Not performing an OGTT results in significant underdiagnosis of (pre)diabetes in a high risk adult Caucasian population.

OBJECTIVE: Type 2 diabetes (T2DM) is known to be underdiagnosed. Tests for diagnosis include fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) and HbA1c. HbA1c can be tested in non-fasting conditions. Therefore, general practitioners almost no longer execute OGTT's. We evaluated the performance of OGTT versus HbA1c in a population consisting of overweight and obese subjects, which can be considered a 'high risk' population. RESEARCH DESIGN AND METHODS: A total of, 1241 overweight and obese subjects without a history of diabetes (male/female: 375/866, age 44±13 years, body mass index 38.0±6.1 kg m-2) were tested for glucose tolerance status using FPG, OGTT and HbA1c. RESULTS: Exactly, 46.8% were found to have prediabetes and 11.9% were newly diagnosed with T2DM (male/female=18.9/8.9%) using ADA criteria. Testing only HbA1c would have resulted in 78 subjects being diagnosed with T2DM, but 47.3% of newly diagnosed patients would have been missed if OGTT would not have been done. Exactly 581 subjects were diagnosed with prediabetes, 1.4% subjects had impaired fasting glucose (IFG) 30.5% had impaired glucose tolerance (IGT), 5.1% subjects had a combined IFG+IGT, and 9.8% had an isolated elevated HbA1c (5.7-6.4%). Of the 581 subjects with prediabetes, 257 had an HbA1c <5.7%. Therefore, 44.2% subjects would have been missed when OGTT would not have been done. CONCLUSION: In a population with only overweight and obese adult subjects, 46.8% were diagnosed with prediabetes and 11.9% were newly diagnosed with diabetes. Exactly, 5.6 and 20.7% of total population met the diagnostic criteria of the OGTT for diabetes and prediabetes, respectively, but did not meet the diagnostic criteria of the HbA1c. These data suggest that not performing an OGTT results in significant underdiagnose of T2DM in an overweight and obese adult population.

Drug-induced obesity and its metabolic consequences: a review with a focus on mechanisms and possible therapeutic options.

Weight gain is a common side effect of many widely used drugs. Weight gain of a few kilograms to an increase of 10% or more of initial body weight has been described. Not only the weight gain as such puts a burden on the health risks of the involved patients, the accompanying increase in the incidence of the metabolic syndrome, type 2 diabetes mellitus, and cardiovascular risk factors urges the caregiver to identify and to closely monitor the patients at risk. In this review, the different classes of drugs with significant weight gaining properties and the metabolic consequences are described. Specific attention is given to pathogenetic mechanisms underlying the metabolic effects and to potential therapeutic measures to prevent them.

Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity.

BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.

[Sitagliptin in the treatment of type 2 diabetes: insights five years after commercialisation]. / La sitagliptine dans le traitement du diabète de type 2: le point, cinq ans après sa commercialisation.

Sitagliptin (Januvia) was the first selective inhibitor of dipeptidyl peptidase-4 commercialized for the management of type 2 diabetes. It is also available as a fixed-dose combination with meformin (Janumet). Almost 5 years after its launch in Belgium, the present review summarizes the most recent data regarding the clinical efficacy of this antidiabetic agent, the controversy about its safety profile, its use at lower dosage in case of moderate to severe renal insufficiency, the various indications that have been successively accepted and reimbursed, and, finally, the perspectives offered by a large ongoing cardiovascular outcome trial (TECOS).

[Jentadueto, fixed combination of linagliptin plus metformin for the treatment of type 2 diabetes]. / Jentadueto, combinaison fixe linagliptine- metformine pour le traitement du diabète de type 2.

In case of failure of metformin monotherapy, several pharmacological strategies may be considered for the treatment of type 2 diabetes. Among these, the addition of an inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme, a medication commonly named as gliptin, is increasingly used because of two main advantages over sulfonylureas, i.e. the absence of both hypoglycaemia and weight gain. The combination of a gliptin and metformin further improves glycaemic control compared to either monotherapy, due to complementary mechanisms of action. Most patients with type 2 diabetes are treated every day with numerous drugs because of the presence of comorbidities so that poor drug compliance is a major concern in such a population. The use of fixed-dose combinations (FDCs) may improve compliance and, therefore, several gliptin-metformin FDCs are now available. The most recent one is Jentadueto, which combines linagliptin, a selective DPP-4 inhibitor without renal excretion, and metformin, the first-line antidiabetic compound. This FDC is commercialized with two dosages of metformin, i.e. 2.5 mg linagliptin/850 mg metformin and 2.5 mg linagliptin/1.000 mg metformin, and should be administered twice daily with meal.While linagliptin may be prescribed whatever the renal function, the use of FDC should take into account classical restrictions imposed by the presence of metformin.

Genetic association between WNT10B polymorphisms and obesity in a Belgian case-control population is restricted to males.

The Wnt pathway has been shown to play an important role in maintenance of stem cells and cell fate decisions in embryonic and adult stem cell populations. Activation of the Wnt pathway in mesenchymal stem cells and 3 T3-L1 cells inhibits adipogenesis and can lead to osteoblastogenesis. To evaluate the role of the Wnt pathway in adipogenesis and obesity further, we analysed the genetic association between polymorphisms in WNT10B, an activator of the Wnt pathway, and various obesity parameters in a Belgian population. Four tagSNPs that captured variation of ten SNPs (MAF>5%) in a 15.2 kb region spanning the WNT10B gene and its 3' and 5' flanking regions were genotyped. Our population consisted of 1013 obese patients (BMI≥30 kg/m(2); 468 males) and 531 lean healthy individuals (18.5 kg/m(2)≤BMI≤24.9 kg/m(2); 194 males). We found a significant association with body mass index (BMI) for three of the genotyped tagSNPs (rs4018511, rs10875902, rs833841) in the male population as analysed by logistic regression. Allelic heterogeneity testing demonstrated that these associations all represent the same significant signal. Two of the three significant SNPs were also found to be associated with BMI and weight in the male population as analysed by linear regression. In conclusion, common variation in WNT10B was shown to be associated with BMI and weight in a case-control population of Belgian males. Nonetheless, replication of this result and elucidation of the molecular actions of WNT10B remain necessary.

Maintained intentional weight loss reduces cardiovascular outcomes: results from the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.

AIM: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. METHODS: Overweight/obese subjects (N = 10 744), ≥55 years with cardiovascular disease and/or type 2 diabetes mellitus, received sibutramine plus weight management during a 6-week Lead-in Period before randomization to continue sibutramine (N = 4906) or to receive placebo (N = 4898). The primary endpoint was the time from randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). RESULTS: For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although more events occurred in the randomized sibutramine group, on an average, a modest weight loss of approximately 3 kg achieved in the Lead-in Period appeared to offset this increased event rate. Moderate weight loss (3-10 kg) reduced cardiovascular deaths in those with severe, moderate or mild cardiovascular disease. CONCLUSIONS: Modest weight loss over short-term (6 weeks) and longer-term (6-12 months) periods is associated with reduction in subsequent cardiovascular mortality for the following 4-5 years even in those with pre-existing cardiovascular disease. While the sibutramine group experienced more primary outcome events than the placebo group, greater weight loss reduced overall risk of these occurring in both groups.

[Linagliptin (Trajenta): a selective DPP-4 inhibitor with limited renal elimination]. / Le médicament du mois: Linagliptine (Trajenta): un inhibiteur sélectif de la DPP-4 à élimination rénale négligeable.

Linagliptin (Trajenta) is a selective inhibitor of dipeptidyl peptidase-4, an enzyme that degrades two incretin hormones, GLP-1 ("Glucagon-Like Peptide-1") and GIP ("Glucose-dependent Insulinotropic Polypeptide"). As other molecules belonging to this pharmacological class, linagliptin improves blood glucose control of type 2 diabetic patients, without increasing hypoglycaemic risk, without promoting weight gain and with a good clinical and biological tolerance profile. Both efficacy and safety have been demonstrated in randomized controlled trials as monotherapy or in combination with other glucose-lowering agents, independent of demographic or clinical patient's characteristics. The pharmacokinetics specificity of linagliptin comprises its biliary excretion, with low hepatic metabolism (no drug-drug interactions) and, in contrast to other gliptins, its negligible renal elimination. Because of these favourable properties, linagliptin may be used without dose adjustment (5 mg once a day) in patients with renal impairment, as well as in elderly people.

Environmental pollutants and type 2 diabetes: a review of mechanisms that can disrupt beta cell function.

The prevalence of diabetes mellitus is currently at epidemic proportions and it is estimated that it will increase even further over the next decades. Although genetic predisposition and lifestyle choices are commonly accepted reasons for the occurrence of type 2 diabetes, it has recently been suggested that environmental pollutants are additional risk factors for diabetes development and this review aims to give an overview of the current evidence for this. More specifically, because of the crucial role of pancreatic beta cells in the development and progression of type 2 diabetes, the present work summarises the known effects of several compounds on beta cell function with reference to mechanistic studies that have elucidated how these compounds interfere with the insulin secreting capacity of beta cells. Oestrogenic compounds, organophosphorus compounds, persistent organic pollutants and heavy metals are discussed, and a critical reflection on the relevance of the concentrations used in mechanistic studies relative to the levels found in the human population is given. It is clear that some environmental pollutants affect pancreatic beta cell function, as both epidemiological and experimental research is accumulating. This supports the need to develop a solid and structured platform to fully explore the diabetes-inducing potential of pollutants.

[Glycemic control before and after sitagliptin in general medical practice: analysis of determinant factors in the Belgian observational study "SUGAR"]. / Contrôle glycémique avant et après sitagliptine en médecine générale: analyse des facteurs déterminants dans l'étude observationnelle belge "SUGAR".

Sitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4 with a so-called incretin effect, has been evaluated in SUGAR, a large Belgian prospective observational study carried out in general practice. Sitagliptin, at a dose of 100 mg once daily, was added to previous treatment of not well controlled type 2 diabetic patients (> 95% on metformin monotherapy). Among 605 patients analysed in intention to treat, the worse the glycaemic control at entry, the greatest the reduction in glycated haemoglobin (HbA1c) and fasting plasma glucose levels after the addition of sitagliptin (p < 0.001). No specific factor was associated with the quality of initial glucose control among age, body mass index, the duration of diabetes or the modalities of its pharmacological treatment. Similarly, among these factors, none was significantly associated with the reduction in HbA1c or fasting plasma glucose levels observed with the addition of sitagliptin. Thus, sitagliptin was as active in older as in younger subjects, in obese as in nonobese people and in patients with diabetes of long versus short duration. In particular, SUGAR recruited data on 191 patients above 70 years in whom sitagliptin was as effective and safe as in younger patients with type 2 diabetes.

Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial.

OBJECTIVE: To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. METHODS: SCOUT is an ongoing, prospective, randomized, double-blind, placebo-controlled outcome trial in cardiovascular high-risk overweight/obese patients. A total of 10 742 patients received single-blind sibutramine and individualized weight management during the 6-week lead-in period; 84% had a history of type 2 diabetes mellitus and additional co-morbidities. Post-hoc analyses assessed anthropomorphic and vital sign responses between patients with and without diabetes. RESULTS: Concomitant antidiabetic medication use was reported by 86% of the diabetic patients (approximately 30% required insulin-alone or in combination). Body weight and waist circumference decreased in diabetic patients: median 2.1 kg; 2.0 cm (both men and women); for those on insulin: 1.9 kg; 1.5/2.0 cm (men/women); without insulin: 2.3 kg; 2.0 cm (both men and women); blood pressure (BP) was also reduced (median systolic/diastolic 3.5/1.0 mmHg) with larger reductions in diabetic patients who were hypertensive and/or lost the most weight (>5%). In diabetic patients who entered with BP at target (<130/<85 mmHg) but did not lose weight (N = 245), increases of 3.5/2.0 mmHg were observed. Non-diabetic patients had greater weight losses (2.5 kg) but smaller reductions in BP (systolic/diastolic -2.5/-0.5 mmHg). Pulse rate increases were less in diabetic vs. non-diabetic patients (1.5 vs. 2.0 bpm). CONCLUSION: In these high-risk diabetic patients, sibutramine and lifestyle modifications for 6 weeks resulted in small, but clinically relevant, median reductions in body weight, waist circumference and BP. A small median increase in pulse rate was recorded.

[Sugar: results of a Belgian observational study on the use of sitagliptin in patients with type 2 diabetes]. / SUGAR: résultats d'une etude observationnelle belge concernant l'utilisation de la sitagliptine chez des patients diabétiques de type 2.

Sitagliptin (Januvia), the first selective inhibitor of dipeptidylpeptidase-4, has been assessed in a large Belgian prospective observational study. The aim of the SUGAR study was to evaluate the efficacy of sitagliptin, at a dose of 100 mg once daily, when it was added in patients with uncontrolled type 2 diabetes followed in real life conditions. In the intent-to-treat population (n = 605), mean glycated haemoglobin level decreased from 8.41 +/- 1.18% to 7.29 +/- 0.86% after a follow up averaging 110 days (p < 0.0001). Similarly, mean fasting plasma glucose level decreased from 180 +/- 50 mg/dl to 141 +/- 37 mg/ dl (p < 0.0001). The improvement of these two parameters was observed independently of basal demographic characteristics, but was directly influenced by baseline initial corresponding values. The vast majority of patients included in SUGAR were initially treated by metformin as monotherapy (current criterion for sitagliptin reimbursement in Belgium); metformin daily dose slightly decreased when sitagliptin was added (from 1975 +/- 681 mg to 1919 +/- 667 mg; p = 0.033). Patients receiving other glucose-lowering agents, as single or combined therapies, had also a significant alleviation of their treatment when sitagliptin was added. After 3-6 months of follow up, more than 95% of patients still received sitagliptin, arguing for both the efficacy and the good tolerance of this new oral antidiabetic agent in clinical practice.

[Liraglutide (Victoza): human glucagon-like peptide-1 used in once daily injection for the treatment of type 2 diabetes]. / Le médicament du mois. Liraglutide (Victoza): analogue du glucagon-like- peptide-1 humain en une injection par jour pour le traitement du diabète de type 2.

Liraglutide (Victoza) is a peptide produced by DNA recombinant technology, which presents 97% homology with human glucagon-like peptide-1 (GLP-1) but is resistant to dipeptidylpeptidase-4, the enzyme that degrades the natural hormone. It actives the GLP-1 receptor and exerts an incretin mimetic effect during at least 24 hours after a single subcutaneous injection. Besides a glucose-dependent stimulatory effect of insulin secretion, liraglutide inhibits glucagon secretion and retards gastric emptying. In patients with type 2 diabetes, it reduces glycated haemoglobin by at least 1%, without inducing hypoglycaemia. It also induces a moderate weight loss and a mild reduction in blood pressure. Gastrointestinal adverse events (nausea, vomiting) may occur during the initial phase of treatment, but rarely impose the interruption of the medication and usually diminish with time.Although indicated in combination with other glucose-lowering agents, liraglutide is currently reimbursed in Belgium only if administered in patients with type 2 diabetes not sufficiently controlled with a combination of metformin plus sulfonylurea or metformin plus a thiazolidinedione. Victoza is presented in prefilled pens and is injected subcutaneously once a day. Treatment will be initiated with 0.6 mg to improve digestive tolerance and the daily dose will be increased to 1.2 mg (usual dose) after at least one week, and up to 1.8 mg (maximal dose) if necessary.

[Clinical study of the month. Accord-lipid and accord-eye: towards a new positioning of fenofibrate in the management of type 2 diabetes]. / L'étude clinique du mois. ACCORD-LIPID et ACCORD-EYE: vers un nouveau positionnement du fénofibrate chez le patient diabétique de type 2.

Fenofibrate has been evaluated in the ACCORD trial, in combination with a statin, to prevent vascular complications in patients with type 2 diabetes. In ACCORD-Lipid, the addition of fenofibrate was not able to significantly reduce the incidence of a composite cardiovascular endpoint (no positive effect was also observed with the intensification of blood glucose or blood pressure control in this population). However, an interaction effect was observed according to basal lipid profile, suggesting a better protection by fenofibrate in patients with hypertriglyceridaemia and low HDL cholesterol (so-called atherogenic dyslipidaemia). In ACCORD-Eye, the addition of fenofibrate to a basal statin therapy resulted in a significant reduction of the progression of diabetic retinopathy, in a similar manner as that observed with intensifying blood glucose control (but with a good safety profile and without increasing the risk of hypoglycaemia). These observations, confirming earlier results from FIELD also with this fibrate, open new perspectives for a useful prescription of fenofibrate in patients with type 2 diabetes.

[Improved glucose control and weight loss with exenatide in patients with type 2 diabetes: results of a retrospective observational multicentre Belgian study]. / Amélioration du contrôle glycémique et perte de poids sous exénatide chez des patients diabétiques de type 2: résultats d'une étude rétrospective observationnelle multicentrique belge.

This is a retrospective analysis of medical records in 4 Belgian diabetes centres of 3 cohorts of patients with type 2 diabetes, with data available, respectively, after 3 months < or =163 patients exposed), 6 months (n=77) and 9 months (n=28) with exenatide therapy. This analysis mainly focuses on the 3 and 6 month cohorts. The mean HbA1 level at baseline averaged 9% and decreased by -1.3% and -1.4% at 3 and 6 months, respectively (-1.5% at 9 months). Neither the duration of diabetes nor initial body weight did influence the metabolic response. The decrease in HbA(1c) at 6 months was greater in patients with higher baseline HbA(1c):-0.5%, -1.4% and -2.4% for a baseline HbA(1c) level <8%, 8-10% and >10%, respectively. At 6 months, the composite criterion of a reduction of HbA(1c) by >1% or a final level <7% was reached by 69% of the cohort. Body weight decreased continuously over time, with a mean reduction of -2.1 kg at 3 months and -3.0 kg at 6 months (-4.9 kg at 9 months). The greater the baseline body weight, the greater the weight loss at final evaluation. Minor nausea and more rarely vomiting were observed, essentially during the first months of exenatide treatment. According to this observational study in routine practice, exenatide may be a valuable alternative to insulin for intensification of treatment of patients with type 2 diabetes after failure of oral drug combination, independently of baseline HbA(1c), body weight and duration of diabetes.

Sarcopenia in patients with non-alcoholic fatty liver disease: is it a clinically significant entity?

Sarcopenia, described as the loss of muscle mass and/or strength, is gaining importance as it can be increasingly related to many chronic diseases. It is also associated with chronic liver disease, and recently it has been more frequently linked to non-alcoholic fatty liver disease (NAFLD) in particular. Both sarcopenia and NAFLD are subject to complex and intermingled pathophysiological processes, of which some are in common. Furthermore, it is presently unclear if sarcopenia directly contributes to NAFLD or vice versa. The mechanisms that are involved may include obesity, insulin resistance, vitamin D deficiency, aging, physical inactivity and certain cytokines. Current clinical evidence is subject to an important heterogeneity in methods and definitions, with additionally also a relative overrepresentation of evidence in Asian ethnicities. Nonetheless, all studies so far point towards the same association between sarcopenia and NAFLD, including an association with NAFLD-severity and NAFLD-related fibrosis. Since the field is in its infancy, clear definitions and further research are needed to aid to improve understanding of the association between NAFLD and sarcopenia. This can eventually lead to additional potential therapeutic interventions. This review attempts to give an overview of the current published literature that links sarcopenia to NAFLD, followed by a discussion of the presumably involved pathophysiological factors, and ends by discussing current unmet needs.

[Medication of the month. Rimonabant (Acomplia): first CB1 receptor antagonist of the endocannabinoid system]. / Le médicament du mois. Rimonabant (Acomplia): premier antagoniste des récepteurs CB1 du système endocannabinoïde.

Rimonabant (Acomplia) is the first selective CB1 receptor blocker of the endocannabinoid system. Clinical trials showed that, compared to placebo, rimonabant 20 mg/ day consistently increases weight loss, reduces waist circumference, improves atherogenic dyslipidaemia (low HDL cholesterol, high triglycerides, high small dense LDL), diminishes insulin resistance, reduces HbA1c levels, and contributes to lower blood pressure and C-reactive protein levels. Almost half of the most important metabolic effects occur beyond weight loss, suggesting direct peripheral effects of rimonabant, especially in visceral adipose tissue as suggested by the increase in adiponectin levels. Rimonabant at a daily dose of 20 mg is indicated as an adjunct to diet and exercise for the treatment of obese patients, or overweight patients with associated risk factor(s) such as type 2 diabetes or dyslipidaemia. Adverse effects concern digestive tract (nausea, mostly transient) and psychological disorders (depressed mood, anxiety), in relation to the mechanism of action of the drug. Therefore, rimonabant is contra-indicated in case of depression and/or in patients receiving antidepressants.

[Sitagliptine (Januvia): incretin enhancer potentiating insulin secretion for the treatment of type 2 diabetes]. / Le médicament du mois. Sitagliptine (Januvia): incrétinopotentiateur indiqué comme insulinosécrétagogue dans le traitement du diabète de type 2.

Sitagliptin (Januvia) is the first selective antagonist of dipeptidylpeptidase-4, an enzyme that degrades glucagon-like peptide-1 (GLP-1). This hormone is mainly secreted by ileal L cells and this secretion is abnormally low in patients with type 2 diabetes. Sitagliptin increases post-meal insulin secretion ("incretin effect) by enhancing the postprandial GLP-1 response ("incretin enhancer"), in a glucose-dependent manner. It improves glycaemic control (HbA1c) in type 2 diabetic patients treated by diet alone, by metformin, by sulfonylurea, by glitazone or by a metformin-sufonylurea combined therapy. The glucose-lowering effect is similar to that of glipizide, but with the advantage of no weight gain and no hypoglycaemic episodes. The tolerance to sitagliptin is excellent. Treatment is simple, with 100 mg once daily, without need of titration or home blood glucose monitoring. In Belgium, sitagliptin is currently reimbursed in patients with type 2 diabetes not adequately controlled with diet and metformin monotherapy.

[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. / Le médicament du mois. Exénatide (Byetta). Incrétinomimétique indiqué dans le traitement du diabète de type 2 après échec et en complément des antidiabétiques oraux.

Exenatide (Byetta) is a synthetic derivative of exendin-4 and an agonist of receptors of glucagon-like peptide-1 (GLP-1). It is resistant to the rapid inactivation by dipeptidylpeptidase-4 and acts as an incretin mimetic. It stimulates insulin secretion by the B cell in a glucose-dependent manner whereas it inhibits glucagon secretion. Exenatide improves mainly postprandial glucose concentrations and lowers glycated haemoglobin (HbA(1c)) levels, without being directly responsible for hypoglycaemia or requiring mandatory home blood glucose monitoring. Furthermore, it slows down gastric emptying and promotes sustained body weight reduction, even in absence of frequently reported nausea following treatment initiation. Exenatide is recommended and reimbursed in Belgium for the treatment of type 2 diabetes, in combination with metformin and a sulfonylurea, in patients not adequately controlled with maximal tolerated doses of these oral glucose-lowering agents. Exenatide is presented as pre-filled pens for subcutaneous injection. The recommended initial dose is 5 microg before morning and evening meals, to be up titrated to 10 microg twice daily. Exenatide may represent a valuable alternative to insulin therapy, especially in overweight or obese patients with type 2 diabetes and not ready to perform home blood glucose monitoring.

[Endocannabinoid system in the brain...and elsewhere]. / Le système endocannabinoïde dans le cerveau...et ailleurs.

The endocannabinoid system is a complex system with endogenous ligands, synthesis and transport processes, specific receptors (CB1 and CB2) and intracellular degrading enzymes. It is widely distributed in the central nervous system, but also in peripheral organs. In the brain, endocannabinoids and CB1 receptors are almost ubiquitous and play a role in synaptic plasticity: they modulate, through an inhibitory retrograde action, the release of classical neurotransmitters such as amines, acetylcholine or amino acids. They may exert a neuroprotective effect, but are also involved in appetite and alcohol/drug dependence. At the periphery, they are present (and overexpressed in case of abdominal obesity) in various organs involved in energy control and metabolic regulation. Furthermore, CB2 receptors are also present in the brain, although less numerous than CB1 receptors. They could attenuate pain and also be neuroprotective. Selective agonists, antagonists and inverse agonists of CB1 and CB2 receptors are currently developed and open new interesting therapeutic perspectives. Rimonabant, a CB1 antagonist, has been recently launched for the treatment of obese or overweight patients at high cardiometabolic risk.