Effect on cardiovascular disease risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes: A systematic review and meta-analysis of trials in primary care.

OBJECTIVE: To examine the effect on cardiovascular (CVD) risk factors of interventions to alter consultations between practitioners and patients with type 2 diabetes. SEARCH STRATEGY: Electronic and manual citation searching to identify relevant randomized controlled trials (RCTs). INCLUSION CRITERIA: RCTs that compared usual care to interventions to alter consultations between practitioners and patients. The population was adults aged over 18 years with type 2 diabetes. Trials were set in primary care. DATA EXTRACTION AND SYNTHESIS: We recorded if explicit theory-based interventions were used, how consultations were measured to determine whether interventions had an effect on these and calculated weighted mean differences for CVD risk factors including glycated haemoglobin (HbA1c ), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C). RESULTS: We included seven RCTs with a total of 2277 patients with type 2 diabetes. A range of measures of the consultation was reported, and underlying theory to explain intervention processes was generally undeveloped and poorly applied. There were no overall effects on CVD risk factors; however, trials were heterogeneous. Subgroup analysis suggested some benefit among studies in which interventions demonstrated impact on consultations; statistically significant reductions in HbA1c levels (weighted mean difference, -0.53%; 95% CI: [-0.77, -0.28]; P<.0001; I2 =46%). CONCLUSIONS: Evidence of effect on CVD risk factors from interventions to alter consultations between practitioners and patients with type 2 diabetes was heterogeneous and inconclusive. This could be explained by variable impact of interventions on consultations. More research is required that includes robust measures of the consultations and better development of theory to elucidate mechanisms.

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

AIMS/HYPOTHESIS: The 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. METHODS: Among 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. RESULTS: Individuals 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/INTERPRETATION: Encouraging 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.

Residential neighbourhood greenspace is associated with reduced risk of incident diabetes in older people: a prospective cohort study.

BACKGROUND: Three cross sectional studies suggest that neighbourhood greenspace may protect against incident diabetes. This study uses data from a longitudinal study with a large sample size to investigate the association between greenspace and the occurrence of incident diabetes over time. METHODS: Data was from the European Prospective Investigation of Cancer Norfolk, UK, cohort, recruitment 1993-2007 (N = 23,865). Neighbourhoods were defined as 800 m circular buffers around participants' home locations, according to their home postcode (zip code). Greenspace exposure was defined as the percentage of the home neighbourhood that was woodland, grassland, arable land, mountain, heath and bog, according to the UK Land Cover Map. Cox proportional hazards regression examined the association between neighbourhood greenspace exposure and incident diabetes. The population attributable fraction assessed the proportion of diabetes cases attributable to exposure to least green neighbourhoods. Mediation analysis assessed if physical activity explained associations between greenspace and diabetes. Interaction analysis was used to test for the modifying effect of rurality and socio-economic status on the relationship between greenspace and diabetes. Models were adjusted for known and hypothesised confounders. RESULTS: The mean age of participants was 59 years at baseline and 55.1% were female. The mean follow-up time was 11.3 years. Individuals living in the greenest neighbourhood quartile had a 19% lower relative hazard of developing diabetes (HR 0.81; 95% CI 0.67, 0.99; p = 0.035; linear trend p = 0.010). The hazard ratio remained similar (HR 0.81; 95% CI 0.65, 0.99; p = 0.042) after adjusting for age, sex, BMI, whether a parent had been diagnosed with diabetes and socio-economic status at the individual and neighbourhood level. A HR of 0.97 was attributed to the pathway through physical activity in a fully adjusted model, although this was non-significant (95% CI 0.88, 1.08; p = 0.603). The incidence of diabetes in the least green neighbourhoods (with 20% greenspace on average) would fall by 10.7% (95% CI -2.1%, 25.2%; p = 0.106) if they were as green as the average neighbourhood observed across the whole cohort (59% greenspace on average). There were no significant interactions between rurality or socio-economic status and level of greenspace. CONCLUSIONS: Greener home neighbourhoods may protect against risk of diabetes in older adults, although this study does not support a mediation role for physical activity. Causal mechanisms underlying the associations require further investigation.

Protocol for Get Moving: a randomised controlled trial to assess the effectiveness of three minimal contact interventions to promote fitness and physical activity in working adults.

BACKGROUND: Web-based interventions for physical activity offer several advantages over face-to-face, print-and telephone-based interventions and are scalable and potentially cost-effective. Recent reviews of web-based interventions in adults show that they have positive but small effects on physical activity but identify a number of limitations including a reliance on self-report measures of outcome. This trial used an objective measure of physical activity to assess the effectiveness of three minimal contact interventions: 1) A multi-component web-based intervention incorporating objective monitoring and graphical feedback of physical activity; 2) A version of the first intervention that consisted only of objective monitoring plus web-based graphical feedback; and 3) Self-monitoring of physical activity using a paper diary. METHODS/DESIGN: Get Moving is an individually randomised controlled trial with allocation of 488 participants to one of three interventions or to a no-intervention control group. Participants are physically inactive working adults aged 18-65 years. They attended a baseline assessment session at which anthropometric, biological and questionnaire measures were taken and they completed a treadmill exercise test. They then wore a combined movement and heart rate monitor for six days and nights before being randomised to one of the four trial arms. The baseline measures were repeated at the follow-up assessment which took place approximately 12 weeks post-randomisation, conducted by staff blind to group allocation. Participants wore the movement and heart rate monitor for six days and nights before this. The co-primary outcomes are: physical activity energy expenditure measured using individually calibrated combined heart-rate and movement data; and cardiorespiratory fitness measured using a sub-maximal treadmill exercise test. DISCUSSION: Strengths of the trial include the use of an objective measure of physical activity, a measure of cardiorespiratory fitness, relatively large sample size and the use of robust methods of randomisation, allocation concealment and blinding to outcome assessment. Get Moving will contribute to the evidence base on minimal contact interventions for increasing physical activity. The interventions could be implemented in other settings such as primary care. TRIAL REGISTRATION: ISRCTN31844443. Registered 18 June 2010.

Association between objectively assessed sedentary time and physical activity with metabolic risk factors among people with recently diagnosed type 2 diabetes.

AIMS/HYPOTHESIS: The aim of our study was to examine the associations between sedentary time (SED-time), time spent in moderate-to-vigorous-intensity physical activity (MVPA), total physical activity energy expenditure (PAEE) and cardiorespiratory fitness with metabolic risk among individuals with recently diagnosed type 2 diabetes. METHODS: Individuals participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION)-Plus trial underwent measurement of SED-time, MVPA and PAEE using a combined activity and movement sensor (n = 394), and evaluation of cardiorespiratory fitness (n = 291) and anthropometric and metabolic status. Clustered metabolic risk was calculated by summing standardised values for waist circumference, triacylglycerol, HbA1c, systolic blood pressure and the inverse of HDL-cholesterol. Multivariate linear regression analyses were used to quantify the associations between SED-time, MVPA, PAEE and cardiorespiratory fitness with individual metabolic risk factors and clustered metabolic risk. RESULTS: Each additional 1 h of SED-time was positively associated with clustered metabolic risk, independently of sleep duration and MVPA (ß = 0.16 [95% CI 0.03, 0.29]). After accounting for SED-time, MVPA was associated with systolic blood pressure (ß = -2.07 [-4.03, -0.11]) but not with clustered metabolic risk (ß = 0.01 [-0.28, 0.30]). PAEE and cardiorespiratory fitness were significantly and independently inversely associated with clustered metabolic risk (ß = -0.03 [-0.05, -0.02] and ß = -0.06 [-0.10, -0.03], respectively). Associations between SED-time and metabolic risk were generally stronger in the low compared with the high fitness group. CONCLUSIONS/INTERPRETATION: PAEE was inversely associated with metabolic risk, whereas SED-time was positively associated with metabolic risk. MVPA was not associated with clustered metabolic risk after accounting for SED-time. Encouraging this high-risk group to decrease SED-time, particularly those with low cardiorespiratory fitness, and increase their overall physical activity may have beneficial effects on disease progression and reduction of cardiovascular risk. TRIAL REGISTRATION: ISRCTN99175498.

Effectiveness of Minimal Contact Interventions: An RCT.

INTRODUCTION: Around 23% of adults worldwide are insufficiently active. Wearable devices paired with virtual coaching software could increase physical activity. The effectiveness of 3 minimal contact interventions (paper-based physical activity diaries, activity trackers, and activity trackers coupled with virtual coaching) in increasing physical activity energy expenditure and cardiorespiratory fitness were compared over 12 weeks among inactive adults. METHODS: This was an open label, parallel-group RCT. Inactive adults (aged ≥18 years, N=488) were randomized to no intervention (Control; n=121), paper-based diary (Diary; n=124), activity tracker (Activity Band; n=122), or activity tracker plus virtual coaching (Activity Band PLUS; n=121) groups. Coprimary outcomes included 12-week changes in physical activity energy expenditure and fitness (May 2012-January 2014). Analyses were conducted in 2019-2020. RESULTS: There were no differences between groups overall (physical activity energy expenditure: p=0.114, fitness: p=0.417). However, there was a greater increase in physical activity energy expenditure (4.21 kJ/kg/day, 95% CI=0.42, 8.00) in the Activity Band PLUS group than in the Diary group. There were also greater decreases in BMI and body fat percentage in the Activity Band PLUS group than in the Control group (BMI= -0.24 kg/m2, 95% CI= -0.45, -0.03; body fat= -0.48%, 95% CI= -0.88, -0.08) and in theActivity Band PLUS group than in the Diary group (BMI= -0.30 kg/m2, 95% CI= -0.50, -0.09; body fat= -0.57%, 95% CI= -0.97, -0.17). CONCLUSIONS: Coupling activity trackers with virtual coaching may facilitate increases in physical activity energy expenditure compared with a traditional paper‒based physical activity diary intervention and improve some secondary outcomes compared with a traditional paper‒based physical activity diary intervention or no intervention. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov ISRCTN31844443.

Prevalence and Incidence Trends for Diagnosed Prescription Opioid Use Disorders in the United Kingdom.

INTRODUCTION: The prevalence of prescription opioid use disorders in the US has increased markedly in parallel with increases in opioid prescribing. Whilst an increase in opioid prescribing has also occurred in the UK, it remains unknown if there have been concurrent increases in opioid use disorders. The aim of this study was to examine national trends in the prevalence and incidence of physician-diagnosed opioid use disorders in the UK. METHODS: In a retrospective electronic health care database analysis using data from the UK Clinical Practice Research Datalink (CPRD), we identified persons receiving a first opioid prescription between January 1, 2008 and December 31, 2012. Persons with an opioid use disorder were identified by Read codes assigned by patients' physicians within 6 months following an opioid prescription. We calculated prevalence and incidence rates by dividing the analysis population by the total number of patients exposed (prevalence) or the total patient-years of exposure (incidence) using the 'exact' Clopper-Pearson Binomial method. RESULTS: Our analysis included 714,699 person-years of prescription opioid exposure. The 5-year period prevalence of opioid use disorders was 4.61 (95% CI 4.28-4.96) per 10,000 individuals, or 0.05%. The incidence rate of opioid use disorders was of 6.51 (95% CI 5.93-7.13) patients per 10,000 patient-years exposed. When examined by study year, there was no clear suggestion of a changing trend over time. When stratified by opioid drug, trends in the incidence rate during the study were either stable (i.e., codeine and tramadol), increasing (i.e., morphine) or decreasing (i.e., dihydrocodeine). CONCLUSIONS: Our study demonstrates that despite the marked increase in overall opioid prescribing in the UK in the past decade, there has not been an increase in the incidence of physician-diagnosed opioid use disorders.

Patient-centred care, health behaviours and cardiovascular risk factor levels in people with recently diagnosed type 2 diabetes: 5-year follow-up of the ADDITION-Plus trial cohort.

OBJECTIVE: To examine the association between the experience of patient-centred care (PCC), health behaviours and cardiovascular disease (CVD) risk factor levels among people with type 2 diabetes. DESIGN: Population-based prospective cohort study. SETTING: 34 general practices in East Anglia, UK, delivering organised diabetes care. PARTICIPANTS: 478 patients recently diagnosed with type 2 diabetes aged between 40 and 69 years enrolled in the ADDITION-Plus trial. MAIN OUTCOME MEASURES: Self-reported and objectively measured health behaviours (diet, physical activity, smoking status), CVD risk factor levels (blood pressure, lipid levels, glycated haemoglobin, body mass index, waist circumference) and modelled 10-year CVD risk. RESULTS: Better experiences of PCC early in the course of living with diabetes were not associated with meaningful differences in self-reported physical activity levels including total activity energy expenditure (ß-coefficient: 0.080 MET h/day (95% CI 0.017 to 0.143; p=0.01)), moderate-to-vigorous physical activity (ß-coefficient: 5.328 min/day (95% CI 0.796 to 9.859; p=0.01)) and reduced sedentary time (ß-coefficient: -1.633 min/day (95% CI -2.897 to -0.368; p=0.01)). PCC was not associated with clinically meaningful differences in levels of high-density lipoprotein cholesterol (ß-coefficient: 0.002 mmol/L (95% CI 0.001 to 0.004; p=0.03)), systolic blood pressure (ß-coefficient: -0.561 mm Hg (95% CI -0.653 to -0.468; p=0.01)) or diastolic blood pressure (ß-coefficient: -0.565 mm Hg (95% CI -0.654 to -0.476; p=0.01)). Over an extended follow-up of 5 years, we observed no clear evidence that PCC was associated with self-reported, clinical or biochemical outcomes, except for waist circumference (ß-coefficient: 0.085 cm (95% CI 0.015 to 0.155; p=0.02)). CONCLUSIONS: We found little evidence that experience of PCC early in the course of diabetes was associated with clinically important changes in health-related behaviours or CVD risk factors. TRIAL REGISTRATION NUMBER: ISRCTN99175498; Post-results.

Objective Sedentary Time, Moderate-to-Vigorous Physical Activity, and Physical Capability in a British Cohort.

PURPOSE: Sedentariness has been proposed as an independent risk factor for poor health. However, few studies have considered associations of sedentary time (ST) with physical functional health independent of time spent in moderate-to-vigorous physical activity (MVPA). METHODS: Community-based men and women (n = 8623, 48-92 yr old) in the European Prospective Investigation of Cancer-Norfolk study attended a health examination for objective measurement of physical capability, including grip strength (Smedley dynamometer (kg)), usual walking speed (UWS (cm·s(-1))), and timed chair stand speed (TCSS (stands per minute)). Of these, 4051 participants wore an accelerometer (GT1M ActiGraph) for 7 d to estimate time spent in MVPA (MVPA, ≥1952 counts per minute) and ST (ST, <100 counts per minute). Relations between physical capability outcomes and both MVPA and ST were explored using linear regression. The mutual independence of associations was also tested, and ST-MVPA interactions were explored using fractional polynomial models to account for nonlinear associations. RESULTS: Men in the highest compared with those in the lowest sex-specific quartile of MVPA were stronger (1.84 kg; 95% confidence interval (CI), 0.79-2.89), had faster UWS (11.7 cm·s(-1); 95% CI, 8.4-15.1) and faster TCSS (2.35 stands per minute; 95% CI, 1.11-3.59) after multivariable adjustment. Similarly, women in the highest quartile of MVPA were stronger (2.47 kg; 95% CI, 1.79-3.14) and had faster UWS (15.5 cm·s(-1); 95% CI, 12.4-18.6) and faster TCSS (3.27 stands per minute; 95% CI, 2.19-4.25). Associations persisted after further adjustment for ST. Associations between higher ST and lower physical capability were also observed, but these were attenuated after accounting for MVPA. Furthermore, no MVPA-ST interactions were observed (Pinteractions > 0.05). CONCLUSIONS: More time spent in MVPA was associated with higher physical capability, but there were no independent ST associations.

Physical activity, sedentary time and physical capability in early old age: British birth cohort study.

PURPOSE: To investigate the associations of time spent sedentary, in moderate-to-vigorous-intensity physical activity (MVPA) and physical activity energy expenditure (PAEE) with physical capability measures at age 60-64 years. METHODS: Time spent sedentary and in MVPA and, PAEE were assessed using individually calibrated combined heart rate and movement sensing among 1727 participants from the MRC National Survey of Health and Development in England, Scotland and Wales as part of a detailed clinical assessment undertaken in 2006-2010. Multivariable linear regression models were used to examine the cross-sectional associations between standardised measures of each of these behavioural variables with grip strength, chair rise and timed up-&-go (TUG) speed and standing balance time. RESULTS: Greater time spent in MVPA was associated with higher levels of physical capability; adjusted mean differences in each capability measure per 1 standard deviation increase in MVPA time were: grip strength (0.477 kg, 95% confidence interval (CI): 0.015 to 0.939), chair rise speed (0.429 stands/min, 95% CI: 0.093 to 0.764), standing balance time (0.028 s, 95% CI: 0.003 to 0.053) and TUG speed (0.019 m/s, 95% CI: 0.011 to 0.026). In contrast, time spent sedentary was associated with lower grip strength (-0.540 kg, 95% CI: -1.013 to -0.066) and TUG speed (-0.011 m/s, 95% CI: -0.019 to -0.004). Associations for PAEE were similar to those for MVPA. CONCLUSION: Higher levels of MVPA and overall physical activity (PAEE) are associated with greater levels of physical capability whereas time spent sedentary is associated with lower levels of capability. Future intervention studies in older adults should focus on both the promotion of physical activity and reduction in time spent sedentary.

Sleep duration and cardiometabolic risk factors among individuals with type 2 diabetes.

OBJECTIVE: To examine the association between sleep duration and cardiometabolic risk factors among individuals with recently diagnosed type 2 diabetes (n = 391). METHODS: Sleep duration was derived using a combination of questionnaire and objective heart rate and movement sensing in the UK ADDITION-Plus study (2002-2007). Adjusted means were estimated for individual cardiometabolic risk factors and clustered cardiometabolic risk (CCMR) by five categories of sleep duration. RESULTS: We observed a J-shaped association between sleep duration and CCMR - individuals sleeping 7 to <8 h had a significantly better CCMR profile than those sleeping ≥9 h. Independent of physical activity and sedentary time, individuals sleeping 7 to <8 h had lower triacylglycerol (0.62 mmol/l (0.29, 1.06)) and higher high-density lipoprotein (HDL)-cholesterol levels (0.23 mmol/l (0.16, 0.30)) compared with those sleeping ≥9 h, and a lower waist circumference (7.87 cm (6.06, 9.68)) and body mass index (BMI) (3.47 kg/m(2) (2.69, 4.25)) than those sleeping <6 h. Although sleeping 7 to <8 h was associated with lower levels of systolic and diastolic blood pressure, HbA1c, total cholesterol, and low-density lipoprotein (LDL)-cholesterol, these associations were not statistically significant. CONCLUSIONS: Sleep duration has a J-shaped association with CCMR in individuals with diabetes, independent of potential confounding. Health promotion interventions might highlight the importance of adequate sleep in this high-risk population.

Healthy behavior change and cardiovascular outcomes in newly diagnosed type 2 diabetic patients: a cohort analysis of the ADDITION-Cambridge study.

OBJECTIVE: To examine whether improvements in health behaviors are associated with reduced risk of cardiovascular disease (CVD) in individuals with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS: Population-based prospective cohort study of 867 newly diagnosed diabetic patients aged between 40 and 69 years from the treatment phase of the ADDITION-Cambridge study. Because the results for all analyses were similar by trial arm, data were pooled, and results were presented for the whole cohort. Participants were identified via population-based stepwise screening between 2002 and 2006, and underwent assessment of physical activity (European Prospective Investigation into Cancer-Norfolk Physical Activity Questionnaire), diet (plasma vitamin C and self-report), and alcohol consumption (self-report) at baseline and 1 year. A composite primary CVD outcome was examined, comprised of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and revascularization. RESULTS: After a median (interquartile range) follow-up period of 5.0 years (1.3 years), 6% of the cohort experienced a CVD event (12.2 per 1,000 person-years; 95% CI 9.3-15.9). CVD risk was inversely related to the number of positive health behaviors changed in the year after diabetes diagnosis. The relative risk for primary CVD event in individuals who did not change any health behavior compared with those who adopted three/four healthy behaviors was 4.17 (95% CI 1.02-17.09), adjusting for age, sex, study group, social class, occupation, and prescription of cardioprotective medication (P for trend = 0.005). CONCLUSIONS: CVD risk was inversely associated with the number of healthy behavior changes adopted in the year after the diagnosis of diabetes. Interventions that promote early achievement of these goals in patients with newly diagnosed diabetes could help reduce the burden of diabetes-related morbidity and mortality.

Serum carbon and nitrogen stable isotopes as potential biomarkers of dietary intake and their relation with incident type 2 diabetes: the EPIC-Norfolk study.

BACKGROUND: Stable-isotope ratios of carbon (¹³C/¹²C, expressed as δ¹³C) and nitrogen (¹5N/¹4N, or δ¹5N) have been proposed as potential nutritional biomarkers to distinguish between meat, fish, and plant-based foods. OBJECTIVE: The objective was to investigate dietary correlates of δ¹³C and δ¹5N and examine the association of these biomarkers with incident type 2 diabetes in a prospective study. DESIGN: Serum δ¹³C and δ¹5N (‰) were measured by using isotope ratio mass spectrometry in a case-cohort study (n = 476 diabetes cases; n = 718 subcohort) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population-based cohort. We examined dietary (food-frequency questionnaire) correlates of δ¹³C and δ¹5N in the subcohort. HRs and 95% CIs were estimated by using Prentice-weighted Cox regression. RESULTS: Mean (±SD) δ¹³C and δ¹5N were -22.8 ± 0.4‰ and 10.2 ± 0.4‰, respectively, and δ¹³C (r = 0.22) and δ¹5N (r = 0.20) were positively correlated (P < 0.001) with fish protein intake. Animal protein was not correlated with δ¹³C but was significantly correlated with δ¹5N (dairy protein: r = 0.11; meat protein: r = 0.09; terrestrial animal protein: r = 0.12, P ≤ 0.013). δ¹³C was inversely associated with diabetes in adjusted analyses (HR per tertile: 0.74; 95% CI: 0.65, 0.83; P-trend < 0.001], whereas δ¹5N was positively associated (HR: 1.23; 95% CI: 1.09, 1.38; P-trend = 0.001). CONCLUSIONS: The isotope ratios δ¹³C and δ¹5N may both serve as potential biomarkers of fish protein intake, whereas only δ¹5N may reflect broader animal-source protein intake in a European population. The inverse association of δ¹³C but a positive association of δ¹5N with incident diabetes should be interpreted in the light of knowledge of dietary intake and may assist in identifying dietary components that are associated with health risks and benefits.