arm (CON), a group-based lifestyle intervention of 6 core and up to 15 maintenance sessions (INT), or the same intervention with additional support from volunteers with type 2 diabetes trained to co-deliver the lifestyle intervention (INT-DPM). The pre-specified primary end point was mean HbA1c compared between groups at 12 months.ResultsWe randomised 432 participants (CON 149; INT 142; INT-DPM 141) with a mean (SD) age of 63.5 (10.0) years, body mass index (BMI) of 32.4 (6.4) kg/m2, and HbA1c of 52.5 (10.2) mmol/mol. The primary outcome of mean HbA1c at 12 months (CON 48.5 (9.1) mmol/mol, INT 46.5 (8.1) mmol/mol, and INT-DPM 45.6 (6.0) mmol/mol) was significantly lower in the INT-DPM arm compared to CON (adjusted difference −2.57 mmol/mol; 95% CI −4.5, −0.6; p = 0.007) but not significantly different between the INT-DPM and INT arms (−0.55 mmol/mol; 95% CI −2.46, 1.35; p = 0.57), or INT vs CON arms (−2.14 mmol/mol; 95% CI −4.33, 0.05; p = 0.07). Subgroup analyses showed the intervention had greater effect in participants < 65 years old (difference in mean HbA1c compared to CON −4.76 mmol/mol; 95% CI −7.75, −1.78 mmol/mol) than in older participants (−0.46 mmol/mol; 95% CI −2.67, 1.75; interaction p = 0.02). This effect was most significant in the INT-DPM arm (−6.01 mmol/mol; 95% CI −9.56, −2.46 age < 65 years old and −0.22 mmol/mol; 95% CI −2.7, 2.25; aged > 65 years old; p = 0.007). The use of oral hypoglycaemic medication was associated with a significantly lower mean HbA1c but only within the INT-DPM arm compared to CON (−7.0 mmol/mol; 95% CI −11.5, −2.5; p = 0.003).ConclusionThe NDPS lifestyle intervention significantly improved glycaemic control after 12 months in people with screen-detected type 2 diabetes when supported by trained peer mentors with type 2 diabetes, particularly those receiving oral hypoglycaemics and those under 65 years old. The effect size was modest, however, and not sustained at 24 months.Trial registrationISRCTN34805606. Retrospectively registered 14.4.16

The association between age at diagnosis of type 2 diabetes and albuminuria in Chinese adults: A nationwide population study.

Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

Association of weight loss and weight loss maintenance following diabetes diagnosis by screening and incidence of cardiovascular disease and all-cause mortality: An observational analysis of the ADDITION-Europe trial.

Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis. Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5-year overall change in weight. Incident CVD events (n = 229) and all-cause mortality (n = 225) from 5 to 10 years follow-up were ascertained from medical records. Gaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all-cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30-7.82)]. Losing ≥5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99-6.21) and 2.72 (1.17-6.30), respectively. Losing ≥10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m2 [4.62 (1.87-11.42)]. Associations with CVD incidence were inconclusive. Both weight loss and weight gain after screen-detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted.

Circulating miR-30a-5p and miR-182-5p in Prediabetes and Screen-Detected Diabetes Mellitus

BackgroundmicroRNAs (miRNAs) have been touted as potential diagnostic and prognostic biomarkers for various diseases. The aim of the present study was to evaluate the diagnostic value of miR-30a-5p and miR-182-5p for prediabetes and screen-detected type 2 diabetes mellitus (T2DM).MethodsThe study included 1270 participants (207 prediabetes, 94 screen-detected diabetes and 969 normotolerant) from the Vascular and Metabolic Health (VMH) study. Whole blood levels of miR-30a-5p and miR-182-5p were quantitated by RT-qPCR. Multivariable logistic regressions were used to relate miRNAs with prediabetes or T2DM and receiver operating characteristic (ROC) curves were used to evaluate the ability of each miRNA to diagnose these conditions.ResultsBoth miRNAs were significantly highly expressed in individuals with prediabetes or T2DM (both ≥3.2-fold, and p<0.001). We also observed significant under-expression in T2DM relative to prediabetes for miR-182-5p (0.49-fold, p=0.001). Age, sex and BMI-adjusted partial correlation coefficient analysis revealed a significant correlation between the two miRNAs across glucose tolerance statuses (r≥0.932, p<0.001). In normotolerant individuals, both miRNAs showed a negative correlation with waist circumference and positive correlation with HDL-cholesterol whilst in T2DM they correlated positively with hip circumference, 2-hour insulin, HDL- and LDL-cholesterol. Multivariable logistic regressions revealed both miRNAs to be consistently and continuously associated with prediabetes or T2DM (OR≥1.18, 95% 95% CI: 1.10–1.28, p<0.001), while only miR-182-5p associated with a reduced prevalence of T2DM relative to prediabetes (OR: 0.89, 95% CI: 0.83–0.96, p=0.003). In ROC analyses, miR-182-5p almost outperformed HbA1c in diagnosing prediabetes; area under the curve 0.74 vs 0.69.ConclusionOur findings demonstrate that miR-30a-5p and miR-182-5p are associated with dysglycaemia and could potentially predict prediabetes, particularly miR-182-5p.

Patient-reported outcomes after 10-year follow-up of intensive, multifactorial treatment in individuals with screen-detected type 2 diabetes: the ADDITION-Europe trial.

To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.

In screen-detected type 2 diabetes, intensive therapy did not differ from usual care for CV events at 10 years.

Source Citation Griffin SJ, Rutten GEHM, Khunti K, et al. Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-u...

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...

Glucose metabolism in midlife predicts participation in working life: a Northern Finland Birth Cohort 1966 study

ObjectiveTo evaluate how clinically measured glucose metabolism categories predict registered participation in working life.MethodsIn the 46-year follow-up of Northern Finland Birth Cohort 1966 (n=5328, 2342 men and 2986 women), we...

Long-term effects of intensive multifactorial therapy in individuals with screen-detected type 2 diabetes in primary care: 10-year follow-up of the ADDITION-Europe cluster-randomised trial

The multicentre, international ADDITION-Europe study investigated the effect of promoting intensive treatment of multiple risk factors among people with screen-detected type 2 diabetes over 5 years. Here we report the results of a post-hoc 10-year follow-up analysis of ADDITION-Europe to establish whether differences in treatment and cardiovascular risk factors have been maintained and to assess effects on cardiovascular outcomes. As previously described, general practices from four centres (Denmark, Cambridge [UK], Leicester [UK], and the Netherlands) were randomly assigned by computer-generated list to provide screening followed by routine care of diabetes, or screening followed by intensive multifactorial treatment. Population-based stepwise screening programmes among people aged 40-69 years (50-69 years in the Netherlands), between April, 2001, and December, 2006, identified patients with type 2 diabetes. Allocation was concealed from patients. Following the 5-year follow-up, no attempts were made to maintain differences in treatment between study groups. In this report, we did a post-hoc analysis of cardiovascular and renal outcomes over 10 years following randomisation, including a 5 years post-intervention follow-up. As in the original trial, the primary endpoint was a composite of first cardiovascular event, including cardiovascular mortality, cardiovascular morbidity (non-fatal myocardial infarction and non-fatal stroke), revascularisation, and non-traumatic amputation, up to Dec 31, 2014. Analyses were based on the intention-to-treat principle. ADDITION-Europe is registered with ClinicalTrials.gov, NCT00237549. 343 general practices were randomly assigned to routine diabetes care (n=176) or intensive multifactorial treatment (n=167). 317 of these general practices (157 in the routine care group, 161 in the intensive treatment group) included eligible patients between April, 2001, and December, 2006. Of the 3233 individuals with screen-detected diabetes, 3057 agreed to participate (1379 in the routine care group, 1678 in the intensive treatment group), but at the 10-year follow-up 14 were lost to follow-up and 12 withdrew, leaving 3031 to enter 10-year follow-up analysis. Mean duration of follow-up was 9·61 years (SD 2·99). Sustained reductions over 10 years following diagnosis were apparent for bodyweight, HbA1c, blood pressure, and cholesterol in both study groups, but between-group differences identified at 1 and 5 years were attenuated at the 10-year follow-up. By 10 years, 443 participants had a first cardiovascular event and 465 died. There was no significant difference between groups in the incidence of the primary composite outcome (16·1 per 1000 person-years in the routine care group vs 14·3 per 1000 person-years in the intensive treatment group; hazard ratio [HR] 0·87, 95% CI 0·73-1·04; p=0·14) or all-cause mortality (15·6 vs 14·3 per 1000 person-years; HR 0·90, 0·76-1·07). Sustained reductions in glycaemia and related cardiovascular risk factors over 10 years among people with screen-detected diabetes managed in primary care are achievable. The differences in prescribed treatment and cardiovascular risk factors in the 5 years following diagnosis were not maintained at 10 years, and the difference in cardiovascular events and mortality remained non-significant. National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Novo Nordisk, Novo Nordisk Foundation, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Wellcome Trust, UK Medical Research Council, UK National Institute for Health Research, UK National Health Service, Merck, Julius Center for Health Sciences and Primary Care, UK Department of Health, and Nuts-OHRA.

Factors associated with attendance at clinical follow-up of a cohort with screen-detected type 2 diabetes: ADDITION-Denmark

AimsTo determine the association between concurrent overall burden of disease, cardiovascular disease, cancer, self-rated health, HbA1c levels, and attendance at clinical follow-up of the Danish arm of the ADDITION-study. MethodsLogistic regression models were used to study factors proposed being associated with attendance in clinical follow-up. We used data from clinical examinations, questionnaires and national registers at a time-point near the follow-up examination. ResultsA total of 1119 participants were eligible for the follow-up conducted a median of 12.8 years (IQR 11.6; 13.4) after type 2 diabetes diagnosis by screening. Concurrent high burden of disease was associated with lower attendance (OR 0.6 (95% CI: 0.4; 0.9) for high-versus no burden of disease). Concurrent cardiovascular disease and cancer showed no statistically significant association with attendance (OR 1.0 (95% CI: 0.7; 1.4)) and (OR 0.8 (95% CI: 0.6; 1.1) for (disease versus no disease). Similarly, self-rated health (OR 0.7 (95% CI: 0.5; 1.0) poor-versus good self-rated health) and HbA1c levels (OR 1.0 (95% CI: 0.9; 1.2 unit=10mmol/mol)) were not statistically significant associated with attendance. ConclusionsThis study showed a lower attendance in clinical follow-up after nearly 13years among individuals with concurrent high burden of disease. No associations were found between concurrent CVD, cancer, self-rated health and Hba1c levels and attendance.

Behaviour change, weight loss and remission of Type 2 diabetes: a community-based prospective cohort study.

AimTo quantify the association between behaviour change and weight loss after diagnosis of Type 2 diabetes, and the likelihood of remission of diabetes at 5‐year follow‐up.MethodWe conducted a prospective cohort study in 867 people with newly diagnosed diabetes aged 40–69 years from the ADDITION‐Cambridge trial. Participants were identified via stepwise screening between 2002 and 2006, and underwent assessment of weight change, physical activity (EPAQ2 questionnaire), diet (plasma vitamin C and self‐report), and alcohol consumption (self‐report) at baseline and 1 year after diagnosis. Remission was examined at 5 years after diabetes diagnosis via HbA1c level. We constructed log binomial regression models to quantify the association between change in behaviour and weight over both the first year after diagnosis and the subsequent 1–5 years, as well as remission at 5‐year follow‐up.ResultsDiabetes remission was achieved in 257 participants (30%) at 5‐year follow‐up. Compared with people who maintained the same weight, those who achieved ≥ 10% weight loss in the first year after diagnosis had a significantly higher likelihood of remission [risk ratio 1.77 (95% CI 1.32 to 2.38; p<0.01)]. In the subsequent 1–5 years, achieving ≥10% weight loss was also associated with remission [risk ratio 2.43 (95% CI 1.78 to 3.31); p<0.01].ConclusionIn a population‐based sample of adults with screen‐detected Type 2 diabetes, weight loss of ≥10% early in the disease trajectory was associated with a doubling of the likelihood of remission at 5 years. This was achieved without intensive lifestyle interventions or extreme calorie restrictions. Greater attention should be paid to enabling people to achieve weight loss following diagnosis of Type 2 diabetes.

Changes in behaviors after diagnosis of type 2 diabetes and 10-year incidence of cardiovascular disease and mortality

BackgroundLarge changes in health behaviors achieved through intensive lifestyle intervention programs improve cardiovascular disease (CVD) risk factors among adults with type 2 diabetes. However, such interventions are not widely available, and there is limited evidence as to whether changes in behaviors affect risk of CVD events.MethodsAmong 852 adults with screen-detected type 2 diabetes in the ADDITION-Cambridge study, we assessed changes in diet, physical activity, and alcohol use in the year following diabetes diagnosis. Participants were recruited from 49 general practices in Eastern England from 2002 to 2006, and were followed through 2014 for incidence of CVD events (n = 116) and all-cause mortality (n = 127). We used Cox proportional hazards regression to estimate hazard ratios (HR) for the associations of changes in behaviors with CVD and all-cause mortality. We estimated associations with CVD risk factors using linear regression. We considered changes in individual behaviors and overall number of healthy changes. Models adjusted for demographic factors, bodyweight, smoking, baseline value of the health behavior, and cardio-protective medication use.ResultsDecreasing alcohol intake by ≥ 2 units/week was associated with lower hazard of CVD vs maintenance [HR: 0.56, 95% CI 0.36, 0.87]. Decreasing daily calorie intake by ≥ 300 kcal was associated with lower hazard of all-cause mortality vs maintenance [HR: 0.56, 95% CI 0.34, 0.92]. Achieving ≥ 2 healthy behavior changes was associated with lower hazard of CVD vs no healthy changes [HR: 0.39, 95% CI 0.18, 0.82].ConclusionsIn the year following diabetes diagnosis, small reductions in alcohol use were associated with lower hazard of CVD and small reductions in calorie intake were associated with lower hazard of all-cause mortality in a population-based sample. Where insufficient resources exist for specialist-led interventions, achievement of moderate behavior change targets is possible outside of treatment programs and may reduce long-term risk of CVD complications.Trial registration This trial is registered as ISRCTN86769081. Retrospectively registered 15 December 2006

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.

Validity of Danish register diagnoses of myocardial infarction and stroke against experts in people with screen-detected diabetes

BackgroundAdministrative patient registers are often used to estimate morbidity in epidemiological studies. The validity of register data is thus important. This study aims to assess the positive predictive value of myocardial infarction and stroke registered in the Danish National Patient Register, and to examine the association between cardiovascular risk factors and cardiovascular disease based on register data or validated diagnoses in a well-defined diabetes population.MethodsWe included 1533 individuals found with screen-detected type 2 diabetes in the ADDITION-Denmark study in 2001–2006. All individuals were followed for cardiovascular outcomes until the end of 2014. Hospital discharge codes for myocardial infarction and stroke were identified in the Danish National Patient Register. Hospital medical records and other clinically relevant information were collected and an independent adjudication committee evaluated all possible events. The positive predictive value for myocardial infarction and stroke were calculated as the proportion of cases recorded in the Danish National Patient Register confirmed by the adjudication committee.ResultsThe positive predictive value was 75% (95% CI: 64;84) for MI and 70% (95% CI: 54;80) for stroke. The association between cardiovascular risk factors and incident cardiovascular disease did not depend on using register-based or verified diagnoses. However, a tendency was seen towards stronger associations when using verified diagnoses.ConclusionsOur results show that studies using only register-based diagnoses are likely to misclassify cardiovascular outcomes. Moreover, the results suggest that the magnitude of associations between cardiovascular risk factors and cardiovascular outcomes may be underestimated when using register-based diagnoses.

Corneal confocal microscopy as a tool for detecting diabetic polyneuropathy in a cohort with screen-detected type 2 diabetes: ADDITION-Denmark

AimsIn this cross-sectional study, we explored the utility of corneal confocal microscopy (CCM) measures for detecting diabetic polyneuropathy (DPN) and their association with clinical variables, in a cohort with type 2 diabetes. MethodsCCM, nerve conduction studies, and assessment of symptoms and clinical deficits of DPN were undertaken in 144 participants with type 2 diabetes and 25 controls. DPN was defined according to the Toronto criteria for confirmed DPN. ResultsCorneal nerve fiber density (CNFD) was lower both in participants with confirmed DPN (n = 27) and in participants without confirmed DPN (n = 117) compared with controls (P = 0.04 and P = 0.01, respectively). No differences were observed for CNFD (P = 0.98) between participants with and without DPN. There were no differences in CNFL and CNBD between groups (P = 0.06 and P = 0.29, respectively). CNFD was associated with age, height, total- and LDL cholesterol. ConclusionsCCM could not distinguish patients with and without neuropathy, but CNFD was lower in patients with type 2 diabetes compared to controls. Age may influence the level of CCM measures.

Risk Factors for Incident Diabetic Polyneuropathy in a Cohort With Screen-Detected Type 2 Diabetes Followed for 13 Years: ADDITION-Denmark.

To study incident diabetic polyneuropathy (DPN) prospectively during the first 13 years after a screening-based diagnosis of type 2 diabetes and determine the associated risk factors for the development of DPN. We assessed DPN longitudinally in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment of Diabetes in Primary Care (ADDITION) using the Michigan Neuropathy Screening Instrument questionnaire (MNSIQ), defining DPN with scores ≥4. Risk factors present at the diabetes diagnosis associated with the risk of incident DPN were estimated using Cox proportional hazard models adjusted for trial randomization group, sex, and age. Of the total cohort of 1,533 people, 1,445 completed the MNSIQ at baseline and 189 (13.1%) had DPN at baseline. The remaining 1,256 without DPN entered this study (median age 60.8 years [interquartile range 55.6; 65.6], 59% of whom were men). The cumulative incidence of DPN was 10% during 13 years of diabetes. Age (hazard ratio [HR] 1.03 [95% CI 1.00; 1.07]) (unit = 1 year), weight (HR 1.09 [95% CI 1.03; 1.16]) (unit = 5 kg), waist circumference (HR 1.14 [95% CI 1.05; 1.24]) (unit = 5 cm), BMI (HR 1.14 [95% CI 1.06; 1.23]) (unit = 2 kg/m2), log2 methylglyoxal (HR 1.45 [95% CI 1.12; 1.89]) (unit = doubling), HDL cholesterol (HR 0.82 [95% CI 0.69; 0.99]) (unit = 0.25 mmol/L), and LDL cholesterol (HR 0.92 [95% CI 0.86; 0.98]) (unit = 0.25 mmol/L) at baseline were significantly associated with the risk of incident DPN. This study provides further epidemiological evidence for obesity as a risk factor for DPN. Moreover, low HDL cholesterol levels and higher levels of methylglyoxal, a marker of dicarbonyl stress, are identified as risk factors for the development of DPN.