Patient medication management, understanding and adherence during the transition from hospital to outpatient care - a qualitative longitudinal study in polymorbid patients with type 2 diabetes.

BACKGROUND: Continuity of care is under great pressure during the transition from hospital to outpatient care. Medication changes during hospitalization may be poorly communicated and understood, compromising patient safety during the transition from hospital to home. The main aims of this study were to investigate the perspectives of patients with type 2 diabetes and multimorbidities on their medications from hospital discharge to outpatient care, and their healthcare journey through the outpatient healthcare system. In this article, we present the results focusing on patients' perspectives of their medications from hospital to two months after discharge. METHODS: Patients with type 2 diabetes, with at least two comorbidities and who returned home after discharge, were recruited during their hospitalization. A descriptive qualitative longitudinal research approach was adopted, with four in-depth semi-structured interviews per participant over a period of two months after discharge. Interviews were based on semi-structured guides, transcribed verbatim, and a thematic analysis was conducted. RESULTS: Twenty-one participants were included from October 2020 to July 2021. Seventy-five interviews were conducted. Three main themes were identified: (A) Medication management, (B) Medication understanding, and (C) Medication adherence, during three periods: (1) Hospitalization, (2) Care transition, and (3) Outpatient care. Participants had varying levels of need for medication information and involvement in medication management during hospitalization and in outpatient care. The transition from hospital to autonomous medication management was difficult for most participants, who quickly returned to their routines with some participants experiencing difficulties in medication adherence. CONCLUSIONS: The transition from hospital to outpatient care is a challenging process during which discharged patients are vulnerable and are willing to take steps to better manage, understand, and adhere to their medications. The resulting tension between patients' difficulties with their medications and lack of standardized healthcare support calls for interprofessional guidelines to better address patients' needs, increase their safety, and standardize physicians', pharmacists', and nurses' roles and responsibilities.

Navigating outpatient care of patients with type 2 diabetes after hospital discharge - a qualitative longitudinal study.

BACKGROUND: The transition from hospital to outpatient care is a particularly vulnerable period for patients as they move from regular health monitoring to self-management. This study aimed to map and investigate the journey of patients with polymorbidities, including type 2 diabetes (T2D), in the 2 months following hospital discharge and examine patients' encounters with healthcare professionals (HCPs). METHODS: Patients discharged with T2D and at least two other comorbidities were recruited during hospitalization. This qualitative longitudinal study consisted of four semi-structured interviews per participant conducted from discharge up to 2 months after discharge. The interviews were based on a guide, transcribed verbatim, and thematically analyzed. Patient journeys through the healthcare system were represented using the patient journey mapping methodology. RESULTS: Seventy-five interviews with 21 participants were conducted from October 2020 to July 2021. The participants had a median of 11 encounters (min-max: 6-28) with HCPs. The patient journey was categorized into six key steps: hospitalization, discharge, dispensing prescribed medications by the community pharmacist, follow-up calls, the first medical appointment, and outpatient care. CONCLUSIONS: The outpatient journey in the 2 months following discharge is a complex and adaptive process. Despite the active role of numerous HCPs, navigation in outpatient care after discharge relies heavily on the involvement and responsibilities of patients. Preparation for discharge, post-hospitalization follow-up, and the first visit to the pharmacy and general practitioner are key moments for carefully considering patient care. Our findings underline the need for clarified roles and a standardized approach to discharge planning and post-discharge care in partnership with patients, family caregivers, and all stakeholders involved.

Knowledge and practice attitudes regarding the relationship between diabetes and periodontitis: a survey among Swiss endocrinologists and general physicians.

BACKGROUND: The objective of the present survey is to assess the knowledge about the relationship between oral health and diabetes and to identify the practice behaviors of Swiss endocrinologists and general practitioners regarding oral health in diabetic patients. METHODS: A thirty- item questionnaire was mailed to 428 internists and 99 endocrinologists working in the French speaking part of Switzerland. Participants were asked about their awareness of the relationship between diabetes and periodontal disease, their practice behaviors as well as their willingness for an interdisciplinary education and collaboration with oral health professionals. The questions were answered according to a three-point or five-point Likert scale. RESULTS: The response rate was 23%. All participants were aware of the inflammatory and infectious nature of periodontal disease. They all agreed that good periodontal health is important for overall health. However, most of the practitioners responded that only rarely received information during their education curricula on the link between systemic and oral health or concerning periodontal problems in diabetic patients (60.9% for endocrinologists and 54.1% for general physicians); thus, only a minority of health practitioners addresses oral health care to their patients (13% and 15.3%, respectively). Both endocrinologists and general health physicians agreed that an oral health screening could be included in their practice (79% for both groups). CONCLUSIONS: An interdisciplinary education and collaboration among medical and dental health providers should be established to effectively prevent, manage, and control both diabetes and periodontal disease in diabetic patients.

Enhancing identification and treatment of patients with concomitant chronic venous insufficiency and diabetes mellitus. A modified Delphi study from the CODAC (ChrOnic venous disease and Diabetes Advisory Council) group.

BACKGROUND: Chronic venous insufficiency (CVI) and diabetes mellitus (DM) pose significant burdens to patients and healthcare systems. While the two diseases share a number of commonalities in risk factors and pathophysiology, they are often assessed and managed separately. This can lead to a worsening of comorbidities and limitations in a patient's quality of life. This project aims to develop recommendations to enhance the identification and treatment of patients with concomitant CVI and DM. METHODS: Using a modified Delphi method, a panel of experts developed 38 Likert Scale and two multiple choice questions across six key themes. These were used to form an online survey which was disseminated through a convenience sampling approach to CVI and DM healthcare professionals across Europe, Central America, South America, and the Middle East. The threshold for consensus was set at ≥75%. RESULTS: A total of 238 responses were received. 27/38 statements attained >90% agreement, nine of 38 attained between 75-90%, and two failed to meet the threshold (<75%). The awareness around the impact of the two diseases was high, but a gap was highlighted in the identification of patients with concomitant CVI and DM. CONCLUSIONS: The high level of agreement shows that healthcare professionals are aware of the gaps in identification and treatment of patients with concomitant CVI and DM, and of the need to approach this as a combined therapy area. An algorithm is proposed to help the identification of at-risk patients and to provide recommendations on the management of patients with concomitant disease.

Lower extremity arterial disease perspective: IUA consensus document on "lead management". Part 1.

Atherosclerotic cardiovascular disease (ASCVD) is defined as coronary heart disease (CHD), cerebrovascular disease, or lower extremity arterial disease (LEAD) also named peripheral arterial disease (PAD). ASCVD is considered to be of atherosclerotic origin and is the leading cause of morbidity and mortality mainly for individuals with diabetes mellitus (DM). In this consensus document of the International Union of Angiology the authors discuss epidemiology, risk factors, primary and secondary prophylaxis, the correlation between diabetes mellitus and LEAD, conservative and surgical treatment.

Swiss recommendations of the Society for Endocrinology and Diabetes (SGED/SSED) for the treatment of type 2 diabetes mellitus (2023).

As a first step, the authors emphasise lifestyle changes (increased physical activity, stopping smoking), blood pressure control, and lowering cholesterol). The initial medical treatment should always be a combination treatment with metformin and a sodium-glucose transporter 2 (SGLT-2) inhibitor or a glucagon-like 1 peptide (GLP-1) receptor agonist. Metformin is given first and up-titrated, followed by SGLT-2 inhibitors or GLP-1 receptor agonists. In persons with type 2 diabetes, if the initial double combination is not sufficient, a triple combination (SGLT-2 inhibitor, GLP-1 receptor agonist, and metformin) is recommended. This triple combination has not been officially tested in cardiovascular outcome trials, but there is more and more real-world experience in Europe and in the USA that proves that the triple combination with metformin, SGLT-2 inhibitor, and GLP-1 receptor agonist is the best treatment to reduce 3-point MACE, total mortality, and heart failure as compared to other combinations. The treatment with sulfonylurea is no longer recommended because of its side effects and higher mortality compared to the modern treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. If the triple combination is not sufficient to reduce the HbA1c to the desired target, insulin treatment is necessary. A quarter of all patients with type 2 diabetes (sometimes misdiagnosed) require insulin treatment. If insulin deficiency is the predominant factor at the outset of type 2 diabetes, the order of medications has to be reversed: insulin first and then cardio-renal protective medications (SGLT-2 inhibitors, GLP-1 receptor agonists).

[Diabetes and pancreatic cancer - When diabetes indicates a pancreatic cancer]. / Diabète et cancer du pancréas - Quand le diabète est annonciateur de cancer pancréatique.

Diabetes and pancreatic cancer have an intricate relationship where each is a risk factor for developing the other. In case of type 2 diabetes, there is an increased probability of developing pancreatic cancer. Similarly, the onset of diabetes often precedes the diagnosis of pancreatic cancer. Since hyperglycemia is secondary to tumor involvement of the exocrine pancreas, diabetes is considered pancreatogenic. In the current classification, it is part of the entities belonging to type 3c diabetes. The pathophysiology is specific, characterized by a high glycemic variability and a tendency to weight loss. Early identification of inaugural type 3c diabetes would reduce diagnostic delays and could optimize oncologic management. In the absence of specific markers, the challenge for the clinician is indisputable.

Diabète et cancer du pancréas entretiennent une relation intriquée où chacun constitue un risque de développer l'autre. En cas de diabète de type 2, le risque de cancer augmente. La survenue d'un diabète précède aussi souvent le diagnostic de cancer du pancréas. L'hyperglycémie étant secondaire à l'atteinte tumorale du pancréas exocrine, ce diabète est considéré comme pancréatogénique. Dans la dénomination actuelle, il fait partie des entités appartenant au diabète de type 3c. La pathophysiologie est spécifique, caractérisée par une forte variabilité glycémique et une tendance à la perte de poids. Distinguer précocement les diabètes inauguraux de type 3c permettrait de réduire les délais diagnostiques et d'optimiser la prise en charge oncologique. En l'absence de marqueurs spécifiques, le challenge est indiscutable pour le clinicien.

Short-term glucocorticoid-related side effects and adverse reactions: a narrative review and practical approach.

Glucocorticoids are the mainstay treatment of a variety of inflammatory and autoimmune disorders. Unfortunately, metabolic side effects, drug interactions and adverse reactions commonly lead to glucocorticoid-related side effects, thereby compromising their intended anti-inflammatory and immunosuppressive effects. The goal of this review is to help clinicians to monitor the broad spectrum of side effects of short-term systemic glucocorticoid administration, defined as glucocorticoid treatment shorter than 30 days. We review the various systems affected, with a focus on metabolic conditions and hyperglycaemia management.

COVID: The Missing Trigger to Start a Remote FIT Course.

Type 1 diabetes management is a highly demanding task that largely falls on people with diabetes, their family, and their peers. Diabetes self-management education and support aim at increasing knowledge, skills, and confidence to take appropriate diabetes management decisions. The current evidence shows that efficient diabetes self-management relies on person-centered interventions and a team of pluri-disciplinary educators with expertise in diabetes care and education. The irruption of the COVID-19 pandemic has increased diabetes burden and the need to offer remote diabetes self-management education services. The present article offers a perspective about expectations and quality issues related to the implementation of a remote version of the FIT course, a validated structured diabetes management educational program.

Chronic venous disease and diabetic microangiopathy: pathophysiology and commonalities.

Chronic venous disease and diabetes mellitus are highly prevalent and debilitating conditions affecting millions of individuals globally. Although these conditions are typically considered as separate entities, they often co-exist which may be important in both understanding their pathophysiology and determining the best treatment strategy. Diabetes mellitus is twice as common in patients with chronic venous disease compared with the general population. Notably, a large proportion of patients with diabetes mellitus present with venous disorders, although this is often overlooked. The etiology of chronic venous disease is multifactorial, involving hemodynamic, genetic, and environmental factors which result in changes to the venous endothelium and structural wall as well as inflammation. Inflammation, endothelial dysfunction and hyperfiltration or leakage, are commonly observed in diabetes mellitus and cause various diabetic microvascular complications. Both diseases are also influenced by the increased expression of adhesion molecules, chemokines, and cytokines, and are characterized by the presence of vessel hypertension. Consequently, despite differences in etiology, the pathophysiology of both chronic venous disease and diabetic microangiopathy appears to be driven by endothelial dysfunction and inflammation. Treatment strategies should take the co-existence of chronic venous disease and diabetic microangiopathy into account. Compression therapy is recommended in inflammatory conditions that have an edema component as seen in both chronic venous disease and diabetes mellitus. Lifestyle changes like weight loss and exercise, will improve metabolic state and lower inflammation and should be promoted in these patients. Additionally, both patient populations may benefit from venoactive drugs.

[Hospital to home transition of care: challenges for patients with type 2 diabetes]. / Transition hôpital-ambulatoire : les enjeux pour les patients avec un diabète sucré.

The transition from hospital to ambulatory care is a high-risk period for patients with diabetes mellitus and is a challenge for health care professionals. Various interprofessional collaborative interventions have shown a positive impact on continuity of care at discharge. Communication and transmission of information between the hospital and ambulatory settings as well as coordination between healthcare professionals are key points to explore and to improve to ensure optimal continuity of care.

La transition entre l'hôpital et l'ambulatoire est une période à risque pour les patients avec un diabète sucré et un enjeu pour les professionnels de la santé. Différentes interventions en collaboration interprofessionnelle ont montré un impact positif sur la continuité des soins à la sortie de l'hôpital. La communication et la transmission d'informations entre les milieux hospitalier et ambulatoire ainsi qu'une coordination entre les professionnels de la santé sont des points clés à explorer et à continuer d'améliorer pour garantir une continuité des soins optimale.

[Total pancreatectomy and islet auto-transplantation: current state and new perspectives]. / Pancréatectomie totale et autotransplantation d'îlots†: état actuel et nouvelles perspectives.

Total pancreatectomy is a procedure primarily performed for chronic pancreatitis refractory to conservative therapy. It may nevertheless be indicated in the event of a malignant tumor, either as a treatment for a surgical complication or as a prevention of anastomotic leakage. If possible, islet auto-transplantation should be combined with total pancreatectomy for benign disease, in order to prevent a severe diabetes. Until recently, malignant disease was considered an absolute contraindication to islet auto-transplantation. A recent series from Milan showed promising oncological results in auto-transplantation for malignant disease, opening up new perspectives for total pancreatectomy for cancer.

La pancréatectomie totale est une procédure principalement effectuée pour une pancréatite chronique réfractaire au traitement conservateur. Elle peut néanmoins être indiquée en cas de tumeur maligne, soit comme traitement d'une complication chirurgicale, soit en prévention de fuite anastomotique. Dans la mesure du possible, une autogreffe d'îlots de Langerhans devrait être associée à une pancréatectomie totale pour maladie bénigne, dans le but de prévenir un diabète pancréatoprive. Jusqu'à récemment, une pathologie maligne était considérée comme une contre-indication absolue à une autogreffe d'îlots. Une série récente de Milan a montré des résultats oncologiques prometteurs en cas d'autogreffe pour pathologies malignes, ouvrant de nouvelles perspectives à la pancréatectomie totale pour cancer.

Gingival crevicular fluid biomarkers in type 1 diabetes mellitus: A case-control study.

OBJECTIVE: The aim of the study is to compare the levels of Gingival Crevicular Fluid (GCF) interleukin 8 (IL-8), matrix metalloproteinase 8 (MMP-8) and advanced glycated-end products (AGEs) in a cohort of type 1 diabetic (T1D) subjects and healthy controls. MATERIAL AND METHODS: GCF samples and periodontal examination were assessed in 50 subjects with T1D (30 males and 20 females; mean age: 35.2 years) recruited from the Diabetology Unit of the Geneva University Hospitals and in 50 control subjects matched for gender, age and smoking status. Samples were assessed for IL-8 and MMP-8 using a bead array multianalyte detection system and for AGEs the ELISA. The two groups were compared using the Wilcoxon signed rank test. RESULTS: The mean HbA1c differed significantly between the groups (8.3% for the T1D group vs. 5.2% for the control group, p < 0.001). T1D subjects had significantly more plaque and gingival inflammation and presented more sites with bleeding on probing compared to the controls. The GCF levels of IL-8, MMP-8 and AGEs did not differ significantly between the groups. Further analysis of the GCF markers in younger (<40 years) and older (≥40 years) cohorts, revealed no significant differences between younger diabetics and controls or between older diabetics and controls. When the groups were divided according to their glycemic status (HbA1c 6.1-8, and > 8%), again no significant differences could be identified for any of the biochemical markers. CONCLUSIONS: T1D subjects, particularly the younger ones, exhibited more inflammation compared to the matched healthy controls. Results on the GCF expression of IL-8, MMP-8 and AGEs did not differ between the groups. The diabetic population of our cohort was for the most part fairly-controlled, with little if any complications and with presence of only mild type of periodontal disease, as 68% had gingivitis.

Beyond the virus: Ensuring continuity of care for people with diabetes during COVID-19.

The current COVID-19 pandemic is a major concern for the diabetes community. A meta-analysis in China found that the proportions of people with COVID-19 and diabetes was 9.7% and that having diabetes resulted in a two-fold increased risk of having a severe case. Global guidance on confinement measures for the prevention of COVID-19 have a particular emphasis on vulnerable populations which include people with diabetes. These recommendations are coherent to avoid the spread of SARSCoV-2 infection, but are in contradiction with comprehensive diabetes care, which requires regular patient-provider interactions for patient education, prescriptions and possible management of complications or mental health. Moreover, confinement drives risk for unhealthy diets, decreased physical activity, mental health related concerns, in parallel to delayed care-seeking due to fear of contracting COVID-19. Another weakness in the current COVID-19 response is the focus on hospital care which overlooks the importance of Primary Care in guaranteeing continuity of care. Ensuring the availability of insulin, other medicines, self-monitoring and diagnostic tools is another challenge. These are all global concerns for the diabetes community, as well as for those suffering from other chronic conditions. Undoubtedly, the global priority is to contain the spread and impact of COVID-19. However, health systems still need to meet the needs of the entire population, including individuals with diabetes. Clear guidance for preparedness, crisis and post-crisis management of diabetes and chronic diseases during mass disruptions to health systems are lacking. Therefore, in parallel to the epidemic response efforts to ensure existing healthcare services keep running should be supported to avoid health consequences that might be worse than the epidemic itself. This includes targeted messaging for people with diabetes and vulnerable populations with regards to possible risk of infection as well as their disease-related management; continued support via telephone, video conferencing or even home visits; ensuring access to insulin and other medicines and supplies both nationally and individually; and most importantly, preparing for the future.

Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial.

BACKGROUND: In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks) duration compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with noninferior results for clinical remission and adverse events (AEs). METHODS: In this prospective, randomized, noninferiority pilot trial, we randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after the end of therapy was 2 months. We compared outcomes using Cox regression and noninferiority analyses (25% margin, power 80%). RESULTS: Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridements was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared with 36 (73%) in the 6-week arm (P = .21). The number of AEs was similar in the 2 study arms (17/44 vs 16/49; P = .51), as were the remission incidences in the per-protocol (PP) population (33/39 vs 32/43; P = .26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (ITT population: hazard ratio [HR], 1.1 [95% confidence interval {CI}, .6-1.7]; PP population: HR, 0.8 [95% CI: .5-1.4]). CONCLUSIONS: In this randomized controlled pilot trial, a postdebridement systemic antibiotic therapy course for DFO of 3 weeks gave similar (and statistically noninferior) incidences of remission and AE to a course of 6 weeks. CLINICAL TRIALS REGISTRATION: NCT03615807; BASEC 2016-01008 (Switzerland).

[Diabetes mellitus: impact of affects on self-management skills]. / Diabète sucré: impact des affects sur les compétences d'autogestion.

Diabetes self-management (DSM) is a process based on a series of complex learnings. The conceptualization of the role of the emotional dimensions that underlie and structure this process is critical to better understand why living with diabetes can become a burden. A clinical case illustrates the intertwining of the affective and cognitive dimensions of diabetes burden and its influence on DSM skills. Emotional regulation is a recognized determinant to implement effective and long-term DSM skills as well as access to DSM interventions. In order to improve DSME/S interventions efficacy, the role of emotional dimensions, new technologies and therapeutic advances needs to be considered.

L'autogestion du diabète sucré (AGDM) est un processus basé sur une série d'apprentissages complexes. La conceptualisation du rôle des dimensions affectives qui sous-tendent et structurent ce processus permet d'appréhender différemment le vécu des patients avec un diabète sucré. Une vignette clinique illustre l'intrication des dimensions affectives et cognitives et les possibles conséquences sur l'AGDM. La régulation des émotions s'avère être un des facteurs déterminants de l'AGDM, tout comme l'accès à des dispositifs d'éducation thérapeutique du patient (ETP). La prise en compte du rôle respectif des dimensions émotionnelles, des nouvelles technologies et des avancées thérapeutiques sur l'AGDM est à considérer pour développer des dispositifs d'ETP performants.

[Intensive treatment in family medicine : use of pumps and continuous glucose measurement systems]. / Traitements intensifs en médecine de famille : usage de pompes et systèmes de mesure en continu du glucose.

New technologic devices are presented: insulin pumps and continuous glucose monitoring (CGM) devices as well as morphine pumps to help general practitioners to deal different intensive situations. Insulin pumps and CGM devices are revolutionary for the management of diabetes. However, their use requires strong patient involvement, the opposite of automated diabetes management. Morphine pumps are a great help when patients in end-of-life stage cannot swallow oral morphine anymore. This article summarizes the main principles of use of these technological devices, common problems and situations at risk primary care practice.

Les dispositifs technologiques font partie de la médecine actuelle. Les pompes à insuline, la mesure en continu du glucose (MCG) ainsi que les pompes à morphine sont présentées ici pour aider le médecin de famille à gérer ces différentes situations intensives. Les pompes à insuline externes et la MCG ont révolutionné la prise en charge du diabète sucré. Pourtant, leur utilisation demande une forte implication du patient, soit l'opposé d'une gestion automatisée du diabète. Les pompes à morphine sont une grande aide lorsque le patient en fin de vie ne peut plus avaler de comprimés ou lorsque l'absorption orale est aléatoire. Cet article résume les principes de fonctionnement de ces dispositifs technologiques, les problématiques communes et les situations à risque pour la pratique du médecin de premier recours.

Hyperinsulinism associated with GLUD1 mutation: allosteric regulation and functional characterization of p.G446V glutamate dehydrogenase.

BACKGROUND: Gain-of-function mutations in the GLUD1 gene, encoding for glutamate dehydrogenase (GDH), result in the hyperinsulinism/hyperammonemia HI/HA syndrome. HI/HA patients present with harmful hypoglycemia secondary to protein-induced HI and elevated plasma ammonia levels. These symptoms may be accompanied by seizures and mental retardation. GDH is a mitochondrial enzyme that catalyzes the oxidative deamination of glutamate to α-ketoglutarate, under allosteric regulations mediated by its inhibitor GTP and its activator ADP. The present study investigated the functional properties of the GDH-G446V variant (alias c.1496G > T, p.(Gly499Val) (NM_005271.4)) in patient-derived lymphoblastoid cells. RESULTS: The calculated energy barrier between the opened and closed state of the enzyme was 41% lower in GDH-G446V compared to wild-type GDH, pointing to altered allosteric regulation. Computational analysis indicated conformational changes of GDH-G446V in the antenna region that is crucial for allosteric regulators. Enzymatic activity measured in patient-derived lymphoblastoid cells showed impaired allosteric responses of GDH-G446V to both regulators GTP and ADP. In particular, as opposed to control lymphoblastoid cells, GDH-G446V cells were not responsive to GTP in the lower range of ADP concentrations. Assessment of the metabolic rate revealed higher mitochondrial respiration in response to GDH-dependent substrates in the GDH-G446V lymphoblastoid cells compared to control cells. This indicates a shift toward glutaminolysis for energy provision in cells carrying the GDH-G446V variant. CONCLUSIONS: Substitution of the small amino acid glycine for the hydrophobic branched-chain valine altered the allosteric sensitivity to both inhibitory action of GTP and activation by ADP, rendering cells metabolically responsive to glutamine.

Treatment with direct-acting antivirals improves peripheral insulin sensitivity in non-diabetic, lean chronic hepatitis C patients.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is associated with insulin resistance, which may lead to type 2 diabetes and its complications. Although HCV infects mainly hepatocytes, it may impair insulin sensitivity at the level of uninfected extrahepatic tissues (muscles and adipose tissue). The aim of this study was to assess whether an interferon-free, antiviral therapy may improve HCV-associated hepatic vs. peripheral insulin sensitivity. METHODS: In a single-arm exploratory trial, 17 non-diabetic, lean chronic hepatitis C patients without significant fibrosis were enrolled, and 12 completed the study. Patients were treated with a combination of sofosbuvir/ledipasvir and ribavirin for 12 weeks, and were submitted to a 2-step euglycemic hyperinsulinemic clamp with tracers, together with indirect calorimetry measurement, to measure insulin sensitivity before and after 6 weeks of antivirals. A panel of 27 metabolically active cytokines was analyzed at baseline and after therapy-induced viral suppression. RESULTS: Clamp analysis performed in 12 patients who achieved complete viral suppression after 6 weeks of therapy showed a significant improvement of the peripheral insulin sensitivity (13.1% [4.6-36.7], p = 0.003), whereas no difference was observed neither in the endogenous glucose production, in lipolysis suppression nor in substrate oxidation. A distinct subset of hepatokines, potentially involved in liver-to-periphery crosstalk, was modified by the antiviral therapy. CONCLUSION: Pharmacological inhibition of HCV improves peripheral (but not hepatic) insulin sensitivity in non-diabetic, lean individuals with chronic hepatitis C without significant fibrosis.