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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.

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.

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.

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.

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.

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.

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.

Introduction La cardiomyopathie diabetique est definie comme une alteration myocardique structurelle et/ou fonctionnelle due au diabete en l’absence de facteur de confusion : hypertension arterielle (HTA) ou coronaropathie. Ce dernier critere est habituellement non rapporte dans les etudes. Patients et methodes 656 diabetiques de type 2 depuis 14 ± 8 ans (359 hommes, 59,7 ± 8,7 ans, HbA1c 8,7 ± 2,1 %), asymptomatiques sur le plan cardiaque avec au moins 1 facteur de risque (HTA 74 %; dyslipidemie 70 %; tabagisme 22 %; arteriopathie peripherique 10 %, nephropathie 39 %) ont eu une echographie cardiaque de repos contributive; une scintigraphie a la recherche d’ischemie myocardique silencieuse (IMS, n = 206), avec coronarographie en cas de positivite (stenoses coronaires, SC : n = 71). Resultats Chez les DT2 sans HTA ni SC (n = 157), l’hypertrophie ventriculaire gauche (HVG : 24,1 %) etait l’anomalie la plus frequente, suivie par dilatation du VG (8,6 %), hypokinesie (5,3 %), trouble de relaxation de type 1 (TbRelax 4,8 %) et dysfonction systolique (3,8 %). Aucune variable n’etait associee a HVG ni dilatation du VG ni TbRelax. En analyse multivariee, les determinants de l’hypokinesie etait l’IMS (Odds ratio 14,7 [2,7–81,7], p Conclusion Chez les DT2 asymptomatiques, la cardiomyopathie diabetique constitue une entite tres frequente et caracterisee essentiellement par une HVG. L’IMS, l’obesite et le desequilibre glycemique participent a la dysfonction systolique et/ou l’hypokinesie. L’HTA est associee a plus d’HVG, les SC a plus d’hypokinesie.

Rationnel Dans le contexte du plan de gestion des risques de la duloxetine (3 indications : trouble depressif majeur, trouble anxiete generalisee et douleur neuropathique peripherique du diabete chez l’adulte), l’AFSSAPS a demande a Lilly d’etudier ses conditions reelles d’utilisation en medecine de ville. L’etude, observationnelle, prospective et transversale (approuvee par l’AFSSAPS) a ete realisee dans des pharmacies de ville avec des donnees complementaires fournies par les patients et les medecins prescripteurs. L’objectif principal a ete d’evaluer les conditions d’utilisation de la duloxetine (indications, respect des contre-indications et posologie). Objectifs secondaires : evaluer le profil des patients, des medecins prescripteurs et du traitement (medicaments concomitants, duree du traitement). Materiels et methodes Donnees recueillies dans les pharmacies : a) registre des patients : date de delivrance, âge, genre, accord pour participer a l’etude, et b) feuille de dispensation : donnees concernant le patient, le/s medecins prescripteurs et la prescription de duloxetine (notamment indication, posologie, duree du traitement, initiation ou renouvellement). Les analyses realisees ont ete descriptives. Resultats 1 104 patients inclus par 290 pharmacies, 288 medecins ont fourni les donnees de 338 patients, 294 patients ont ete inclus dans population de l’analyse principale (PAP). Dans la PAP, 74 % des patients etaient des femmes, 55 ans d’âge moyen, 87 % en renouvellement de traitement. Les medecins prescripteurs (PAP) etaient des generalistes (70 %), psychiatres (21 %) ou autres specialistes (neurologues, algologues, diabetologues ou autres) (9 %). Dans la PAP, le taux d’indications approuvees a ete de 82 % (86 % apres reclassification de prescriptions avec indication equivoque). 95 % des prescriptions respectaient les contre-indications et 99 % des patients recevaient une dose approuvee de duloxetine (60 mg/j dans 70 % des cas). Le taux d’utilisation appropriee (indication approuvee, respect des contre-indications et posologie approuvee) a ete de 77 %. Conclusion en France, la duloxetine est utilisee selon les criteres stricts du RCP dans f des cas.

Introduction La toxoplasmose cerebrale est la manifestation inaugurale du SIDA dans environ 15 a 20 % des cas. Elle se manifeste habituellement par des signes neurologiques (convulsions febriles, meningo-encephalite, signes de localisation). Nous presentons le cas d’une patiente ayant developpe une insuffisance hypophysaire et un diabete insipide lors d’une toxoplasmose cerebrale inaugurale d’une infection VIH. Observation Il s’agit d’une patiente âgee de 53 ans, adressee pour un syndrome polyuropolydipsique et une alteration de l’etat general avec amaigrissement de4 kg. Il existait une hypernatremie a 155 mmol/l. La TSH etait basse a 0,21 mU/l avec T4l et T3l normales. Le taux du cortisol plasmatique a 8 h etait bas (46 nmol/l) et non reactif au Synacthene®, avec une ACTH indosable. Devant ce tableau, un bilan hypophysaire complet a ete realise, retrouvant une insuffisance gonadotrope et thyreotrope et une hyperprolactinemie a 104 μg/l. Le bilan decouvre egalement une pancytopenie accompagnee d’une hypergammaglobulinemie polyclonale. Rapidement la patiente a presente un etat febrile et une dyspnee aigue. La serologie VIH est revenue positive et l’IRM cerebrale a visualise des lesions multiples evoquant une toxoplasmose cerebrale. Sous traitement anti-toxoplasmose, hydrocortisone, levothyroxine et desmopressine, l’etat de la patiente s’est ameliore. A 6 mois de traitement, l’insuffisance corticotrope s’est amendee, tandis que persistent le diabete insipide et l’insuffisance thyreotrope. Discussion La toxoplasmose cerebrale est une infection due a un parasite ubiquitaire, Toxoplasma gondii, touchant les sujets immunodeprimes par reactivation. L’insuffisance hypophysaire est rare, mais peut persister durablement, malgre le traitement etiologique, comme chez notre patiente.

Introduction Nous avons precedemment montre que le NT-proBNP est un marqueur de stenoses coronaires (SC) chez les diabetiques asymptomatiques au plan cardiaque. Ce marqueur est reconnu comme predicteur d’evenements cardiaques. Le but etait ici de determiner sa valeur pronostique independante de la maladie coronaire silencieuse et d’une hypertrophie ventriculaire gauche (HVG). Patients et methodes Nous avons inclus 323 patients diabetiques (17 type 1, 306 type 2) sans antecedent ni symptome cardiaque mais ayant ≥ 1 facteur de risque associe. L’ischemie myocardique silencieuse (IMS) a ete recherchee par scintigraphie myocardique de stress et les SC par une coronarographie pratiquee en cas de positivite. La masse ventriculaire gauche a pu etre evaluee de facon fiable par echocardiographie (convention ASE) chez 282 d’entre eux, l’HVG etant definie par une masse VG ≥ 106 (femmes) ou 110 g/m2 (hommes). Le NT-proBNP a ete dose. Resultats Une HVG etait presente chez 92 patients, l’IMS chez 108 patients dont 39 avaient des SC. Les tertiles superieurs de NT-proBNP s’associaient a une plus forte prevalence d’HVG (19,4, 35,1 et 43,2 % ; p 34 pg/ml) predisait les evenements independamment de l’IMS (OR 2,9 [1,4–6,0], p Conclusion Cette etude suggere que le taux plasmatique de NT-proBNP constitue, chez les diabetiques asymptomatiques, un marqueur de risque d’evenements cardio-vasculaires independant du statut coronarien et de l’HVG.

Although effective medications are available for the treatment of acne, tolerance problems may preclude adequate treatment regimens such as topical retinoic acid, and reduce patient compliance. The present study was conducted to evaluate whether a medical water (Avène) in conjunction with retinoic acid may improve local tolerance in acne. A controlled, open, randomised, multicentric study was completed after 28 days of treatment in 69 acne patients, 34 applying a retinoic acid preparation alone, and 35 applying retinoic acid in association with the water spray used ad libitum. Topical retinoic acid treatment induced prominent signs of irritation in both groups. However, a statistically significant reduction between the two treatment groups could be demonstrated on scaling at all assessment visits (por =0.02, Wilcoxon test). No significant water effect on erythema, burning and itching was shown during the treatment period. The overall tolerance assessed by the investigator was significantly improved with the water (p = 0.04, Wilcoxon). Taken together, water with a low mineral content appears to be a promising adjunctive treatment for improving the tolerance of topical retinoids in acne.

Bone localisations of amyloidosis are rare, usually diffuse and associated with myeloma. We report the case of a patient with massive obesity complicated by diabetes, hypertension, sleep apnea and liver steatosis, who complained of rapidly worsening bilateral polyradiculalgia of the lower limbs. After sufficient weight loss made nuclear magnetic resonance imaging feasible, a spinal tumour was visualised on the 5th lumbar vertebra, extending to soft tissues. Total excision was performed, and pathological studies revealed an amyloid bone tumour with no evidence of myeloma.

Left ventricular hypertrophy (LVH) is a recognized independent risk factor for cardiovascular morbidity and mortality. The purpose of this study was to assess the determinants of left ventricular mass index (LVMI), according to the presence or absence of silent myocardial ischaemia (SMI), in diabetic patients with at least two additional risk factors but with no known coronary artery disease. Eighty diabetic patients (14 Type 1 and 66 Type 2) were studied, and LVMI was measured echocardiographically. Three non-invasive tests (the ECG stress test, thallium-201 myocardial scintigraphy with intravenous dipyridamole infusion, and ambulatory 48-h ECG monitoring) were performed on all patients. Forty-five percent of patients had LVH (LVMIor = 110 g/m2 in men andor = 106 g/m2 in women). Twenty-six patients (37%) had SMI assessed on at least one of the non-invasive tests, 7 of whom had significant coronary stenoses on angiography. LVMI was significantly higher in patients with coronary stenoses on angiography than in those with SMI but without coronary stenoses or in those without SMI (p0.05), and was correlated with systolic blood pressure. In patients free of SMI, LVMI correlated with creatininemia. In patients with SMI and normal coronary arteries on angiography, LVMI correlated with the waist/hip girth ratio, the log urinary albumin excretion rate and the red blood cell filtration index (a rigidity index). This study suggests that LVH is very frequent in diabetic patients and that the main factor contributing to the increase of LVMI differs according to the presence or absence of SMI and coronary stenoses: volume load in patients free of SMI, microcirculatory disorders in those with SMI but with normal coronary arteries, and blood pressure in those with coronary stenoses.

Microangiopathic disorders, characterized by capillary vasodilation and increases in capillary blood flow and permeability, are common in diabetes and can occur before the development of microangiopathic complications. In a study of 163 diabetic patients, capillary permeability, measured by albumin retention (AR), was increased in 39% of patients. AR was increased more frequently in women than in men, and in patients without microangiopathic complications than in patients with complications. Increased AR was significantly associated with insulin-dependent diabetes in male patients. Lymphatic function was abnormal in 72% of patients; this abnormality was often present before AR increased. The pathophysiology of microangiopathy is complex and involves metabolic, haemodynamic, neurological and hormonal factors. Improved control of glycaemia and blood pressure can reduce capillary permeability. In addition, studies with a flavonoid fraction and n-3 polyunsaturated fatty acids suggest that these agents may also be beneficial.

The purpose of this study was to evaluate the ability of three noninvasive techniques to detect silent myocardial ischaemia and analyse the factors associated with this condition, particularly left ventricular hypertrophy, in diabetic patients. An ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole intravenous infusion, ambulatory 48 h ECG monitoring and an echocardiographic study were performed in 92 diabetic patients without cardiac symptoms but withor = 2 additional cardiovascular risk factors. At least one of these tests was positive in 28 patients (30.4%), suggesting silent myocardial ischaemia. Twenty-four of these patients had a coronary angiography which showed significant coronary stenosis in only 9 cases. An accurate echocardiographic tracing was obtained in 79 patients, particularly in 7 of the 9 with coronary stenosis. Left ventricular hypertrophy was detected in 34 patients, 6 of whom had coronary stenosis. In patients with left ventricular hypertrophy, the positive predictive values of myocardial scintigraphy and the ECG stress test were respectively 50% and 100%, as compared to only 33% and 11% in those without hypertrophy. In summary, coronary stenoses were found in10% of asymptomatic diabetic patients withor = 2 cardiovascular risk factors, but more frequently in individuals with left ventricular hypertrophy. Thus, silent myocardial ischaemia should be searched for first in diabetic patients with hypertrophy, for which the stress test was the most accurate detection method in this study.

It is difficult to treat obese non-insulin-dependent diabetic patients (NIDDs) whose glycaemic control remains poor despite maximal oral antidiabetic therapy. We studied the effect of a continuous subcutaneous insulin infusion (CSII) associated with a low-calorie diet and metformin 1,700 mg/day on glycaemic control and basal and stimulated insulin secretion in a series of 82 overweight NIDD before (T1), during CSII (T2), and after CSII withdrawal (T3). Patients were treated for 8 to 23 days with a mean amount of 0.50 +/- 0.02 IU/kg/day. Glycaemic control was very good after 3-5 days of CSII and remained good at T3. At T2, fasting and postprandial plasma C peptide levels decreased significantly. At T3, fasting C peptide was very similar to T1, and postprandial C peptide was significantly higher than at T1. The molar fasting and postprandial plasma C peptide/glycaemia ratios increased significantly at T3. After glucagon injection, the molar delta C peptide/glycaemia ratio was significantly increased at T2 and even higher at T3. At T2, as at T1 and T3, there were significant correlations between fasting and postprandial C peptide levels and between the glucagon-induced C peptide peak and fasting and postprandial C peptide levels. Between T1 and T3 weight changes correlated significantly with the molar fasting C peptide/glycaemia ratio at T1. Twenty-nine of the 30 patients for whom this ratio was6.6 x 10(-8) lost weight. The length of CSII treatment did not correlate with weight changes or other biological parameters. This study shows that CSII with moderate amounts of insulin associated with a low-calorie diet and metformin provided rapid glycaemic control, led to weight loss, maintained regulation of insulin secretion and seemed to improve insulin secretion and sensitivity. These results were obtained in only 8 to 10 days.

Objectif Evaluer l'impact de la dyslipidemie atherogene (DA) sur les taux d'hospitalisation pour complications cardiovasculaires des patients diabetiques de type 2 (DT2) ayant un LDL-cholesterol controle. Patients et methodes Pour l'enquete Entred 2007, 8 926 adultes diabetiques (definis par le remboursement d'au moins 3 antidiabetiques entre aout 2006 et juillet 2007) ont ete tires au sort dans les bases de donnees de l'assurance maladie. Pour 48 %, un questionnaire patient et pour 28 % un questionnaire medecin ont ete recueillis. Les sejours hospitaliers ont ete extraits du PMSI pour 84 % sur la periode aout 2008-juillet 2009. Selon le type de complications, les diagnostics ont ete recherches dans les diagnostics principaux et/ou associes. La DA etait definie par HDL-C Resultats Nous avons inclus dans l'etude 1299 DT2 ayant un LDL-C ‰ personnes DT2, superieur a celui des DT2 sans DA (20 ‰ , p=0,02). Conclusion Chez les personnes DT2 ayant un LDL-C controle, les hospitalisations pour cardiopathie ischemique sont plus frequentes chez ceux ayant une DA. La DA pourrait jouer un role dans le developpement de la cardiopathie ischemique.

To investigate the rheological properties of RBC in obese subjects and the factors associated with their changes.Two consecutive studies of non diabetic obese subjects.Filtration index of RBC using the Hanss hemorheometer, RBC filterability using a cell transit time analyser and RBC aggregation measured on the Myrenne aggregometer.In both studies an increase in the filtration index of RBC, namely a reduction in their deformability, was found. In the first study the filtration index correlated negatively with hematocrit and positively with plasma C peptide levels. In the second study RBC filterability was also studied by the cell transit time analyzer in which there is no aggregate formation. The RBC transit time was not found to be different in the obese patients and in the controls, but RBC aggregation was increased and correlated significantly with body weight and BMI. RBC aggregation worsened after four days of hypocaloric diet.(1) obesity, independently of the other cardiovascular risk factors, is associated with significant changes in RBC rheology; (2) these changes are probably related for the most part to plasma factors, possibly via hyperinsulinemia, even if changes in the chemical composition of the RBC membrane are not excluded, (3) RBC aggregation worsens during the first days of a hypocaloric diet; (4) rheological changes in RBC seem to be another component of the insulin resistance syndrome.

To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.

Extrahepatic manifestations have been reported in hepatitis C virus infection. To assess the relationship between diabetes mellitus and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152 controls hospitalized during the same period with hepatitis B virus (n = 51) or alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy, prothrombin activity65%, or serum albumin35 g/L were excluded.Diabetes, defined by fasting serum glycemia1.4 g/L on at least two separate occasions or previously treated overt diabetes, was present in 38 patients with chronic hepatitis C (24%) and in 13 patients in the control group (9%, P0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis. Family history of diabetes or obesity was observed in 2 (5%) of the diabetic patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P = 0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17 diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched for in 77 patients with chronic hepatitis C, was not different in diabetic and non diabetic patients, and, was similar to the reference population. Serum islet-cell antibodies were found in 5 patients with chronic hepatitis C (3 with diabetes) and in 2 controls.Diabetes mellitus is more prevalent in patients with chronic hepatitis C than in patients with other liver diseases, and usually occurs in the absence of predisposing factors. These results suggest a role of hepatitis C virus infection in the pathogenesis of diabetes.

Various types of microcirculation disturbances have been described in the course of systemic diseases, hypertension, diabetes, obesity, and the so-called "idiopathic oedema" syndrome. This article summarizes the relevant microcirculatory disorders associated with diabetes and their pathophysiology. These functional disorders occur before or in association with anatomical lesions of diabetic microangiopathy. Increased capillary permeability to albumin is frequently observed in diabetes. In a placebo-controlled trial, Daflon 500 mg, a purified, micronized, flavonoidic fraction, significantly improved this disorder. Patients complaining of an oedematous syndrome almost always have an increased extracellular fluid volume, probably largely due to increased capillary permeability. Diabetes and "idiopathic oedema" therefore constitute two examples of the major clinical implications of impaired microcirculation.

The aim of this work was to determine the presence and prevalence of alterations in cardiac autonomic function in obese, non-diabetic subjects.These were 121 obese people, 15 with glucose intolerance and none with diabetes, and a group of 40 healthy people.A series of five standardized tests was carried out, three of which were based mainly on parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip).The response to the deep breathing test correlated negatively with age, as it did in control subjects. At least one parasympathetic test, age-adjusted, was abnormal in 49 patients (40.5%). Five other patients had an abnormal handgrip test, and no patient had orthostatic hypotension. No correlation was found between the parasympathetic test results and sex or body mass index. Prevalence of cardiac autonomic dysfunction, considered to be present when at least one parasympathetic test was abnormal, did not differ according to a gynoid or android type of obesity. A significant negative correlation was found between heart rate response to deep breathing and fasting glycemia.It was concluded that cardiac autonomic dysfunction evidenced by means of simple, reliable, reproducible tests is frequent in the non-diabetic obese subject. This disorder could explain the poor cardiovascular prognosis associated with obesity. Whether it is a complication of obesity or a marker associated with certain kinds of obesity (of hypothalamic origin) remains to be clarified.