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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.

Special issue devoted to language and history. (VM)

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.