Assessment of arterial stiffness in paediatric patients with type 1 diabetes mellitus.

AIMS: To investigate early indicators of cardiovascular disease (CVD) in children and adolescents with type 1 diabetes mellitus (T1DM), focusing on pulse wave velocity (PWV) and its associations with various anthropometric and glycemic parameters. PATIENTS AND METHODS: A total of 124 children and adolescents with T1D (mean age 10.75 ± 3.57 years) were included in this cross-sectional study. Anthropometric data, including height, weight, body mass index (BMI), glycemic parameters, such as HbA1c and time in range (TIR) were assessed. PWV was assessed by oscillometric method using the Mobil-O-Graph PWA device. Univariate and multivariate linear regression were used to explore the association of PWV z-score with anthropometric, demographic, and glycaemic variables. RESULTS: Significant negative association between PWV and age and height (ß = -0.336, 95 % CI -0.44 to -0.25, p < 0.001 and ß = -0.491, 95 % CI -0.62 to -0.36, p < 0.001, respectively), while gender showed a significant positive association with PWV, with females displaying higher PWV values compared to males (ß = 0.366, 95 % CI 0.17 to 0.56, p < 0.001). TIR was positively associated with PWV (ß = 0.092, 95 % CI 0.01 to 0.16, p = 0.017 only for patients having TIR ≤ 50 %. Finally, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were positively associated with PWV (ß = 0.086, 95 % CI 0.02 to 0.14, p = 0.007 and ß = 0.152, 95 % CI 0.07 to 0.23, p < 0.001, respectively). CONCLUSION: Youth with T1DM who spend <50 % of time in range exhibit uniquely increased signs of arterial stiffness, indicating that poor glycemic control may contribute to early vascular damage. Differences related to age, gender and height should be considered.

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.

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

BACKGROUND: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. METHODS: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. RESULTS: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. CONCLUSIONS: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.

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.

Metformin Should Not Be Used to Treat Prediabetes.

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110-125 vs. 100-109 mg/dL (6.1-6.9 vs. 5.6-6.0 mmol/L) and A1C levels 6.0-6.4% (42-46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.

Health Care Costs Associated With Macrovascular, Microvascular, and Metabolic Complications of Type 2 Diabetes Across Time: Estimates From a Population-Based Cohort of More Than 0.8 Million Individuals With Up to 15 Years of Follow-up.

OBJECTIVE: Developing country-specific unit-cost catalogs is a key area for advancing economic research to improve medical and policy decisions. However, little is known about how health care costs vary by type 2 diabetes (T2D) complications across time in Asian countries. We sought to quantify the economic burden of various T2D complications in Taiwan. RESEARCH DESIGN AND METHODS: A nationwide, population-based, longitudinal study was conducted to analyze 802,429 adults with newly diagnosed T2D identified during 1999-2010 and followed up until death or 31 December 2013. Annual health care costs associated with T2D complications were estimated, with multivariable generalized estimating equation models adjusted for individual characteristics. RESULTS: The mean annual health care cost was $281 and $298 (2017 U.S. dollars) for a male and female, respectively, diagnosed with T2D at age <50 years, with diabetes duration of <5 years, and without comorbidities, antidiabetic treatments, and complications. Depression was the costliest comorbidity, increasing costs by 64-82%. Antidiabetic treatments increased costs by 72-126%. For nonfatal complications, costs increased from 36% (retinopathy) to 202% (stroke) in the event year and from 13% (retinopathy or neuropathy) to 49% (heart failure) in subsequent years. Costs for the five leading costly nonfatal subtype complications increased by 201-599% (end-stage renal disease with dialysis), 37-376% (hemorrhagic/ischemic stroke), and 13-279% (upper-/lower-extremity amputation). For fatal complications, costs increased by 1,784-2,001% and 1,285-1,584% for cardiovascular and other-cause deaths, respectively. CONCLUSIONS: The cost estimates from this study are crucial for parameterizing diabetes economic simulation models to quantify the economic impact of clinical outcomes and determine cost-effective interventions.

Within-Trial Evaluation of Medical Resources, Costs, and Quality of Life Among Patients With Type 2 Diabetes Participating in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

OBJECTIVE: To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS: Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs. RESULTS: Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ∼$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time. CONCLUSIONS: Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated.

Impact of Treating Oral Disease on Preventing Vascular Diseases: A Model-Based Cost-effectiveness Analysis of Periodontal Treatment Among Patients With Type 2 Diabetes.

OBJECTIVE: Previous randomized trials found that treating periodontitis improved glycemic control in patients with type 2 diabetes (T2D), thus lowering the risks of developing T2D-related microvascular diseases and cardiovascular disease (CVD). Some payers in the U.S. have started covering nonsurgical periodontal treatment for those with chronic conditions, such as diabetes. We sought to identify the cost-effectiveness of expanding periodontal treatment coverage among patients with T2D. RESEARCH DESIGN AND METHODS: A cost-effectiveness analysis was conducted to estimate lifetime costs and health gains using a stochastic microsimulation model of oral health conditions, T2D, T2D-related microvascular diseases, and CVD of the U.S. POPULATION: Model parameters were obtained from the nationally representative National Health and Nutrition Examination Survey (NHANES) (2009-2014) and randomized trials of periodontal treatment among patients with T2D. RESULTS: Expanding periodontal treatment coverage among patients with T2D and periodontitis would be expected to avert tooth loss by 34.1% (95% CI -39.9, -26.5) and microvascular diseases by 20.5% (95% CI -31.2, -9.1), 17.7% (95% CI -32.7, -4.7), and 18.4% (95% CI -34.5, -3.5) for nephropathy, neuropathy, and retinopathy, respectively. Providing periodontal treatment to the target population would be cost saving from a health care perspective at a total net savings of $5,904 (95% CI -6,039, -5,769) with an estimated gain of 0.6 quality-adjusted life years per capita (95% CI 0.5, 0.6). CONCLUSIONS: Providing nonsurgical periodontal treatment to patients with T2D and periodontitis would be expected to significantly reduce tooth loss and T2D-related microvascular diseases via improved glycemic control. Encouraging patients with T2D and poor oral health conditions to receive periodontal treatment would improve health outcomes and still be cost saving or cost-effective.

Eligibility of patients with type 2 diabetes for sodium-glucose co-transporter-2 inhibitor cardiovascular outcomes trials: An assessment using the Diabetes Collaborative Registry.

Generalizability of findings from cardiovascular outcomes trials (CVOTs) to patients with type 2 diabetes (T2D) in clinical practice is unknown. We assessed the proportions of patients in the Diabetes Collaborative Registry who would have met enrolment criteria for pivotal CVOTs of sodium-glucose co-transporter-2 inhibitors (SGLT-2is): EMPA-REG OUTCOME, CANVAS, DECLARE and VERTIS CV. In 172 643 patients, mean [standard deviation (SD)] age and HbA1c were 68.1 (11.8) years and 7.8% (2.2), respectively; 56.8% of patients were men and SGLT-2i use was 4.4%. Atherosclerotic cardiovascular disease (ASCVD) prevalence was 64.3% and mean 10-year ASCVD risk was 28.6% in patients without ASCVD. Proportions of patients eligible for CVOTs ranged from 26% (EMPA-REG OUTCOME) to 44% (DECLARE); 48% of patients were ineligible for all CVOTs. Mean (SD) ASCVD risk was 25.4% (22.6), 32.1% (20.6) and 37.7% (19.4) in patients eligible for no, one or two CVOTs, respectively. SGLT-2i use was low in patients eligible for no CVOTs (3.5%) and at least one CVOT (5.2%). In conclusion, applicability of CVOT results to patients with T2D in clinical practice varies based on trial eligibility criteria.

Assessment of red cell distribution width, glycaemic control and diabetes related complications - the ARDENT Study.

OBJECTIVE: To assess the association of red cell distribution width with glycaemic control and the presence of complications in diabetes patients. METHODS: The cross-sectional study was done at the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from September to November 2017, and comprised patients with type 2 diabetes. Clinical and demographical characteristics were documented and they were subjected to complete blood count, red cell distribution width, glycated haemoglobin, fasting and random blood glucose, lipid profile, urea and creatinine. The presence of complications were assessed during clinical examination. SPSS 20 was used for data analysis.. RESULTS: There were 349 patients with a mean age of 53.14±11.77 years. The mean duration of diabetes was 8.36±6.64 years and mean glycated haemoglobin was 9.05±1.93. Red cell distribution width was significantly associated with the duration of diabetes, hypertension, macrovascular and microvascular complications and extent of glycaemic control (p<0.0001 each). A statistically significant linear relationship was observed between red cell distribution width and the number of macrovascular and microvascular complications (p<0.0001) and glycated haemoglobin (p<0.0001). Mean red cell distribution width was 13.94±1.66, 14.72±1.38, and 15.76±1.55 for optimal control, borderline control and poor control respectively. This linear incremental pattern was statistic ally significant (p<0.0001). CONCLUSIONS: The linear association of red cell distribution width with glycated haemoglobin may enable its use as a measure of the extent of hyperglycaemia.

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.

Combined effects of diabetes and low household income on mortality: a 12-year follow-up study of 505 677 Korean adults.

AIM: To examine the effects of diabetes, low income and their combination on mortality in the Korean population. METHODS: We analysed a total of 505 677 people (53.9% male) aged 40-79 years old from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort. Ten levels of household income were used as indicators of economic status. Diabetes was defined as elevated fasting blood glucose (≥ 6.9 mmol/l) and/or use of glucose-lowering drugs or insulin. Covariates of age, sex, BMI, smoking and Charlson Comorbidity Index were determined at baseline. Outcomes were total and cause-specific mortality over 12 years. Cox's proportional hazard regression models were used to estimate hazard ratios (HRs) for mortality according to the presence of diabetes, household income and their combination. RESULTS: Lower household income was associated with higher mortality from all causes, cardiovascular disease, cancer and non-cancer non-cardiovascular causes. Excessive mortality due to low incomes was observed in both people with and without diabetes. In men, the adjusted HR [95% confidence interval (CI)] of mortality was 1.38 (1.34 to 1.42) for low-income only, 1.48 (1.42 to 1.55) for diabetes only and 1.95 (1.86 to 2.05) for diabetes and low-income combined, relative to the normal glucose and high income group. Corresponding HR (95% CI) in women were 1.19 (1.14 to 1.24), 1.54 (1.44 to 1.64) and 1.87 (1.75 to 2.01), respectively. CONCLUSION: Both low household income and the presence of diabetes independently increase the risk of mortality, but their combined effects on mortality may be different between men and women.

Mental health visits and low socio-economic status in adolescence are associated with complications of Type 1 diabetes in early adulthood: a population-based cohort study.

AIM: To determine the association of mental health visits and socio-economic status in late adolescence with the risk of mortality and acute and chronic diabetes complications in early adulthood. METHODS: We conducted a population-based cohort study of individuals in Ontario, Canada, who had their 20th birthday between January 1999 and March 2015 and a diagnosis of diabetes prior to their 15th birthday, using linked administrative databases (n=8491). The main outcome was death; other outcomes were hypoglycaemia or hyperglycaemia-related hospitalizations and emergency department visits and chronic diabetes complications (dialysis, ophthalmological and macrovascular complications). RESULTS: Over the course of 59 361 person-years there were 127 deaths.. Low socio-economic status and mental health visits were both associated with a higher risk of death [hazard ratio 2.03, (95% CI 1.13 to 3.64) and 2.45 (95% CI 1.71 to 3.51), respectively]. Those with the lowest socio-economic status and a mental health visit had a higher rate of diabetes-related hospitalizations (rate ratio 4.84, 95% CI 3.64 to 6.44) and emergency department visits (rate ratio 3.15, 95% CI 1.79 to 5.54). Low socio-economic status and mental health visits were both associated with an increased risk of any chronic complication [hazard ratio 1.54 (95% CI 1.21 to 1.96) and 1.57 (95% CI 1.35 to 1.81), respectively]. CONCLUSION: We identified significant socio-economic and mental health disparities in the risk of death and acute and chronic complications in early adulthood for people with childhood-onset diabetes. Targeted interventions to prevent adverse events for these adolescents at highest risk should be evaluated.

SGLT2 inhibitors and risk of stroke in patients with type 2 diabetes: A systematic review and meta-analysis.

The effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on risk of stroke have not been conclusively established. Therefore, we conducted a meta-analysis to evaluate the effects of SGLT2 inhibitors on stroke risk in patients with type 2 diabetes mellitus (T2DM) by searching available randomized trials in PubMed, Embase, CENTRAL, Web of Science, Scopus and ClinicalTrials.gov databases. We identified 32 eligible trials involving 75 540 participants. The incidence of stroke in groups receiving SGLT2 inhibitor monotherapy or combination therapy did not differ significantly from that in control groups, with a relative risk (RR) of 1.01 and 1.0, respectively. Three SGLT2 inhibitors were tested, with similar RR values (canagliflozin [RR, 0.91], dapagliflozin [RR, 0.99] and empagliflozin [RR, 1.03]). Subgroup analyses showed that RR values were not affected by gender, age, diabetes duration, BMI or HbA1C levels, but Black patients had a lower incidence of stroke than White or Asian patients. This meta-analysis indicated that SGLT2 inhibitor therapy did not increase stroke incidence, and no significant differences in stroke risk were observed among 3 SGLT2 inhibitors (class effect). However, the small racial disparity requires further study and confirmation.

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.

Diabetes and number of years of life lost with and without cardiovascular disease: a multi-state homogeneous semi-Markov model.

AIMS: We quantified the impact of type 2 diabetes on incidence of non-fatal cardiovascular disease (CVD) and mortality, considering CVD as a continuum from occurrence of diabetes to the end point, and estimated the 15-year life expectancy with and without CVD. METHODS: A total of 7239 Iranian adults (3246 men), aged ≥ 30 years, were followed from 1999 to 2014. We applied a multi-state semi-Markov model with three transitions including CVD-free to non-fatal CVD, CVD-free to death and non-fatal CVD to death, and studied the influence of diabetes on each transition rate, stratifying by sex and adjusting for confounders. RESULTS: Diabetes was significantly associated with increased risk of non-fatal CVD in men [hazard ratio, 1.70 (1.36-3.53)] and women [2.19 (1.74-2.77)], and of all-cause death [2.72 (2.03-3.63) and 1.92 (1.37-2.67) in men and women, respectively]. An increased risk of mortality was found only among diabetic men, when non-fatal CVD was occurred [2.19 (1.36-3.53)]. Men with diabetes experienced first non-fatal CVD and death without CVD 1.7 and 1.4 years, respectively, earlier than those without diabetes; the corresponding values were 1.4 and 0.7 years for women. Moreover, diabetic men lived 1.3 years less than non-diabetic counterparts when non-fatal CVD was occurred. CONCLUSIONS: Diabetes increased the risk of non-fatal CVD events and all-cause mortality and consequently decreased the number of years lived without CVD. A decrease in LE was found only among diabetic men compared to non-diabetics after non-fatal CVD occurred.

Cost-utility of empagliflozin in patients with type 2 diabetes at high cardiovascular risk.

AIMS: In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG) trial, empagliflozin reduced cardiovascular and all-cause mortality in type 2 diabetes (T2D) patients at high cardiovascular risk. We sought to estimate the cost-effectiveness of empagliflozin versus standard treatment for the prevention of cardiovascular morbidity and mortality in patients with T2D. METHODS: A Markov model was developed to assess the cost-effectiveness of empagliflozin (versus standard treatment) for the prevention of cardiovascular morbidity and mortality in patients with T2D using a 3-month cycle length and a lifetime horizon. Data sources included the EMPA-REG randomized clinical trial and other published epidemiological studies. Outcomes included treatment costs (in 2016 US$), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Probabilistic sensitivity analysis (PSA) was performed to test the robustness of conclusions. RESULTS: Empagliflozin use resulted in higher total lifetime treatment costs ($371,450 versus $272,966) but yielded greater QALYs (10.712 vs. 9.419) compared to standard treatment. This corresponded to an ICER of $76,167 per QALY gained. PSA suggested empagliflozin would be cost-effective in 96% of 10,000 iterations assuming a willingness-to-pay threshold of $100,000 per QALY gained. CONCLUSION: Empagliflozin may be cost-effective compared to standard treatment in T2D patients at high cardiovascular risk.