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.

Can HbA1c be Used to Screen for Glucose Abnormalities Among Adults with Severe Mental Illness?

Aim: Prediabetes and type 2 diabetes are highly prevalent among individuals with serious mental illness and increased by antipsychotic medication. Although widely recommended, many obstacles prevent these patients from obtaining a proper screening for dysglycemia. Currently, glycated hemoglobin (HbA1c), fasting glucose, and 2-hour glucose levels from the oral glucose tolerance test are used for screening prediabetes and type 2 diabetes. The objective of this study was to investigate if HbA1c could be used as the only screening test among individuals with serious mental illness. Methods: Cross sectional study comparing the sensitivity of HbA1c, fasting glucose, and 2-h oral glucose tolerance test to detect dysglycemias in serious mental illness participants referred for metabolic complications. Results: A total of 84 participants (43 female; aged: 38.5±12.8 years; BMI: 35.0±6.8 kg/m²) was included. Regarding prediabetes, 44, 44 and 76% were identified by HbA1c, fasting glucose, and 2 h- oral glucose tolerance test respectively and for type 2 diabetes, 60, 53 and 66% were identified by HbA1c, fasting glucose and 2 h-oral glucose tolerance test. The overlap between the 3 markers was low (8% of participants for prediabetes and 26% for Type 2 diabetes). Sensitivity of HbA1c were moderate (range 40-62.5%), while its specificity was excellent (92-93%). Conclusion: The present study indicates a low agreement between HbA1c, fasting glucose and 2-h oral glucose tolerance test. It appears that these markers do not identify the same participants. Thus, HbA1c may not be used alone to detect all glucose abnormalities among individuals with serious mental illness.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Physical activity targeted at maximal lipid oxidation: a meta-analysis.

Exercise is recognized as a part of the management of obesity and diabetes. Various protocols of exercise are proposed for the management of obesity, diabetes, and other metabolic diseases. One of the strategies proposed by several authors is low intensity endurance training targeted at the level of maximal oxidation. Large series using this technique are lacking. Addressing this issue, we performed a meta-analysis of the studies on anthropometric measurements. From a database of 433 articles, 15 were selected, including 279 subjects with 6 different populations. Studies duration ranged from 2 months to 12 months. Concerning weight loss, in the intervention versus control analysis, five studies with 185 participants were included with a significant effect size favors exercise (P = 0.02) without significant heterogeneity (I(2) = 0.0%, P = 0.83). Further randomized controlled trials for comparing it with other exercise protocols and defining its dose effectiveness on large samples are needed.

Primary prevention of cardiovascular events and type 2 diabetes: should we prioritize our interventions?

The diagnosis of type 2 diabetes is based on elevated blood glucose levels. However, in most individuals, metabolic abnormalities as well as cardiovascular risk factors co-exist with a significant proportion of patients presenting with elevated blood pressure, high triglycerides and decreased HDL-cholesterol in addition to hyperglycemia. The risk of cardiovascular disease in people with type 2 diabetes is very high as cardiovascular death represents the number 1 killer in this population. An integrated approach controlling all risk factors as well as blood glucose has been demonstrated to effectively reduce the risk of cardiovascular complications. However, this requires the administration of multiple medications and some patients will have difficulties adhering to the prescribed regimen, limiting the number of drugs the physician can prescribe. In this review, we will summarize the efficacy of different approaches in primary prevention to help practitioners prioritize interventions in these situations.

Obesity management: attitudes and practices of French general practitioners in a region of France.

OBJECTIVES: To document the attitudes and practices of French general practitioners (GPs) regarding obesity management. RESEARCH METHODS AND PROCEDURES: A cross-sectional survey of a randomly selected sample of 744 French GPs was conducted, of which 607 questionnaires were returned. The measures included views on weight management, definitions of success, approaches to and strategies recommended for weight management and prevention, problems, frustrations, and expectations in managing obesity. RESULTS: GPs have a high awareness of obesity as a medically relevant issue, with 90% of them considering it to be a disease. However, they are only 42% to consider themselves well prepared to manage obesity and 51% to find obesity management professionally rewarding. They are 66% to believe that only a small percentage of patients can lose weight and maintain that loss but have unrealistic goals, with only 20% of them considering weight maintenance as a success. They do not consider collaboration with other health professionals like dietitians as a priority. Only 34% of the GPs believe that the currently available drugs are effective. Their views regarding bariatric surgery are in agreement with the recommendations of international experts. Their main expectations regarding obesity management are to improve their professional intervention through formation, education and easy-to-use tools, rather than improving their collaboration with other health professionals. DISCUSSION: There remains considerable opportunity to improve GPs' practice in obesity management. Medical education, increased cooperation with dietitians, improved long-term follow-up, and implementing better use of the available documents are key issues.

[Hyperparathyroidism diagnosed during pregnancy]. / Hyperparathyroïdie au cours d'une grossesse.

BACKGROUND: Diagnosis of hyperparathyroidism during pregnancy is rare because symptoms are often moderate and similar to signs observed during normal pregnancy. The gravity of such an association is probably underscored. CASE REPORT: The diagnosis of hyperparathyroidism was made at 9 weeks gestation in a young woman who declined surgery. She was seen again at 32 weeks gestation for in utero fetal death. Nine months later she accepted surgery and a parathyroid adenoma was removed. DISCUSSION: Hyperparathyroidism during pregnancy is associated with significant morbidity with major maternal or fetal complications in 50% of the cases. Surgery during the second trimester of pregnancy is the treatment of choice. If hyperparathyroidism is diagnosed in young women who desire pregnancy, surgery should be performed before advising pregnancy.

NMR identification of heavy metal-binding sites in a synthetic zinc finger peptide: toxicological implications for the interactions of xenobiotic metals with zinc finger proteins.

Lead (Pb), mercury (Hg), and cadmium (Cd) are toxic and interfere with protein metal-binding sites. The Cys(2)/His(2) zinc finger is a structural motif required for sequence-specific DNA binding and is present in zinc finger transcription factors (ZFP): Sp1, Egr-1, and TFIIIA. Neurotoxic studies have shown that heavy metals directly inhibit the DNA binding of ZFP and result in adverse cellular effects. Recently, we demonstrated the ability of heavy metals to alter the DNA binding of a synthetic Cys(2)/His(2) finger peptide (Razmiafshari and Zawia, Toxicol. Appl. Pharmacol. 166, 1-12, 2000). To determine the precise site of interactions between heavy metals and this protein domain, Pb, Hg, Cd, and Ca were reconstituted with the synthetic apopeptide and studied by one- and two-dimensional NMR spectroscopy. In the presence of Zn, Cd, Hg, and Pb, but not Ca, distinct peptide NMR signal changes in the aliphatic region were observed and attributed to metal-cystiene interactions. However, chemical shifts indicative of metal-histidine binding were elicited by all the metals in the peptide's aromatic region. Chemical shift assignments and sequential connectivity were established in the presence and absence of Zn, Pb, and Ca through TOCSY and NOESY spectra. Cysteine and histidine residues showed a distinct change in their amide and beta resonances in the presence of Zn and Pb, suggesting the metal-ligand binding sites were near these residues. However, Ca led to no significant spectral changes in these regions, suggesting that it is not actively involved in the binding site. These studies reveal this structure as a mediator of metal-induced alterations in protein function.

3-Bromotyrosine and 3,5-dibromotyrosine are major products of protein oxidation by eosinophil peroxidase: potential markers for eosinophil-dependent tissue injury in vivo.

Detection of specific reaction products is a powerful approach for dissecting out pathways that mediate oxidative damage in vivo. Eosinophil peroxidase (EPO), an abundant protein secreted from activated eosinophils, has been implicated in promoting oxidative tissue injury in conditions such as asthma, allergic inflammatory disorders, cancer, and helminthic infections. This unique heme protein amplifies the oxidizing potential of H2O2 by utilizing plasma levels of Br- as a cosubstrate to form potent brominating agents. Brominated products might thus serve as powerful tools for identifying sites of eosinophil-mediated tissue injury in vivo; however, structural identification and characterization of specific brominated products formed during EPO-catalyzed oxidation have not yet been reported. Here we explore the role of EPO and myeloperoxidase (MPO), a related leukocyte protein, in promoting protein oxidative damage through bromination and demonstrate that protein tyrosine residues serve as endogenous traps of reactive brominating species forming stable ring-brominated adducts. Exposure of the amino acid L-tyrosine to EPO, H2O2, and physiological concentrations of halides (100 mM Cl-,

Alteration of the binding specificity of cellular retinol-binding protein II by site-directed mutagenesis.

Rat cellular retinol-binding protein II (CRBP II) is an abundant 134-residue intestinal protein that binds all-trans-retinol and all-trans-retinal. It belongs to a family of homologous, 15-kDa cytoplasmic proteins that bind hydrophobic ligands in a noncovalent fashion. These binding proteins include a number of proteins that bind long chain fatty acids. X-ray analyses of the structure of two family members, rat intestinal fatty acid-binding protein and bovine myelin P2 protein, indicate that they have a high degree of conformational similarity and that the carboxylate group of their bound fatty acid interacts with a delta-guanidium group of at least 1 of 2 "buried" arginine residues. These 2 Arg residues are conserved in other family members that bind long chain fatty acids and in cellular retinoic acid-binding protein, but are replaced by Gln109 and Gln129 in CRBP II. We have genetically engineered two amino acid substitutions in CRBP II: 1) Gln109 to Arg and 2) Gln129 to Arg. The purified Escherichia coli-derived CRBP II mutant proteins were analyzed by fluorescence and nuclear magnetic resonance spectroscopy. Both mutants exhibit markedly decreased binding of all-trans-retinol and all-trans-retinaldehyde, but no increased binding of all-trans-retinoic acid. Arg substitution for Gln109 but not for Gln129 produces a dramatic increase in palmitate binding activity. Analysis of the endogenous fatty acids associated with the purified E. coli-derived proteins revealed that E. coli-derived intestinal fatty acid binding protein and the Arg109 CRBP II mutant are complexed with endogenous fatty acids in a qualitatively and quantitatively similar manner. These results provide evidence that this internal Arg may play an important role in the binding of long chain fatty acids by members of this protein family.