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.

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.

Screening for type 2 diabetes mellitus in overweight and obese subjects made easy by the FINDRISC score.

AIM: To evaluate the use of the FINDRISC score in an overweight and obese population to predict glucose status. METHODS: In 651 overweight/obese subjects (M/F: 193/458, age 43±13 y, BMI 38.2±6.1kg/m(2)) glucose status was tested using OGTT and HbA1c. Furthermore, the FINDRISC questionnaire and CT visceral fat (VAT) and subcutaneous fat (SAT) were examined. RESULTS: Exactly 50.4% were found to have prediabetes and 11.1% were newly diagnosed with type 2 diabetes (T2DM) (M/F=22.2/8.8%). Subjects without T2DM had a FINDRISC score of 11±3, those with pre-DM 13±4, and subjects with de novo T2DM 15±5. The aROC of the FINDRISC for detecting T2DM was 0.76 (95% CI 0.72-0.82), with 13 as cutoff point. The FINDRISC score correlated with VAT (r=0.34, p<0.001) and VAT/SAT ratio (r=0.39, p<0.001). The aROC of the FINDRISC to detect excess VAT was 0.79 (95%CI 0.72-0.84). CONCLUSIONS: In a large group of overweight and obese subjects, 50.4% were found to have pre-DM and 11.1% were newly diagnosed with T2DM. The FINDRISC score increased with worsening of glucose tolerance status and proved to be an independent predictor of T2DM status, as did HOMA-B, HOMA-S and VAT. The FINDRISC can also function as a good tool to predict visceral obesity.

Pivotal Role for the Visceral Fat Compartment in the Release of Persistent Organic Pollutants During Weight Loss.

CONTEXT: Polychlorinated biphenyls (PCBs), are implicated as potential endocrine disruptors and obesogens. These lipophilic substances are preferentially stored in the fat compartment and released into the circulation during weight loss. OBJECTIVE: The aim of this study was to examine the contribution of abdominal adiposity, and visceral adiposity in particular, to the increase of serum PCB levels during weight loss. MATERIALS AND METHODS: Fourty-five obese women were prospectively recruited. Twenty individuals received dietary counseling and 25 underwent bariatric surgery. Anthropometric data were collected and intra-abdominal adiposity was assessed by measurement computed tomography scanning of the abdominal fat compartment, delineating the visceral and subcutaneous compartment. Serum levels of 27 PCBs were determined and the sum of all PCBs (ΣPCBs) calculated. Follow-up measurements of anthropometric data, computed tomography scanning, and PCB levels were performed after 6 months in all patients. RESULTS: In patients who lost weight, serum ΣPCB levels displayed an increase after 6 months of approximately 50%. Both correlation and regression analysis, focusing on the relative contribution of the visceral vs the subcutaneous fat compartment, suggested that the increase in ΣPCB serum levels after 6 months of weight loss was more pronounced in patients losing relatively more visceral adipose tissue. This trend could be established in the diet-treated, but not the surgery-treated subgroup. CONCLUSION: Our study suggests that the contribution of PCBs released from the visceral fat compartment might be more pronounced compared with the subcutaneous fat compartment during weight loss. These findings are present in the entire study group whereas subanalysis of the diet vs surgery groups suggested the same effect in the diet group but failed to reach statistical significance in the surgery group. This suggests a possible weight-loss method-specific effect.

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.

Screening for genetic variants in BDNF that contribute to childhood obesity.

UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.

Common genetic variation in sFRP5 is associated with fat distribution in men.

Considering the role of sFRP5 in Wnt signalling, an important group of pathways regulating adipogenesis and inflammation, we performed a genetic association study on sFRP5 polymorphisms in a population of obese and lean individuals. Using information from the HapMap, two tagSNPs were identified in the sFRP5 gene region and genotyped on a population of 1,014 obese, non-diabetic individuals and 606 lean controls. We performed logistic and linear regression analysis including a wide variety of obesity parameters (BMI, waist circumference, height, WHR, fat mass, fat mass percentage and visceral, subcutaneous and total abdominal fat), in addition to OGTT and HOMA-IR values. We were able to show a significant association of sFRP5 with both total abdominal and subcutaneous fat. The association signal was only seen in obese males, and in this population, the minor allele of rs7072751 explains 1.8 % of variance in total abdominal fat. In addition, we saw a trend towards an association of rs10748709 with glucose metabolism. Although further research is necessary, we can conclude that sFRP5 is a significant regulator of fat development and distribution in obese males. We postulate that altered transcription factor binding on the rs7072751 surrounding sequence might play a role in the associations we found with both total abdominal and subcutaneous fat. In addition, although no conclusive evidence was found, our results indicate that sFRP5 genetic variation may affect glucose metabolism and it would be interesting to investigate this further.

[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.

Metabolic disregulation in obese adolescents with sleep-disordered breathing before and after weight loss.

OBJECTIVE: Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. DESIGN AND METHODS: Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. RESULTS: 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation () (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. CONCLUSION: SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.

No conclusive evidence for association of polymorphisms in the adiponectin receptor 1 gene, AdipoR1, with common obesity.

AdipoR1 is one of the adiponectin receptors which are important for adiponectin signaling. Because adiponectin is a candidate gene for common obesity, it is also hypothesized that variations in AdipoR1 may be involved in the development of complex obesity. Therefore, we designed an association study for the AdipoR1 gene. We performed a case-control association study including 1,021 obese subjects (mean age 42 ± 12 years; mean BMI 38.2 ± 6.2 kg/m²) and 226 lean, healthy individuals (mean age 36 ± 7 years; mean BMI 22.1 ± 1.7 kg/m²). Nine tagSNPs were selected to cover the entire AdipoR1 gene and surrounding 7 kb region (based on HapMap data). TagSNPs were genotyped using AcycloPrime-Fluorescence Polarization (FP) SNP Detection kits and TaqMan Pre-Designed SNP Genotyping assays according to manufacturer's protocols. We found that the rs1075399 non-reference allele decreases obesity risk by 45 % in men only [odds ratio (OR) = 0.55, 95 % CI 0.35-0.87, nominal P = 0.010]. However, after Bonferroni correction for multiple testing, this association is lost. None of the other tagSNPs were associated with obesity when studying the entire population, nor when looking at men and women separately. Quantitative analysis of the effect of each SNP on height, weight, and BMI revealed that none of the tagSNPs are associated with weight or BMI. We report here that we found no decisive evidence for association between AdipoR1 tagSNPs and complex obesity in our Belgian Caucasian population.

[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.

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.

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.

[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.

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.

[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.

[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.

[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.