Radiofrequency echographic multi spectrometry (REMS) in the diagnosis and management of osteoporosis: state of the art.

Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

[Gliflozins and finerenone: what are the prospects for their combination?] / Gliflozines et finérénone : quelles perspectives pour leur association?

Chronic kidney disease is a common complication of diabetes. Progressive deterioration of renal function is responsible for an increased risk of cardiovascular diseases. The end-stage renal disease with the vital recourse to dialysis sessions remains a major burden for the patients as well as for the society given the major cost of this treatment. Recently, two classes of drugs have demonstrated significant benefits in terms of cardio-renal protection: SGLT2 inhibitors (gliflozins) and finerenone, a selective nonsteroidal mineralo-receptor antagonist. Given their different mechanisms of action, a combination of the two pharmacological classes seems logical and promising based on a number of exploratory current analyses and considerations.

La maladie rénale chronique (MRC) est une complication fréquente liée à diverses pathologies dont le diabète. La dégradation progressive de la fonction rénale est responsable d'un risque accru de présenter des maladies cardiovasculaires. Son évolution terminale avec le recours vital à la dialyse reste un fardeau majeur pour les personnes qui en souffrent ainsi que pour la société compte tenu du coût qui en résulte. Récemment, deux classes médicamenteuses ont démontré des avantages significatifs en termes de protection cardiorénale : les inhibiteurs du SGLT2 (gliflozines) et la finérénone, un antagoniste sélectif non stéroïdien des récepteurs de l'aldostérone. Compte tenu de mécanismes d'action différents, leur combinaison semble logique et prometteuse sur la base de plusieurs analyses exploratoires.

[Focus on tirzepatide, a dual unimolecular GIP-GLP-1 receptor agonist in type 2 diabetes]. / Focus sur le tirzépatide, un double agoniste unimoléculaire GIP-GLP-1 dans le diabète de type 2.

Tirzepatide is a unimolecular dual agonist of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, which is developed as once-weekly injection for the treatment of type 2 diabetes. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, basal insulin and two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protection (versus dulaglutide) is currently tested in SURPASS-CVOT. Finally, studies for the treatment of obesity and metabolic associated fatty liver disease are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except more diarrhoea.

Le tirzépatide est un agoniste unimoléculaire double des récepteurs du polypeptide insulinotrope dépendant du glucose (GIP) et du Glucagon-Like Peptide-1 (GLP-1) développé, en injection hebdomadaire, pour le traitement du diabète de type 2. De par la complémentarité des 2 incrétines, il a montré, de façon dose-dépendante (5, 10 et 15 mg), une efficacité supérieure (plus forte réduction du taux d'HbA1c (hémoglobine glyquée) et du poids corporel) par rapport au placebo, à l'insuline basale et à 2 analogues du GLP-1 (dulaglutide et sémaglutide) dans le programme SURPASS. Sa protection cardiovasculaire (versus le dulaglutide) est actuellement testée dans SURPASS-CVOT. Enfin, des études sont en cours dans l'obésité et la stéatopathie hépatique. La tolérance digestive du tirzépatide est comparable à celle des analogues du GLP-1, hormis davantage de diarrhée.

[Cardiovascular risk and type 1 diabetes]. / Risque cardiovasculaire et diabète de type 1.

People with diabetes are considered to have an increased cardiovascular risk. Patients with type 1 diabetes (T1D) generally have a cardiovascular risk profile that is different from those with type 2 diabetes. For this reason, we wanted to assess whether a population of T1D designed to be at very high cardiovascular risk achieved the strict goals recommended by the European Society of Cardiology. This is a descriptive cross-sectional analysis of a cohort of patients with T1D for at least 20 years followed at the University Hospital of Liege and considered to be at very high cardiovascular risk. We then discuss the relevance of strict targets in such patients by comparing them to different scientific societies. Finally, we briefly discuss the potential mechanisms by which T1D present an increased cardiovascular risk.

Les personnes diabétiques sont considérées comme ayant un risque cardiovasculaire accru. Les patients diabétiques de type 1 (DT1) ont un profil de risque cardiovasculaire souvent différent de celui des diabétiques de type 2. Nous avons évalué si une population de patients DT1, dits « à très haut risque cardiovasculaire ¼, atteignait les objectifs stricts recommandés par la Société européenne de cardiologie. Il s'agit d'une analyse transversale descriptive d'une cohorte de patients avec au moins 20 ans de DT1, suivis au CHU de Liège et considérés comme à très haut risque cardiovasculaire. Nous discutons de la pertinence de tels objectifs chez de tels patients, en les comparant à ceux de différentes sociétés savantes. Nous abordons brièvement les mécanismes potentiels à l'origine, dans ce groupe, d'un risque cardiovasculaire accru.

Does Oxidative Stress Play a Role in Altered Characteristics of Diabetic Bone? A Systematic Review.

Diabetes mellitus (DM) has been associated with increased bone fracture rates, impaired bone regeneration, delayed bone healing, and depressed osteogenesis. However, the plausible pathogenic mechanisms remain incompletely understood. The aim of the present systematic review was to investigate whether oxidative stress (OS) plays a role in altered characteristics of diabetic bone under in vivo conditions. An electronic search of the MEDLINE (via PubMed) and Embase databases was performed. In vivo animal studies involving DM and providing information regarding assessment of OS markers combined with analyses of bone histology/histomorphometry parameters were selected. A descriptive analysis of selected articles was performed. Ten studies were included in the present review. Both bone formation and bone resorption parameters were significantly decreased in the diabetic groups of animals compared to the healthy groups. This finding was consistent regardless of different animal/bone models employed or different evaluation periods. A statistically significant increase in systemic and/or local OS status was also emphasised in the diabetic groups in comparison to the healthy ones. Markers of OS were associated with histological and/or histomorphometric parameters, including decreased trabecular bone and osteoid volumes, suppressed bone formation, defective bone mineralisation, and reduced osteoclastic activity, in diabetic animals. Additionally, insulin and antioxidative treatment proved to be efficient in reversing the deleterious effects of high glucose and associated OS. The present findings support the hypotheses that OS in the diabetic condition contributes at least partially to defective bone features, and that antioxidative supplementation can be a valuable adjunctive strategy in treating diabetic bone disease, accelerating bone healing, and improving osteointegration.

[Treatment of dyslipidemia in 2014: European versus American guidelines]. / Traitement des dyslipidémies en 2014: recommandations européennes versus américaines.

The recent American guidelines on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults have confused the debate in comparison with the European guidelines. These US guidelines prefer the notion of intensity of reduction of blood cholesterol based on the level of cardiovascular risk rather than a LDL cholesterol level target recommended by the European guidelines. Moreover, only the use of statins is recommended without any consideration for alternative pharmacological approaches in special situations. Even if we can find some similarities between these two guidelines, it is of interest to compare them carefully in order to justify the reasons why preference should be given to European guidelines.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.

[Therapeutic education and continuous glucose monitoring in insulin-treated diabetic patients]. / Education thérapeutique et mesure continue de la glycémie chez le patient diabétique insulino-traité.

The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system to improve glucose control was investigated in patients with type 1 diabetes (glucose sensor combined with a portable insulin pump--Paradigm Real Time) and in patients with type 2 diabetes poorly controlled despite insulin therapy (Guardian RT one week per month for 3 months compared to blood glucose self-monitoring). Both studies showed a reduction in glycated haemoglobin (HbA1c) levels with the glucose sensor, associated with less symptomatic hypoglycaemic episodes. Despite some technical difficulties (mainly in patients with type 2 diabetes), this approach represents a useful tool for therapeutic education. These promising results justify the initiation of larger studies evaluating glucose sensor use in well selected diabetic patients.

Sustained Impact of Real-time Continuous Glucose Monitoring in Adults With Type 1 Diabetes on Insulin Pump Therapy: Results After the 24-Month RESCUE Study.

OBJECTIVE: In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH). RESEARCH DESIGN AND METHODS: This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA1c, with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up. RESULTS: After 24 months, HbA1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P < 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P < 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA1c <7% (<53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P < 0.0001). CONCLUSIONS: Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH.

Cystatin C or creatinine for detection of stage 3 chronic kidney disease in anorexia nervosa.

BACKGROUND: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidney disease (CKD) is often missed in these patients because the serum creatinine is a poor marker of kidney function. We studied the utility of cystatin C to detect renal failure in this population. METHOD: Twenty-seven AN patients were studied. Glomerular filtration rates (GFR) were measured with the chromium-51- ethylenediaminetetraacetate ((51)Cr-EDTA) method. We compared the ability of creatinine and cystatin C to detect stage 3 CKD (GFR below 60 ml/min) by ROC curve analysis. RESULTS: In this cohort, there is no correlation between GFR and serum creatinine, but there is a significant correlation between cystatin C and GFR. By ROC analysis, the cystatin C concentration is better than the serum creatinine concentration for the detection of stage 3 CKD (area under the curve of 0.86 vs. 0.61, p = 0.05). CONCLUSION: Plasma cystatin C is better than serum creatinine in detecting stage 3 CKD in patients with AN.

Effect of Continuous Glucose Monitoring on Glycemic Control, Acute Admissions, and Quality of Life: A Real-World Study.

Context: Randomized controlled trials evaluating real-time continuous glucose monitoring (RT-CGM) patients with type 1 diabetes (T1D) show improved glycemic control, but limited data are available on real-world use. Objective: To assess impact of RT-CGM in real-world settings on glycemic control, hospital admissions, work absenteeism, and quality of life (QOL). Design: Prospective, observational, multicenter, cohort study. Participants: A total of 515 adults with T1D on continuous subcutaneous insulin infusion (CSII) therapy starting in the Belgian RT-CGM reimbursement program. Intervention: Initiation of RT-CGM reimbursement. Main Outcome Measure: Hemoglobin A1c (HbA1c) evolution from baseline to 12 months. Results: Between September 1, 2014, and December 31, 2016, 515 adults entered the reimbursement system. Over this period, 417 (81%) patients used RT-CGM for at least 12 months. Baseline HbA1c was 7.7 ± 0.9% (61 ± 9.8 mmol/mol) and decreased to 7.4 ± 0.8% (57 ± 8.7 mmol/mol) at 12 months (P < 0.0001). Subjects who started RT-CGM because of insufficient glycemic control showed stronger decrease in HbA1c at 4, 8, and 12 months compared with patients who started because of hypoglycemia or pregnancy. In the year preceding reimbursement, 16% of patients were hospitalized for severe hypoglycemia or ketoacidosis in contrast to 4% (P < 0.0005) the following year, with decrease in admission days from 54 to 18 per 100 patient years (P < 0.0005). In the same period, work absenteeism decreased and QOL improved significantly, with strong decline in fear of hypoglycemia. Conclusion: Sensor-augmented pump therapy in patients with T1D followed in specialized centers improves HbA1c, fear of hypoglycemia, and QOL, whereas work absenteeism and admissions for acute diabetes complications decreased.

Lipodystrophy reactions to insulin: effects of continuous insulin infusion and new insulin analogs.

Management of diabetes mellitus can be responsible for cutaneous adverse events. For example, lipoatrophy or lipohypertrophy can develop at the site of insulin injections. Lipohypertrophy remains a frequent complication of insulin therapy irrespective of the insulin source and mode of administration. Lipoatrophy at insulin injection sites is considered to be an immune complex-mediated inflammatory lesion; however, it has become a rare event since the advent of human insulin. Nowadays, continuous subcutaneous insulin infusion (CSII) using a portable pump and/or injections of insulin analogs with an altered amino acid sequence compared with native insulin may cause lipodystrophy in diabetic patients. Some case reports describe the recovery of lipoatrophy following the use of CSII and/or short-acting insulin analogs. Conversely, exceptional cases of lipoatrophy have occurred in patients receiving lispro insulin analog via CSII. Lipodystrophy reactions remain a potential problem when managing diabetic patients with new insulin therapy technologies.

Simultaneous determination of insulin and its analogues in pharmaceutical formulations by micellar electrokinetic chromatography.

A simple and efficient MEKC method was developed to simultaneously determine human insulin, its five analogues, the main degradation products and the excipients usually present in injection formulations. A very fast method with a total analysis time of 3 min was then successfully validated for the analysis of human insulin and the quality control of commercial formulations was carried out.

Assessment of patient-led or physician-driven continuous glucose monitoring in patients with poorly controlled type 1 diabetes using basal-bolus insulin regimens: a 1-year multicenter study.

OBJECTIVE: The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes aged 8-60 years with HbA(1c) ≥ 8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS: A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA(1c): 8.9 ± 0.9%). HbA(1c) improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: -0.52%, P = 0.0006; group 2 vs. group 3: -0.47%, P = 0.0008; groups 1 + 2 vs. group 3: -0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1-Q3] consumption: group 1: 3.42/month [2.20-3.91] vs. group 2: 2.25/month [1.27-2.99], P = 0.001). CONCLUSIONS: Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.