Oral enzyme combination therapy reduces systemic inflammation, urinary CTXII and pain in knee osteoarthritis: a proof-of-mechanism, randomised, crossover, double-blind, placebo-controlled trial.

Objectives: Oral enzyme combination (OEC) therapy with bromelain, trypsin and rutoside reduces pain and improves function in patients with knee osteoarthritis (OA). Here, we investigated several potential biological mechanisms underlying the clinical effects of OEC therapy in patients with established knee OA with respect to innate immunity, systemic inflammation and cartilage turnover (EudraCT 2020-003154-80, NCT05038410).

Methods: Patients (age ≥40 years, body mass index (BMI) ≤35 kg/m) with symptomatic knee OA were randomised to either placebo or OEC, administered 2×3 tablets/day, for 8 weeks before crossing over after a 4-week washout period.

Short-term pre-meal whey protein microgel supplementation reduces postprandial glycemia and appetite in adults with overweight: An open-label randomised controlled trial.

Background: Premeal whey protein (WP) consumption may reduce postprandial glucose (PPG) levels and appetite. We assessed the effects of twice daily consumption of a low-dose non-gelling novel WP formulation (WP microgel [WPM]) on PPG, self-reported appetite, and ad-libitum food consumption.

Methods: This was a randomized, prospective, open-label, controlled, single-center crossover study, and adults with BMI 27-35 kg/m were randomized to consume either 125 mL of 10 g WPM or control (water) 15 min before breakfast and lunch for four consecutive days.

Low plasma pancreatic lipase as a novel predictor of nutritional target achievement and response to nutritional interventions in malnourished inpatients: Secondary analysis of a randomized clinical trial.

Background & Aims: Pancreatic lipase plays an essential role in digesting dietary fats in the intestine, facilitating nutrient absorption. Plasma lipase serves as a surrogate for pancreatic exocrine function, which decreases with age and potentially leads to inadequate nutrient digestion and gastrointestinal symptoms. We investigated clinical implications of plasma lipase among medical inpatients at nutritional risk.

A Randomized, Placebo-Controlled, Single-Center, Crossover Study to Evaluate the Effects of Pre-Meal Whey Protein Microgel on Post-Prandial Glucometabolic and Amino Acid Response in People with Type 2 Diabetes and Overweight or Obesity.

: Whey protein (WP) consumption prior to a meal curbs appetite and reduces postprandial glucose (PPG) through stimulating endogenous GLP-1 secretion and insulin. : We assessed the metabolic effects of a concentrated WP, using a new micelle-technology (WPM), in people with type 2 diabetes (T2D) and overweight or obesity (NCT04639726). In a randomized-crossover design, participants performed two 240 min lunch meal (622 kcal) tests 7 ± 4 days apart.

Corrigendum to "Retrospective review of seven patients with obesity simultaneously treated with a combination of a glucagon-like peptide-1 receptor agonist and a meal replacement product" [Obesity Pillars 12C (2024) 100138].

[This corrects the article DOI: 10.1016/j.obpill.

Effect of medium-chain triglycerides and whey protein isolate preloads on glycaemia in type 2 diabetes: a randomized crossover study.

Background: Small nutritional preloads can reduce postprandial glucose excursions in individuals with and without metabolic syndrome or type 2 diabetes (T2D). However, most studies have focused on preloads administered before single meals and have predominantly used protein-based preloads.

Objectives: To investigate the effects of sequential consumption of medium-chain triglycerides (MCT) and whey protein isolate (WPI) preloads before breakfast, lunch, and dinner on postprandial, diurnal, and 24-h glycaemia in individuals with T2D.

Retrospective review of seven patients with obesity simultaneously treated with a combination of a glucagon-like peptide-1 receptor agonist and a meal replacement product.

Background: The use of meal replacement products (MRPs) to obtain a caloric deficit while maintaining micro- and macronutrient requirements, has a long tradition in obesity medicine. Limitations include low compliance, variability in efficacy, adverse events (related to acute changes in nutrient intake), and risk of weight regain when discontinued, and their popularity has declined after the emergence of potent GLP-1 receptor analogues (GLP1-RAs). However, GLP-1RAs have limitations, including dose-dependent risk for adverse events (AEs), high cost, as well as weight regain when discontinued.

Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin: A Secondary Analysis of Randomized Clinical Trials.

Importance: Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype.

Objective: To evaluate the associations between hypoglycemia and CV outcomes.

Design, Setting, And Participants: This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor.

The OPTIFAST total and partial meal replacement programme reduces cardiometabolic risk in adults with obesity: Secondary and exploratory analysis of the OPTIWIN study.

Aim: The effects of weight loss with a partial or total meal replacement programme (MRP) on atherosclerotic cardiovascular disease (ASCVD) risk factors are not fully understood, in particular in people at higher CV risk. In the 52-week randomized controlled OPTIWIN study in men and women with obesity, meal replacement programme (total for first 26 weeks, partial for the ensuing 26 weeks) with OPTIFAST (OP) resulted in significantly greater weight loss compared with a low-calorie food-based (FB) dietary plan, both as part of a comprehensive lifestyle intervention [OP (n = 135)/FB (n = 138) week 26: -12.4%/-6.

Oral enzyme combination with bromelain, trypsin and the flavonoid rutoside reduces systemic inflammation and pain when used pre- and post-operatively in elective total hip replacement: a randomized exploratory placebo-controlled trial.

Background: Early mobilization after total hip replacement (THR) is key for fast recovery but is often limited by pain. Oral enzyme combinations (OECs) have demonstrated anti-inflammatory and pain-relieving effects.

Objectives And Design: This prospective, randomized, double-blind, placebo-controlled exploratory trial evaluated the effects of pre- and post-operative use of OEC (90 mg bromelain, 48 mg trypsin, 100 mg rutoside) following elective THR, on post-operative recovery.

Oligomalt, a New Slowly Digestible Carbohydrate, Is Well Tolerated in Healthy Young Men and Women at Intakes Up to 180 Gram per Day: A Randomized, Double-Blind, Crossover Trial.

In this randomized, double-blind triple-crossover study (NCT05142137), the digestive tolerance and safety of a novel, slowly digestible carbohydrate (SDC), oligomalt, an α-1,3/α-1,6-glucan α-glucose-based polymer, was assessed in healthy adults over three separate 7-day periods, comparing a high dose of oligomalt (180 g/day) or a moderate dose of oligomalt (80 g/day in combination with 100 g maltodextrin/day) with maltodextrin (180 g/day), provided as four daily servings in 300 mL of water with a meal. Each period was followed by a one-week washout. A total of 24 subjects (15 females, age 34 years, BMI 22.

Development of a tool to predict the risk of incident heart failure in a general population: the HUNT for HF risk score.

Aims: Currently, no incident heart failure (HF) risk score that is in regular use in a general population is available. We aimed to develop this and compare with existing HF risk scores.

Methods And Results: Participants in the third wave (2006-08) of the population-based Trøndelag Health Study 3 (HUNT3) were included if they reported no previous HF.

A Randomized, Placebo-Controlled Crossover Study to Evaluate Postprandial Glucometabolic Effects of Mulberry Leaf Extract, Vitamin D, Chromium, and Fiber in People with Type 2 Diabetes.

Introduction: Reducing postprandial (PP) hyperglycemia and PP glucose excursions is important for overall glycemic management. Although most therapeutic lifestyle interventions that reduce caloric intake would affect this, there is no particular nutritional intervention favored.

Methods: We evaluated the effects of a novel natural food adjuvant combining mulberry leaf extract (MLE) with other bioactive ingredients, in people with type 2 diabetes (T2D) originating from Asia, on improving PP glucometabolic response in a randomized controlled exploratory crossover, two-center study (USA, Singapore).

Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk.

Aims: We addressed the question whether chronic kidney disease (CKD) may contribute to cognitive decline in type 2 diabetes.

Methods: Participants with type 2 diabetes with elevated cardiovascular risk or CKD from cognition substudies of two large trials were studied prospectively (CARMELINA: n = 2666, mean ± SD age 68.1 ± 8.

Females with type 2 diabetes are at higher risk for accelerated cognitive decline than males: CAROLINA-COGNITION study.

Background And Aim: Cognitive dysfunction is increasingly recognized as an important comorbidity of type 2 diabetes (T2D). We aimed to establish if the risk of accelerated cognitive decline (ACD) is higher in females with T2D than males.

Methods And Results: 3163 participants (38% female) with T2D from the cognition substudy of CAROLINA® (NCT01243424) were included (mean age 64.

Erratum to: Effect of linagliptin versus placebo on cardiovascular and kidney outcomes in nephrotic-range proteinuria and type 2 diabetes (t2d): the carmelina randomised controlled trial.

[This corrects the article DOI: 10.1093/ckj/sfaa225.].

Role of a Digital Clinical Decision-Support System in General Practitioners' Management of COPD in Norway.

Background: The study investigated if a web-based clinical decision-support system (CDSS) tool would improve general practitioners' (GPs) accuracy of diagnosis and classification of patients with chronic obstructive pulmonary disease (COPD), and whether nonpharmacological and pharmacological treatment would be better aligned with the COPD guidelines.

Methods: GPs were randomized to either a single use of the CDSS or continuing standard of care. The clinical recommendations of the CDSS were based on the GOLD guidelines and provided suggestions for treatment and management of COPD.

Effect of empagliflozin on cardiorenal outcomes and mortality according to body mass index: A subgroup analysis of the EMPA-REG OUTCOME trial with a focus on Asia.

Aim: To investigate whether the cardiorenal benefits of the sodium-glucose co-transporter-2 inhibitor empagliflozin are affected by body mass index (BMI) in type 2 diabetes patients with established cardiovascular (CV) disease, including Asians.

Methods: In this exploratory analysis of the EMPA-REG OUTCOME trial, we used Cox regression to evaluate the effects of empagliflozin on all-cause mortality, hospitalization for heart failure (HHF) or CV death, and incident or worsening nephropathy by baseline BMI category.

Results: Of the 7020 participants (1517 Asians [21.

Differences in glycemic control between the treatment arms in cardiovascular outcome trials of type 2 diabetes medications do not explain cardiovascular benefits.

Hyperglycemia is an undisputed epidemiological risk factor for microvascular complications in both type 1 and type 2 diabetes, integral in their causal pathways. Importantly, interventions that reduce the hyperglycemic burden in patients with either type of diabetes reduce the risk of microvascular complications (e.g.

Effect of linagliptin versus placebo on cardiovascular and kidney outcomes in nephrotic-range proteinuria and type 2 diabetes: the CARMELINA randomized controlled trial.

Background: Nephrotic-range proteinuria (NRP) is associated with rapid kidney function loss and increased cardiovascular (CV) disease risk. We assessed the effects of linagliptin (LINA) on CV and kidney outcomes in people with Type 2 diabetes (T2D) with or without NRP.

Methods: Cardiovascular and renal microvascular outcome study with LINA randomized participants with T2D and CV disease and/or kidney disease to LINA 5 mg or placebo (PBO).

Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study.

Aims/hypothesis: Type 2 diabetes, particularly with concomitant CVD, is associated with an increased risk of cognitive impairment. We assessed the effect on accelerated cognitive decline (ACD) of the DPP-4 inhibitor linagliptin vs the sulfonylurea glimepiride in individuals with type 2 diabetes.

Methods: The CAROLINA-COGNITION study was part of the randomised, double-blind, active-controlled CAROLINA trial that evaluated the cardiovascular safety of linagliptin vs glimepiride in individuals with age ≥40 and ≤85 years and HbA 48-69 mmol/mol (6.

Impact of polyvascular disease with and without co-existent kidney dysfunction on cardiovascular outcomes in diabetes: A post hoc analysis of EMPA-REG OUTCOME.

Aim: To determine the relationship between polyvascular disease and risk of hospitalization for heart failure (HHF) and cardiovascular (CV) death in the EMPA-REG OUTCOME population, and the relationship of kidney dysfunction co-existent with polyvascular disease on CV/heart failure (HF) outcomes.

Materials And Methods: Patients with type 2 diabetes and atherosclerotic CV (ASCVD) received empagliflozin 10, 25 mg or placebo. Post hoc, subgroups were analyzed by one versus two or more vascular beds, and the estimated glomerular filtration rate ([eGFR] < vs.