An oleuropein-based dietary supplement may improve joint functional capacity in older people with high knee joint pain: findings from a multicentre-RCT and analysis.

Objectives: To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation.

Design: This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive, an OLE containing 50 mg of oleuropein) for 6 months.

A Randomized Study to Compare a Monthly to a Daily Administration of Vitamin D₃ Supplementation.

We aimed to determine whether a cumulative dose of vitamin D₃ produces the same effects on the serum concentration of 25(OH)D₃ if it is given daily or monthly. This is a monocentric, two-armed, randomized, interventional, open, and parallel study conducted from November 2016 to March 2017 in Belgium. We randomized 60 subjects with vitamin D deficiency to receive 2000 IU vitamin D₃ daily or 50,000 IU monthly.

[Complementarity between randomised controlled trials and observational registries : the example of cardiovascular prevention with SGLT2 inhibitors].

Evidence-based medicine (EBM) is mainly supported by the results of randomised controlled trials (RCTs). If the latter offer guarantees of reliability, especially by minimizing the influence of confounding factors and potential biases, they also have limitations. Observational databases resulting from real life registries, if possible build in a prospective manner, may offer some solutions, but are also exposed to limitations.

[Cardiorenal protection with SGLT2 inhibitors (gliflozins) : from EMPA-REG OUTCOME to CANVAS].

The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk: similar and significant reductions in major CV events (-14 vs. -14%), in hospitalisations for heart failure (-35 vs. -33%) and in renal events (-39 vs.

[Cardiovascular protection of patients with type 2 diabetes : from EMPA-REG OUTCOME to LEADER].

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively). A lower progression of kidney disease and less renal events were also reported.

A Randomised, Cross-Over Study to Estimate the Influence of Food on the 25-Hydroxyvitamin D₃ Serum Level after Vitamin D₃ Supplementation.

Vitamin D₃ is known to be liposoluble and its release could be a factor limiting the rate of absorption. It was presumed that the presence of fat could favor absorption of vitamin D₃. However, as bioavailability is related not only to the active molecules but also to the formulations and excipients used, the optimization of the pharmaceutical form of vitamin D₃ is also important.

[STRENGTHS AND WEAKNESSES OF RANDOMISED CLINICAL TRIALS: EVOLVING CHANGES ACCORDING TO PERSONALIZED MEDICINE].

Randomised Controlled Trials (RCTs) represent the cornerstone of Evidence-Based Medicine (EBM). Based upon the rules of Good Clinical Practice (GCP), they offer many strengths but also present some weaknesses. The rigorous methodology used allows avoid bias related to confounding factors (through a control group), selection bias (through randomisation) and interpretation bias (through double blinding).

A Randomized, Double-Blind, Parallel Study to Evaluate the Dose-Response of Three Different Vitamin D Treatment Schemes on the 25-Hydroxyvitamin D Serum Concentration in Patients with Vitamin D Deficiency.

Many people worldwide are vitamin D (VTD) deficient or insufficient, and there is still no consensus on the dose of VTD that should be administered to achieve a 25(OH)D concentration of 20 or 30 ng/mL. In this study, we aimed to determine an adapted supplementation of VTD able to quickly and safely increase the vitamin D status of healthy adults with low 25(OH)D. One hundred and fifty (150) subjects were randomized into three groups, each to receive, orally, a loading dose of 50,000, 100,000 or 200,000 IU of VTD3 at Week 0, followed by 25,000, 50,000 or 100,000 IU at Week 4 and Week 8.

[How I explore ... a risk difference in the occurrence of an event in clinical trials].

Evidence-based medicine often requires the comparison of two therapeutic interventions in controlled clinical trials with the demonstration of a superiority (versus a placebo or an active comparator) or at least a non-inferiority (versus an active reference) concerning a primary endpoint that has been defined a priori (occurrence of a major clinical event, for instance). The difference in the occurrence of such an event between two treatments may be statistically analyzed by absolute risk reduction, relative risk reduction, hazard ratio or odds ratio. The present article discusses the nuances, sometimes of importance, concerning the significance of these various indices and analyses the cautions to be taken and the pitfalls to be avoided in their interpretation and use in practice.

[Renal SGLT2 inhibitors, new agents for the management of type 2 diabetes].

Kidney plays a role in glucose homeostasis, not only by its capacity to produce glucose through local gluconeogenesis, but also, and even more important in presence of diabetes, by its capacity to excrete glucose in urine when hyperglycaemia exceeds tubular reabsorption threshold. Such reabsorption depends on sodium-glucose cotransporters-2 (SGLT2), which can be blocked by selective inhibitors. These pharmacological agents augment glucosuria and reduce hyperglycaemia independently of insulin.

[Strategies avoiding inertia and non compliance in clinical trials].

Randomised controlled trials play a key role in evidence-based medicine as far as the assessment of both efficacy and safety of drugs is concerned. Various strategies are used to avoid physician's inertia and to combat patient's non compliance, two pitfalls that may hinder the demonstration of the therapeutic efficacy of the drug. Clinical inertia may be limited by titration, forced or optional, driven by therapeutic targets, or by the use, if necessary, of rescue medications.

[Optimisation of pharmacological therapy in a patient with a newly diagnosed type 2 diabetes].

The diabetic patient, when type 2 diabetes is newly diagnosed, raises a therapeutic problem commonly observed in clinical practice, which is more complex than expected at first glance. The physician has to select the most appropriate antidiabetic oral agent as first choice, to consider the potential of using combined glucose-lowering therapies, to fix glycaemic target taking into account the individual benefit/risk ratio, and to offer the best protection against cardiovascular complications. The present clinical case illustrates such therapeutic problem describing a patient with a high cardiovascular risk profile who experienced a hypoglycaemic episode after the prescription of glibenclamide following the discovery of a moderate hyperglycaemia.

[Blood glucose control and cardiovascular disease in patients with type 2 diabetes. Results of ACCORD, ADVANCE and VA-Diabetes trials].

Type 2 diabetes is associated with a high risk of complications, essentially macrovascular events. Surprisingly, the effect of improved glucose control on coronary and cerebrovascular complications in this population remains questionable. Furthermore, the target level of glycated haemoglobin (HbA1c) to minimise the risk of diabetic complications is controversial.

[Brain, a gluco-dependent organ: toxic effects of hypoglycaemia and hyperglycaemia].

Glucose is almost the only energy substrate for the brain. Such glucose dependence explains why any large variation of plasma glucose levels could lead to cerebral dysfunction, which may be severe and progress to a coma. Hypoglycaemic coma, the most common one, has a pure metabolic origin (neuroglucopenia) whereas hyperglycaemic coma is more complex and mainly due to osmotic disturbances.

[Alcohol, insulin sensitivity and diabetes].

The relationship between alcohol consumption and insulin resistance shows a U-shaped curve: insulin resistance is minimal in individuals with regular mild to moderate alcohol consumption and increases in both heavy drinkers and subjects without any alcohol consumption. These favourable metabolic effects on insulin sensitivity of moderate alcohol consumption may explain the significant reduction in the development of type 2 diabetes and the risk of cardiovascular complications reported in numerous epidemiological studies. This latter effect has also reported in patients with diabetes mellitus, although this observation remains controversial.

[Prevention of hypoglycemia in patients with type 1 diabetes].

Hypoglycaemia is the most common metabolic disorder in type 1 diabetic patients. It is rarely dangerous, but significantly alters the quality of life and hinders the achievement of "normoglycaemia". Even if hypoglycaemia is impossible to be avoided, both its frequency and severity may be reduced if patients follow several practical recommendations.

[Postprandial hyperglycemia. I. Physiopathology, clinical consequences and dietary management].

Postprandial hyperglycaemia depends on the amount and type of ingested carbohydrates and/or the degree of inhibition of hepatic glucose output following a meal. The kinetics of carbohydrate absorption is directly influenced by the type of food (carbohydrates with variable glycaemic indices, fibre content of the meal) and by the speed of gastric emptying. Hepatic glucose output is remarkably inhibited by insulin and strongly stimulated by glucagon.

[How I explore ... the risk of a patient developing type 2 diabetes].

Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important to detect at risk individuals in order to provide appropriate diet and exercise recommendations or even pharmacological treatment.

[How I explore ... the different forms of sugar diabetes: clinical and biological differental diagnosis].

Owing to the increasing prevalence of diabetes mellitus and the various aspects of this disease, we present a practical approach which allows the clinician to more easily differentiate type 1 diabetes, type 2 diabetes and secondary diabetes of pancreatic origin, i.e. the most common forms of diabetes mellitus.

[Multidisciplinary management of the obese patient: example from the Obesity Center at the University of Liege].

Obesity is a mulfactorial disease whose prevalence is progressively increasing. Ideally, it requires a multidisciplinary management by medical doctors, dieticians, psychologists and kinetherapists. The new "Centre de l'Obésité" at the University of Liège aims at fulfilling such objectives with: 1) a first outpatient visit including the simultaneous participation of an endocrinologist, a dietician and a psychologist; 2) a structured and individualized programme of physical rehabilitation; 3) an individualized management of obese subjects as in-(hospital) and/or outpatients, using medical and/or surgical approaches; and 4) an opportunity to benefit of other specialized medical advices, if necessary, in order to increase both the efficacy and safety of the treatment.

[Muscular exercise in the diabetic patient].

Muscular exercise is recommended in patients with type 1 or type 2 diabetes mellitus and is part of the overall management, in combination with diet, oral antidiabetic agents and/or insulin. From a pathophysiological point of view, regular physical activity enhances insulin sensitivity, thus contributing to improve blood glucose control and to reduce cardiovascular risk factors associated to diabetes mellitus. From a practical point of view, however, muscular exercise in a diabetic patient requires special caution, in particular careful selection of the type of exercise, respect of metabolic and/or cardiovascular contraindications, and appropriate adjustment of current pharmacological/dietary treatment.

[Hormonal-metabolic adaptations to muscular exercise].

Physical exercise induces numerous metabolic and hormonal changes that may be influenced by various factors, among which the intensity and the duration of the exertion seem to play a major role besides the possible influence of the intake of exogenous substrates. Such modifications are necessary to satisfy the marked increase in energy demand by exercising muscles, while maintaining plasma glucose concentrations within physiological range. The purpose of the present concise review is to analyse the most important fuel-hormonal adaptations observed during short heavy muscular exercise or during prolonged exercise of moderate intensity as well as those observed after physical training in normal subjects.

Relationships between metabolic clearance rate of insulin and body mass index in a female population ranging from anorexia nervosa to severe obesity.

Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body composition. This study aimed to investigate the relationship between the MCRI and BMI in an exclusively female population showing a wide range of BMI.