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Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 min during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria. The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of "prediabetes" before prediabetes evolves as conventionally defined.

In asymptomatic patients with type 2 diabetes (T2D), the prevalence of silent myocardial infarction on routine electrocardiograms is about 4% while for silent myocardial ischemia it is 20-30%. Some studies showed that silent myocardial infarction is associated with an increased risk of incident heart failure (HF), whereas no prospective study has ever reported such a risk in patients with silent myocardial ischemia. In patients with HF, however, previously unrecognized coronary artery disease (CAD) often seems to be involved. Brain natriuretic peptide (BNP) and N‑terminal pro-BNP (NT-proBNP) levels represent first-line diagnostic tools for patients with suspected HF and might also serve as biomarkers for silent CAD. Echocardiography provides a detailed report of cardiac alterations that includes changes suggestive of ischemia, heart failure, and left ventricular dysfunction in addition to strong prognostic indices. Diabetic patients with silent myocardial infarction or silent myocardial ischemia should be screened for asymptomatic changes in left ventricular function or structure. In patients with silent CAD, all risk factors need to be better controlled and the choice of antihyperglycemic agents adjusted. In patients with congestive HF and no obvious cause of HF, invasive coronary angiography (or noninvasive computed tomography angiography) should be performed to detect CAD, since the finding of CAD may involve revascularization and requires additional treatments including antiplatelet agents and statins. Future research is needed to examine the cost effectiveness of screening for silent myocardial ischemia as part of HF risk assessment, and to identify preventive therapies to lower the risk of HF among patients with silent myocardial infarction.

Objectifs L’etude Hypoglycemia Assessment Tool (HAT) a evalue l’incidence des hypoglycemies et leur perception chez des patients DT1 et DT2 au cours d’une phase retrospective (6 mois) et d’une phase prospective (1 mois) realisees en Europe du Nord, Canada, Europe de l’Est, Moyen Orient, Amerique Latine, Asie du Sud Est et Russie. Methodes La perception de l’hypoglycemie etait evaluee a l’inclusion par la question « Avez-vous des symptomes en cas de baisse de la glycemie ? ». Les reponses « toujours », « habituellement », « occasionnellement » ou « jamais » indiquaient les differents degres de conscience des patients. Resultats Chez les patients DT1, l’incidence annuelle plus forte d’hypoglycemies severes est associee a une perception plus alteree (incidences dans la phase retrospective : « toujours, 1,87 », « habituellement, 2,00 », « occasionnellement, 3,39 » ou « jamais, 3,58 » ; et respectivement 4,30 ; 4,79 ; 6,46 et 10,49 dans la phase prospective). Chez les patients DT2, l’incidence des hypoglycemies severes diminue au fur et a mesure que l’alteration de la perception est plus marquee (retrouve dans la partie retrospective mais pas dans la partie prospective). Discussion Dans le DT1, l’incidence annuelle des hypoglycemies severes est plus elevee au fur et a mesure que leur perception diminue, avec de larges disparites selon les zones geographiques (Europe de l’Est - Asie du Sud Est) mais cette association n’est pas retrouvee dans le DT2.

La survenue d’hypoglycemies est pratiquement inevitable lorsqu’un equilibre glycemique optimise est recherche. La contribution des hypoglycemies a l’augmentation de mortalite cardiovasculaire dans l’etudeAction to control cardiovascular risk in diabetes (ACCORD) n’est pas clairement etablie. Le delai entre les hypoglycemies et les evenements cardiovasculaires a ete considere trop long pour attribuer aux hypoglycemies une responsabilite directe. Cependant, plusieurs modifications cardiovasculaires, notamment hemodynamiques et de la repolarisation ventriculaire, impliquant en particulier l’activation sympathique, peuvent etre observees au moment, ou au decours, d’une hypoglycemie. L’insuline elle-meme, surtout s’il existe une insulinoresistance vasculaire associee, comme une neuropathie autonome cardiaque, peut induire des modifications voisines et leurs effets peuvent se cumuler avec ceux de l’hypoglycemie. Chez tout patient diabetique, l’objectif glycemique doit etre defini en considerant la balance entre les risques d’hypoglycemies et ceux lies a leurs consequences, et le benefice de l’equilibre glycemique renforce.

Executive SummaryWhen we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: Prevention is Better Than Cure.Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20–79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe.The Good News is That Diabetes is Preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society.A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play.Small Changes in Lifestyle Will Bring Big Changes in Health.Through Joint Efforts, More People Will be Reached.The Time to Act is Now. When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

Many patients at high cardiovascular risk still fail to achieve recommended LDL-C goals. Showing evidence of a difference between two statins at the same dose can significantly contribute to selecting the most appropriate strategy to reduce cardiovascular risk in these patients. ARIANE study was a randomized, open-label comparative study. 844 patients at high cardiovascular risk were recruited by primary care cardiologists in France. They were randomized to receive once-daily dose of 10 mg of rosuvastatin or atorvastatin. The primary objective of this study was to compare the efficacy of rosuvastatin with that of atorvastatin in achieving an LDL-C goal of 20% based on Framingham score. 790 patients were available for intention-to-treat analysis. At 12 weeks, LDL-C goal was reached by 211 of the 411 patients treated with rosuvastatin (51.3%) and 119 of 379 patients treated with atorvastatin (31.4%), the difference being statistically significant (p < 0.0001). Both treatments were well tolerated. Adverse events were equally observed in the 2 groups, one patient in the rosuvastatin group showed a CK elevation without clinical consequence. The risk profile for the patients in this study matched that which, in 2005, had led to the Afssaps lowering the LDL-C target below 1.00g/l. The doses of the two statins compared here correspond to the doses most commonly used in day-to-day clinical practice. The greater efficacy of rosuvastatin versus atorvastatin at the same dose demonstrated here confirms previous data. Therefore, in high risk patients treated by primary care cardiologists, rosuvastatin allows a significantly greater proportion to reach the LDL-C goal of < 1.00 g/l compared to atorvastatin at the same dose. However, many patients remain not at goal.

Resume Situation l’obesite, et plus particulierement l’obesite morbide, entraine une alteration de la qualite de vie. L’objectif des traitements, tant medicaux que chirurgicaux, est fonde sur la perte ponderale, la reduction des comorbidites, et l’amelioration de la qualite de vie. Objectif l’objectif de ce travail etait de comparer la qualite de vie de patients obeses, definis par leur indice de masse corporelle (IMC) (morbides - IMC > 40 - ou severes - IMC > 35 - avec comorbidites), relevant d’une prise en charge chirurgicale, avec celle d’une population temoin a l’aide du questionnaire GIQLI (Gastro-Intestinal Quality of Life Index). Malades entre janvier 2001 et decembre 2002, 127 patients (109 femmes, 18 hommes) d’âge moyen 40 ans, ayant une obesite morbide ou severe avec des comorbidites, ont ete operes par gastroplastie par anneau modulable sous laparoscopie. Dans leur bilan pre-operatoire, l’evaluation de la qualite de vie etait realisee par le questionnaire GIQLI. Pendant la meme periode, un groupe temoin de volontaires sains de 125 personnes comparable par l’âge, les caracteristiques demographiques et les antecedents, etait soumis de facon anonyme au meme questionnaire. Resultats les deux groupes etaient comparables par l’âge et le sexe. Ils differaient de facon significative pour le poids 123 versus 66 kg, l’IMC (49,3 versus 22,2) (p Conclusions La qualite de vie des obesites, severes et morbides, par rapport aux populations temoins, est significativement alteree. Cette evaluation devrait etre realisee systematiquement avant et apres tout traitement medical ou chirurgical.

We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.

Some studies suggest that a high heart rate (HR) would be predictive of the incidence of an elevated blood pressure (BP). Cardiac autonomic dysfunction (CAD) affects a high proportion of obese patients. CAD could be involved in BP increase. Our aim was to examine the relationship between CAD, HR and BP in obese patients without known diabetes.We included 428 overweight or obese patients. CAD was assessed by analyzing HR variations during three standard tests (Valsalva, deep breathing, lying-to-standing), which are mostly dependent on vagal control. An oral load in glucose was performed and the Matsuda index was calculated.The population was separated in 4 groups according to the grade of CAD (no or only one abnormal test, 2 or 3 abnormal tests) and HR (or ≥ 75 bpm). Age was similar in the four groups. Systolic (P=0.05), diastolic (P0.005) and mean BP (P0.001) differed significantly between the 4 groups, and was the highest in the group of patients who had 2 or 3 abnormal tests and HR ≥ 75 bpm. Matsuda index differed across the groups (P=0.018) and was the lowest in this group.These data indicate that among overweight or obese patients with a defect in cardiac vagal activity BP is elevated only in those with a high heart rate, which is indicative of a more marked insulin resistance and probably an excess in sympathetic activity.

Resume Objectif Caracteriser la periode de sevrage de la population des femmes fumeuses au cours de la grossesse. Patientes et methodes Il s'agit d'une enquete descriptive par questionnaire sur un echantillon de femmes accouchant dans quatre regions francaises incluant 979 sujets. Les variables analysees concernent les caracteristiques maternelles de l'accouchement et du nouveau-ne, les habitudes tabagiques avant et pendant la grossesse de la patiente, la notion de risque lie au tabagisme, ainsi que les motivations au sevrage tabagique. Resultats Dans notre population, le taux de femmes fumeuses en debut de grossesse est de 30,9 %, et de 18,1 % au jour de l'accouchement. De plus, environ une fumeuse sur 50 realise son sevrage en vue de la grossesse. Ainsi, 45 % des femmes sont sevrees, essentiellement au premier trimestre : parmi les femmes fumeuses a la date de debut de grossesse et sevrees au jour de l'accouchement, 84 % le sont au premier trimestre, 8,8 % au deuxieme et 7,1 % et troisieme. Discussion et conclusion La plupart des arrets a lieu avant toute intervention specifique de tabacologie. En effet, la premiere consultation de grossesse se produit alors meme que, le plus souvent, la patiente est deja sevree.

To determine the efficacy, safety and tolerability of cetilistat (ATL-962), a novel inhibitor of gastrointestinal (GI) lipases, in obese patients. Phase II, multicentre, randomized, placebo-controlled, parallel group study. Enrolled patients (N=442) were advised a hypocaloric diet (deficient by 500 kcal per day, 30% of calories from fat) for a 2-week run-in period. Patients who satisfied the entry criteria (N=371) continued on the hypocaloric diet and were randomized to either placebo or one of three different doses of cetilistat (60 mg three times daily t.i.d., 120 mg t.i.d. and 240 mg t.i.d.) for 12 weeks, followed by a 4-week post-treatment follow-up. Safety, tolerability and body weight were assessed, together with other parameters associated with obesity. The primary outcome measure was absolute change in body weight from baseline. Secondary outcomes included the proportion of patients achieving pre-defined weight loss targets, changes from baseline in waist circumference and in blood lipids. GI tolerability criteria were specifically assessed, as was safety. Treatment with cetilistat reduced mean body weight to similar extents at all doses, which were statistically significant compared with placebo (60 mg t.i.d. 3.3 kg, P

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 34 - N° 7-C1 - p. 674-678

Before the availability of protease inhibitors, elevated triglyceride levels were frequently observed in patients with advanced-stage HIV infection. Since the addition of protease inhibitors to combination treatments, metabolic side effects (alterations in distribution of adipose tissue and metabolic disorders combining dyslipidemia, insulin-resistance and glucose intolerance) have been observed in HIV-positive patients receiving these treatments. Reverse transcriptase nucleoside inhibitors also provoke metabolic disorders. Dyslipidemia is defined by an increase in triglyceride levels of varying and sometimes major intensity, either isolated or combined with a more moderate increase in LDL-cholesterol, while HDL-cholesterol levels may decrease or remain unchanged. These metabolic alterations are potentially atherogenic and may explain these patients' increased risk of cardiovascular disorders. Their mechanism is complex and not yet clearly elucidated. The infection, the improvement in patients' general health and immune status, and individual predisposing factors are probably involved. Treatment probably plays a major role, since the different drugs in these two classes show effects of clearly different intensity. In vitro and ex vivo studies suggest that protease inhibitors alter adipocyte differentiation and induce insulin resistance. Reverse transcriptase nucleoside inhibitors modify adipocyte metabolism too, promoting tissue atrophy. Endocrine factors (cortisol and growth hormones) are also likely to have a role in this hypertrophy of adipose, especially visceral, tissue. These metabolic abnormalities result mainly from the effects of the antiretroviral drugs, notably protease inhibitors, on the hepatic lipid metabolism and on tissue sensitivity to insulin. Lipodystrophy contributes to these abnormalities, as does the reduction in cytokine secretion by adipose tissue. Management of these metabolic disorders is based primarily on a change in the drug regimen (administration of the least deleterious combinations), followed by standard dietary measures and, when necessary, lipid-lowering agents.

De tres nombreux mecanismes contribuent aux alterations de la paroi arterielle chez les sujets insulinoresistants non diabetiques et chez les patients diabetiques de type 2. La dysfonction endotheliale est observee a un stade tres precoce du developpement de l’atherosclerose, un processus accelere chez les patients diabetiques. A un stade plus avance, la rigidite et l’epaississement arteriel contribuent au developpement des complications macroangiopathiques. L’inflammation joue un role cle dans ces phenomenes, en particulier la secretion de facteurs de croissance vasculaires et de cytokines au sein des lesions de la paroi arterielle. Les glitazones, des ligands pharmacologiques du recepteur nucleaire PPARγ, agissent sur de nombreux mecanismes impliques dans ces atteintes arterielles : diminution des concentrations circulantes de proteine C reactive, effets anti-inflammatoires en reduisant la production de cytokines, diminution des taux d’acides gras libres, effets antagonistes sur l’angiotensine II, augmentation de l’expression et de la production d’adiponectine, etc. Les mecanismes physiopathologiques de ces alterations de la paroi arterielle et leurs methodes d’exploration sont decrits, ainsi que les principaux effets favorables des glitazones sur ces mecanismes, qui sont susceptibles de permettre une prevention et/ou une protection vasculaire chez les patients insulinoresistants et/ou diabetiques de type 2 a haut risque cardio-vasculaire.

International audience

Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m2). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 mumol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NIDDs, n = 15) when compared to controls (n = 42) (0.21 +/- 0.03, 0.33 +/- 0.03 and 0.30 +/- 0.02, respectively, mean +/- SEM). However, this activity was lower in IDDs when compared to NIDDs (P < 0.05). In obese patients, with (n = 13) or without (n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol (r = 0.42, P < 0.0001), triglycerides (r = 0.44, P < 0.0001) and BMI (r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.

A simple non-invasive indicator test (Neuropad(®)) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1-100%) and negative predictive value (63-100%), with moderate specificity (32-78.5%) and positive predictive value (23.3-93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1-89%) and negative predictive value (64.7-91%), but low to moderate specificity (27-78%) and positive predictive value (24-48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.

Introduction and aim Findrisk score has been validated for prediction of diabetes risk in many populations. The aim of this study was to examine the value of this score for the detection of dysglycemia (impaired fasting glucose and/or glucose intolerance or diabetes) in a high-risk population in Constantine (Algeria). Patients and method We had recruited 397 patients (281 women) with risk factors of diabetes, mean age 50.2±11.7 years. All had fasting glycemia (FG) and oral post charge glycemia (PCG). Findrisk score was calculated. Carotid femoral pulse wave velocity (PWV) was measured by Complior ® device. Results FG and PCG were abnormal in 159 and 157 patients, respectively. Dysglycemia was found in 204 patients (51.4%), with diabetes in 17.6% and prediabetes in 33.8% of them. Findrisk score strongly correlated to FG ( r =0.129, P =0.01) and PCG ( r =0.193, P =10 −5 ) but also to systolic ( r =0.33) and diastolic blood pressure ( r =0.20), and to PWV ( r =0.29). Discriminating threshold of this score for predicting dysglycemia was 13. It was significantly associated with prediabetes ( P =0.001) and dysglycemia ( P =10 −5 ), this association was found in women but not in men. Sensibility and specificity of this score for detecting dysglycemia were 76% and 37%, respectively. Their positive and negative predictive values were 54.7% and 60.7%, respectively. Conclusion FG and PCG detected dysglycemia in similar proportions. Identification of dysglycemia through Findrisk score was validated only in women. The correlation between Findrisk score and PWV suggests that a high score testified also of a high cardiovascular risk in these patients without glycemic abnormality or known cardiovascular history.

Introduction En Septembre 2012, l'association Dianefra 93 a mis en place en Seine-Saint-Denis un programme de prevention (PP) du diabete de type 2. Le but est ici d'analyser les modalites de recrutement et le taux d'adhesion au P P. Patients et Methodes Les criteres d'eligibilite au PP etaient un score FIN-DRISK ≥ 15 chez un obese (critere 1), ou ≥ 12 avec une charge orale en glucose anormale ou un antecedent de diabete gestationnel (critere 2). A l'inclusion, etaient realisees une charge en glucose et si possible une mesure d'HbA 1c . Le PP proposait pour 80 personnes 45 activites individuelles et collectives (dietetique et activite physique) sur une periode de 2 ans. Resultats Parmi les 80 personnes inscrites, 57,5 % ont ete recrutees lors de campagnes de depistage du diabete et 42,5 % par des professionnels de sante sensibilises a la demarche ; 52 (65 %) remplissaient le critere 1 et 28 le critere 2. Les modalites de recrutement par les campagnes ont ete analysees sur l'annee 2015 : FINDRISK determine chez 332 personnes ; 83 etaient eligibles (25 %) ; 8 se sont inscrites au PP ; la glycemie capillaire pratiquee lors des campagnes etait anormale dans environ 5 % des cas. Le taux d'HbA 1c a ete determine chez 50 des 80 personnes inscrites, et 31 avaient un resultat ≥ 5,7 %, seuil du pre-diabete, dont 16 avaient une hyperglycemie a jeun et/ou une intolerance au glucose. Deux seulement des 19 personnes avec HbA 1c Conclusions Cette etude pilote montre que lors des campagnes de depistage le taux de sujets repondant aux criteres justifiant la participation au PP est important mais que peu de sujets eligibles s'y inscrivent finalement. Parmi les sujets inclus, 62 % ont une HbA 1c elevee, anomalie glycemique la plus frequente. Une fois dans le programme, l'adhesion aux activites proposees est correcte quoique necessitant des mesures de renforcement de la motivation.

We have studied serum cytokine profiles in BALB/c mice after immunization with influenza vaccine alone or combined with the following adjuvants: alum; MF59 emulsion; MF59 containing the muramyl peptide N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-(1,2- dipalmitoyl-sn-glycero-3-(hydroxyphosphoryloxy)) ethylamide (MTP-PE); MF59 plus the lipid A analogue monophosphoryl lipid A; MF59 plus the Quil A saponin fraction LTC; or LTC alone. Pooled mouse sera were analyzed by ELISA at various times after immunization for IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and TNF-alpha. In naive mice, vaccine alone induced low levels of IL-3 and IL-5 only; vaccine plus alum induced a low IL-6 response as well. The MF59-based adjuvants significantly increased the IL-5 and IL-6 levels, whereas Quil A LTC induced strong IFN-gamma and measurable IL-2 responses, in addition to moderate IL-5 and IL-6. In previously infected mice, MF59 and MF59/MTP-PE were capable of generating IFN-gamma responses, as well as IL-5 and IL-6. All of the cytokine responses were rapid (peaking 3 to 12 h postimmunization) and short lived. In naive mice, the MF59 adjuvants induced serum cytokine profiles that are consistent with a primarily Th2-type response, whereas the Quil A LTC induced cytokines associated with both Th1 and Th2 responses. Ab analyses indicated that, although the adjuvants strongly affected the magnitude of the humoral response, there was no obvious correlation between the cytokine profile observed and the subclasses of Ab induced.

In 2010, the American Diabetes Association has published recommendations on the population to be screened for dysglycaemia; the diagnostic criteria for intermediate hyperglycaemia and diabetes using oral glucose tolerance testing and HbA(1c); and the patients eligible for treatment with metformin. We aimed to evaluate the consequences of screening with oral glucose tolerance test or HbA(1c) in an at-risk population.Among 1177 overweight or obese consecutive adults without known diabetes who were referred to our department for weight management, we selected 1157 individuals (83% female; 80% European) fulfilling the American Diabetes Association 2010 criteria for dysglycaemia screening.Mean age was 41.2 ± 13 years, BMI 37.0 ± 7.2 kg/m(2), fasting plasma glucose 4.9 ± 0.8 mmol/l and HbA(1c) (turbidimetric immunoassay) 5.7 ± 0.7% (39 mmol/mol). Based on oral glucose tolerance test and HbA(1c), respectively, 76 (6.6%) and 113 (9.8%) patients had diabetes, including 34 sharing both criteria; 307 (26.5%) and 478 (41.3%) had intermediate hyperglycaemia; and 130 (11.2%) and 255 (22.0%) would be treated with metformin. The sensitivity/specificity of HbA(1c) ≥ 6.5% (48 mmol/mol) for the diagnosis of diabetes according to the oral glucose tolerance test were 44.7/92.7%. Diabetes risk scores and UK Prospective Diabetes Study cardiovascular risk score were the highest in the 130 patients having both an abnormal oral glucose tolerance test and HbA(1c) ≥ 5.7%.In a population at risk for diabetes, the HbA(1c) strategy could lead to diagnosing more cases of dysglycaemia and to treating more patients with metformin than the oral glucose tolerance test strategy. The consistency of either diagnostic criteria was low. The patients with the highest a priori risk of diabetes and cardiovascular disease were those fulfilling both oral glucose tolerance test and HbA(1c) criteria.

There are substantial advances in understanding disordered gastrointestinal autonomic dysfunction in diabetes. It occurs frequently. The underlying pathogenesis is complex involving defects in multiple interacting cell types of the myenteric plexus as well. These defects may be irreversible or reversible. Gastrointestinal symptoms represent a major and generally underestimated source of morbidity for escalating health care costs in diabetes. Acute changes in glycaemia are both determinants and consequences of altered gastrointestinal motility. 35-90% of diabetic men have moderate-to-severe erectile dysfunction (ED). ED shares common risk factors with CVD. Diagnosis is based on medical/sexual history, including validated questionnaires. Physical examination and laboratory testing must be tailored to patient's complaints and risk factors. Treatment is based on PDE5-inhibitors (PDE5-I). Other explorations may be useful in patients who do not respond to PDE5-I. Patients at high cardiovascular risk should be stabilized by their cardiologists before sexual activity is considered or ED treatment is recommended. Estimates on bladder dysfunction prevalence are 43-87% of type 1 and 25% of type 2 diabetic patients, respectively. Common symptoms include dysuria, frequency, urgency, nocturia and incomplete bladder emptying. Diagnosis should use validated questionnaire for lower urinary tract symptoms. The type of bladder dysfunction is readily characterized with complete urodynamic testing. Sudomotor dysfunction is a cause of dry skin and is associated with foot ulcerations. Sudomotor function can be assessed by thermoregulatory sweat testing, quantitative sudomotor axon reflex test, sympathetic skin response, quantitative direct/indirect axon reflex testing and the indicator plaster.

International audience; OBJECTIVES: To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability. METHODS: Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability. RESULTS: Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r=-0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration. CONCLUSIONS: Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability.

Objectif Explorer la tolerance au glucose dans un modele de minipigs soumis a un regime riche en graisses. Materiels et methodes Onze minipigs Gottingen âges de 5 mois ont ete repartis en 2 groupes : Controle (n = 5) soumis a une alimentation normale (graisses 2,4 %, apport energetique 13,3 MJ/kg) et HFD (n = 6) soumis a un regime gras (graisses 19,3 %, apport energetique 18,5 MJ/Kg), 230 g d’aliments 2 fois/jour dans les 2 groupes. Apres 6 mois de regime, glucose, insuline, glucagon, C peptide, triglycerides et cholesterol plasmatiques ont ete doses et une IVGTT avec injection d’insuline 0,01 UI/kg IV 20 min apres le glucose et un enregistrement CGMS pendant 3 jours ont ete realises. Resultats A 6 mois le poids etait voisin chez HFD et Controles (26,6 ± 0,8 et 25,5 ± 0,5 kg). Chez HFD la glycemie basale etait plus elevee (4,6 ± 0,2 vs 3,9 ± 0,2 mmol/l, p Conclusion Comparativement a d’autres etudes sur le minipig soumis a un regime riche en graisses le poids n’est pas augmente dans notre modele probablement du fait de la restriction alimentaire. Alors que la glycemie est moderement augmentee, seul le CGMS permet de detecter une nette alteration de la tolerance au glucose, associee a une neoglucogenese hepatique probablement augmentee.

To examine the association between cardiac autonomic neuropathy and hypertension and the role of this association in diabetic complications.We included 310 patients, 138 with Type 1 and 172 with Type 2 diabetes, 62 of them with hypertension. Cardiac autonomic neuropathy was assessed by analysing heart rate variations during three standard tests (deep breathing, lying to standing and Valsalva) and looking for postural hypotension.Cardiac autonomic neuropathy was present in 123 patients and 39 also had hypertension. The prevalence of a cardiac autonomic neuropathy/hypertension association was higher in Type 2 patients (P0.002). The prevalence of hypertension increased with the severity of cardiac autonomic neuropathy. In multiple logistic regression analysis, cardiac autonomic neuropathy was an independent risk factor for hypertension [odds ratio 2.86 (1.54-5.32); P0.001]. Only confirmed or severe cardiac autonomic neuropathy (two or more abnormal function tests, respectively) were independent risk factors for hypertension (P0.005 and0.0001). Cardiac autonomic neuropathy was found in most of the patients with macrovascular complications, retinopathy or nephropathy, but a large majority of the patients with these complications exhibited the cardiac autonomic neuropathy/hypertension profile. This profile was more prevalent among the patients with coronary or peripheral artery disease or antecedent stroke than among those free of these complications (P0.001). In logistic regression analyses, the cardiac autonomic neuropathy/hypertension profile associated significantly with macro- and microvascular complications.These data are strongly in favour of the role of cardiac autonomic neuropathy in hypertension in diabetic patients. The association of the cardiac autonomic neuropathy/hypertension profile with vascular complications is consistent with a deleterious effect on vascular hemodynamics and structure, additional to the effects of hypertension.

Background: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. Methods: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. Results: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. Conclusions: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable. BACKGROUND: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. METHODS: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. RESULTS: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. CONCLUSIONS: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable.

Background: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. Aims: This guideline provides evidence-based recommendations for preventing T2DM. Methods: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. Results: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8–4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by ≥ 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. Conclusions: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication. BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions.Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen.Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients.The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

The dramatic increase in newly diagnosed cases of type 2 diabetes is a major public health concern within the European Union. However, it has been demonstrated that prevention programmes can significantly reduce the risk of developing diabetes. There is a clear consensus amongst healthcare professionals that action is urgently needed at both EU and community levels. The challenge is to implement proven intervention methods effectively into clinical reality. To achieve this, action is needed not only in the field of policy development but also in the development of targeted intervention programmes, which address the needs of people with an increased diabetes risk, clinical- and community-based healthcare professionals, and the general population. The Diabetes Prevention Forum (DPF), founded by the European region of the International Diabetes Federation, consists of European diabetes experts from a range of backgrounds. The DPF is taking immediate action to co-ordinate and improve the information flow between all relevant stakeholders to enable more effective communication, so helping to improve the ability to prevent type 2 diabetes in Europe.

Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria.in patients with microalbuminuria, weight reduction, sodium restriction (6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Resume Les auteurs rapportent 9 observations d'hypoparathyroidie primitive sporadique de l'adulte. Le diagnostic a ete pose dans 8 cas devant des manifestations neuropsychiques et dans un cas lors d'un dosage systematique de la calcemie. Le delai du diagnostic par rapport aux premieres manifestations de la maladie a atteint jusqu'a 50 ans chez un patient. Trois patients etaient atteints de comitialite qui n'avait pu etre controlee par la normocalcemie obtenue sous vitaminotherapie D que chez l'un d'entre eux. Chez un autre de ces 3 patients decede des complications d'un coma suivant un etat de mal convulsif, le syndrome de Fahr decele par la tomodensitometrie cerebrale a ete confirme par la verification necropsique. Un autre patient presentait un syndrome de Fahr decele par la tomodensitometrie systematique. La recherche de complications oculaires, digestives, ou cardiaques, d'une endocrinopathie et d'autres affections auto-immunes associees a donne les resultats suivants: 4 patients avaient une cataracte, 3 une steatorrhee, le segment QT etait allonge chez 7 des 8 patients en rythme sinusal, aucun n'avait de stigmate de cardiomyopathie, une patiente avait une thyroidite de Hashimoto et un diabete insulino-dependant, 1 patient avait un syndrome de Sjogren, une candidose a ete decouverte dans 2 cas. Cette etude demontre 1) le retard frequent du diagnostic d'hypoparathyroidie primitive chez l'adulte et la necessite de rechercher une hypocalcemie devant des manifestations neuropsychiques inexpliquees meme mineures et devant une cataracte survenant avant 40 ans; 2) la necessite d'un bilan systematique, notamment oculaire, digestif et cardiaque, du retentissement de l'hypoparathyroidie primitive.

Morbid obesity decreases the quality of life. The aims of surgical and medical treatment are weight loss, reduction of co-morbidity, and improved quality of life.To compare the quality of life between obese patients (BMI: 40 or35+comorbidity) and healthy volunteers using the GIQLI (Gastrointestinal Quality of Life) questionnaire.Between January 2001 and December 2002, 127 morbidly obese patients (109 female, 18 male) with a mean age of 40.1 years were surgically treated with laparoscopic gastric banding. Quality of life, as measured by the GIQLI questionnaire, was systematically evaluated pre-operatively. During the same period, a control group of 125 healthy volunteers of comparable age, gender, and prior surgical history were evaluated using the same questionnaire.The two groups, while comparable in age and gender, were significantly different in terms of weight (123 vs. 66 kg), BMI (44.3 vs. 22.2) (p0.001), co-morbidity factors (p=0.001), and professional activity (p=0.02). The mean global GICLI score was 122 for healthy individuals and 95 for morbidly obese patients. (p=0.001), and the differences were most marked in the super obese. These differences particularly involved social dysfunction, physical status, and emotional symptoms but were not significantly different for gastrointestinal symptoms.The quality of life in morbidly obese and super obese patients is significantly diminished from that of a control population. There was good correlation between the degree of obesity (BMI) and the alteration of the GIQLI global and subscales scores. Quality of life should be systematically evaluated before and after both medical and surgical therapy.

Many patients at high cardiovascular risk still fail to achieve recommended LDL-C goals. Showing evidence of a difference between two statins at the same dose can significantly contribute to selecting the most appropriate strategy to reduce cardiovascular risk in these patients. ARIANE study was a randomized, open-label comparative study. 844 patients at high cardiovascular risk were recruited by primary care cardiologists in France. They were randomized to receive once-daily dose of 10 mg of rosuvastatin or atorvastatin. The primary objective of this study was to compare the efficacy of rosuvastatin with that of atorvastatin in achieving an LDL-C goal of1.00 g/1 at 12 weeks. High cardiovascular risk was defined by either history of cardiovascular event, or a type IIa or IIb dyslipidemia associated with more than 2 other cardiovascular risk factors or 2 risk factors and a 10-year coronary risk20% based on Framingham score. 790 patients were available for intention-to-treat analysis. At 12 weeks, LDL-C goal was reached by 211 of the 411 patients treated with rosuvastatin (51.3%) and 119 of 379 patients treated with atorvastatin (31.4%), the difference being statistically significant (p0.0001). Both treatments were well tolerated. Adverse events were equally observed in the 2 groups, one patient in the rosuvastatin group showed a CK elevation without clinical consequence. The risk profile for the patients in this study matched that which, in 2005, had led to the Afssaps lowering the LDL-C target below 1.00g/l. The doses of the two statins compared here correspond to the doses most commonly used in day-to-day clinical practice. The greater efficacy of rosuvastatin versus atorvastatin at the same dose demonstrated here confirms previous data. Therefore, in high risk patients treated by primary care cardiologists, rosuvastatin allows a significantly greater proportion to reach the LDL-C goal of1.00 g/l compared to atorvastatin at the same dose. However, many patients remain not at goal.

To investigate the smoking cessation period during pregnancy.Questionnaire-based, descriptive study of 979 pregnant women in four regions of France. The variables analysed included the characteristics of the mother and neonate at delivery, the smoking habits of the mother before and during pregnancy, the perception of risk linked to smoking, and the reasons for giving up smoking.Eighteen percent of women smoked until delivery. Forty-five percent of women gave up smoking during pregnancy, usually in the first trimester. More precisely, about one woman who smoked out of 50 gives up in order to prepare pregnancy. The proportion of women who stop smoking in each of the three trimesters of pregnancy is 84,1, 8,8 and 7,1% respectively.Most women appear to stop smoking before any intervention therapy is possible. The first contact with a midwife or an obstetrician takes place whereas smoking cessation is already successful.

It is difficult to summarize in a few pages the wealth of information appeared during the year 2005 in the field of epidemiology and cardiovascular prevention. The general epidemiological data on the evolutionary tendencies of coronary mortality and morbidity make it possible to underline the effectiveness of the control of the great risk factors within the framework of the primary prevention. Although lipids and diabetes have still this year held the front of the scene through many trials, this analysis is also focused on smoking, subject more and more tackled in the cardiologic journals, and to which a larger attention should be paid in our daily practice. The Paris Prospective Study I brought new data concerning the early identification of the subjects at risk of sudden death, starting from the analysis of the evolution of heart rate profile during and after exercise. Is the concept of metabolic syndrome a phenomenon of mode or does it constitute in itself an autonomous prognostic factor beyond the risk related to the plurality of the factors which define it? The cardiologist will have to be interested more and more in the living conditions of his patients and in particular with the environmental factors such as the air pollution, who seems to have a considerable impact on the incidence of the acute coronary events. Lastly, the ADMA (asymmetric dimethylarginine), seems a possible new marker of cardiovascular risk, but its real prognostic interest remains to be defined.

Before the availability of protease inhibitors, elevated triglyceride levels were frequently observed in patients with advanced-stage HIV infection. Since the addition of protease inhibitors to combination treatments, metabolic side effects (alterations in distribution of adipose tissue and metabolic disorders combining dyslipidemia, insulin-resistance and glucose intolerance) have been observed in HIV-positive patients receiving these treatments. Reverse transcriptase nucleoside inhibitors also provoke metabolic disorders. Dyslipidemia is defined by an increase in triglyceride levels of varying and sometimes major intensity, either isolated or combined with a more moderate increase in LDL-cholesterol, while HDL-cholesterol levels may decrease or remain unchanged. These metabolic alterations are potentially atherogenic and may explain these patients' increased risk of cardiovascular disorders. Their mechanism is complex and not yet clearly elucidated. The infection, the improvement in patients' general health and immune status, and individual predisposing factors are probably involved. Treatment probably plays a major role, since the different drugs in these two classes show effects of clearly different intensity. In vitro and ex vivo studies suggest that protease inhibitors alter adipocyte differentiation and induce insulin resistance. Reverse transcriptase nucleoside inhibitors modify adipocyte metabolism too, promoting tissue atrophy. Endocrine factors (cortisol and growth hormones) are also likely to have a role in this hypertrophy of adipose, especially visceral, tissue. These metabolic abnormalities result mainly from the effects of the antiretroviral drugs, notably protease inhibitors, on the hepatic lipid metabolism and on tissue sensitivity to insulin. Lipodystrophy contributes to these abnormalities, as does the reduction in cytokine secretion by adipose tissue. Management of these metabolic disorders is based primarily on a change in the drug regimen (administration of the least deleterious combinations), followed by standard dietary measures and, when necessary, lipid-lowering agents.

Macronutrients may induce various hemodynamic effects. In the fructose-fed rat blood pressure increase is associated with insulin resistance and enhanced sympathetic activity. In humans, oral glucose intake induces a slight and transient increase of blood pressure secondary to sympathetic activation. This increase may be higher in hypertensive subjects and followed by a significant fall in blood pressure in elderly subjects. Saturated fatty acid-enriched diet induces in male rats a significant increase in blood pressure related to sympathetic activation. Some observational and interventional studies suggest that n-3 polyunsaturated fatty-acids may reduce blood pressure in humans. Thus, both carbohydrates and fatty acid balance may contribute to blood pressure changes. The clinical relevance of these data should be evaluated in long-term trials, in particular in overweight and hypertensive subjects.

More than half of diabetic individuals will die from a coronary event. Coronary artery disease often presents an atypical form among diabetic subjects. Silent myocardial ischaemia may be detected in 20 to 35% of diabetic patients with associated cardiovascular risk factors. When a coronarography is performed in patients with silent myocardial ischaemia, it demonstrates significant coronary stenosis in one to two thirds of patients. The prognosis of diabetic patients with silent myocardial ischaemia is associated with a higher incidence of cardiac events in the next three years, especially when silent ischaemia is associated with angiographically coronary stenosis. French guidelines jointly published in 2004 by the ALFEDIAM and the French Society of Cardiology propose the search for silent myocardial ischaemia--in diabetic patients with peripheral arteriopathy or overt nephropathy with proteinuria,--in diabetic patients with microalbuminuria and two other classical cardiovascular risk factors,--in a sedentary diabetic patient who wants to begin a physical activity,--in type I diabetic patients above 45 years or with a disease lasting for more than 15 years and in type 2 diabetic patients above 60 years or with a known disease lasting for more than 10 years, when at least two other traditional cardiovascular risk factors are present. Besides the standard annual electrocardiogram, these high risk patients should benefit first from an exercise test or when the latter is impossible, under-maximal or doubtful, from a myocardial scintigraphy combined with dipyridamole injection or from a stress echocardiography. The demonstration of a silent myocardial ischaemia should lead to a coronarography when the general status of the patient and the absence of severe comorbidities allow considering a coronary revascularisation procedure in these diabetic patients.

Numerous mechanisms contribute to impaired arterial wall in insulin resistant subjects and in type 2 diabetic patients. Endothelial dysfunction appears at an early stage of atherosclerosis progression, an accelerated process in diabetic patients. At a more advanced stage, arterial stiffness and thickening contribute to development of macroangiopathies. Inflammation plays a key role in these phenomena, particularly through growth factors and cytokines secretion in arterial wall cells. Thiazolidinediones, are pharmacological ligands of nuclear receptor PPARgamma and appear to act favorably on several pathophysiological mechanisms involved in these vascular dysfunctions and complications. Thiazolidinediones decrease plasma levels of C reactive protein, possess antiinflammatory effects through a reduction of inflammatory cytokines production, decrease free fatty acids levels, antagonize angiotensin II effects, increase adiponectin expression and production, etc. Pathophysiological mechanisms leading to vascular function impairment and their evaluation techniques are described, as well as the main thiazolidinediones beneficial effects on these mechanisms, which may lead to vascular prevention and/or protection in high cardiovascular risk insulin resistant and/or type 2 diabetic patients.

A sympathetic hyperactivity is a common feature in hypertension, type 2 diabetes (T2D), ageing and obesity-induced hypertension. This increase in sympathetic activity may lead to an elevation of arterial rigidity. By contrast, cardiac parasympathetic impairment is observed in these pathologies. Recently we showed in a model of rats with massive obesity (ventromedial hypothalamic lesions) that an enhanced vagal activity may be protective against hypertension. The aim of the present study was to evaluate the influence of an increase in sympathetic activity and a change in vagal activity on arterial rigidity and hypertension in T2D patients. Fourteen hypertensive T2D patients aged 54 +/- 2 years were compared to 22 elderly normotensive subjects (75 +/- 1 years: 11 controls and 11 T2D) and 34 middle aged normotensive subjects (43 +/- 1 years; 17 controls and 17 T2D). Cardiovascular vagosympathetic activity was investigated by spectral analysis of heart rate (HR) and blood pressure (BP) (Finapres) during 6 min at a controlled breathing rate (12 cycles/min). BP and the low frequencies of systolic BP (LF-SBP) were significantly (p0.01) higher in hypertensive T2D and elderly patients. Pulse pressure (PP) and the high frequencies of HR (HF-HR) were lower in hypertensive T2D patients. PP was positively correlated to LF-SBP (r=0.58; p=0.03) only in hypertensive T2D patients. Diastolic BP was negatively correlated to HF-HR in elderly control subjects (r=-0.63; p=0.03) but not in hypertensive T2D patients. The present results suggest that: sympathetic nervous system activity is enhanced in subjects over 70 years without any aggravating effect of T2D and in middle-aged hypertensive patients with type 2 diabetes; the increase in pulse pressure, an index of arterial rigidity, in elderly subjects may result from sympathetic override; the decrease in the cardiac sympathovagal balance, mainly due to a high vagal activity, may be protective against the occurrence of hypertension in patients with type 2 diabetes.