PET/CT-identified atrial hypermetabolism is an index of atrial inflammation in patients with atrial fibrillation.

BACKGROUND: Although atrial inflammation has been implicated in the pathophysiology of atrial fibrillation (AF), the identification of atrial inflammation remains challenging. We aimed to establish a positron emission tomography/computed tomography (PET/CT) protocol with 18Fluor-labeled fluorodeoxyglucose (18F-FDG) for the detection of atrial hypermetabolism as surrogate for inflammation in AF. METHODS: We included n = 75 AF and n = 75 non-AF patients undergoing three common PET/CT protocols (n = 25 per group) optimized for the detection of (a) inflammation and (b) malignancy in predefined fasting protocols, and (c) cardiac viability allowing for maximized glucose uptake. 18F-FDG-uptake was analyzed in predefined loci. RESULTS: Differences of visual atrial uptake in AF vs non-AF patients were observed in fasting (inflammation [13/25 vs 0/25] and malignancy [10/25 vs 0/25]) protocols while viability protocols showed non-specific uptake in both the groups. In the inflammation protocol, AF patients showed higher uptake in the right atrium [(SUVmax: 2.5 ± .7 vs 2.0 ± .7, P = .01), atrial appendage (SUVmax: 2.4 ± .7 vs 2.0 ± .6, P = .03), and epicardial adipose tissue (SUVmax: 1.4 ± .5 vs 1.1 ± .4, P = .04)]. Malignancy and viability protocols failed to differentiate between AF and non-AF. CONCLUSION: Glucose uptake suppression protocols appear suitable in detecting differential atrial 18F-FDG uptake between AF and non-AF patients. Imaging-based assessment of inflammation might help to stratify AF patients offering individualized therapeutic approaches.

Equivalent tumor detection for early and late FAPI-46 PET acquisition.

INTRODUCTION: Positron emission tomography (PET) using small ligands of the fibroblast activation protein (FAP) was recently introduced. However, optimal uptake time has not been defined yet. Here, we systematically compare early (~ 10 min p.i.) and late (~ 60 min p.i.) FAPI-46 imaging in patients with various types of cancer. METHODS: This is a retrospective single-institutional study. Imaging was performed at the Essen University Hospital, Germany. A total of 69 patients who underwent dual time-point imaging for either restaging (n = 52, 75%) or staging (n = 17, 25%) of cancer were included. Patients underwent PET with two acquisitions: early (mean 11 min, SD 4) and late (mean 66 min, SD 9). Mean injected activity was 148 MBq (SD 33). RESULTS: In total, 400 lesions were detected in 69 patients. Two of 400 (0.5%) lesions were only seen in early time-point imaging but not in late time-point imaging. On a per-patient level, there was no significant difference between SUVmax of hottest tumor lesions (Wilcoxon: P = 0.73). Organ uptake demonstrated significant early to late decrease in SUVmean (average ∆SUVmean: - 0.48, - 0.14, - 0.27 for gluteus, liver, and mediastinum, respectively; Wilcoxon: P < 0.001). On a per-lesion basis, a slight increase of SUVmax was observed (average ∆SUVmax: + 0.4, Wilcoxon: P = 0.03). CONCLUSION: In conclusion, early (~ 10 min p.i.) versus late (~ 60 min p.i.) FAPI-46 imaging resulted in equivalent lesion uptake and tumor detection. For improved feasibility and scan volume, we implement early FAPI-46 PET in future clinical and research protocols.

Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling.

BACKGROUND: Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging. METHOD AND RESULTS: Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUVmax 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUVmean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUVmean uptake, the latter with a very strong correlation with remote uptake (R2 = .74, P < .01). CONCLUSION: Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.

ANTECEDENTES: Proteína de activación de fibroblastos (FAP) como marcador específico de fibroblastos maduros activados se puede visualizar mediante tomografía por emisión de positrones (PET) usando inhibidores de Ga-68-FAP (FAPI). El FAPI marcado con galio 68 se usa cada vez más en la estatificación de varios tipos de cáncer.Además, se han reportado los primeros casos de abordajes teranósticos. En este trabajo describimos el fenómeno de la captación de FAPI miocárdica en pacientes que recibieron Ga-68 FAPI PET para estatificación tumoral. MéTODO Y RESULTADOS: Los exámenes de PET Ga-68 FAPI para estadificación de cáncer se analizaron retrospectivamente con respecto a la captación del marcador cardíaco. Los valores de absorción estandarizados (SUV) se correlacionaron con covariables clínicas en un modelo de regresión univariante. Del 09/2018 al 11/2019 con una n = 32 pacientes fueron sometidos a PET FAPI en nuestra institución. Seis de 32 pacientes (18.8%) demostraron un aumento de acumulación del marcador localizado en el miocardio, con la captación remota de FAPI siendo significativamente mayor en pacientes con aumento de la captación vs sin captación focalizada de miocardio (SUVmax 2.2 ± 0.6 vs. 1.5 ± 0.4, p <0.05 y SUV mean 1.6 ± 0.4 vs. 1.2 ± 0.3, p <0.05, respectivamente). La regresión univariante demostró una correlación significativa de la enfermedad de la arteria coronaria (CAD), la edad y la fracción de eyección ventricular izquierda (FEVI) con absorción SUV remota, esta última con una muy fuerte correlación con la captación remota (R² = 0.74, p <0.01). CONCLUSIóN: Nuestro estudio indica una asociación de CAD, edad y FEVI con la captación de FAPI. Se necesitan más estudios para evaluar si la activación de fibroblastos se puede medir de manera confiable y se puede usar para la estratificación de riesgo con respecto a la detección temprana o la progresión de la CAD y la remodelación ventricular izquierda.

CONTEXTE: La protéine d'activation des fibroblastes (FAP) activés et matures peut être visualisée par tomographie à émission de positons (TEP) à l'aide d'inhibiteurs de l'activation des fibroblastes (FAPI). FAPI marqué au gallium 68 est de plus en plus utilisé dans la stratification de divers cancers. De plus, les premiers exemples d'approches théranostiques ont été rapportés. Dans ce travail nous décrivons la captation myocardique de FAPI chez les patients qui bénéficié d'une TEP au Ga-68 FAPI pour stratification tumorale. MéTHODE ET RéSULTATS: Les examens TEP Ga-68 FAPI pour la stratification oncologique ont été analysés rétrospectivement pour l'absorption du traceur au niveau cardiaque. Les valeurs d'absorption normalisées (SUV) font été corrélées aux variables cliniques selon un modèle de régression univarié. A partir de septembre 2018 jusqu'en novembre 2019, 32 patients ont bénéficié d'une TEP FAPI dans notre établissement. Six de nos 32 patients (18,8%) ont démontré une augmentation focale de captation du tracer au niveau myocardique. Les foyers systémiques se sont révélés significativement plus élevé chez les patients avec foyers myocardiques localisés (SUV max 2,2 ± 0,6 vs 1,5 ± 0,4, p <0,05 et SUV mean 1,6 ± 0,4 vs 1,2 ± 0,3, p <0,05, respectivement). Nous avons observé une corrélation significative entre la maladie coronarienne, l'âge, la fraction d'éjection du ventricule gauche et la présence de foyer myocardiques FAPI (R² = 0,74, p <0,01) CONCLUSION: Notre étude indique une association entre la maladie cardiovasculaire coronarienne, l'âge et la FEVG et la captation myocardique de FAPI. Des études additionnelles sont nécessaires pour déterminer si l'activation des fibroblastes peut être mesurée de manière fiable et utilisée pour la détection et la progression de la maladie coronarienne et le remodelage du ventricule gauche.

PRODIG (Prevention of new onset diabetes after transplantation by a short term treatment of Vildagliptin in the early renal post-transplant period) study: study protocol for a randomized controlled study.

BACKGROUND: Post-transplant diabetes is a frequent and serious complication of kidney transplantation. There is currently no treatment to prevent or delay the disease. Nevertheless, identification of risk factors make it possible to target a population at risk of developing de novo diabetes. We hypothesized that a short-term treatment with vildagliptin may prevent new onset diabetes after transplantation (NODAT) in high-risk patients. METHODS/DESIGN: This is a multicenter, double-blind, placebo-controlled randomized clinical trial. Patients undergoing first kidney transplantation will be included from ten French transplant centers. Included patients will be randomized (1:1) to receive either vildagliptin 100 or 50 mg/day (depending on glomerular filtration rate) during 2 months (the first dose being administered before entering the operating theatres) or placebo. Additional antidiabetic therapy could be administered according to glycemic control. The primary outcome is the proportion of diabetic patients 1 year after transplantation, defined as patients receiving a diabetic treatment, or having a fasting glucose above 7 mmol/l, and/or with an abnormal oral glucose tolerance test. Secondary outcomes include glycated hemoglobin, the occurrence of acute rejection, infection, graft loss and patient death at 3 months, 6 months, and 12 months after transplantation. Outcomes will be correlated to clinical and general characteristics of the patient, cardiovascular history, nephropathy, dialysis history, transplantation data, biological data, health-related quality of life, and the cost-effectiveness of prevention of diabetes with vildagliptin. DISCUSSION: We have scarce data on the pharmacological prevention of post-transplant diabetes. If our hypothesis is verified, our results will have a direct application in clinical practice and could limit diabetes-associated morbidity, reduce cardiovascular complications, increase quality of life of renal transplant patients, and consequently promote graft and patient survival. Our results may possibly serve for non-transplant patients carrying a high-risk of diabetes associated with other co-morbidities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02849899 . Registered on 8 February 2016.

Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d'endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie - dialyse - transplantation (SFNDT).

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Obstructive sleep apnoea syndrome in patients living with diabetes: Which patients should be screened?

AIM: Because type 2 diabetes (T2D) is related to obesity, it is often associated with obstructive sleep apnoea syndrome (OSAS), although OSAS is also frequently diagnosed in patients with type 1 diabetes (T1D) and may promote gestational diabetes. Thus, this systematic review of the scientific evidence aimed to evaluate the epidemiological association between OSAS and all forms of diabetes, the current understanding of the pathophysiological mechanisms behind these associations, the expected benefits and limitations of OSAS treatment in patients with diabetes and, finally, to propose which patients require screening for OSAS. METHODS: A panel comprising French expert endocrinologists and pneumologists was convened. Two of these experts made a search of the relevant literature for each subpart of the present report; all panel experts then critically reviewed the entire report separately as well as collectively. RESULTS: There is little evidence to support the notion that OSAS treatment improves glycated haemoglobin, although it may improve nighttime blood glucose control and insulin sensitivity. However, there is robust evidence that OSAS treatment lowers 24-h blood pressure. CONCLUSION: The high prevalence of OSAS in patients with T1D and T2D justifies screening for the syndrome, which should be based on clinical symptoms, as the benefits of OSAS treatment are mainly improvement of symptoms related to sleep apnoea. There are also several clinical situations wherein screening for OSAS seems justified in patients with diabetes even when they have no symptoms, particularly to optimalize control of blood pressure in cases of resistant hypertension and microvascular complications.

[Membranous microparticles and respiratory disease]. / Microparticules membranaires et maladies respiratoires.

Microparticles (MP) are plasmic membrane fragments released from cells after physiological stimulation or stress conditions like inflammation or infection. Their production is correlated to the rate of cell apoptosis. All types of cells can produce MP but they are produced mainly by platelets, endothelial cells, and leukocytes. They carry many bio-active molecules on their surface, specific to the parental cell, giving them the ability to be biomarkers and bio-effectors. MP are present in circulating blood, tissues and many biological fluids. Circulating MP levels can change during the course of many diseases. They have been the subject of many studies in the fields of cardiovascular disease and oncology. In the lungs, they are present in circulating blood and in the airways. They seem to have a role in pulmonary homeostasis in physiological situations and also in the expression of several disease processes. In this review of the literature, we were interested in the quantitative and qualitative variations in MP and their impact in airway diseases like chronic obstructive pulmonary disease (COPD) and asthma, pulmonary fibrosis and pulmonary hypertension.

Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function.

Pancreatic islet grafting restores endogenous insulin production in type 1 diabetic patients, but long-term outcomes remain disappointing as a result of immunological destruction of allogeneic islets. In solid organ transplantation, donor-specific anti-HLA antibodies (DSA) are the first cause of organ failure. This retrospective multicentric study aimed at providing in-depth characterization of DSA response after pancreatic islet grafting, identifying the risk factor for DSA generation and determining the impact of DSA on graft function. Forty-two pancreatic islet graft recipients from the Groupe Rhin-Rhône-Alpes-Genève pour la Greffe d'Ilots de Langerhans consortium were enrolled. Pre- and postgrafting sera were screened for the presence of DSA and their ability to activate complement. Prevalence of DSA was 25% at 3 years postgrafting. The risk of sensitization increased steeply after immunosuppressive drug withdrawal. DSA repertoire diversity correlated with the number of HLA and eplet mismatches. DSA titer was significantly lower from that observed in solid organ transplantation. No detected DSA bound the complement fraction C3d. Finally, in contrast with solid organ transplantation, DSA did not seem to negatively affect pancreatic islet graft survival. This might be due to the low DSA titers, specific features of IgG limiting their ability to activate the complement and/or the lack of allogenic endothelial targets in pancreatic islet grafts.

Unexpected Massive Hemothorax After Pancreatic Islet Transplantation: A Case Report.

The percutaneous transhepatic portal approach is the most commonly used technique for islet transplantation, largely owing to its safety and minimally invasive characteristic. Bleeding complications after islet transplantation are rare and include portal vein thrombosis and subcapsular liver hematoma. We report a massive hemothorax after portal vein catheterization in a patient with brittle type 1 diabetes undergoing hepatic islet embolization. The patient was under long-term aspirin therapy because of vascular complications and received heparin in low doses to prevent the instant blood-mediated inflammatory reaction and reduce the risk of portal vein thrombosis. The present case illustrates the particular risk of bleeding complications in patients with brittle type 1 diabetes, who represent a frail population. This uncommon adverse event highlights the importance of close monitoring in the first days following islet transplantation.

[Pancreatic infringement exocrine and endocrine in cystic fibrosis]. / Atteinte pancréatique exocrine et endocrine dans la mucoviscidose.

The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent phase of diabetes, screening it is recommended by the realization of an annual OGTT from 10 years of age, or before in severe forms of CF. New treatments of CF able to target CFTR showed their efficacy in slowing the decline of lung function, and could also contribute to slow or prevent the onset of diabetes.

Obstructive sleep apnoea in people with Type 1 diabetes: prevalence and association with micro- and macrovascular complications.

AIMS: Few reports have assessed the relationship between Type 1 diabetes and sleep disorders. The purposes of our study were to determine the prevalence of obstructive sleep apnoea in Type 1 diabetes and to compare the clinical profile of people with Type 1 diabetes with or without obstructive sleep apnoea. METHODS: In this cross sectional study of 67 consecutive people with Type 1 diabetes, we performed polysomnography as part of their yearly check-ups. RESULTS: In our cohort, with a mean BMI of 25.8 ± 4.7 kg/m(2), the prevalence of obstructive sleep apnoea [apnoea-hypopnoea index (AHI) > 10/h] was 46%. Severe obstructive sleep apnoea (AHI ≥ 30/h) was present in 19% of the patients. We found no significant differences in age, sex, body mass index, HbA1c or Epworth sleepiness scale score between people with or without obstructive sleep apnoea. People with obstructive sleep apnoea had a longer course of diabetes mellitus (P < 0.01) and a higher prevalence of retinopathy (P < 0.01), neuropathy (P = 0.05), cardiovascular disease (P < 0.01) and hypertension (P < 0.01). The occurrence of macrovascular complications was independently associated with the presence of OSA [odds ratio (OR) 8.28; 95% confidence interval (CI), 1.56-43.97; P = 0.013] and the duration of diabetes (OR 1.08; 95% CI, 1.02-1.15; P = 0.01). Moreover, retinopathy was independently associated with OSA (OR 4.54; 95% CI, 1.09-18.82; P = 0.04) and the duration of diabetes (OR 1.09; 95% CI, 1.04-1.15; P = 0.001). CONCLUSIONS: The prevalence of obstructive sleep apnoea was high in people with Type 1 diabetes. Obstructive sleep apnoea was independently associated with macrovascular complications and retinopathy. Obesity and excessive daytime sleepiness were uncommon in this population.

Early effects of liver regeneration on endocrine pancreas: in vivo change in islet morphology and in vitro assessment of systemic effects on ß-cell function and viability in the rat model of two-thirds hepatectomy.

Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is associated with systemic modifications and depends especially on pancreatic hormones. The aim of the study was to investigate the role of systemic factors released after two-thirds hepatectomy (2/3H) on early possible consequences of liver regeneration on endocrine pancreas structure and function. The pancreas and serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats. The HGF and VEGF serum concentrations and plasma microparticles levels were measured. The fate of endocrine pancreas was examined through islets histomorphometry and function in sham and 2/3H rats. ß-Cell line RIN-m5F viability was assessed after 24 h of growth in media supplemented with 10% serum from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p < 0.05) and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs. 15%, p < 0.05). Compared to Sham, sera obtained 3 days after hepatectomy were more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p < 0.01). Three days after surgery, no significant differences in serum HGF, a trend to significant increase in VEGF concentration and a significant increase in microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd Ser Eq., p < 0.05). Liver regeneration is associated with early effects on islets and could influence ß-cell viability and function by systemic effect.

Prenatal diagnosis in haemophilia A: experience of the genetic diagnostic laboratory.

The paper describes the experience of the Genetic Diagnostic Laboratory in prenatal testing for haemophilia A, an X-linked recessive disease caused by mutations in the F8 gene. Knowledge of a familial mutation prior to pregnancy can benefit prenatal diagnosis and decrease wait time for molecular testing during pregnancy. This is a retrospective review of a series of pregnant women who pursued F8 gene testing from December 1997 through May 2012, highlighting three cases, which demonstrate the technical complexities of analysis and the implications of not knowing carrier status prior to pregnancy. Mutations of the F8 gene were detected in affected males, obligate female carriers and suspected female carriers by DNA sequencing, inverse-PCR, qRT-PCR, Southern blot and exonic dosage analysis. The same methods were used to analyse prenatal samples from obligate or suspected female carriers upon request. Maternal cell contamination studies were performed for all prenatal samples analysed. Ninety-nine women pursued F8 testing during pregnancy, either for carrier status alone or carrier status and prenatal diagnosis. Ninety-one women (91%) requested carrier testing because they did not know their F8 mutation carrier status prior to pregnancy. Eight women requested prenatal diagnosis only, and only 4 of these were aware of their mutation status. Thirty-seven individuals were found to be mutation carriers. Forty-two prenatal samples were received for prenatal diagnosis. In total 21 foetuses were identified as mutation carriers. Mutation detection was complex and increased the turnaround time in some cases. Only four of 99 women who submitted samples for F8 testing were aware of their F8 mutation status prior to pregnancy. Knowledge of F8 mutation status prior to pregnancy allows for efficient prenatal diagnosis, when desired. Thus, preconception genetic counselling is required to inform patients of the available options and the complex and time-consuming nature of F8 testing.

Influence of dialysis on the glucose profile in patients with diabetes: usefulness of continuous glucose monitoring.

We sought to investigate the impact of dialysis on glucose profiles of diabetic patients using continuous glucose monitoring (CGM). The study included 33 hemodialyzed patients with diabetes (14 females and 19 males; mean age: 66±8 years; patients with type 2 diabetes: 30; mean duration of dialysis: 3.8±2.6 years) who were under insulin treatment. After a run-in period, CGM was performed for 48 h, including a dialysis session. Three CGM sessions were proposed for each patient over a 3-month period. CGM results were analyzed during and after dialysis at 6 different time points. Moreover, data were analyzed in 7 different day periods according to meals. Of the 99 CGM available, 21 were excluded because of technical issues or patient refusal. The CGM results indicated that mean glucose values (7.5±2.5 mmol/l vs. 9.4±1.9 mmol/l; p<0.001) and variability indices (p<0.001) were lower, whereas the frequency of hypoglycemia (4.4±9.6% vs. 2.1±7.9%; p<0.001) was higher during hemodialysis sessions. Significant differences were observed in glucose values only before and 2 h after breakfast (p<0.001). Compared with other day periods, glucose values were lower during the second half of the night and higher before and after dinner (p<0.001). In summary, CGM allows the identification of a particular glucose profile in hemodialyzed diabetic patients. CGM seems feasible and clinically useful for the analysis of glucose profiles in this group of patients.

Early assessment of glucose abnormalities during continuous glucose monitoring associated with lung function impairment in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is correlated with a decline in lung function. Under certain circumstances, oral glucose tolerance test (OGTT) screening, used to diagnose CFRD, fails to reveal early glucose tolerance abnormalities. In this situation, continuous glucose monitoring (CGM) could be a useful tool for evaluating early abnormalities of glucose tolerance in CF patients. We aimed to study the CGM glucose profile in CF patients with normal OGTT screening results and to evaluate lung function and nutritional status according to the CGM glucose profile. METHODS: We assessed glycemic control, the CGM glucose profile, nutritional status, lung function antibiotic courses and colonization (P. aeruginosa and S. aureus) in CF patients, aged 10 years and over, with normal screening OGTT results (blood glucose at T120 min < 7.8 mmol/l). Two groups were identified according to the max CGM glucose value: Group 1<11 mmol/l and Group 2 ≥ 11 mmol/l. RESULTS: Among the 38 patients with normal OGTT, 12 (31.6%) were in Group 2. Compared to Group 1, Group 2 patients exhibited a significant impairment in lung function: FEV1, 68.2 ± 25.6% vs. 87.3 ± 17%, p = 0.01 and FVC, 86.1% ± 19.4% vs. 99.3% ± 13.4%, p=0.021, as well as a higher rate of colonization by P. aeruginosa: 83.3% vs. 44%, p=0.024. Nevertheless, there were no differences in nutritional status (BMI standard deviation score: p = 0.079; prealbumin: p = 0.364). CONCLUSIONS: CGM reveals early abnormalities of glucose tolerance that remain undiagnosed by OGTT screening and are associated with worse lung function and a higher prevalence of P. aeruginosa colonization in patients with CF. CLINICAL TRIAL REGISTRATION NUMBER: NCT00476281.

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.