UK Prospective Diabetes Study Research Articles

Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91).

The 20-year UK Prospective Diabetes Study showed major clinical benefits for people with newly diagnosed type 2 diabetes randomly allocated to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. 10-year post-trial follow-up identified enduring and emerging glycaemic and metformin legacy treatment effects. We aimed to determine whether these effects would wane by extending follow-up for another 14 years. 5102 patients enrolled between 1977 and 1991, of whom 4209 (82·5%) participants were originally randomly allocated to receive either intensive glycaemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycaemic control (primarily diet). At the end of the 20-year interventional trial, 3277 surviving participants entered a 10-year post-trial monitoring period, which ran until Sept 30, 2007. Eligible participants for this study were all surviving participants at the end of the 10-year post-trial monitoring period. An extended follow-up of these participants was done by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. We examined seven prespecified aggregate clinical outcomes (ie, any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by the randomised glycaemic control strategy on an intention-to-treat basis using Kaplan-Meier time-to-event and log-rank analyses. This study is registered with the ISRCTN registry, number ISRCTN75451837. Between Oct 1, 2007, and Sept 30, 2021, 1489 (97·6%) of 1525 participants could be linked to routinely collected NHS administrative data. Their mean age at baseline was 50·2 years (SD 8·0), and 41·3% were female. The mean age of those still alive as of Sept 30, 2021, was 79·9 years (SD 8·0). Individual follow-up from baseline ranged from 0 to 42 years, median 17·5 years (IQR 12·3-26·8). Overall follow-up increased by 21%, from 66 972 to 80 724 person-years. For up to 24 years after trial end, the glycaemic and metformin legacy effects showed no sign of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% (95% CI 2-17; p=0·015) for death from any cause, 17% (6-26; p=0·002) for myocardial infarction, and 26% (14-36; p<0·0001) for microvascular disease. Corresponding absolute risk reductions were 2·7%, 3·3%, and 3·5%, respectively. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% (95% CI 5-32; p=0·010) for death from any cause and 31% (12-46; p=0·003) for myocardial infarction. Corresponding absolute risk reductions were 4·9% and 6·2%, respectively. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy. Early intensive glycaemic control with sulfonylurea or insulin, or with metformin, compared with conventional glycaemic control, appears to confer a near-lifelong reduced risk of death and myocardial infarction. Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible. University of Oxford Nuffield Department of Population Health Pump Priming.

Diabetic Cardiomyopathy-From Basics through Diagnosis to Treatment.

Diabetic cardiomyopathy (DCM) is the development of myocardial dysfunction in patients with diabetes despite the absence of comorbidities such as hypertension, atherosclerosis or valvular defect. The cardiovascular complications of poorly controlled diabetes are very well illustrated by the U.K. Prospective Diabetes Study (UKPDS), which showed a clear association between increasing levels of glycated hemoglobin and the development of heart failure (HF). The incidence of HF in patients with diabetes is projected to increase significantly, which is why its proper diagnosis and treatment is so important. Providing appropriate therapy focusing on antidiabetic and hypolipemic treatment with the consideration of pharmacotherapy for heart failure reduces the risk of CMD and reduces the incidence of cardiovascular complications. Health-promoting changes made by patients such as a low-carbohydrate diet, regular exercise and weight reduction also appear to be important in achieving appropriate outcomes. New hope for the development of therapies for DCM is offered by novel methods using stem cells and miRNA, which, however, require more thorough research to confirm their efficacy.

Comparison of prediction models for cardiovascular and mortality risk in people with type 2 diabetes: An external validation in 23 685 adults included in the UK Biobank.

To validate cardiovascular risk prediction models for individuals with diabetes using the UK Biobank in order to assess their applicability. We externally validated 19 cardiovascular risk scores from seven risk prediction models (Chang et al., Framingham, University of Hong Kong-Singapore [HKU-SG], Li et al, RECODe [risk equations for complications of type 2 diabetes], SCORE [Systematic Coronary Risk Evaluation] and the UK Prospective Diabetes Study Outcomes Model 2 [UKPDS OM2]), identified from systematic reviews, using UK Biobank data from 2006 to 2021 (n = 23 685; participant age 40-71 years, 63.5% male). We evaluated performance by assessing the discrimination and calibration of the models for the endpoints of mortality, cardiovascular mortality, congestive heart failure, myocardial infarction, stroke, and ischaemic heart disease. Over a total of 269 430 person-years of follow-up (median 11.89 years), the models showed low-to-moderate discrimination performance on external validation (concordance indices [c-indices] 0.50-0.71). Most models had low calibration with overprediction of the observed risk. RECODe outperformed other models across four comparable endpoints for discrimination: all-cause mortality (c-index 0.67, 95% confidence interval [CI] 0.65-0.69), congestive heart failure (c-index 0.71, 95% CI 0.69-0.72), myocardial infarction (c-index 0.67, 95% CI 0.65-0.68); and stroke (c-index 0.65, 95% CI 0.62-0.68), and for calibration (except for all-cause mortality). The UKPDS OM2 had comparable performance to RECODe for all-cause mortality (c-index 0.67, 95% CI 0.66-0.69) and cardiovascular mortality (c-index 0.71, 95% CI 0.70-0.73), but worse performance for other outcomes. The models performed better for younger participants and somewhat better for non-White ethnicities. Models developed from non-Western datasets showed worse performance in our UK-based validation set. The RECODe model led to better risk estimations in this predominantly White European population. Further validation is needed in non-Western populations to assess generalizability to other populations.

Impact of lifestyle-based interventions on absolute cardiovascular disease risk: a systematic review and meta-analysis.

The objective of the review was to synthesize the evidence of the effectiveness of lifestyle-based interventions for mitigating absolute cardiovascular disease (CVD) risk. Evidence-based guidelines recommend employing an absolute CVD risk score to inform the selection and intensity of preventive interventions. However, studies employing this strategy have reported mixed results, hence the need for a systematic review of the current evidence. Studies published in English that included a lifestyle-based intervention to mitigate CVD risk were considered. Studies were eligible if they enrolled individuals aged ≥18 years, with no history of CVD at baseline. The primary outcome was change in absolute CVD risk score post-intervention. PubMed, Embase, and CINAHL searches were conducted from database inception to February 2022. The trial registers searched included Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov. Searches for unpublished studies/gray literature were conducted in ProQuest Dissertations and Theses Global, GreyLit Report, and OCLC First Search Proceedings. Two independent reviewers selected the studies and critically appraised them for methodological quality using JBI tools. Data extraction was performed for main outcome variables. Data were presented using separate pooled statistical meta-analysis for quasi-experimental and randomized clinical trials. Random effects models were employed in the analyses. Effect sizes (Cohen's d) were expressed as standardized mean difference at 95% CI. Heterogeneity was assessed via Cochran's Q statistic, and the inconsistency index ( I2 ) was used to describe variability in effect estimates due to heterogeneity rather than sampling error. Twenty-nine studies with a total sample of 5490 adults with no CVD at baseline were included. Fifteen were randomized controlled trials (RCTs; n=3605) and 14 were quasi-experimental studies (n=1885). The studies were conducted in Europe (n=18), the United States (n = 5), Asia (n=3), Mexico (n=1), Canada (n = 1), and Australia (n=1) and included the following lifestyle interventions: diet, physical activity, motivational interviewing, problem-solving, psychological counseling, cardiovascular risk assessment and feedback, health self-management education, and peer support. Six validated absolute CVD risk assessment tools were used to measure the study outcomes, including Framingham, SCORE, Heart Health Risk Assessment Score, Dundee, ASSIGN, and The UK Prospective Diabetes Study risk score. Overall, the methodological rigor of the RCTs and quasi-experimental studies was high. Of the 15 RCTs included in the meta-analysis, lifestyle intervention was favored over control in reducing absolute CVD risk score (Cohen's d = -0.39; P =0.032; Z= -2.14; I2 = 96). Similarly, in the 14 quasi-experimental studies, the absolute CVD risk score after lifestyle intervention was significantly lower compared to baseline (Cohen's d = -0.39; P <0.001; Z= -3.54; I2= 88). RCTs that combined diet and physical activity reported no significant impact on absolute CVD risk score, but those that used either intervention independently reported significant improvement in the absolute CVD risk score. There is evidence supporting the positive impact of lifestyle modification on absolute CVD risk score in adult populations without CVD. Our analysis further suggests that diet and physical activity had significant impact on absolute CVD risk, and a variety of validated screening tools can be used to monitor, evaluate, and communicate changes in absolute risk score after lifestyle modification. A Spanish-language version of the abstract of this review is available [ http://links.lww.com/SRX/A29 ].

Estimation of HbA1c after weight loss using a beta-regression for an economic evaluation of a behavioural weight management programme from the GLoW trial: a methodological study

BackgroundIn economic evaluations, average intervention effects are usually applied to a population. However, this fails to reflect the change in the distribution of HbA1c due to heterogeneous responses to weight loss. We aimed to investigate whether allowing heterogeneous treatment effects using a beta regression better represented the distribution of HbA1c after a weight-loss intervention, and how this affected cost effectiveness. MethodsThe Glucose Lowering through Weight Management (GLoW) trial evaluated the effectiveness of a diabetes education and weight-loss intervention against a standard diabetes education programme. Adults diagnosed with type 2 diabetes within 3 years were recruited from Clinical Commissioning Groups across 159 sites in England from July 20, 2018, to July 22, 2018. Ethics approval (18/ES/0048) and participant informed consent were obtained. Considering the between-treatment-arm difference in HbA1c after 12 months, we compared a mean-effect estimated from a mixed-effects regression to a heterogeneous effect estimated from a beta regression performed on 12-month HbA1c conditional on baseline HbA1c, gender, diabetes duration and intervention group. We used the School of Public Health Research (SPHR) Diabetes Treatment model to apply these treatment effects and evaluate the lifetime NHS costs and quality-adjusted life-years (QALYs), discounted at 3·5%. The microsimulation model estimated diabetes-related health outcomes using the UK Prospective Diabetes Study Outcomes Model 2 risk equations and risk factor trajectory equations, alongside estimating diabetes remission, osteoarthritis, and cancer. We calculated the incremental net benefit (INB) of the intervention using a £20 000 per QALY valuation, by deterministic analysis. The GLoW trial is registered with the ISRCTN Registry, ISRCTN18399564. FindingsThe trial recruited 577 participants (mean age 60 years; 278 [53%] female, 247 [47%] male; 474 [91%] white ethnic background). Applying heterogeneous HbA1c changes better reproduced the skewness in post-intervention HbA1c than applying a mean-effect (Kolmogorov-Smirnov test p=0·02 compared with p=0·0000007). The beta-regression method suggested the intervention was more cost-effective, estimating an INB of £736 per person, compared with £584 when applying the mean-effect. InterpretationAlternative regression specification methods should be considered when evaluating the cost-effectiveness of interventions if the key intervention outcomes are not normally distributed. However, this alternative method requires further investigation to conclude its appropriateness in evaluating cost-effectiveness in different contexts. FundingNational Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (Reference Number RP-PG0216-20010).

The long-term benefits of early intensive therapy in chronic diseases-the legacy effect.

The 'legacy effect' refers to the long-term benefits of intensive therapy that are observed long after the end of clinical trials and trial interventions in chronic diseases such as diabetes, hyperlipidaemia and hypertension. It emphasizes the importance of intensive treatment to prevent long-term complications and mortality. In chronic kidney disease (CKD), the legacy effect is evident in various studies. Long-term nephroprotection in diabetes is well documented in major studies in the early stages of diabetes, such as Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC), UK Prospective Diabetes Study (UKPDS) and Intensified Multifactorial Intervention in Patients with Type 2 Diabetes and Microalbuminuria (STENO-2). These studies highlight the importance of intensive glycaemic control in reducing microvascular complications, including nephropathy, in patients with recently diagnosed type 1 and type 2 diabetes. However, the legacy effect is less evident in patients with long-term, established diabetes. In chronic glomerulonephritis, studies on immunoglobulin A nephropathy showed that early immunosuppressive treatment could have long-term beneficial effects on kidney function in children and adults with CKD. The Frequent Hemodialysis (FH) and the EXerCise Introduction To Enhance Performance in Dialysis (EXCITE) trials indicated that frequent haemodialysis and a personalized walking exercise program could improve clinical outcomes and reduce the long-term risk of death and hospitalization. The legacy effect concept underscores the importance of intensive intervention in chronic diseases, including CKD. This concept has significant implications for public health and warrants in-depth basic and clinical research to be better understood and exploited in clinical practice. However, its limitations should be considered when interpreting long-term observational data collected after a clinical trial. Appropriate study designs are necessary to investigate an unbiased legacy effect.

Paradigm Shift in Management of Hyperglycemia in Patients with Type 2 Diabetes: Glucocentric versus Organ Protection

The first research for managing patients with type 2 diabetes (T2DM) was the UK Prospective Diabetes Study. Subsequent studies have investigated the effects of intensive glucose control on diabetes-associated morbidities and mortality. Study results were intended to change a paradigm to control glycated hemoglobin and prevent diabetes-associated complications, but limited in microvascular diseases rather than diabetes-associated cardio-renal diseases and deaths. Comprehensive management of risk factors other than hyperglycemia (hypertension, dyslipidemia, chronic kidney disease) was emphasized to prevent atherosclerotic cardiovascular (CV) diseases and end-stage renal disease in T2DM. Since 2008, based clinical trials demonstrating CV safety, sodium-glucose transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists have shown beneficial effects on macrovascular and renal complications in patients with T2DM. A recent new paradigm of diabetes care focuses on cardio-renal outcome-oriented care, namely organ-protection, instead of the typical glucocentric view endorsed by major societies across the world including the Korean Diabetes Association and disseminated into clinical practice even in primary care. Although there are many mechanisms by which those glucose-lowering agents protect CV and renal disease in patients with T2DM to be clarified, it is time to redefine diabetes care and to verify the CV effect of anti-diabetic medications beyond glucose lowering.

Health and economic impact of improved glucose, blood pressure and lipid control among German adults with type 2 diabetes: a modelling study.

The aim of this study was to estimate the long-term health and economic consequences of improved risk factor control in German adults with type2 diabetes. We used the UK Prospective Diabetes Study Outcomes Model2 to project the patient-level health outcomes and healthcare costs of people with type2 diabetes in Germany over 5, 10 and 30 years. We parameterised the model using the best available data on population characteristics, healthcare costs and health-related quality of life from German studies. The modelled scenarios were: (1) a permanent reduction of HbA1c by 5.5 mmol/mol (0.5%), of systolic BP (SBP) by 10 mmHg, or of LDL-cholesterol by 0.26 mmol/l in all patients, and (2) achievement of guideline care recommendations for HbA1c (≤53 mmol/mol [7%]), SBP (≤140 mmHg) or LDL-cholesterol (≤2.6 mmol/l) in patients who do not meet the recommendations. We calculated nationwide estimates using age- and sex-specific quality-adjusted life year (QALY) and cost estimates, type2 diabetes prevalence and population size. Over 10 years, a permanent reduction of HbA1c by 5.5 mmol/mol (0.5%), SBP by 10 mmHg or LDL-cholesterol by 0.26 mmol/l led to per-person savings in healthcare expenditures of €121, €238 and €34, and 0.01, 0.02 and 0.015 QALYs gained, respectively. Achieving guideline care recommendations for HbA1c, SBP or LDL-cholesterol could reduce healthcare expenditure by €451, €507 and €327 and gained 0.03, 0.05 and 0.06 additional QALYs in individuals who did not meet the recommendations. Nationally, achieving guideline care recommendations for HbA1c, SBP and LDL-cholesterol could reduce healthcare costs by over €1.9 billion. Sustained improvements in HbA1c, SBP and LDL-cholesterol control among diabetes patients in Germany can lead to substantial health benefits and reduce healthcare expenditures.

External validation of the UK prospective diabetes study (UKPDS) risk engine in patients with type 2 diabetes identified in the national diabetes program in Iran.

Cardiovascular diseases are the first leading cause of mortality in the world. Practical guidelines recommend an accurate estimation of the risk of these events for effective treatment and care. The UK Prospective Diabetes Study (UKPDS) has a risk engine for predicting CHD risk in patients with type 2 diabetes, but in some countries, it has been shown that the risk of CHD is poorly estimated. Hence, we assessed the external validity of the UKPDS risk engine in patients with type 2 diabetes identified in the national diabetes program in Iran. The cohort included 853 patients with type 2diabetes identified between March 21, 2007, and March 20, 2018 in Lorestan province of Iran. Patients were followed for the incidence of CHD. The performance of the models was assessed in terms of discrimination and calibration. Discrimination was examined using the c-statistic and calibration was assessed with the Hosmer-Lemeshow χ2 statistic (HLχ2) test and a calibration plot was depicted to show the predicted risks versus observed ones. During 7464.5 person-years of follow-up 170 first Coronary heart disease occurred. The median follow-up was 8.6 years. The UKPDS risk engine showed moderate discrimination for CHD (c-statistic was 0.72 for 10-year risk) and the calibration of the UKPDS risk engine was poor (HLχ2 = 69.9, p < 0.001) and the UKPDS risk engine78% overestimated the risk of heart disease in patients with type 2 diabetes identified in the national diabetes program in Iran. This study shows that the ability of the UKPDS Risk Engine to discriminate patients who developed CHD events from those who did not; was moderate and the ability of the risk prediction model to accurately predict the absolute risk of CHD (calibration) was poor and it overestimated the CHD risk. To improve the prediction of CHD in patients with type 2 diabetes, this model should be updated in the Iranian diabetic population.

Potential Value of Identifying Type 2 Diabetes Subgroups for Guiding Intensive Treatment: A Comparison of Novel Data-Driven Clustering With Risk-Driven Subgroups.

To estimate the impact on lifetime health and economic outcomes of different methods of stratifying individuals with type 2 diabetes, followed by guideline-based treatment intensification targeting BMI and LDL in addition to HbA1c. We divided 2,935 newly diagnosed individuals from the Hoorn Diabetes Care System (DCS) cohort into five Risk Assessment and Progression of Diabetes (RHAPSODY) data-driven clustering subgroups (based on age, BMI, HbA1c, C-peptide, and HDL) and four risk-driven subgroups by using fixed cutoffs for HbA1c and risk of cardiovascular disease based on guidelines. The UK Prospective Diabetes Study Outcomes Model 2 estimated discounted expected lifetime complication costs and quality-adjusted life-years (QALYs) for each subgroup and across all individuals. Gains from treatment intensification were compared with care as usual as observed in DCS. A sensitivity analysis was conducted based on Ahlqvist subgroups. Under care as usual, prognosis in the RHAPSODY data-driven subgroups ranged from 7.9 to 12.6 QALYs. Prognosis in the risk-driven subgroups ranged from 6.8 to 12.0 QALYs. Compared with homogenous type 2 diabetes, treatment for individuals in the high-risk subgroups could cost 22.0% and 25.3% more and still be cost effective for data-driven and risk-driven subgroups, respectively. Targeting BMI and LDL in addition to HbA1c might deliver up to 10-fold increases in QALYs gained. Risk-driven subgroups better discriminated prognosis. Both stratification methods supported stratified treatment intensification, with the risk-driven subgroups being somewhat better in identifying individuals with the most potential to benefit from intensive treatment. Irrespective of stratification approach, better cholesterol and weight control showed substantial potential for health gains.

Brief history of the UK Prospective Diabetes Study

The UK Prospective Diabetes Study (UKPDS) epidemiological findings confirmed that T2DM is not a “mild” disease, with roughly 50% of patients having clinically evident complica- tions at diagnosis, emphasising the need for its early detection and treatment. Hyperglycaemia was identified as an independent coronary heart disease risk factor, with progressive hyperglycaemia shown to be a major pathophysiological feature of T2DM, driven by declining beta-cell function. People with T2DM and hypertension were found to be at double jeopardy for any diabetes endpoint, and worsening kidney function was shown to increase the risk of death substantially. The UKPDS 20-year trial results were the first to demon- strate that diabetic complications are not inevitable but can be prevented by more intensive blood glucose control and by metformin therapy, changing T2DM management guide- lines worldwide. The UKPDS also showed that tighter blood pressure control prevents diabetic complications; the benefits of the glucose and blood pressure interventions are additive. The UKPDS 10-year post-trial monitoring study was the first to identify the T2DM glycaemic and metformin legacy effects, with early more intensive therapy having continuing benefits long after the trial terminated. The trial demon- strated the need to achieve good glycaemic control as early as possible to minimise the risk of future complications.

Effectiveness of a Health Coaching Intervention for Patient-Family Dyads to Improve Outcomes Among Adults With Diabetes

More than 75% of US adults with diabetes do not meet treatment goals. More effective support from family and friends ("supporters") may improve diabetes management and outcomes. To determine if the Caring Others Increasing Engagement in Patient Aligned Care Teams (CO-IMPACT) intervention improves patient activation, diabetes management, and outcomes compared with standard care. This randomized clinical trial was conducted from November 2016 to August 2019 among participants recruited from 2 Veterans Health Administration primary care sites. All patient participants were adults aged 30 to 70 years with diabetes who had hemoglobin A1c (HbA1c) levels greater than 8% of total hemoglobin (to convert to proportion of total hemoglobin, multiply by 0.01) or systolic blood pressure (SBP) higher than 150 mm Hg; each participating patient had an adult supporter. Of 1119 recruited, 239 patient-supporter dyads were enrolled between November 2016 and May 2018, randomized 1:1 to receive the CO-IMPACT intervention or standard care, and followed up for 12 to 15 months. Investigators and analysts were blinded to group assignment. Patient-supporter dyads received a health coaching session focused on dyadic information sharing and positive support techniques, then 12 months of biweekly automated monitoring telephone calls to prompt dyadic actions to meet diabetes goals, coaching calls to help dyads prepare for primary care visits, and after-visit summaries. Standard-care dyads received general diabetes education materials only. Intent-to-treat analyses were conducted according to baseline dyad assignment. Primary prespecified outcomes were 12-month changes in Patient Activation Measure-13 (PAM-13) and UK Prospective Diabetes Study (UKPDS) 5-year diabetes-specific cardiac event risk scores. Secondary outcomes included 12-month changes in HbA1c levels, SBP, diabetes self-management behaviors, diabetes distress, diabetes management self-efficacy, and satisfaction with health system support for the involvement of family supporters. Changes in outcome measures between baseline and 12 months were analyzed using linear regression models. A total of 239 dyads enrolled; among patient participants, the mean (SD) age was 60 (8.9) years, and 231 (96.7%) were male. The mean (SD) baseline HbA1c level was 8.5% (1.6%) and SBP was 140.2 mm Hg (18.4 mm Hg). A total of 168 patients (70.3%) lived with their enrolled supporter; 229 patients (95.8%) had complete 12-month outcome data. In intention-to-treat analyses vs standard care, CO-IMPACT patients had greater 12-month improvements in PAM-13 scores (intervention effect, 2.60 points; 95% CI, 0.02-5.18 points; P = .048) but nonsignificant differences in UKPDS 5-year cardiac risk (intervention effect, 1.01 points; 95% CI, -0.74 to 2.77 points; P = .26). Patients in the CO-IMPACT arm also had greater 12-month improvements in healthy eating (intervention effect, 0.71 d/wk; 95% CI, 0.20-1.22 d/wk; P = .007), diabetes self-efficacy (intervention effect, 0.40 points; 95% CI, 0.09-0.71 points; P = .01), and satisfaction with health system support for the family supporter participants' involvement (intervention effect, 0.28 points; 95% CI, 0.07-0.49 points; P = .009); however, the 2 arms had similar improvements in HbA1c levels and in other measures. In this randomized clinical trial, the CO-IMPACT intervention successfully engaged patient-supporter dyads and led to improved patient activation and self-efficacy. Physiological outcomes improved similarly in both arms. More intensive direct coaching of supporters, or targeting patients with less preexisting support or fewer diabetes management resources, may have greater impact. ClinicalTrials.gov Identifier: NCT02328326.

Improving diabetic patients’ adherence to treatment and prevention of cardiovascular disease (Office Guidelines Applied to Practice—IMPACT Study)—a cluster randomized controlled effectiveness trial

BackgroundDespite nationwide improvements in cardiovascular disease (CVD) mortality and morbidity, CVD deaths in adults with type 2 diabetes (T2DM) are 2–4 times higher than among those without T2DM. A key contributor to these poor health outcomes is medication non-adherence. Twenty-one to 42% of T2DM patients do not take blood sugar, blood pressure (BP), or statin medications as prescribed. Interventions that foster and reinforce patient-centered communication show promise in improving health outcomes. However, they have not been widely implemented, in part due to a lack of compelling evidence for their effectiveness in real-life primary care settings.MethodsThis pragmatic cluster-randomized trial randomizes 17 teams in 12 Federally Qualified Healthcare Centers (FQHCs) to two experimental groups: intervention (group 1): Office-Gap + Texting vs. control (group 2): Texting only. Office-GAP (Office-Guidelines Applied to Practice) is a patient activation intervention to improve communication and patient-provider partnerships through brief patient and provider training in shared decision-making (SDM) and use of a guideline-based checklist. The texting intervention (Way2Health) is a cell phone messaging service that informs and encourages patients to adhere to goals, adhere to medication use and improve communication. After recruitment, patients in groups 1 and 2 will both attend (1) one scheduled group visit, (90–120 min) conducted by trained research assistants, and (2) follow-up visits with their providers after group visit at 0–1, 3, 6, 9, and 12 months. Data will be collected over 12-month intervention period. Our primary outcome is medication adherence measured using eCAP electronic monitoring and self-report. Secondary outcomes are (a) diabetes-specific 5-year CVD risk as measured with the UK Prospective Diabetes Study (UKPDS) Engine score, (b) provider engagement as measured by the CollaboRATE Shared-Decision Making measure, and (c) patient activation measures (PAM).DiscussionThis study will provide a rigorous pragmatic evaluation of the effectiveness of combined mHealth, and patient activation interventions compared to mHealth alone, targeting patients and healthcare providers in safety net health centers, in improving medication adherence and decreasing CVD risk. Given that 20–50% of adults with chronic illness demonstrate medication non-adherence, increasing adherence is essential to improve CVD outcomes as well as healthcare cost savings.Trial registrationThe ClinicalTrials.gov registration number is NCT04874116.

EE366 Contrasting Three HbA1c Progression Equations Using the IQVIA Core Diabetes Model

Diabetes management guidelines recommend escalating treatment when a certain HbA1c threshold is reached. Thus, predicting in an accurate way the natural progression of HbAc1 and as such treatment duration is of key importance in diabetes models (shorter or longer use of expensive therapies). Recently, the UK Prospective Diabetes Study (UKPDS) investigators published progression equations for several risk factors including HbA1c (UKPDS90). The aim of this study was to assess the duration to treatment escalation applying the different HbA1c progression equations included in the IQVIA Core Diabetes Model v9.5Plus (CDM9.5Plus).

Overcoming therapeutic inertia: ADA perspective

Good outcomes are obtained with early glycemic control, as shown by the UK Prospective Diabetes Study (UKPDS), but the legacy benefits continue ten years after the study ending, and are also present for lipid and blood pressure management. The ADA and EASD consensus report now has, for the first time, evidence-based recommendations: among them, on a blue circle on the top of the flowchart, it is recommended to “avoid clinical inertia”, and “to reassess and modify clinical treatment regularly, every 3-6 months”(1).

Metformin and high-sensitivity cardiac troponin I and T trajectories in type 2 diabetes patients: a post-hoc analysis of a randomized controlled trial

BackgroundMetformin has favorable effects on cardiovascular outcomes in both newly onset and advanced type 2 diabetes, as previously reported findings from the UK Prospective Diabetes Study and the HOME trial have demonstrated. Patients with type 2 diabetes present with chronically elevated circulating cardiac troponin levels, an established predictor of cardiovascular endpoints and prognostic marker of subclinical myocardial injury. It is unknown whether metformin affects cardiac troponin levels. The study aimed to evaluate cardiac troponin I and T trajectories in patients with diabetes treated either with metformin or placebo.MethodsThis study is a post-hoc analysis of a randomized controlled trial (HOME trial) that included 390 patients with advanced type 2 diabetes randomized to 850 mg metformin or placebo up to three times daily concomitant to continued insulin treatment. Cardiac troponin I and T concentrations were measured at baseline and after 4, 17, 30, 43 and 52 months. We evaluated cardiac troponin trajectories by linear mixed-effects modeling, correcting for age, sex, smoking status and history of cardiovascular disease.ResultsThis study enrolled 390 subjects, of which 196 received metformin and 194 received placebo. In the treatment and placebo groups, mean age was 64 and 59 years; with 50% and 58% of subjects of the female sex, respectively. Despite the previously reported reduction of macrovascular disease risk in this cohort by metformin, linear mixed-effects regression modelling did not reveal evidence for an effect on cardiac troponin I and cardiac troponin T levels [− 8.4% (− 18.6, 3.2), p = 0.150, and − 4.6% (− 12, 3.2), p = 0.242, respectively]. A statistically significant time-treatment interaction was found for troponin T [− 1.6% (− 2.9, − 0.2), p = 0.021] but not troponin I concentrations [− 1.5% (− 4.2, 1.2), p = 0.263].ConclusionsIn this post-hoc analysis of a 4.3-year randomized controlled trial, metformin did not exert a clinically relevant effect on cardiac troponin I and cardiac troponin T levels when compared to placebo. Cardioprotective effects of the drug observed in clinical studies are not reflected by a reduction in these biomarkers of subclinical myocardial injury.Trial registration ClinicalTrials.gov identifier NCT00375388.

Metformin: A Narrative Review of Its Potential Benefits for Cardiovascular Disease, Cancer and Dementia.

The biguanide metformin has been used as first-line therapy in type 2 diabetes mellitus (T2DM) treatment for several decades. In addition to its glucose-lowering properties and its prevention of weight gain, the landmark UK Prospective Diabetes Study (UKPDS) demonstrated cardioprotective properties in obese T2DM patients. Coupled with a favorable side effect profile and low cost, metformin has become the cornerstone in the treatment of T2DM worldwide. In addition, metformin is increasingly being investigated for its potential anticancer and neuroprotective properties both in T2DM patients and non-diabetic individuals. In the meantime, new drugs with powerful cardioprotective properties have been introduced and compete with metformin for its place in the treatment of T2DM. In this review we will discuss actual insights in the various working mechanisms of metformin and the evidence for its beneficial effects on (the prevention of) cardiovascular disease, cancer and dementia. In addition to observational evidence, emphasis is placed on randomized trials and recent meta-analyses to obtain an up-to-date overview of the use of metformin in clinical practice.

Cost-effectiveness analysis of dapagliflozin for the treatment of type 2 diabetes mellitus in Spain: results of the DECLARE-TIMI 58 study

BackgroundThe objective of this study was to carry out a cost-effectiveness analysis of dapagliflozin, as an add-on therapy to standard of care (SoC), for the treatment of type 2 diabetes mellitus (T2DM) in Spain, based on the results of the DECLARE-TIMI 58 trial.MethodsA discrete event simulation model (Cardiff T2DM) based on the data observed in the DECLARE-TIMI 58 trial was adapted to the Spanish setting to estimate the costs and health outcomes of treatment with dapagliflozin in patients with T2DM who had or were at risk of atherosclerotic cardiovascular disease. Macrovascular events (hospitalization for heart failure, myocardial infarction, stroke, and unstable angina), end-stage renal disease and cardiovascular and non-cardiovascular mortality were modeled according to the survival equations of the DECLARE-TIMI 58 study. Microvascular events (blindness and ulcers) were estimated based on the risk equations of the UK Prospective Diabetes Study. The analysis was conducted from the Spanish National Health System perspective and the time horizon was 30 years. The results were evaluated in terms of cost per quality-adjusted life year (QALY) gained. Only direct health costs were included, and a 3% discount rate was applied to costs and health outcomes. Univariate and probabilistic sensitivity analyses (PSA) were made to assess the robustness of the results.ResultsIn the main analysis, dapagliflozin was a dominant therapeutic option compared with placebo, with greater effectiveness (0.08 QALYs) and lower associated total costs per patient (€ -2,921). The univariate sensitivity analysis and the PSA confirmed the robustness of the results. The PSA showed the probability that dapagliflozin was a dominant alternative compared with placebo was 84.2% and that it was cost-effective of 92.1%, under a willingness-to-pay of € 20,000/QALY gained. ConclusionsThe analysis of data from the DECLARE-TIMI 58 trial shows that dapagliflozin would be a cost-effective option in Spain for the treatment of adult patients with T2DM, as an add-on therapy to SoC, compared with placebo.

Healthy food prescription incentive programme for adults with type 2 diabetes who are experiencing food insecurity: protocol for a randomised controlled trial, modelling and implementation studies

IntroductionThe high cost of many healthy foods poses a challenge to maintaining optimal blood glucose levels for adults with type 2 diabetes mellitus who are experiencing food insecurity, leading to...

Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings

Aims/hypothesisWe aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes.MethodsScores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation.ResultsWe evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001).Conclusions/interpretationCVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability.Graphical abstract