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1.
Vaccines (Basel) ; 11(2)2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36851321

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection in the world. HPV vaccination adherence rates in men are generally lower than in women. The aim of this systematic review and meta-analysis was to assess adherence to HPV vaccination in young working-age males (18-30 years old). METHODS: A systematic review was performed using three databases: PubMed, Scopus, and Web of Science, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: After duplicate removal, the initial search resulted in 478 eligible papers. With the exclusion of 425 papers after screening the abstracts, full texts of 53 articles were reviewed. Subsequently, 45 were excluded. Among the eight studies included, four (50%) examined the vaccination adherence in young adults through data registered in nationwide insurance or private companies' databases, three (37.5%) in young adults in different settings through data collected from surveys and questionnaires, and one (12.5%) an HPV vaccination campaign in a family medicine residency practice. CONCLUSION: Adherence to HPV vaccination in men of working age (18-30 years) does not appear to be adequate (pooled prevalence 11%). In order to achieve a higher level of compliance, it is important to place an emphasis on vaccination campaigns in schools as well as in the workplace, after consultation with and approval from local, regional, and federal public health agencies.

2.
Blood Coagul Fibrinolysis ; 33(3): 188-192, 2022 Apr 01.
Article in English | MEDLINE | ID: mdl-34693913

ABSTRACT

CHA2DS2-VASC score associates with worse prognosis in coronavirus-disease-19 (COVID-19). This study investigated laboratory correlates of increasing CHA2DS2- VASc in patients with COVID-19. Patients with COVID-19 were stratified by CHA2DS2-VASc (Group 1: CHA2DS2-VASc 0-1; Group 2: CHA2DS2-VASc 2-3; Group 3: CHA2DS2-VASc ≥4). We found stepwise increase of D-dimer, hs-Troponin and in-hospital mortality across groups (all P < 0.01). D-dimer and hs-Troponin remained independently associated with CHA2DS2-VASc (B = 0.145, P = 0.03; B = 0.320, P < 0.001, respectively). We found significant correlations between D-dimer and C-reactive protein (CRP) in Group 1 and 2, not in Group 3 (r2 = 0.103, P = 0.005; r2 = 0.226, P = 0.001; r2 = 0.021, P = 0.253 respectively), and between D-dimer and hs-Troponin in group 2 and 3, not in Group 1 (r2 = 0.122, P = 0.003; r2 = 0.120, P = 0.007; r2 = 0.006, P = 0.514 respectively). In our cohort, CHA2DS2- VASc was independently associated with D-dimer and hs- Troponin increase. Variable relationships of D-dimer with hs-Troponin and CRP within different CHA2DS2-VASc strata suggest multiple mechanisms to be responsible for D-dimer increase in COVID-19.


Subject(s)
COVID-19 , Thrombosis , Biomarkers , C-Reactive Protein , COVID-19/complications , Humans , Inflammation/complications , Prognosis , Risk Assessment , Risk Factors , Thrombosis/etiology , Troponin
3.
J Virol Methods ; 300: 114419, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34896451

ABSTRACT

The new virus called severe acute respiratory syndrome coronavirus 2 (SARSCov-2) causing Coronavirus disease 2019 (COVID-19) has spread quickly in several countries and it has become pandemic. Different types of clinical manifestations are attributed to this infection. Some mechanisms related to the infection regarding the immune response are not still elucidated. Herein we reported a case of a 66-years-old patient affected by myelodysplasia who was referred to our hospital because of clinical and radiological manifestations of viral pneumonia. The clinical course has become complicated due to bacterial secondary over-infection by Pseudomonas aeruginosa during stay in internal medicine unit whilst a persistent positive oral and naso-pharyngeal swab test was reported up to 100 days of admission. The patient had a fast clinical and radiological worsening that led her to be admitted to an intensive care unit. Despite intubation and mechanical ventilation she died in a few days.


Subject(s)
COVID-19 , SARS-CoV-2 , Aged , Female , Humans , Pandemics , Pseudomonas aeruginosa , Retrospective Studies
4.
J Cardiovasc Med (Hagerstown) ; 22(11): 832-839, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34482324

ABSTRACT

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.


Subject(s)
COVID-19 , Cardiovascular Diseases , Natriuretic Peptides/blood , Troponin/blood , Aged , Biomarkers/blood , COVID-19/blood , COVID-19/diagnosis , COVID-19/mortality , Cardiovascular Diseases/classification , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Comorbidity , Female , Fibrin Fibrinogen Degradation Products/analysis , Hospital Mortality , Humans , Italy/epidemiology , Male , Outcome Assessment, Health Care , Prognosis , Risk Assessment , Risk Factors , SARS-CoV-2/isolation & purification
6.
Expert Rev Neurother ; 21(7): 793-803, 2021 07.
Article in English | MEDLINE | ID: mdl-34128449

ABSTRACT

INTRODUCTION: Tension-type headache (TTH) is the most common primary headache disorder with a prevalence of up to 78% in general population and huge expenses in terms of health service. Despite its high incidence and impact on life's quality the knowledge on the pathophysiology and efficacious treatment of TTH was still limited. AREAS COVERED: In recent years, a series of studies highlighted the heterogeneous nature of this pathology that seems to be determined by a complex interaction between genetic, environmental, and neuromuscular factors, which result in nociceptive system activation. In this setting, alongside the simple analgesic therapies used during the acute attack, a series of therapeutic options based on newly acquired experiences have taken hold. EXPERT REVIEW: Not having a single substrate or a typical site of pathophysiology, TTH must be analyzed in a global and multidisciplinary way. Herein, we perform a narrative review of the most recent advancement stimulating the concept of this disease as the tip of the iceberg of a more complex individual malaise secondary to different alterations. Strategies based solely on symptomatic drugs should therefore be avoided by experienced personnel and treatment should aim at taking charge of the patient considering the processes behind this complex pathology.


Subject(s)
Tension-Type Headache , Analgesics , Humans , Prevalence , Tension-Type Headache/therapy , Treatment Outcome
7.
Expert Opin Biol Ther ; 21(8): 999-1011, 2021 08.
Article in English | MEDLINE | ID: mdl-34009094

ABSTRACT

INTRODUCTION: Migraine is one of the most common illnesses in the world, with severe economical and subjective implications. Nowadays specific and nonspecific drugs are used for migraine chronic therapy, but a portion of patients have no benefit from these administrations. CGRP receptor antagonists are a good preventive treatment for episodic and chronic migraine. AREAS COVERED: This article reviews both preclinical and clinical studies on eptinezumab as a potential preventive therapy for migraine, as well as pharmacokinetic and pharmacodynamic features. Thus, it summarizes safety and tolerability data based on human studies. EXPERT OPINION: Eptinezumab had good results in several trials, making this molecule a promising migraine preventive drug. Although preclinical and clinical studies showed a significant efficacy, there are no data on the use of Eptinezumab during pregnancy or breastfeeding. There are still some knowledge limits about its pharmacokinetics and metabolism. This is a matter of concern that should be addressed in future studies.


Subject(s)
Graft vs Host Disease , Migraine Disorders , Antibodies, Monoclonal, Humanized/therapeutic use , Calcitonin Gene-Related Peptide , Humans , Migraine Disorders/drug therapy , Migraine Disorders/prevention & control
8.
J Headache Pain ; 22(1): 32, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33910499

ABSTRACT

Chronic headache is particularly prevalent in migraineurs and it can progress to a condition known as medication overuse headache (MOH). MOH is a secondary headache caused by overuse of analgesics or other medications such as triptans to abort acute migraine attacks. The worsening of headache symptoms associated with medication overuse (MO) generally ameliorates following interruption of regular medication use, although the primary headache symptoms remain unaffected. MO patients may also develop certain behaviors such as ritualized drug administration, psychological drug attachment, and withdrawal symptoms that have been suggested to correlate with drug addiction. Although several reviews have been performed on this topic, to the authors best knowledge none of them have examined this topic from the addiction point of view. Therefore, we aimed to identify features in MO and drug addiction that may correlate. We initiate the review by introducing the classes of analgesics and medications that can cause MOH and those with high risk to produce MO. We further compare differences between sensitization resulting from MO and from drug addiction, the neuronal pathways that may be involved, and the genetic susceptibility that may overlap between the two conditions. Finally, ICHD recommendations to treat MOH will be provided herein.


Subject(s)
Headache Disorders, Secondary , Migraine Disorders , Substance-Related Disorders , Analgesics/therapeutic use , Headache Disorders, Secondary/chemically induced , Headache Disorders, Secondary/drug therapy , Headache Disorders, Secondary/epidemiology , Humans , Migraine Disorders/drug therapy , Prescription Drug Overuse , Substance-Related Disorders/complications , Substance-Related Disorders/drug therapy , Substance-Related Disorders/epidemiology , Tryptamines/therapeutic use
11.
SN Compr Clin Med ; 4(1): 3, 2021.
Article in English | MEDLINE | ID: mdl-34977463

ABSTRACT

The coronavirus disease 19 (COVID-19) infection requires major efforts in healthcare systems, due to the high risk of mortality, particularly in subjects with significant comorbidity (≥ 2 pathologies) and polypharmacy (≥ 5 drugs). The treatment of COVID-19 needs a careful evaluation, to reduce the risk of potentially adverse drug reactions. The aim of the study was to examine the use of computerized prescription support in the management and treatment of the COVID-19 infection. We evaluated n.33 patients (51% females) admitted to the west COVID Low-Medium Intensity of Care of Sant'Andrea Hospital during the period March-April 2020 and n.42 subjects (50% females) admitted to the Internal Medicine ward (as control group), by INTERCheck® and Drug-PIN®. The comorbidity (n. pathologies), polypharmacy (n. drugs), and total INTERCheck score in COVID-19 patients and controls were, respectively (mean ± standard deviation): 5.8 ± 3.8, 7.9 ± 4.5, and 9.2 ± 7.1 and 6.8 ± 2.6, 8.0 ± 2.6, and 4.9 ± 3.8 (statistically significant for comorbidity p < 0.01 and INTERCheck score p < 0.01). The correlation between the scores obtained by the INTERCheck and Drug-PIN software was statistically significant, either at admission (p < 0.0000001) or during hospitalization (p < 0.00000001). Both the computerized prescription support systems, INTERCheck® and Drug-PIN®, are useful to better characterize the patients and to ameliorate the drugs prescriptions in COVID-19 infection, with particular attention to the elderly population.

12.
Expert Rev Neurother ; 21(3): 277-285, 2021 03.
Article in English | MEDLINE | ID: mdl-33297780

ABSTRACT

Introduction: Headache is the fifth most common reason to visit an emergency department (ED). In most of the cases, headache is benign and has a primary origin, with migraine as the most common diagnosis. Inappropriate use of ED for non-emergency conditions causes overcrowding, unnecessary testing, and increased medical costs.Areas covered: All stages of headache management in ED, from the reasons to go there, the diagnosis that is made and the investigations necessary to make it, to get to the therapies administered and those prescribed at discharge, if there were any. Finally, the authors evaluated the habit of recommending medical follow-up and how often the headache is still present at discharge or returns within 24 hours.Expert Opinion: Primary headaches are underdiagnosed, misdiagnosed, and the majority do not receive drug therapy either in ED or on discharge, and in cases where the therapy is prescribed is not specific. Increase the number of primary care medical services, spread the 'headaches culture' among GPs and ED doctors, the adoption of ICHD in the diagnostic protocols used in EDs and a fast referral to a headache center could decrease the inappropriate use of ED and improve the headache management in the emergency units.


Subject(s)
Migraine Disorders , Physicians , Emergency Service, Hospital , Headache/diagnosis , Headache/therapy , Humans
13.
Am J Infect Control ; 49(5): 640-642, 2021 05.
Article in English | MEDLINE | ID: mdl-33031863

ABSTRACT

Clostridium difficile is the most common pathogen between health care-associated infections and its incidence has increased during the last years. lack of enough evidence about effective hygiene interventions to prevent this disease. Due to the coronavirus disease 2019 (COVID­19) pandemic, several strategies to reduce microorganism spread were adopted in hospital setting. The objective of this study was to establish whether such strategies can reduce health care associated C difficile infection (HA-CDI) incidence. We found that, during the pandemic (2020) HA-CDI incidence was significantly lower with respect to the previous years. This work demonstrates that maintaining this level of attention regarding control activities related to prevention of microorganism transmission significantly reduce HA-CDI and related expenses in terms of health costs and human lives.


Subject(s)
COVID-19/prevention & control , Clostridioides difficile/isolation & purification , Clostridium Infections/diagnosis , Cross Infection/prevention & control , Guideline Adherence , COVID-19/epidemiology , Clostridium Infections/epidemiology , Cross Infection/epidemiology , Delivery of Health Care , Humans , Incidence , Italy/epidemiology , SARS-CoV-2
14.
SN Compr Clin Med ; 2(12): 2509-2510, 2020.
Article in English | MEDLINE | ID: mdl-33263101

ABSTRACT

Headache occurs in only about 13% of patients within the cohort of presenting COVID-19 symptoms. The hypothesis that such a painful symptomatic picture could be considered a prognostic factor for COVID-19 positive evolution or its trend of severity, or the co-generation of hyposmia/anosmia and/or hypogeusia/ageusia, needs robust epidemiological data, punctual pathophysiological demonstrations, and a detailed comparative analysis on drug-drug interactions (DDIs).

15.
SN Compr Clin Med ; 2(11): 2419-2422, 2020.
Article in English | MEDLINE | ID: mdl-33103062

ABSTRACT

COVID-19 is a respiratory tract infection caused by the new coronavirus SARS-COV2 that can be complicated by acute distress respiratory syndrome and multiorgan failure. In light of the high rate of mortality associated with COVID-19, pharmacological and non-pharmacological strategies to prevent the infection are currently being tested. Among non-pharmacological preventive measures, vaccines represent one of the main resources for public health. It has been suggested that Bacille Calmette-Guérin (BCG) vaccine may protect individuals against infection from COVID-19 virus, and two clinical trials addressing this question are underway. Here, we report the case of a 32-year-old woman, vaccinated with BCG when she was 1 year old, who was diagnosed with apical tuberculous pneumonia of the right lung along with COVID 19 pneumonia.

16.
Intern Emerg Med ; 15(8): 1467-1476, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32986136

ABSTRACT

BACKGROUND: Myocardial involvement in the course of coronavirus disease 2019 (COVID-19) pneumonia has been reported, though not fully characterized yet. The aim of the present study is to undertake a joint evaluation of hs-Troponin and natriuretic peptides (NP) in patients hospitalized for COVID-19 pneumonia. METHODS: In this multicenter observational study, we analyzed data from n = 111 patients. Cardiac biomarkers subgroups were identified according to values beyond reference range. RESULTS: Increased hs-Troponin and NP were found in 38 and 56% of the cases, respectively. As compared to those with normal cardiac biomarkers, these patients were older, had higher prevalence of cardiovascular diseases (CVD) and had more severe COVID-19 pneumonia by higher CRP and D-dimer and lower PaO2/FIO2. Two-dimensional echocardiography performed in a subset of patients (n = 24) showed significantly reduced left ventricular ejection fraction in patients with elevated NP (p = 0.02), whereas right ventricular systolic function (tricuspid annular plane systolic excursion) was significantly reduced both in patients with high hs-Troponin and NP (p = 0.022 and p = 0.03, respectively). Both hs-Troponin and NP were higher in patients with in-hospital mortality (p = 0.001 and p = 0.002, respectively). On multivariable analysis, independent associations were found of hs-Troponin with age, PaO2/FIO2 and D-dimer (B = 0.419, p = 0.001; B = - 0.212, p = 0.013; and B = 0.179, p = 0.037, respectively) and of NP with age and previous CVD (B = 0.480, p < 0.001; and B = 0.253, p = 0.001, respectively). CONCLUSIONS: Myocardial involvement at admission is common in COVID-19 pneumonia. Independent associations of hs-Troponin with markers of disease severity and of NP with underlying CVD might point toward existing different mechanisms leading to their elevation in this setting.


Subject(s)
Coronavirus Infections/blood , Natriuretic Peptides/analysis , Pneumonia, Viral/blood , Pneumonia/blood , Troponin/analysis , Aged , Aged, 80 and over , Biomarkers/analysis , Biomarkers/blood , COVID-19 , Disease Progression , Female , Humans , Incidence , Male , Middle Aged , Natriuretic Peptides/blood , Pandemics/statistics & numerical data , Troponin/blood
17.
SN Compr Clin Med ; 2(6): 694-699, 2020.
Article in English | MEDLINE | ID: mdl-32838135

ABSTRACT

Coronavirus disease 2019 (COVID-2019) is a viral infection which is rapidly spreading on a global scale and causing a severe acute respiratory syndrome that affects today about four and a half million registered cases of people around the world. The aim of this narrative review is to provide an urgent guidance for the doctors who take care of these patients. Recommendations contained in this protocol are based on limited, non-definitive, evidence and experience-based opinions about patients with low and medium intensity of care. A short guidance on the management of COVID-19 is provided for an extensive use in different hospital settings. The evidence-based knowledge of COVID-19 is rapidly evolving, and we hope that, in the near future, a definitive and most efficacious treatment will be available including a specific vaccine for SARS-CoV-2.

18.
SN Compr Clin Med ; 2(9): 1401-1406, 2020.
Article in English | MEDLINE | ID: mdl-32838177

ABSTRACT

Due to its extreme virulence, COVID-19 virus has rapidly spread, developing a severe pandemic. SARS-COV-2 mostly affected the respiratory tract, causing a severe acute lung failure. Although the infection of airways, COVID-19 can be associated with chronic and systemic damages still not so much known. The purpose of this research is to collect recent evidence in literature about systemic diseases caused by COVID-19. The format of the present article has features of a systematic case-based review (level of evidence), and it is structured as a case series report (patients of our COVID-19 Medicine Ward have been selected as cases). Data for this review have been selected systematically, taking evidence only from indexed journals and databases: PubMed, Scopus, MEDLINE, and Cochrane systems. Papers chosen included systematic reviews, case series, clinical cases, meta-analysis studies, and RCTs. We start collecting studies since 2003. The main keywords used were "COVID-19" "OR" "SARS" "OR" "SARS - COV 2" "AND" "systemic disease" / "nephropathy" / "cardiac pathology" / "central nervous system." Clinical cases belong to our COVID-19 Medicine Ward. One of the most severe COVID-19 clinical presentations includes cardiovascular problems, like myocarditis, pericarditis, and acute hearth failure. Cytokine release syndrome caused by COVID-19 develops severe acute kidney failure. It is still unknown the way coronavirus damages the liver, brain, and reproductive system. Considering the majority of the new studies about this pathology, it issues that COVID-19 is considered to be a multi-organ disease.

19.
J Headache Pain ; 21(1): 44, 2020 May 04.
Article in English | MEDLINE | ID: mdl-32366217

ABSTRACT

BACKGROUND: Cluster headache (CH) is the most frequent trigemino-autonomic cephalgia. CH can manifest as episodic (ECH) or chronic cluster headache (CCH) causing significant burden of disease and requiring attack therapy and prophylactic treatment. The few data available on the economic burden of CH come from retrospective studies based on questionnaires, population surveys and medical insurance claims database. Although all these studies showed an important economic burden, they provided different estimates depending on variability of CH awareness and management, healthcare systems, available therapies and use of treatments according to different guidelines. METHODS: This prospective study aimed to quantify the total direct and indirect cost of ECH and CCH over a cluster period, both for the patient and for the National Health System (NHS), using data from subjects who consecutively attended an Italian tertiary headache centre between January 1, 2018 and December 31, 2018. RESULTS: A total 108 patients (89 ECH, 19 CCH) were included. Mean attack frequency was 2.3 ± 1.4 per day. Mean total cost of a CH bout was €4398 per patient and total cost of CCH was 5.4 times higher than ECH (€13,350 vs. €2487, p <  0.001). Direct costs represented the 72.1% of total cost and were covered for the 94.8% by the NHS. The costs for any item of expense were higher for CCH than for ECH (p <  0.001). Mean indirect costs for a CH bout were €1226 per patient and were higher for CCH compared to ECH (€3.538 vs. €732), but the difference was not significant. Days with reduced productive capacity impacted for the 64.6% of the total indirect costs. The analysis of the impact CH on work showed that 27%% of patients felt that CH had limited their career, 40% had changed their work pattern, 20% had changed their place of employment and 10% had lost a job due to the disease. CONCLUSION: Our results provide a valuable estimate of the direct and indirect costs of ECH and CCH in the specific setting of a tertiary headache centre and confirm the high economic impact of CH on both the NHS and patients.


Subject(s)
Cluster Headache/economics , Cost of Illness , Health Care Costs , National Health Programs/economics , Tertiary Care Centers/economics , Adult , Cluster Headache/epidemiology , Cluster Headache/therapy , Cross-Sectional Studies , Databases, Factual/trends , Female , Health Care Costs/trends , Health Expenditures/trends , Humans , Italy/epidemiology , Male , Middle Aged , National Health Programs/trends , Prospective Studies , Retrospective Studies , Surveys and Questionnaires , Tertiary Care Centers/trends , Young Adult
20.
Diabetologia ; 63(7): 1382-1395, 2020 07.
Article in English | MEDLINE | ID: mdl-32385603

ABSTRACT

AIMS/HYPOTHESIS: The small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels. METHODS: In this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (Ra) and disappearance (Rd) and endogenous glucose production (EGP) were calculated by infusing [6,6-2H2]glucose with or without oral [U-13C6]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment. RESULTS: Glucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 ± 6 for IGIVI vs 7.4 ± 3 ml min-1 kg-1 per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 ± 1820 vs 5000 ± 2360 (ml min-1 kg-1 (nmol/l)-1 pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 ± 0.82 vs 2.16 ± 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration. CONCLUSIONS/INTERPRETATION: Our study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03223129. Graphical abstract.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Insulin Resistance/physiology , Blood Glucose/metabolism , Cohort Studies , Diabetes Mellitus, Type 2/blood , Glucagon/metabolism , Glucagon-Like Peptide 1/metabolism , Glucose/metabolism , Humans , Incretins/metabolism
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