S. Halimi

Early Disturbances of Ambulatory Blood Pressure Load in Normotensive Type I Diabetic Patients With Microalbuminuria

OBJECTIVE To compare 24-h ABP in normotensive type 1 diabetic patients with and without microalbuminuria. RESEARCH DESIGN AND METHODS The study was a retrospective comparison of cases and matched control subjects. The first phase included 35 type 1 diabetic patients, normotensive by OMS criteria. The 23 patients with normoalbuminuria (< 15 μg/min) were compared with 12 patients with microalbuminuria (≥ 15 μg/min). In the second phase, the 12 microalbuminuric patients were paired by sex- and age-matched with 12 normoalbuminuric patients and 12 nondiabetic healthy control subjects. We measured casual systolic and diastolic BP and HR, 24-h ABP and AHR (recorded with a Spacelabs automatic recorder), and microalbuminuria. RESULTS No correlation between microalbuminuria and casual BP was observed. Microalbuminuria was correlated significantly with diastolic 24-h APR and nocturnal systolic and diastolic ABP (r = 0.35, 0.38, and 0.33, respectively; P < 0.05) and with AHR during all time periods (24-h, r = 0.46; day, r = 0.39; night, r = 0.39; P < 0.05). Normo- and microalbuminuric patients did not differ in casual BP and HR. However, microalbuminuric patients had a significant increase in systolic 24-h ABP (119.1 ± 8.2 vs. 113.1 ± 8.1, P = 0.05), diastolic 24-h ABP (74.9 ± 7.5 vs. 70.2 ± 5.7, P = 0.04), nocturnal systolic ABP (112.8 ± 7.1 vs. 105.8 ± 7.9, P = 0.01), and AHR during all time periods. The same results were observed when patients were paired by age and sex. CONCLUSIONS Normotensive microalbuminuric type 1 patients, although strictly comparable with normoalbuminuric patients for casual BP and HR, have an increased ABP and HR, especially during the night. This difference might reflect dysautonomia. Ambulatory measurement of BP and HR is more appropriate than casual measurements in hemodynamic studies of incipient diabetic nephropathies and could be proposed as an interesting tool for an early prediction of diabetic nephropathy.

Type 2 diabetes treatment intensification in general practice in France in 2008–2009: the DIAttitude Study

AIMSnTo evaluate the current procedures in French general practice of intensifying hypoglycaemic treatment in orally treated type 2 diabetic patients, according to the French recommendations.nnnMETHODSnType 2 diabetic patient characteristics, HbA(1c) values, hypoglycaemic treatment and physician characteristics were collected from the electronic records of a panel of French general practitioners. Factors associated with the time until intensification of treatment were studied with the Cox model.nnnRESULTSnAmong 17 493 orally treated patients with at least two available HbA(1c) values, 3118 patients (18%) required treatment intensification; 65% were on monotherapy, 31% on bitherapy and 4% on tritherapy. These patients were followed for a maximum of 14 months or until treatment was intensified. Treatment was intensified after the second high HbA(1c) value for 1212 patients (39%); this was immediate for 13% of these patients, within 6 months for 39% and within one year for 59%. Treatment intensification was less likely the older the patient, and more likely the higher the first HbA(1c) value, up to an HbA(1c) threshold of 9%.nnnCONCLUSIONSnTherapeutic inertia in caring for type 2 diabetic patients in France is frequent, at least for patients treated in general practice. This inadequate glycaemic control would be expected to have significant patient and public health consequences, with higher rates of associated diabetic complications.

Therapeutic management of orally treated type 2 diabetic patients, by French general practitioners in 2010: the DIAttitude Study

AIMnTo describe the behaviour of French general practitioners (GP) regarding intensification of hypoglycaemic agents in orally treated type 2 diabetic (T2D) patients, according to their HbA(1c) level.nnnMETHODSnGeneral practitioners were recruited from a panel of office-based general practitioners. T2D patients who had been orally treated for at least 6 months were included in the study; their characteristics were recorded, and their HbA(1c) values and hypoglycaemic treatments over the previous 24 months extracted from electronic records The major reasons for intensification (or no intensification) of hypoglycaemic agents were recorded at the inclusion visit.nnnRESULTSnA total of 236 general practitioners recruited 2109 T2D patients: 1732 had at least one HbA(1c) value recorded in the previous 6 months, and 52%, 33% and 14% had been treated, with oral hypoglycaemic agents in monotherapy, bitherapy or tri-or quadritherapy, respectively. Of these patients, 702 (41%) remained uncontrolled (47%, 39% and 20% respectively) and according to the current French guidelines needed treatment intensification. Only 46 (7%) had their treatment intensified at inclusion. Of those without intensified treatment, 60% were treated with monotherapy; the main reason given by the general practitioners for not intensifying treatment was a satisfactory HbA(1c) level (53%), although 32% had an HbA(1c)>7%. Other reasons were: lifestyle advice had greater priority (20%); decision was postponed until the next visit (11%); HbA(1c) had decreased since last visit (7%; not confirmed by available data in 58% of cases); a medical priority other than diabetes (6%) and other reasons related to the patient (3%).nnnCONCLUSIONnFor T2D patients managed by French general practitioners, guidelines are not consistently followed: HbA(1c) should be monitored more frequently and treatment adjusted according to HbA(1c) levels.

A prospective study of quality of life in 77 type 1 diabetic patients 12 months after a hospital therapeutic educational programme

AIMnThe aim of therapeutic education includes improvement of quality of life (QOL). However, the majority of studies are focused on biomedical or behavioural markers only. We performed a prospective study to assess QOL in adult type 1 diabetic patients for one year following a hospital educational programme.nnnMETHODSnDuring this prospective single-centre study, QOL was assessed by the DQOL questionnaire in 77 consecutive patients at baseline and three, six and 12 months after a three-day educational programme.nnnRESULTSnThe rate of response was 72.7% (n=55) at three months and 67.5% (n=52) at one year. The overall DQOL score improved at three months from 65.6+/-10.1 to 70.1+/-10.4 (P<0.001), and at one year from 65.1+/-10.4 to 68.5+/-11.7 (P=0.001). Patients exhibited greater satisfaction (66.3+/-15 versus 75.3+/-14.1, P<0.001), a diminished impact of diabetes (61.2+/-10 versus 63.4+/-9.6, P=0.016) as well as of anxiety related to diabetes (67.6+/-18.6 versus 73.6+/-16.2, P=0.009) at three months. This significant improvement was maintained at one year. Improvement in DQOL score at three months was positively correlated with a reduction in HbA(1c) (7.6+/-1.4% versus 7.8+/-1.4%, P=0.032), (r=-0.293, P<0.037). Patients with serious hypoglycaemia before the programme appeared to derive greater benefit from therapeutic education (OR: 9.88, 95% CI: 1.094-89.20).nnnCONCLUSIONnQOL assessed by DQOL improved after therapeutic education and during the following year. The improvement in DQOL score at three months correlated with a reduction in HbA(1c) levels and appeared to particularly benefit to those who had severe hypoglycaemia before the programme.

Regulation of oxidative stress and inflammation by glycaemic control: evidence for reversible activation of the 5-lipoxygenase pathway in type 1, but not in type 2 diabetes.

Trial registrationClinicalTrials.gov NCT00324792FundingThis work was supported by a grant from the University Hospital of Grenoble, France (Direction Régionale de la Recherche Clinique).

Impact of flexible insulin therapy on blood glucose variability, oxidative stress and inflammation in type 1 diabetic patients: The VARIAFIT study

AIMSnHbA1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.nnnMETHODSnTests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E4 (LTE4), 11-dehydro-thromboxane B2 (TXB2) and 8-iso-prostaglandin F2α (PGF2).nnnRESULTSnHbA1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P=0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r≥0.84, P<0.0001).nnnCONCLUSIONnA FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).

Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment

To investigate the impact of renal function on the safety and efficacy of insulin glargine 300u2009U/mL (Gla‐300) and insulin glargine 100u2009U/mL (Gla‐100).

PO48 Motifs de non intensification thérapeutique chez des patients DT2 non contrôlés par une monothérapie en Médecine Générale en France – Phase prospective étude DIAttitude

Objectif Realisee aupres de 198 medecins generalistes (MG), lobjectif de cette etude etait didentifier les motifs de non intensification therapeutique de patients DT2 non controles par monotherapie antidiabetique orale. Materiels et methodes Des MG appartenant a 1 panel representatif de MG exercant une activite liberale ont ete sollicites. 937 patients ont ete suivis 1 an, suivi observationnel. Tous les 3 mois, les motifs dintensification / non intensification therapeutique etaient renseignes. La necessite dintensification etant definie comme 2 dosages consecutifs dHbA1c≥6,5 % distants ≥3 mois (critere retenu comme relevant du renforcement de la monotherapie). Resultats Parmi 916 DT2 disposant de 2 valeurs dHbA1c, 398 (43 %) necessitaient une intensification therapeutique : hommes 60 % ; âge moyen 68 ans ; anciennete moyenne diabete 8 ans ; HbA1c moyenne 8,1 %, HbA1c entre 6,5–7 % 53 %, >7 % 47 % ; ≥1 complication macrovasculaire 22 %, microvasculaire 27 % ; obesite/surpoids 82 %. 181/398 (45 %) ont ete intensifies. 217/398 patients (55 %) nont pas ete intensifies. La plupart des caracteristiques de ces patients etaient similaires a celles de la population precedemment decrite. Seule difference, le niveau dHbA1c, HbA1c moyenne 7,0 % vs 8,1 %, HbA1c entre 6,5–7 % 65 % vs 53 % et > 7 % 35 % vs 47 %. Les motifs de non intensification pour ces 217 patients etaient : taux dHbA1c juge satisfaisant 67 %, renforcement prealable des mesures hygieno-dietetiques juge utile 14 %, decision repoussee a la consultation suivante 7 %, venus pour autre motif 4 %, taux dHbA1c en baisse depuis la visite precedente 4 %, autre raison 5 %. Cette repartition des motifs etait constante au cours du suivi. Conclusion Linertie therapeutique demeure importante (55 %) dans la prise en charge des DT2 en monotherapie en MG en France en 2010–2012. Au 1 er plan des motifs de non intensification therapeutique, taux dHbA1c juge satisfaisant pour 67 %, malgre une HbA1c>7 % pour 35 % des patients.

P2097 L’hypoxie nocturne, et non l’excès d’adiposité abdominale, est associée à une détérioration de l’insulino-sensibilité chez des hommes apnéiques, non obèses

Introduction Le syndrome d’apnees du sommeil (SAS) est associe a une repartition abdominale des graisses. Quel que soit l’indice de masse corporelle, cette distribution abdominale de l’adiposite peut contribuer a l’alteration du profil cardiometabolique des patients apneiques. Cette etude evalue la contribution respective de la severite du SAS et de l’adiposite abdominale sur les marqueurs du risque cardiometabolique chez 38 hommes apneiques (index d’apnees-hypopnees, IAHxa0>xa015) mais non obeses. Patients et methodes Un test d’hyperglycemie provoquee orale (75xa0g) a ete realise duquel l’index d’insulino-resistance a jeun, HOMA-IR, et l’index global d’insulino-sensibilite (ISI Matsuda) ont ete calcules. Leurs profils lipidique, inflammatoire et redox ont egalement ete mesures. Vingt-et-un hommes presentant un tour de taille (TDT) eleve (> 94xa0cm) ont ete compares a 17 hommes presentant un TDT normal. Resultats La pression arterielle systolique, la CRP-us, les triglycerides, l’aire sous la courbe du glucose et de l’insuline, l’insulino-sensibilite a jeun et globale etaient deteriores chez les hommes a TDT eleve compares aux hommes a TDT normal. La structure du sommeil et la severite du SAS mesuree par l’IAH n’etaient pas differents entre les groupes. En revanche, les patients a TDT eleve presentaient une saturation en oxygene (SpO2) nocturne plus basse. Tour de taille et SpO2 nocturne etaient inversement correles (rxa0=xa0− 0,43, pxa0=xa00,011), et tous deux etaient associes aux indices plasmatiques de l’homeostasie du glucose : plus le tour de taille etait eleve et la SpO2 nocturne basse, plus l’insulino-resistance etait importante. Dans un modele de regression lineaire multivariee incluant tour de taille et SpO2 nocturne, seule la SpO2 nocturne etait independamment associee aux indices d’insulino-resistance. Conclusion L’exces d’adiposite abdominale, chez des hommes apneiques non obeses, est associe a une plus grande insulino-resistance. Cette association semble mediee par une hypoxemie nocturne plus marquee lorsque le TDT augmente.

P164 Rôle du Pore de transition de perméabilité mitochondriale dans la mort cellulaire béta induite par l’ischémie-reperfusion

Introduction L’apoptose des cellules β pancreatiques au cours de la greffe d’ilots de Langerhans est un obstacle majeur de cette technique : 50 % du greffon est perdu dans les quinze jours suivants la transplantation en raison de phenomenes non specifiques (Ischemie-reperfusion, glucotoxicite…). Le pore de transition de permeabilite mitochondriale (PTP) est un complexe proteique mitochondrial dont l’ouverture est un element cle du declenchement de l’apoptose. L’ischemie-reperfusion combine plusieurs conditions favorables a l’ouverture du PTP (surcharge calcique, stress oxydant, depletion nucleotidique). Si l’implication du PTP dans l’apoptose de cardiomyocytes soumis a l’ischemie – reperfusion et le benefice de l’utilisation d’inhibiteurs du PTP est desormais bien connus sur ce type cellulaire, aucune donnee n’est disponible concernant le role du PTP dans l’apoptose des cellules β soumises a l’ischemie-reperfusion. Materiels et methodes Nous avons etudie l’implication du PTP dans l’apoptose de cellules β murines (INS-1) soumises a l’ischemie-reperfusion et le benefice d’un traitement par les inhibiteurs connus du PTP (Cyclosporine A et Metformine) sur la viabilite cellulaire β. Les INS-1, soumises a une heure d’ischemie simulee (Fi02 3 % et perfusion par un milieu sans substrat), sont reperfusees par du milieu complet et reoxygenees sous Fi02 21 %. Le statut du PTP est determine par analyse de la co-localisation de deux signaux de fluorescence (NADH et tetramethylrhodaminemethyether) en microscopie confocale. La viabilite cellulaire est etudiee par cytometrie en flux par marquage Annexin V et Iodure de Propidium. Resultats L’exposition des INS-1 aux phenomenes d’ischemie-reperfusion conduit a une alteration considerable de la viabilite cellulaire β via une ouverture du PTP. La Cyclosporine A, et la Metformine, en inhibant l’ouverture du PTP, previennent l’apoptose induite par l’ischemie-reperfusion. Conclusion Le PTP occupe une place fondamentale dans l’apoptose cellulaire – induite par l’ischemie-reperfusion. Cibler pharmacologiquement le PTP au cours de la greffe d’ilots de Langerhans peut etre une strategie interessante pour preserver la viabilite cellulaire β.