A. Fontbonne

The Effect of Metformin on the Metabolic Abnormalities Associated With Upper-Body Fat Distribution. BIGPRO Study Group

OBJECTIVE The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Effects of 1-year treatment with metformin on metabolic and cardiovascular risk factors in non-diabetic upper-body obese subjects with mild glucose anomalies: a post-hoc analysis of the BIGPRO1 trial.

AIMnMetformin has recently been considered as a possible pharmacological complement to lifestyle measures for preventing type 2 diabetes in high-risk subjects. However, little is known of its effects on metabolic and cardiovascular risk factors in non-diabetic subjects.nnnMETHODSnThe BIGPRO1 trial was a 1-year multicentre, randomized, double-blind, controlled clinical trial of metformin versus placebo, carried out in the early 1990s, in 457 upper-body obese non-diabetic subjects with no cardiovascular diseases or contraindications to metformin. We compared the changes (1-year minus baseline) in cardiometabolic risk factors between treatment groups in two subsets of trial subjects: those with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=101); and those who fulfilled the inclusion criteria of the Diabetes Prevention Program (DPP) (n=51). Comparisons were adjusted for age and gender.nnnRESULTSnIn the IFG/IGT subset, significant differences in 1-year changes were observed for systolic blood pressure, which decreased markedly more in the metformin group than in the placebo group (P<0.003), and for fasting plasma glucose, and total and LDL cholesterol, which decreased slightly in the metformin group, but increased in the placebo group (P<0.04). Similar results were observed in the subset with DPP criteria. Also, there were no significant differences in 1-year changes for weight, waist-to-hip ratio, 2-h post-load blood glucose, fasting and 2-h post-load insulin, HDL cholesterol, triglycerides and fibrinolytic markers between the two treatment groups.nnnCONCLUSIONnIn subjects at high risk of developing diabetes, the use of metformin showed beneficial and no untoward effects on cardiometabolic risk factors.

A real-life study of the use, effectiveness and tolerability of rosiglitazone in France: The AVANCE study

AIMnThe study aimed to determine the effectiveness and tolerability of rosiglitazone, and its profile in terms of treatment adherence, treated patients and prescribing recommendations under everyday conditions of care.nnnMETHODSnThis was a real-life observational longitudinal study including patients with type 2 diabetes mellitus (T2DM) starting treatment with rosiglitazone and followed for up to 2 years. A questionnaire was completed at the time of inclusion and during routine consultations at around 6, 12, 18 and 24 months following inclusion. Information was collected on sociodemographics, clinical history, treatments, co-morbidities, laboratory data and compliance with treatment. There were three primary outcome measures: treatment response (defined as an HbA1c ≤ 8.0% or a decrease in HbA1c ≥ 0.7%); switch to insulin (as considered necessary by the physician); and occurrence of adverse events requiring a change or discontinuation of treatment.nnnRESULTSnThe evaluation included 670 patients (61.1%) treated with rosiglitazone/metformin as fixed-dose combination tablets and 427 (38.9%) with standard rosiglitazone tablets. Rates of HbA1c response, defined as an HbA1c less than or equal to 8.0% or a decrease in HbA1c greater than or equal to 0.7%, ranged from 80.6% to 92.1% depending on the follow-up time. The percentage of patients with an HbA1c less than 7% was 18.4% before rosiglitazone was prescribed, and ranged from 48.2% to 57.8% depending on the follow-up period. Sixty-two patients (6.1%, 95% CI: 4.6-7.6%) switched to insulin therapy during the follow-up period. Spontaneously reported adverse events leading to a change or discontinuation of treatment were seen in 45 patients (4.4%, 95% CI: 3.2-5.6%).nnnCONCLUSIONnRosiglitazone showed sustained efficacy, with around 90% of patients defined as responders to the treatment in terms of reduction in HbA1c, and was relatively well tolerated. The adverse-event profile was consistent with the known effects of rosiglitazone, and no signs of increased cardiovascular ischaemic risk were observed. These results are in agreement with previous studies on rosiglitazone.

Participative decentralization of diabetes care in Davao City (Philippines) according to the Chronic Care Model: A program evaluation

AIMnTo assess the effectiveness of the Diabetes Project in Davao City, Philippines, regarding diabetes care access, diabetes management and cardiovascular risk factors. The project was developed in accordance with the Chronic Care Model (CCM) framework.nnnMETHODSnA non-randomized cross-sectional survey was conducted in nine intervention and five control Barangays (villages). People with diabetes aged ≥20 years were interviewed using a structured questionnaire; height, weight, waist circumference, and blood pressure were measured; HbA1c was tested with a NSGP-certified point-of-care device. Logistic regression models were used to compare the two groups.nnnRESULTSnThe intervention group (n=503) scored better than the controls (n=136) on the following (OR, 95% CI): percentage of patients taking metformin (1.5, 1.0-2.2); and in the last 12 months: laboratory test for fasting blood sugar (1.6, 1.1-2.3), HbA1c (6.0, 2.4-15.1), lipid profile (1.7, 1.1-2.5), nutritionist visit (1.6, 1.0-2.5) and therapeutic education session (2.7, 1.8-4.0). Glycemic control (HbA1c<7%) was also better in the intervention Barangays (1.6, 1.0-2.4). There were no statistical differences between the two groups for number of visits, and levels of other cardiovascular risk factors.nnnCONCLUSIONSnOur findings support the effectiveness of implementing the CCM framework in a low-to-middle income country on glycemic control and diabetes management.

P7 INTENSIA : Enquête de pratiques auprès de diabétologues libéraux français sur l’intensification de l’insulinothérapie des patients diabétiques de type 2

Objectif L’intensification du traitement insulinique chez le patient diabetique de type 2 en echec d’une insuline basale, est laissee a l’appreciation du diabetologue (HAS 2006). L’objectif de notre etude est d’evaluer le type d’intensification utilise par les diabetologues, leurs facteurs de choix et les messages educatifs delivres aux patients. Materiels et Methodes 727 diabetologues liberaux ont ete contactes par l’institut BVA. Ils devaient repondre a une enquete en 3 parties : definition de l’intensification, analyse du dernier patient intensifie, 2 cas cliniques permettant de decrire les schemas insuliniques choisis. Resultats 18 % des medecins sollicites ont repondu a l’enquete (echantillon representatif, sans biais majeur par rapport aux non-repondants). A la question sur la definition de l’intensification, la reponse etait dans 84 % des cas « Augmentation du nombre d’injections d’insuline ». Le schema majoritairement choisi chez le dernier patient intensifie, etait un basal bolus (BB, 59 %), suivi par le schema 2 insulines pre-melangees (2 PREMIX, 22 %) puis 3 insulines premelangees (3 PREMIX, 5 %). En echec d’une association d’antidiabetiques oraux et d’une insuline lente (cas clinique 1), on retrouve une distribution proche : 55 % de BB, 29 % de 2 PREMIX, 9 % de 3 PREMIX. En cas d’echec d’un schema de 2 PREMIX, le choix se porte sur le schema 3 PREMIX (48 %) ou 2 PREMIX avec un analogue rapide le midi (24 %), versus le BB (26 %). Les facteurs influencant le choix du diabetologue sont : l’HbA1c avant intensification, l’objectif d’HbA1c et le profil glycemique. Le choix des schemas PREMIX est surtout influence par le style de vie du patient (30 % vs 16 % BB, p Conclusion En cas d’intensification, 2/3 des diabetologues privilegient un schema BB et un tiers un schema PREMIX. Les facteurs de choix sont les memes quel que soit le schema choisi. L’experience personnelle a certainement un poids important dans nos attitudes therapeutiques au dela des criteres biocliniques.

P97 Relations entre caractéristiques anthropométriques et facteurs de risque cardio-métaboliques chez des adultes sénégalais. L’étude LiNuMet

Introduction Les donnees sur les maladies chroniques liees a la nutrition et leurs facteurs de risque sont rares en Afrique sub-saharienne. Notre objectif est de decrire dans un echantillon dadultes senegalais vivant en ville les caracteristiques anthropometriques et les facteurs de risque cardio-metaboliques, et danalyser leurs relations. Patients et methodes A loccasion dune etude sur les lipodystrophies menee chez des adultes seropositifs a Dakar, des temoins apparies ont ete selectionnes dans la population generale par des visites systematiques a domicile. Sils acceptaient de participer, le recueil des donnees (dont une prise de sang a jeun) se faisait sur place. Resultats Lâge moyen est de 43,2±9,4 ans. La prevalence du surpoids et de lobesite est de respectivement 23,3 % et 3,4 % chez les hommes (n = 60), et de 30,2 % et 29,2 % chez les femmes (n = 106) ( p p versus peripherique), et la forme generale du corps (carrure). La glycemie et linsulinemie correlent fortement avec le 1 er axe et la pression arterielle avec le 2 e . Les lipides sont lies aux deux axes. Aucun parametre cardio-metabolique nest correle au 3 e axe. Conclusion Les femmes senegalaises vivant en ville sont souvent obeses, sans que cela saccompagne dune prevalence elevee de diabete. Par contre, dans les deux sexes, lHTA est frequente et les lipides pourraient poser probleme en cas de progression de lobesite. Meme si les maladies chroniques liees a la nutrition sont encore rares dans cette population africaine urbaine, la surveillance individuelle et en sante publique des facteurs de risque cardio-metaboliques ne doit pas etre negligee.