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Background: Dietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow's milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow's milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow's milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology., Results: Eligibility criteria were met by 17 trials (n = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow's milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow's milk resulted in moderate reductions in non-HDL-C (mean difference, - 0.26 mmol/L [95% confidence interval, - 0.43 to - 0.10]), systolic blood pressure (- 8.00 mmHg [- 14.89 to - 1.11]), and diastolic blood pressure (- 4.74 mmHg [- 9.17 to - 0.31]); small important reductions in LDL-C (- 0.19 mmol/L [- 0.29 to - 0.09]) and c-reactive protein (CRP) (- 0.82 mg/L [- 1.26 to - 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified., Conclusions: Current evidence provides a good indication that replacing cow's milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets., Trial Registration: ClinicalTrials.gov identifier, NCT05637866., (© 2024. The Author(s).)

Background: The estimated glomerular filtration rate (eGFR) and the albumin-to-creatinine ratio (ACR) are risk factors for diabetes-related outcomes. A composite that captures information from both may provide a simpler way of assessing risk., Methods: 9115 of 9901 Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) participants with both an ACR and eGFR at baseline were included in this post hoc epidemiologic analysis. The hazard of higher baseline levels of 1/eGFR and natural log transformed ACR (calculated as ln [ACR × 100] to eliminate negative values) and their interaction for incident major adverse cardiovascular events (MACE), kidney outcomes, and deaths was estimated. The hazard of the geometric mean of these two baseline measures (the kidney disease index or KDI) was also assessed., Results: A non-linear relationship was observed between 1/eGFR and all three outcomes, and between ln [ACR × 100] and the kidney outcome. There was also a negative interaction between these two risk factors with respect to MACE and death. Conversely, a linear relationship was noted between the KDI and all three outcomes. People in the highest KDI fifth experienced the highest incidence of MACE, death, and the kidney outcome (4.43, 4.56, and 5.55/100 person-years respectively). C statistics for the KDI were similar to those for eGFR and albuminuria., Conclusions: The KDI combines the baseline eGFR and ACR into a novel composite risk factor that has a simple linear relationship with incident serious outcomes in people with diabetes and additional CV risk factors. Trial Registration clinicaltrials.gov NCT01394952., (© 2022. The Author(s).)

Background: Type-2 diabetes (T2D), chronic kidney disease, and heart failure (HF) share epidemiological and pathophysiological features. Although their prevalence was described, there is limited contemporary, high-resolution, epidemiological data regarding the overlap among them. We aimed to describe the epidemiological intersections between T2D, HF, and kidney dysfunction in an entire database, overall and by age and sex., Methods: This is a cross-sectional analysis of adults ≥ 25 years, registered in 2019 at Maccabi Healthcare Services, a large healthcare maintenance organization in Israel. Collected data included sex, age, presence of T2D or HF, and last estimated glomerular filtration rate (eGFR) in the past two years. Subjects with T2D, HF, or eGFR < 60 mL/min/1.73 m 2 were defined as within the diabetes-cardio-renal (DCR) spectrum., Results: Overall, 1,389,604 subjects (52.2% females) were included; 445,477 (32.1%) were 25- < 40 years, 468,273 (33.7%) were 40- < 55 years, and 475,854 (34.2%) were ≥ 55 years old. eGFR measurements were available in 74.7% of the participants and in over 97% of those with T2D or HF. eGFR availability increased in older age groups. There were 140,636 (10.1%) patients with T2D, 54,187 (3.9%) with eGFR < 60 mL/min/1.73m 2 , and 11,605 (0.84%) with HF. Overall, 12.6% had at least one condition within the DCR spectrum, 2.0% had at least two, and 0.23% had all three. Cardiorenal syndrome (both HF and eGFR < 60 mL/min/1.73m 2 ) was prevalent in 0.40% of the entire population and in 2.3% of those with T2D. In patients with both HF and T2D, 55.2% had eGFR < 60 mL/min/1.73m 2 and 15.8% had eGFR < 30 mL/min/1.73m 2 . Amongst those within the DCR spectrum, T2D was prominent in younger participants, but was gradually replaced by HF and eGFR < 60 mL/min/1.73m 2 with increasing age. The congruence between all three conditions increased with age., Conclusions: This large, broad-based study provides a contemporary, high-resolution prevalence of the DCR spectrum and its components. The results highlight differences in dominance and degree of congruence between T2D, HF, and kidney dysfunction across ages., (© 2022. The Author(s).)

During the last decade we experienced a surge in the number of glucose lowering agents that can be used to treat patients with type 2 diabetes. Especially important are the discoveries that sodium glucose co-transporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve patients' cardiovascular and renal outcomes. Accordingly, various medical associations have updated their guidelines for the treatment of diabetes in this new era. Though not agreeing on every issue, these position-statements generally share a detailed and often complex workflow that may be too complicated for the busy and overworked primary care setting, where the majority of patients with type 2 diabetes are managed in many countries. Other guidelines, generally those from the cardiology associations focus primarily on the population of patients with high risk for or pre-existing cardiovascular disease, which represent only the minority of patients with type 2 diabetes. We believe that we should re-define SGLT2i and GLP-1 RA as diabetes/disease modifying drugs (DMDs) given the recent evidence of their cardiovascular and renal benefits. Based on this definition we have designed a SIMPLE approach in order to assist primary care teams in selecting the most appropriate therapy for their patients. We believe that most subjects newly diagnosed with type 2 diabetes should initiate early combination therapy with metformin and a prognosis changing DMD. The decision whether to use GLP-1 RA or SGLT2i should be made based on specific patient's risk factors and preferences. Importantly, DMDs are known to have a generally safe side-effect profile, with lower risk for hypoglycemia and weight gain, further promoting their wider usage. Early combination therapy with DMDs may improve the multiple pathophysiological abnormalities responsible for type 2 diabetes and its complications, thus resulting in the greatest long term benefits.

Background: The Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) double blind randomized trial demonstrated that weekly subcutaneous dulaglutide 1.5 mg, a glucagon like peptide-1 receptor agonist, versus matched placebo reduced the first outcome of major adverse cardiovascular event (MACE), cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (594 versus 663 events) in 9901 persons with type 2 diabetes and either chronic cardiovascular disease or risk factors, and followed during 5.4 years. These findings were based on a time-to-first-event analysis and preclude relevant information on the burden of total major events occurring during the trial. This analysis reports on the total cardiovascular or fatal events in the REWIND participants METHODS: We compared the total incidence of MACE or non-cardiovascular deaths, and the total incidence of expanded MACE (MACE, unstable angina, heart failure or revascularization) or non-cardiovascular deaths between participants randomized to dulaglutide and those randomized to placebo. Incidences were expressed as number per 1000 person-years. Hazard ratios (HR) were calculated using the conditional time gap and proportional means models., Results: Participants had a mean age of 66.2 years, 46.3% were women and 31% had previous cardiovascular disease. During the trial there were 1972 MACE or non-cardiovascular deaths and 3673 expanded MACE or non-cardiovascular deaths. The incidence of total MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 35.8 and 40.3 per 1000 person-years, respectively [absolute reduction = 4.5 per 1000 person-years; conditional time gap HR 0.90 (95% CI, 0.82-0.98) p = 0.020, and proportional means HR 0.89 (95% CI, 0.80-0.98) p = 0.022]. The incidence of total expanded MACE or non-cardiovascular deaths in the dulaglutide and placebo groups was 67.1 and 74.7 per 1000 person-years, respectively [absolute reduction = 7.6 per 1000 person-years; conditional time gap HR 0.93 (95% CI, 0.87-0.99) p = 0.023, and proportional means HR 0.90 (95% CI, 0.82-0.99) p = 0.028]., Conclusions: These findings suggest that weekly subcutaneous dulaglutide reduced total cardiovascular or fatal event burden in people with type 2 diabetes at moderate cardiovascular risk., Clinical Trial Registration: https://www.clinicaltrials.gouv . Unique Identifier NCT01394952).

Background: Mixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM., Methods: The previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non-HDL-C ≥ 100 mg/dL and TGs ≥ 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). This post hoc subgroup analysis of the primary trial investigated the effects of alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at Week 12] versus usual care [ezetimibe, fenofibrate, or no additional lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with T2DM and baseline TGs ≥ 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women)., Results: Alirocumab significantly reduced non-HDL-C [LS mean difference (standard error (SE)), - 35.0% (3.9)], ApoB [LS mean difference (SE), - 34.7% (3.6)], LDL-C [LS mean difference (SE), - 47.3% (5.2)], LDL particle number [LS mean difference (SE), - 40.8% (4.1)], and Lp(a) [LS mean difference (SE), - 29.9% (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were similar for alirocumab versus usual care. TG reductions were similar between alirocumab and usual care (no significant difference), but greater with fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate were non-significant. Most individuals receiving alirocumab achieved ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event frequency was similar between alirocumab (67.2%) and usual care (70.7%). Additionally, no clinically relevant effect of alirocumab on change in glycemic parameters or use of antihyperglycemic agents was observed., Conclusions: Alirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, fenofibrate, or no LLT. Consistent with previous studies, alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov, NCT02642159. Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159.

Background: To examine the impact on glycemic control of achieving postprandial glucose (PPG) target with lixisenatide, a once-daily glucagon-like peptide-1 receptor agonist approved in the US, in patients with uncontrolled type 2 diabetes (T2D) on basal insulin, an agent that primarily targets fasting plasma glucose., Methods: A post hoc pooled analysis was conducted using clinical trial data extracted from the intent-to-treat subpopulation of patients with T2D who participated in the 24-week, phase 3, randomized, double-blind, placebo-controlled, 2-arm parallel-group, multicenter GetGoal-L (NCT00715624), GetGoal-Duo 1 (NCT00975286) and GetGoal-L Asia trials (NCT00866658)., Results: Data from 587 lixisenatide-treated patients and 484 placebo-treated patients were included. Patients on lixisenatide were more likely to achieve a PPG target of < 10 mmol/L (< 180 mg/dL) than placebo-treated patients (P < 0.001), regardless of baseline fasting plasma glucose (FPG) levels. More importantly, those who reached the PPG target experienced a significantly greater reduction in mean HbA1c, were more likely to achieve HbA1c target of < 53 mmol/mol (< 7.0%), and experienced weight loss. Those outcomes were achieved with no significant differences in the risk of symptomatic hypoglycemia compared with placebo., Conclusion: Compared with placebo, addition of lixisenatide to basal insulin improved HbA1c and reduced PPG, without increasing hypoglycemia risk. These findings highlight the importance of PPG control in the management of T2D, and provide evidence that adding an agent to basal insulin therapy that also impacts PPG has therapeutic value for patients who are not meeting glycemic targets., Trial Registration: NCT00715624. Registered 15 July 2008, NCT00975286 . Registered 11 September 2009, NCT00866658 . Registered 20 March 2009., Competing Interests: Competing interestsJAD has been a consultant or served on the advisory board for Amgen Inc., Aspire Bariatrics, AstraZeneca, Boston Therapeutics, Eli Lilly & Co., GSK, Janssen Pharmaceuticals, Merck & Co., Inc., Novo Nordisk, and Valeritas; has been a speaker for AstraZeneca, Janssen, Merck-Serono, Novo Nordisk, and Takeda; and has received a research grant from AstraZeneca. WS, SP, and RB are employees and stockholders of Sanofi. LAL. has been a consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Janssen, Merck & Co., Inc., Novo Nordisk, Sanofi, and Servier; has received research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Janssen, Merck & Co., Inc., Novo Nordisk, and Sanofi; and has provided continuing medical education on behalf of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Janssen, Merck & Co., Inc., Novo Nordisk, Sanofi, and Servier., (© The Author(s). 2020.)

Background: Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778)., Methods: In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies., Results: This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls., Conclusions: Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015.

Background: The SUSTAIN 6 trial demonstrated that once-weekly semaglutide (0.5 and 1.0 mg) significantly reduced major adverse cardiovascular (CV) events (MACE) vs placebo in subjects with type 2 diabetes (T2D) and high CV risk. The effects of gender, age and baseline CV risk on outcomes are important considerations for further study., Methods: Subjects were grouped according to gender, age (50-65 years and > 65 years), and CV risk profile at baseline (prior myocardial infarction [MI] or stroke vs no prior MI or stroke, and established CV disease [CVD] vs CV risk factors alone, including subjects with chronic kidney disease). Time to MACE and its individual components (CV death, nonfatal MI, nonfatal stroke), hospitalization for unstable angina or heart failure, and revascularization (coronary and peripheral) were analyzed for all subgroups. Additional analyses were performed for gender and age to investigate change from baseline in HbA 1c and body weight, as well as tolerability., Results: A total of 3297 subjects were included. The majority of subjects (60.7%) were male; 43% were > 65 years of age; 41.5% had a history of MI or stroke; and 76.8% had established CVD. Compared with placebo, semaglutide reduced the risk of the first occurrence of MACE and each MACE component consistently across all subgroups (gender, age, and baseline CV risk profile). Revascularizations, HbA 1c and body weight were also reduced consistently across all subgroups compared with placebo. Gastrointestinal adverse events in all treatment groups were more common among women than men, but rates of premature treatment discontinuation were similar for both genders., Conclusions: In this post hoc analysis of SUSTAIN 6, once-weekly semaglutide vs placebo reduced the risk of MACE in all subjects included in the trial, regardless of gender, age, or baseline CV risk profile. Trial registry Clinicaltrials.gov, Identifying number: NCT01720446, Date of registration: October 29, 2012.

Background: Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide) remain an important option because of a variety of patient and health system factors. The large, real world, observational, and international EASYDia trial evaluated the effectiveness of gliclazide modified release (MR) 60 mg in individuals with type 2 diabetes with a broad range of diabetes history, body mass index (BMI) and background antihyperglycemic treatment., Methods: A total of 7170 participants from eight countries, age ≥ 35 years with HbA1c ≥ 7.5% and not treated with insulin, were prescribed 30-120 mg of gliclazide MR 60 mg once daily. HbA1c goals were individualized and dosing uptitrated, as required, over the 6-month long study. In this post hoc subanalysis, efficacy endpoints were analyzed according to stratified baseline HbA1c levels, weight and glucose-lowering regimens. Episodes of hypoglycemia requiring assistance were documented., Results: At baseline, mean age was 58.9 years, HbA1c 8.8%, BMI 30.1 kg/m 2 , and diabetes duration 5.1 years. At study end, clinically significant HbA1c improvements (mean change - 1.78%) were noted across all baseline HbA1c strata (> 7.0 to ≤ 8.0%, > 8.0 to ≤ 9.0%, > 9.0 to ≤ 10.0%, and > 10.0%), BMI classifications (18.5 to < 25.0, 25.0 to < 30.0, and ≥ 30.0 kg/m 2 ), and regardless of the original diabetes treatment regimen ( P  < 0.001 in all cases). In contrast to the subgroups with BMI 25.0-30.0 and ≥ 30.0 kg/m 2 that registered weight losses of 0.9 and 2.2 kg, respectively ( P  < 0.001 vs. baseline weight); the BMI 18.5-24.9 kg/m 2 subgroup gained a mean 0.5 kg ( P  < 0.02 vs. baseline weight). Severe hypoglycemic events were rare (0.06%)., Conclusions: Progressive gliclazide MR 60 mg uptitration was well tolerated and lowered HbA1c across a broad range of HbA1c, BMI and background glucose-lowering therapy. Weight loss was noted when BMI was ≥ 25.0 kg/m 2 . Individuals with the highest baseline HbA1c and BMI experienced the greatest HbA1c and weight improvements. Trial registration ISRCTN Registry ISRCTN00943368 on 1st July 2011.

Background: Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy. For the first time, atherogenic cholesterol-lowering with a PCSK9 inhibitor will be assessed with non-HDL-C as the primary endpoint with usual care as the comparator., Methods: DM-DYSLIPIDEMIA is a Phase 3b/4, randomised, open-label, parallel group, multinational study that planned to enrol 420 individuals. Main inclusion criteria were T2DM and mixed dyslipidaemia (non-HDL-C ≥100 mg/dl [≥2.59 mmol/l], and triglycerides ≥150 and <500 mg/dl [≥1.70 and <5.65 mmol/l]) with documented atherosclerotic cardiovascular disease or ≥1 additional cardiovascular risk factor. Participants were randomised (2:1) to alirocumab 75 mg every 2 weeks (Q2W) or lipid-lowering usual care on top of maximally tolerated statin (or no statin if intolerant). If randomised to usual care, investigators were able to add their pre-specified choice of one of the following to the patient's current statin regimen: ezetimibe, fenofibrate, omega-3 fatty acids or nicotinic acid, in accordance with local standard-of-care. Alirocumab-treated individuals with non-HDL-C ≥100 mg/dl at week 8 will undergo a blinded dose increase to 150 mg Q2W at week 12. The primary efficacy endpoint is non-HDL-C change from baseline to week 24 with alirocumab versus usual care; other lipid levels (including LDL-C), glycaemia-related measures, safety and tolerability will also be assessed. Alirocumab will be compared to fenofibrate in a secondary analysis., Results: Recruitment completed with 413 individuals randomised in 14 countries worldwide. Results of this trial are expected in the second quarter of 2017., Conclusions: ODYSSEY DM-DYSLIPIDEMIA will provide information on the efficacy and safety of alirocumab versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk using non-HDL-C as the primary efficacy endpoint. Trial registration NCT02642159 (registered December 24, 2015).

Background: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC., Methods: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048)., Results: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol., Conclusions: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints.

Background: Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption., Objective: The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins., Methods: Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months., Results: No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels., Conclusion: Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction., Trial Registration: clinicaltrials.gov Identifier: NCT00438425.

Background: Lifestyle behavior modification is an essential component of self-management of type 2 diabetes. We evaluated the prevalence of engagement in lifestyle behaviors for management of the disease, as well as the impact of healthcare professional support on these behaviors., Methods: Self-reported data were available from 2682 adult respondents, age 20 years or older, to the 2011 Survey on Living with Chronic Diseases in Canada's diabetes component. Associations with never engaging in and not sustaining self-management behaviors (of dietary change, weight control, exercise, and smoking cessation) were evaluated using binomial regression models., Results: The prevalence of reported dietary change, weight control/loss, increased exercise and smoking cessation (among those who smoked since being diagnosed) were 89.7%, 72.1%, 69.5%, and 30.6%, respectively. Those who reported not receiving health professional advice in the previous 12 months were more likely to report never engaging in dietary change (RR = 2.7, 95% CI 1.8 - 4.2), exercise (RR = 1.7, 95% CI 1.3 - 2.1), or weight control/loss (RR = 2.2, 95% CI 1.3 - 3.6), but not smoking cessation (RR = 1.0; 95% CI: 0.7 - 1.5). Also, living with diabetes for more than six years was associated with not sustaining dietary change, weight loss and smoking cessation., Conclusion: Health professional advice for lifestyle behaviors for type 2 diabetes self-management may support individual actions. Patients living with the disease for more than 6 years may require additional support in sustaining recommended behaviors.

Background: Some patients administered cholesterol-lowering therapies may experience an increase in the proportion of small LDL particles, which may be misinterpreted as a worsening of atherosclerotic coronary heart disease risk. This study assessed the lipid effects of adding ezetimibe to atorvastatin or doubling the atorvastatin dose on low-density lipoprotein cholesterol (LDL-C) levels (and the cholesterol content of LDL subclasses), LDL particle number (approximated by apolipoprotein B), and LDL particle size. This was a multicenter, double-blind, randomized, parallel-group study of hypercholesterolemic, high atherosclerotic coronary heart disease risk patients. After stabilization of atorvastatin 40 mg, 579 patients with LDL-C >70 mg/dL were randomized to 6 weeks of ezetimibe + atorvastatin 40 mg or atorvastatin 80 mg. Efficacy parameters included changes from baseline in LDL-C, apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), and lipoprotein subclasses (Vertical Auto Profile II) and pattern for the overall population, as well as patient subgroups with baseline triglyceride levels <150 mg/dL or ≥150 mg/dL., Results: Both treatments significantly reduced LDL-C (and the cholesterol content of most LDL subfractions [LDL1-4]) apolipoprotein B, non-HDL-C levels, but did not reduce the proportion of smaller, more dense LDL particles; in fact, the proportion of Pattern B was numerically increased. Results were generally similar in patients with triglyceride levels <150 or ≥150 mg/dL., Conclusions: When assessing the effects of escalating cholesterol-lowering therapy, effects upon Pattern B alone to assess coronary heart disease risk may be misleading when interpreted without considerations of other lipid effects, such as reductions in LDL-C, atherogenic lipoprotein particle concentration, and non-HDL-C levels., Trial Registration: (Registered at clinicaltrials.gov: Clinical trial # NCT00276484).