Prevalence of diabetes, epidemiological characteristics and vascular complications.

OBJECTIVE: To estimate prevalence of diabetes in outpatient care and to describe its epidemiological characteristics, comorbidities, and related vascular complications. METHODS: Observational cross-sectional study which included all adults affiliated from a private insurance health plan on March 2019, at Hospital Italiano de Buenos Aires, from Argentina. RESULTS: The global prevalence of diabetes resulted in 8.5% with 95% CI 8.3-8.6 (12,832 out of a total of 150,725 affiliates). The age stratum with the highest prevalence was the group between 65 and 80 years old with 15.7% (95% CI 15.3-16.1). People with diabetes had a mean age of 70 years (SD 14), 52% were women, and the most frequently associated cardiovascular risk factors were: dyslipidaemia (88%), arterial hypertension (74%) and obesity (55%). In relation to metabolic control, 60% had at least one glycosylated hemoglobin measured in the last year, 70% of which were less than 7%. Almost 80% have LDL measured at least once in the last 2 years, 55% of them had an LDL value equal to or less than 100 mg/dl. The macrovascular complications present in order of frequency were: acute myocardial infarction (11%), cerebrovascular accident (8%) and peripheral vascular disease (4%); while the microvascular complications were found to be diabetic neuropathy (4%) and retinopathy (2%). 7% had diabetic foot, with less than 1% amputations. CONCLUSION: Diabetes represents a prevalent problem, even in elderly patients. This population continues to present a high cardiovascular risk, with little compliance with therapeutic goals.

OBJETIVO: Estimar la prevalencia de diabetes en atención ambulatoria y describir sus características epidemiológicas, comorbilidades y complicaciones vasculares relacionadas. MÉTODO: Corte transversal que incluyó la totalidad de adultos afiliados a la prepaga del Hospital Italiano de Buenos Aires en marzo de 2019, Argentina. RESULTADOS: La prevalencia global de diabetes resultó del 8.5% con intervalo de confianza del 95% (IC95%): 8.3-8.6 (12,832 de un total de 150,725 afiliados). El estrato etario con mayor prevalencia fue el grupo entre 65 y 80 años, con un 15.7% (IC95%: 15.3-16.1). Las personas con diabetes presentaban una media de edad de 70 años (desviación estándar: 14), el 52% eran mujeres, y los factores de riesgo cardiovasculares más frecuentemente asociados fueron: dislipidemia (88%), hipertensión arterial (74%) y obesidad (55%). En relación con el control metabólico, el 60% tenía al menos una hemoglobina glucosilada medida en el último año, siendo el 70% de estas menores al 7%. Casi el 80% tiene medido el colesterol vinculado a lipoproteínas de baja densidad (c-LDL) al menos una vez en los últimos dos años, de ellos el 55% presentaba un valor de c-LDL igual o menor a 100 mg/dl. Las complicaciones macrovasculares presentes en orden de frecuencia fueron: infarto agudo de miocardio (11%), accidente cerebrovascular (8%) y enfermedad vascular periférica (4%); mientras que las complicaciones microvasculares resultaron ser neuropatía diabética (4%) y retinopatía (2%). El 7% tuvo pie diabético, con menos del 1% de amputaciones. CONCLUSIONES: La diabetes representa un problema prevalente, incluso en pacientes ancianos. Esta población sigue presentando un elevado riesgo cardiovascular, con escaso cumplimiento de objetivos terapéuticos.

Interdisciplinary assessment and diagnostic algorithm: The role of the diabetologist.

In recent years, many studies have revealed the importance of heart failure (HF) development in type 2 diabetes (T2D), which increases the morbidity and mortality during the course of diabetes. In this context, it became important to emphasize the role of both cardiologists and diabetologists in the early diagnosis and further adequate treatment of HF in T2D. While HF appears in two major forms, with reduced or preserved ejection fraction (EF), namely HFrEF and HFpEF, it became important to define the optimal approach to the diagnostics. Regarding HFrEF, the role of cardiological methods remained dominant, while the complexity of early diagnosis requires nowadays more active participation of diabetologists. The absence of abundant symptoms and echocardiographic findings imposed the need for the use of risk markers based on metabolic variables and low-grade inflammation parameters. Following that unmet need, numerous studies have defined the possible relationship between metabolic variables in diabetes and the risk for HF. Moreover, attempts have been made to integrate biochemical and clinical parameters into risk score engines and some of them gave promising results. However, the follow-up studies in T2D subjects are needed to determine the clinical relevance of these new approaches.

Heart failure management; a perspective from diabetes care.

People with type 2 diabetes (T2DM) are recognized as having a 2-4 times increased risk of heart failure (HF). Ambulatory diabetes care has long concentrated on the prevention of microvascular and arterial disease, and surveillance for manageable problems such as with the feet and retinae. Accordingly, management of heart failure has never been a specific focus, although the preventative management of cardiac and kidney disease through glucose-lowering, blood pressure (BP) control, and blood lipid control, have had a positive impact on its incidence. Indeed, the very complexity of routine diabetes care, and its enormous prevalence, has generally excluded the management of any of the advanced late complications, whether cardiac, arterial, retinal, renal, or neurodegenerative. Furthermore, advances in HF management itself, in diagnostics, medications, and technology, has carried it deeper into the remit of specialist cardiological care. More recently and in addition to medications already routinely used in diabetes care such as renin-angiotensin system (RAS) blockers, some glucose-lowering therapies such as sodium glucose transporter inhibitors 2 (SGLT-2 inhibitors), have been found to have very positive effects on hospitalization for HF, indeed even in people who do not have T2DM. Here, from the perspective of the diabetologist, we review the clinical scenario of ambulatory diabetes care, in regard of how HF prevention and management should fit in to clinical practice.

Association Between Systolic Blood Pressure and Cardiovascular Inpatient Cost Moderated by Peer-Support Intervention Among Adult Patients With Type 2 Diabetes: A 2-Cohort Study.

OBJECTIVES: People with type 2 diabetes and increased systolic blood pressure (SBP) are at high risk of cardiovascular disease (CVD). In this study, we aimed to investigate the association between CVD-related hospital payments and SBP and tested whether this association is influenced by diabetes peer support. METHODS: Two cohorts comprising people with type 2 diabetes were included in the study. The first cohort comprised 4,704 patients with type 2 diabetes assessed between 2008 and 2009 from 18 general practices in Cambridgeshire and followed up to 2009-2011. The second cohort comprised 1,121 patients with type 2 diabetes from post-trial follow-up data, recruited between 2011 and 2012 and followed up to 2015. SBP was measured at baseline. Inpatient payments for CVD hospitalization within 2 years since baseline was the main outcome. The impact of 1:1, group or combined diabetes peer support and usual care were investigated in the second cohort. Adjusted mean CVD inpatient payments per person were estimated using a 2-part model after adjusting for baseline characteristics. RESULTS: A "hockey-stick" relationship between baseline SBP and estimated CVD inpatient payment was identified in both cohorts, with a threshold at 133 to 141 mmHg, suggesting increased payments for patients with SBP below and above the threshold. The combined peer-support intervention altered the aforementioned association, with no increased payment with SBP above the threshold, and payment slightly decreased with SBP beyond the threshold. CONCLUSIONS: SBP maintained between 133 and 141 mmHg is associated with the lowest CVD disease management costs for patients with type 2 diabetes. Combined peer-support intervention could significantly decrease CVD-related hospital payments.

[Teleconsultation for vascular- and diabetes-associated chronic wounds : A systematic review of health-related and economic implications]. / Telekonsultation bei vaskulär und diabetisch bedingten chronischen Wunden : Eine systematische Übersicht der gesundheitlichen und ökonomischen Implikationen.

BACKGROUND: In addition to lowering the quality of life of those affected, long periods of treatment and high recurrence rates of chronic wounds cause major economic costs for health care systems. Furthermore, inadequate health care and undersupply of care can be observed in Germany. Thus, new forms of care such as teleconsultation are being discussed increasingly. Recent changes in the remuneration system and macerations in the ban of remote treatment support those trends. METHODS: A systematic review was conducted in July 2018 using PubMed and CENTRAL databases for randomized controlled trials between 2008 and 2018. Only randomized clinical trials in which patients with chronic wound who received treatment and follow-up by teleconsultation using information and communication technology to share data were included. In total, 6 international clinical trials were identified. RESULTS: Regarding the current state of research, there is no definite evidence that teleconsultation can improve the care of chronic wound patients. Most likely, wound healing time was positively influenced. No correlation was found between mortality and hospitalizations when teleconsultation was used. CONCLUSION: On the basis of the included studies, the evidence for the care of chronic wounds by teleconsultation is unclear. Further research is needed to examine the health-related and economic benefits of teleconsultation to support integration into health care systems.

Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management.

Hypoglycaemia has long been recognised as a dangerous side-effect of treatment of diabetes with insulin or insulin secretagogues. With its potential to disrupt cerebral function, hypoglycaemia can have a major effect on peoples' lives. Study findings have suggested that hypoglycaemia is associated with an increased risk of cardiovascular events and mortality. Different mechanisms by which hypoglycaemia might provoke cardiovascular events have been identified in experimental studies, and in clinical studies cardiac arrhythmias have been reported to be induced by hypoglycaemia, with one report describing sudden death during a severe episode. Emerging evidence suggests that the association between hypoglycaemia and cardiovascular events and mortality is likely to be multifactorial. The association is probably partly caused by confounding, with hypoglycaemia occurring more frequently in people with comorbidities who are also more likely to die than those without. However, people with type 1 or type 2 diabetes also seem at risk of hypoglycaemia-induced cardiovascular effects. This risk should be recognised by clinicians when agreeing glycaemic goals with patients and choosing appropriate glucose-lowering therapies.

Assessing the readiness of health facilities for diabetes and cardiovascular services in Bangladesh: a cross-sectional survey.

OBJECTIVE: The objective of this study was to assess the readiness of health facilities for diabetes and cardiovascular services in Bangladesh. DESIGN: This study was a cross-sectional survey. SETTING: This study used data from a nationwide Bangladesh Health Facility Survey conducted by the Ministry of Health and Social Welfare in 2014. PARTICIPANTS: A total of 319 health facilities delivering services focused on diabetes and cardiovascular diseases (CVD) were included in the survey. Some of these facilities were run by the public sector while others were managed by the private sector and non-governmental organisations. It was a mix of primary and secondary care facilities. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was readiness of health facilities for diabetes and cardiovascular services. We analysed relevant data following the Service Availability and Readiness Assessment manual of the WHO to assess the readiness of selected health facilities towards services for diabetes and CVD. RESULTS: 58% and 24.1% of the facilities had diagnosis and treatment services for diabetes and CVD, respectively. Shortage of trained staff (18.8% and 14.7%) and lack of adequate medicine supply (23.5% and 43.9%) were identified to be factors responsible for inadequate services for diabetes and CVD. Among the facilities that offer services for diabetes and CVD, only 0.4% and 0.9% had all the four service readiness factors (guideline, trained staff, equipment and medicine). CONCLUSIONS: The study suggests that health facilities suffered from numerous drawbacks, such as shortage of trained staff and required medicine. Most importantly, they lack effective guidelines on the diagnosis and treatment for diabetes and CVD. It is, therefore, essential now to ensure that there are trained staff, adequate medicine supply, and appropriate guidelines on the diagnosis and treatment for diabetes and CVD in Bangladesh.

High-Deductible Insurance and Delay in Care for the Macrovascular Complications of Diabetes.

Background: Little is known about the long-term effects of high-deductible insurance on care for chronic medical conditions. Objective: To determine whether a transition from low-deductible to high-deductible insurance is associated with delayed medical care for macrovascular complications of diabetes. Design: Observational longitudinal comparison of matched groups. Setting: A large national health insurer during 2003 to 2012. Participants: The intervention group comprised 33 957 persons with diabetes who were continuously enrolled in low-deductible (≤$500) insurance plans during a baseline year followed by up to 4 years in high-deductible (≥$1000) plans. The control group included 294 942 persons with diabetes who were enrolled in low-deductible plans contemporaneously with matched intervention group members. Intervention: Employer-mandated transition to a high-deductible plan. Measurements: The number of months it took for persons in each study group to seek care for their first major macrovascular symptom, have their first major diagnostic test for macrovascular disease, and have their first major procedure-based treatment was determined. Between-group differences in time to reach a midpoint event rate were then calculated. Results: No baseline differences were found between groups. During follow-up, the delay for the high-deductible group was 1.5 months (95% CI, 0.8 to 2.3 months) for seeking care for the first major symptom, 1.9 months (CI, 1.4 to 2.3 months) for the first diagnostic test, and 3.1 months (CI, 0.5 to 5.8 months) for the first procedure-based treatment. Limitation: Health outcomes were not examined. Conclusion: Among persons with diabetes, mandated enrollment in a high-deductible insurance plan was associated with delays in seeking care for the first major symptoms of macrovascular disease, the first diagnostic test, and the first procedure-based treatment. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study.

The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.

Atherosclerosis imaging to refine cardiovascular risk assessment in diabetic patients: Computed tomography and positron emission tomography applications.

The lifetime cardiovascular risk of a diabetic patient is approximately 4-5 times higher than that of an age and sex matched individual without diabetes mellitus. Despite the well-publicized cardiovascular risk equivalence of diabetes mellitus, it has become apparent that not all diabetic patients are equally at high-risk and many patients may have a level of risk similar to that of the general population. Cardiovascular imaging has been employed to address the dilemma of a more accurate risk stratification of diabetic patients. Two randomized clinical trials aiming at uncovering the presence of unknown obstructive coronary artery disease (CAD) gave disappointing results. In fact, the number of patients with inducible myocardial ischemia and/or severe obstructive disease was lower than expected and the overall outcome was not improved after having brought the existence of CAD to light. Other techniques that may help identify a diabetic patient susceptible to suffer future events have therefore being explored. In this review we discuss two imaging tools that provide anatomical and functional information on pre-clinical coronary atherosclerosis: computed tomography for calcium scoring, and plaque characterization and myocardial ischemia detection and positron emission tomography using tracers to identify functionally unstable plaques. Despite the availability of several imaging techniques there remain numerous questions as to the utility of imaging to define risk in diabetes mellitus and an optimal approach has yet to be found.

Multimodal Assessment of Mesenchymal Stem Cell Therapy for Diabetic Vascular Complications.

Peripheral arterial disease (PAD) is a debilitating complication of diabetes mellitus (DM) that leads to thousands of injuries, amputations, and deaths each year. The use of mesenchymal stem cells (MSCs) as a regenerative therapy holds the promise of regrowing injured vasculature, helping DM patients live healthier and longer lives. We report the use of muscle-derived MSCs to treat surgically-induced hindlimb ischemia in a mouse model of type 1 diabetes (DM-1). We serially evaluate several facets of the recovery process, including αVß3 -integrin expression (a marker of angiogenesis), blood perfusion, and muscle function. We also perform microarray transcriptomics experiments to characterize the gene expression states of the MSC-treated is- chemic tissues, and compare the results with those of non-ischemic tissues, as well as ischemic tissues from a saline-treated control group. The results show a multifaceted impact of mMSCs on hindlimb ischemia. We determined that the angiogenic activity one week after mMSC treatment was enhanced by approximately 80% relative to the saline group, which resulted in relative increases in blood perfusion and muscle strength of approximately 42% and 1.7-fold, respectively. At the transcriptomics level, we found that several classes of genes were affected by mMSC treatment. The mMSCs appeared to enhance both pro-angiogenic and metabolic genes, while suppressing anti-angiogenic genes and certain genes involved in the inflammatory response. All told, mMSC treatment appears to exert far-reaching effects on the microenvironment of ischemic tissue, enabling faster and more complete recovery from vascular occlusion.

Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

AIMS: To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). METHODS: The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. RESULTS: Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. CONCLUSIONS: In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment.

Use of medical services and medicines attributable to type 2 diabetes care in Yaoundé, Cameroon: a cross-sectional study.

BACKGROUND: The increasing numbers of people with type 2 diabetes (T2D) is a global concern and especially in sub-Saharan Africa, where diabetes must compete for resources with communicable diseases. Diabetes intensifies health care utilisation and leads to an increase in medical care costs. However, In Cameroon like in most developing countries, data on the impact of diabetes on the medical health system are scarce. We aimed to analyse the use of medical services and medicines attributable to T2D care in Yaoundé, Cameroon. METHODS: We conducted a cross-sectional study comparing the use of medical services and medicines on 500 people with T2D attending the diabetic outpatient units of three hospitals in Yaoundé and 500 people without diabetes matched for age, sex and residence. We performed multivariate logistic and quantile regressions to assess the effect of diabetes on the use of medical services and medicines and the presence of other chronic health problems. Models were adjusted for age, educational level, marital status, occupation and family income. RESULTS: Overall, the rate of use of health services was found to be greater in people with T2D than those without diabetes. People with T2D had greater odds of having an outpatient visit to any clinician (OR 97.1 [95% CI: 41.6-226.2]), to be hospitalised (OR 11.9 [95% CI: 1.6-87.9]), to take at least one medicine (OR 83.1 [37.1-185.8]) compared with people without diabetes. We also observed an association between diabetes and some chronic diseases/diabetes complications including hypertension (OR 9.2 [95% CI: 5.0-16.9]), cardiovascular diseases (OR 1.9 [95% CI: 0.8-4.9]), peripheral neuropathy (OR 6.2 [95% CI: 3.4-11.2]), and erectile dysfunction (OR 5.8 [95% CI: 2.7-12.1]). CONCLUSIONS: This study showed that the presence of diabetes is associated with an increased use of health care services and medicines as well as with some chronic diseases/diabetes complications.

A model to estimate cost-savings in diabetic foot ulcer prevention efforts.

BACKGROUND: Sustained efforts at preventing diabetic foot ulcers (DFUs) and subsequent leg amputations are sporadic in most health care systems despite the high costs associated with such complications. We sought to estimate effectiveness targets at which cost-savings (i.e. improved health outcomes at decreased total costs) might occur. METHODS: A Markov model with probabilistic sensitivity analyses was used to simulate the five-year survival, incidence of foot complications, and total health care costs in a hypothetical population of 100,000 people with diabetes. Clinical event and cost estimates were obtained from previously-published trials and studies. A population without previous DFU but with 17% neuropathy and 11% peripheral artery disease (PAD) prevalence was assumed. Primary prevention (PP) was defined as reducing initial DFU incidence. RESULTS: PP was more than 90% likely to provide cost-savings when annual prevention costs are less than $50/person and/or annual DFU incidence is reduced by at least 25%. Efforts directed at patients with diabetes who were at moderate or high risk for DFUs were very likely to provide cost-savings if DFU incidence was decreased by at least 10% and/or the cost was less than $150 per person per year. CONCLUSIONS: Low-cost DFU primary prevention efforts producing even small decreases in DFU incidence may provide the best opportunity for cost-savings, especially if focused on patients with neuropathy and/or PAD. Mobile phone-based reminders, self-identification of risk factors (ex. Ipswich touch test), and written brochures may be among such low-cost interventions that should be investigated for cost-savings potential.

Physician step prescription and monitoring to improve ARTERial health (SMARTER): A randomized controlled trial in patients with type 2 diabetes and hypertension.

AIMS: There are few proven strategies to enhance physical activity and cardiometabolic profiles in patients with type 2 diabetes and hypertension. We examined the effects of physician-delivered step count prescriptions and monitoring. METHODS: Participants randomized to the active arm were provided with pedometers and they recorded step counts. Over a 1-year period, their physicians reviewed their records and provided a written step count prescription at each clinic visit. The overall goal was a 3000 steps/day increase over 1 year (individualized rate of increase). Control arm participants were advised to engage in physical activity 30 to 60 min/day. We evaluated effects on step counts, carotid femoral pulse wave velocity (cfPWV, primary) and other cardiometabolic indicators including haemoglobin A1c in diabetes (henceforth abbreviated as A1c) and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) in participants not receiving insulin therapy. RESULTS: A total of 79% completed final evaluations (275/347; mean age, 60 years; SD, 11). Over 66% of participants had type 2 diabetes and over 90% had hypertension. There was a net 20% increase in steps/day in active vs control arm participants (1190; 95% CI, 550-1840). Changes in cfPWV were inconclusive; active vs control arm participants with type 2 diabetes experienced a decrease in A1c (-0.38%; 95% CI, -0.69 to -0.06). HOMA-IR also declined in the active arm vs the control arm (ie, assessed in all participants not treated with insulin; -0.96; 95% CI, -1.72 to -0.21). CONCLUSIONS: A simple physician-delivered step count prescription strategy incorporated into routine clinical practice led to a net 20% increase in step counts; however, this was below the 3000 steps/day targeted increment. While conclusive effects on cfPWV were not observed, there were improvements in both A1c and insulin sensitivity. Future studies will evaluate an amplified intervention to increase impact.

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

BACKGROUND: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients. METHODS: COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A. CONCLUSION: COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) for diabetic microvascular complications: A population-based cohort study.

AIM: To evaluate the effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) in reducing the risks of microvascular complications. METHODS: This prospective cohort study was conducted with 29,670 propensity-score-matched RAMP-DM participants and diabetes patients under the usual primary care (14,835 in each group). Study endpoints were the first occurrence of any diabetic microvascular complications, non-proliferative diabetic retinopathy/preproliferative diabetic retinopathy (NPDR/prePDR), sight-threatening diabetic retinopathy (STDR) or blindness, nephropathy, end-stage renal disease (ESRD), neuropathy and lower-limb ulcers or amputation. Log-rank tests and multivariable Cox proportional-hazards regressions were employed to estimate between-group differences in incidences of study endpoints. RESULTS: After a median follow-up of 36 months with>41,000 person-years in each group, RAMP-DM participants had a lower incidence of microvascular complications (760 vs 935; adjusted hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.66-0.81; P<0.001) and lower incidences of all specific microvascular complications except neuropathy (adjusted HR: 0.94; 95% CI: 0.61-1.45; P=0.778). Adjusted HRs for the RAMP-DM vs control group for ESRD, STDR or blindness, and lower-limb ulcers or amputation were 0.40 (95% CI: 0.24-0.69; P<0.001), 0.55 (95% CI: 0.39-0.78; P=0.001) and 0.49 (95% CI: 0.30-0.80; P=0.005), respectively. CONCLUSION: The RAMP-DM intervention was associated with lower incidences of all microvascular complications except neuropathy over a 3-year follow-up. These encouraging results constitute evidence that structured risk assessment and risk-stratified management provided by a multidisciplinary team is effective for reducing microvascular complications in diabetes patients. CLINICAL TRIAL REGISTRY: NCT02034695, www.ClinicalTrials.gov.