To develop a 10-year risk score to predict lower-limb amputation (LLA) in individuals with type 1 diabetes, and to assess whether this score also predicts kidney failure, and cardiovascular disease (CVD). The LLA risk score was derived from GENEDIAB and GENESIS, two prospective French and Belgian cohorts of 828 individuals with type 1 diabetes. External validation was assessed in SURGENE, an independent cohort of 247 individuals with type 1 diabetes. LLA was defined as a non-traumatic amputation above the metatarsophalangeal joint, kidney failure as the need for renal replacement therapy, transplantation, or an estimated glomerular filtration rate (eGFR) < 15 ml/min/1.73 m2, CVD as the occurrence of myocardial infarction, heart failure, or stroke, and major adverse cardiac event (MACE) as a composite of myocardial infarction, stroke, heart failure, or all-cause death. During 12 years of follow-up, LLA, kidney failure, CVD and MACE occurred in 71 (9

Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their ability to reduce major adverse cardiovascular events (MACEs) among at-risk patients living with type 2 diabetes (T2D). Tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrated a better control of hyperglycaemia, body weight and several cardiovascular risk factors than pure GLP-1RAs (including semaglutide) in dedicated studies of the SURPASS programme. SURPASS CVOT has the primary objective to demonstrate, in a population with T2D and atheromatous cardiovascular disease, the non-inferiority of tirzepatide regarding both efficacy and safety compared with dulaglutide, a selective GLP-RA that has already proven a significant reduction in MACEs versus placebo in the REWIND trial. Non-inferiority was met in SURPASS CVOT (p = 0.003), but not superiority of tirzepatide compared to dulaglutide (hazard ratio [HR] 0.92; 95 % confidence interval [IC] 0.83 to 1.01; P = 0.09) regarding the primary end point (reduction in MACEs). Several secondary end points tended to favour tirzepatide versus dulaglutide, among which a reduction in the incidence of all-cause deaths after four years of median follow-up (HR 0.84 ; 95 % CI 0.75 to 0.94; exploratory analysis). SURPASS CVOT, the first and unique study that used an active comparator rather than a placebo, confirms the efficacy and safety of the dual agonist tirzepatide in patients with T2D and atheromatous cardiovascular disease.

Metformin remains the first-line pharmacological agent for the treatment of type 2 diabetes. This clinical vignette first recalls the fundamental reasons supporting this recommendation. It then considers situations that may raise concerns, particularly in patients with renal disease and those with cardiovascular disease. Finally, several practical advises for a cautious use and an optimization of both tolerance and safety are outlined.

This article discusses the potential roles of global warming and various environmental pollutants in the increasing prevalence of obesity and type 2 diabetes. Global warming may exert detrimental effects through both biological pathways (reduced thermogenesis, adipocyte dysfunction) and behavioural mechanisms (decreased physical activity, sleep disturbances). Pollutants - whether present in ambient air (fine particulate matter), water, or food (broadly defined pesticides, industrial and domestic chemicals) - can alter metabolic processes, particularly within adipocytes, a key site where they tend to accumulate. They can induce "adiposopathy," low grade inflammation, oxidative stress, and insulin resistance. Pancreatic β cell dysfunction has also been reported. Thus, climate change and its environmental consequences should be taken into account when interpreting the global epidemic of obesity and type 2 diabetes that societies worldwide are currently facing.

The current special issue of the Revue Médicale de Liège assembles 21 articles, which all are devoted to one of the different aspects of One Health, an emergent polymorphic concept. Taken together, these contributions illustrate the diversity of this concept that requires a coordinated interdisciplinary approach to tackle major challenges to which our modern society is confronted.

Rivaroxaban, an oral direct anticoagulant that is a selective inhibitor of Xa factor, was commercialized in Belgium in 2009 with as unique reimbursed indication the prevention of thromboembolic events before a programmed hip or knee prosthesis. Since that time, both the efficacy and safety of rivaroxaban have been validated in a variety of indications : prevention and treatment of venous thromboembolic disease with or without pulmonary embolism, non valvular atrial fibrillation, symptomatic coronary disease and peripheral arteriopathy. Different presentations are currently available from 2.5 mg to 20 mg to allow the practitioner adjust the dosage of rivaroxaban to the specific indication (for instance, in patents with symptomatic atheromatous cardiovascular disease, 2 x 2.5 mg/day in combination with a antiplatelet agent).

The management of dyslipidaemias, especially of LDL hypercholesterolaemia (LDL-c), is at the forefront in the prevention of atherosclerotic cardiovascular disease (ASCVD). The latest international guidelines specifically devoted to dyslipidaemias were published in 2019. They allocated the people in four cardiovascular risk categories : very high risk, high risk, moderate risk and low risk. However, in the last recommendations for the prevention of ASCVD published in 2021 by the European Society of Cardiology, only three risk categories are recognized : very high, high and low-to-moderate. Current guidelines propose target LDL-c levels that are lowered according to the risk category : very high risk : LDL-c < 55 mg/dL; high risk : < 70 mg/dL; low-to-moderate risk : < 100 mg/dL. They support a step-by-step approach with a progressive intensification of the pharmacological treatment, moving from a monotherapy with statin to a combined therapy (addition of ezetimibe and/or PCSK9 inhibitor) in order to reach the recommended target levels. However, an earlier use of combined therapies should be recommended in secondary prevention and in primary prevention at very high risk.

Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, recently commercialized and reimbursed in Belgium for the treatment of type 2 diabetes (T2D). Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg as a once-weekly subcutaneous injection), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. Tirzepatide tolerance is almost similar to that of pure GLP-1 receptor agonists, with digestive adverse events, most often during the first weeks after initiation, which justifies the recommendation of progressive titration every four weeks. Tirzepatide is now refunded under conditions in Belgium for the treatment of TD2 in patients with a body mass index ≥ 30 kg/m² and a HbA1c level > 7.5 % with antihyperglycaemic therapy including metformin. These reimbursement conditions are similar to those of pure GLP-1 receptor agonists but are more restrictive than the indications validated by the European Medicines Agency and the latest guidelines by international scientific societies.

Type 2 diabetes management evolved considerably over the past few decades. The present article summarizes three successive key steps : the glucocentric target, the multirisk approach and the organ protection strategy.

Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which is developed as once-weekly subcutaneous injection. It has been developed in two huge research clinical programmes, SURPASS in type 2 diabetes and SURMOUNT in obesity. Obesity is often complicated by an obstructive sleep apnoea (OSA), which is associated with an increased morbidity and mortality. The controlled study SURMOUNT-OSA has been carried out in people with obesity and OSA, possibly already treated with a continuous positive airway pressure (CPAP). When compared to placebo, tirzepatide (10 or 15 mg/week) reduces body weight, diminishes the frequency and severity of sleep apnoea episodes, dampens hypoxia burden, lowers arterial blood pressure, reduces systemic inflammation and, in fine, improves the parameters of sleep quality reported by patients. Tirzepatide is indicated in the management of people with obesity or overweight who present at least one weight-related comorbidity factor among which OSA.

Chronic kidney disease (CKD), heart failure (HF) and atherosclerotic cardiovascular disease (ASCVD) are pathologies that may remain silent for a long time and thus are largely underdiagnosed in clinical practice. The use of biomarkers may help detect people already suffering from these diseases at an early stage or at increased risk to develop them in a near future. The aim of this article is to discuss the place of the assays of albuminuria, natriuretic peptide (BNP/proBNP) and high-sensitivity troponin as well as lipoprotein(a) to help in the diagnosis and prognosis assessment of individuals at risk of presenting or developing a CKD, HF or ASCVD. The use of these biomarkers remains too low in clinical practice whereas medications are now available (or will come very soon as for lipoprotein (a) - which allow minimizing the risk and improving the overall prognosis. Notably, it is the case with sodium-glucose cotransporter type 2 inhibitors (gliflozins) as far as CKD and HF are concerned.

Type 1 diabetes (T1D) is an autoimmune chronic disease that leads to the destruction of pancreatic beta cells and thus requires lifelong insulin therapy. Constraints and adverse events associated to insulin therapy are well known as well as the risk of long-term complications linked to chronic hyperglycaemia. Symptomatic T1D is preceded by a preclinical asymptomatic period, which is characterized by the presence of at least two auto-antibodies against beta cell without disturbances of blood glucose control (stage 1) or, in addition to immunological biomarkers, by the presence of mild dysglycaemia reflecting a defect of early insulin secretion (stage 2). Recent objectives for the management of this disease are to detect people with auto-antibodies in order to propose an early specific management to delay the shift to clinical stage (stage 3) and to limit its severity as well. The screening concerns as first step relatives of patients living with T1D and individuals presenting other auto-immune diseases, but may be extended to the general population (especially in young people) with the improvement of techniques of auto-antibody assays. Teplizumab, an anti-CD3 monoclonal antibody, slows down the decline of insulin secretion by beta cells, both in people at stage 2 and early stage 3. This medication, which may be considered as a disease-modifying agent of T1D, was approved in November 2022 by the U.S. Food and Drug Administration (FDA) and is currently evaluated by the European Medicines Agency (EMA).

Our modern society has to face several health problems, among which climate change characterized by global warming and increased pollution and obesity epidemic and associated morbidities are prominent ones. Interestingly, several epidemiological studies argue for a closed connection between these two health concerns, in fact pointing out a bidirectional relationship. Global warming and its associated exposure to pollutants could contribute to weight gain through different mechanisms, including some endocrine disorders linked to adipocyte dysfunction (adiposopathy) and reduced thermogenesis, as well as a reluctance to physical activity in a hot ambient temperature. Conversely, obesity epidemic may play a role in global warming by an increased consumption of energetic ultra-processed foods and an enhanced energy waste for transportation, both leading to increased greenhouse gas emission. Thus, there is an urgent need for greater action to slow the process of global warming also to prevent harmful effects on health linked to obesity epidemic.

Semaglutide (Ozempic®), administered as a weekly subcutaneous injection up to 1.0 mg, holds a privileged place in the international guidelines for the management of type 2 diabetes. Commercialized under the trade name Wegovy®, semaglutide is also indicated at a weekly dose up to 2.4 mg for the management of obesity or over-weight with at least one weight-related comorbidity, after failure and in combination with life-style interventions. Its efficacy and tolerance were investigated in the STEP clinical research programme. Gastrointestinal adverse events after initiation of therapy, as with all glucagon-like peptide-1 receptor agonists, requires a progressive titration every 4 weeks from 0.25 mg to 2.4 mg/week. It is the first anti-obesity medication that has shown a significant reduction of major cardiovascular events and all-cause mortality in the large placebo-controlled SELECT trial. Wegovy® is commercialized in Belgium (currently not reimbursed) according to the indications supported by the European Medicines Agency (EMA) both in adults and adolescents suffering from obesity or overweight with at least one weight-related complication, ideally within a holistic multidisciplinary approach.

Practitioners are increasing confronted to the management of type 2 diabetes (T2DM) among older patients. Specificities of the elderly should be considered, especially fragility and geriatric syndromes, and glycaemic objectives should be adapted according to the patient's individual profile, «vigorous», «fragile» or «ill», being stricter in individuals with the longer life expectancy. The basics of the therapy of T2DM are similar in older patients as in younger patients with, however, some specificities. A key objective is to avoid hypoglycaemic episodes that are particularly feared among older patients. The therapeutic approach should be personalized. It should take into account both patient's quality of life and environment as well as the presence of comorbidities that could influence the drug choice, for instance atheromatous cardiovascular disease, heart failure and chronic kidney disease.

Chronic kidney disease (CKD) is a common and severe complication in patients with type 2 diabetes (T2D). While inhibitors of the renin-angiotensin system remained for a long time the only medications that had proven nephroprotective effects, several other pharmacological classes also recently showed such a benefit : sodium-glucose cotransporter type 2 (SGLT2) inhibitors (gliflozins), glucagon-like peptide-1 receptor agonists (semaglutide), and mineralocorticoid receptor antagonists (MRA, finerenone). This clinical vignette aims at explaining the pharmacotherapy strategy for a patient with T2D who presents a progressive CKD. The interest of prescribing a combination of several medications with complementary actions that had proven a nephroprotection is emphasized.

Good clinical practice guidelines are intended to facilitate and improve patient care. However, it is clear that recommended targets are not reached among numerous patients in real life. It is the case for the control of cardiovascular risk factors such as hypercholesterolaemia, arterial hypertension and type 2 diabetes, both in primary and secondary prevention. Barriers are multiple and concern all field actors : prescribing doctors, patients regarding their medications, health care system and pharmaceutical industry. Identifying barriers and proposing solutions should help narrow the gap between guidelines and clinical practice.

This article outlines the 2024 KDIGO («Kidney Disease: Improving Global Outcomes») guidelines to slow the progression of chronic kidney disease in adults. Non-pharmacological measures include a healthy diet (Mediterranean or vegetarian), regular physical activity (150 minutes per week), smoking cessation, and weight loss. A low-salt diet (less than 5 g of salt per day) is also recommended. The latest KDIGOs advise a protein intake of 0.8 g/kg/day, with a potential reduction for some non-diabetic patients. Concerning drug-based therapies, renin-angiotensin system inhibitors remain crucial, particularly for patients with pathological albuminuria. Sodium-glucose cotransporter 2 inhibitors are becoming a key pillar of nephroprotection, even in non-diabetic patients. Mineralocorticoid receptor antagonists like finerenone and glucagon-like peptide-1 receptor agonists further enhance therapeutic options, especially in diabetic nephropathy. Finally, contrary to previous assumptions, reducing uric acid and systematically correcting acidosis are not considered as nephroprotective measures.