RESUMO
AIMS/HYPOTHESIS: The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. METHODS: In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. RESULTS: Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). CONCLUSIONS/INTERPRETATION: In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance.
RESUMO
AIMS: The HypoCOMPaSS multi-centre trial achieved improvement in hypoglycaemia awareness and 20-fold reduction in severe hypoglycaemia (SH) in a cohort with long-standing type 1 diabetes (T1D). All participants received 'my hypo compass' (MHC) brief structured psycho-educational intervention in addition to optimisation of insulin delivery/glucose monitoring. In this 24-week, prospective, single-centre feasibility RCT, we piloted MHC as a sole intervention in comparison to standard clinical care alone (CON). METHODS: Participants with T1D and impaired hypoglycaemia awareness (IAH) (Clarke score ≥4) were recruited. MHC comprised a group/individual 1-2 h face-to-face session followed by a telephone call and second face-to-face session at 4 weeks. Outcome measures at 24 weeks were compared with baseline. RESULTS: Fifty-two individuals provided consent for screening with 39 fulfilling eligibility criteria. Fifteen withdrew before any study intervention. Twenty-four adults with (mean ± SD) T1D duration 41.0 ± 15.1 years commenced/completed the study (100% visit attendance); 12 randomised to MHC and 12 to CON. All had IAH at baseline and at 24 weeks. Annualised SH rate following MHC was 3.8 ± 19.0 (24 weeks) versus 12.6 ± 3.5 (Baseline) and in CON group 2.0 ± 19.0 (24 weeks) versus 4.6 ± 11.5 (Baseline). 'Immediate Action' for and 'Worry' about hyperglycaemia measured by the Hyperglycaemia Avoidance Scale appeared lower following MHC. Participants attended all study visits and reflected positively on the MHC intervention. CONCLUSIONS: Feasibility of MHC implementation without additional intervention has been demonstrated. MHC education was associated with positive changes in attitudes and behaviours with the potential to reduce SH risk. MHC provides a validated, simple, well-received programme to fulfil the educational component within RCTs targeting problematic hypoglycaemia and as part of holistic clinical care.
Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Estudos de Viabilidade , Hipoglicemia , Educação de Pacientes como Assunto , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Hipoglicemia/prevenção & controle , Feminino , Masculino , Educação de Pacientes como Assunto/métodos , Adulto , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Conscientização , Estudos Prospectivos , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
AIMS: To determine the frequency, severity, burden, and utility of hypoglycaemia symptoms among adults with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) at baseline and week 24 following the HypoCOMPaSS awareness restoration intervention. METHODS: Adults (N = 96) with T1D (duration: 29 ± 12 years; 64% women) and IAH completed the Hypoglycaemia Burden Questionnaire (HypoB-Q), assessing experience of 20 pre-specified hypoglycaemia symptoms, at baseline and week 24. RESULTS: At baseline, 93 (97%) participants experienced at least one symptom (mean ± SD 10.6 ± 4.6 symptoms). The proportion recognising each specific symptom ranged from 15% to 83%. At 24 weeks, symptom severity and burden appear reduced, and utility increased. CONCLUSIONS: Adults with T1D and IAH experience a range of hypoglycaemia symptoms. Perceptions of symptom burden or utility are malleable. Although larger scale studies are needed to confirm, these findings suggest that changing the salience of the symptomatic response may be more important in recovering protection from hypoglycaemia through regained awareness than intensifying symptom frequency or severity.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 1/complicações , Conscientização , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemia/diagnóstico , Inquéritos e QuestionáriosRESUMO
AIMS: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.
Assuntos
Diabetes Mellitus Tipo 1 , Neuropatias Diabéticas , Hipoglicemia , Humanos , Feminino , Masculino , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/fisiopatologia , Pessoa de Meia-Idade , Hipoglicemia/epidemiologia , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Conscientização , Hipoglicemiantes/uso terapêuticoRESUMO
AIMS/HYPOTHESIS: The aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months). METHODS: This analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring. RESULTS: The age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier 'hyperglycaemia avoidance prioritised' (η2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in 'asymptomatic hypoglycaemia normalised' from baseline (η2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for 'asymptomatic hypoglycaemia normalised', reduced change in 'asymptomatic hypoglycaemia normalised' scores at 24 weeks, and lower baseline 'hypoglycaemia concern minimised' scores (all p<0.05). CONCLUSIONS/INTERPRETATION: Participation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with 'hyperglycaemia avoidance prioritised' most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition 'asymptomatic hypoglycaemia normalised'. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes. CLINICAL TRIALS REGISTRATION: www.isrctn.org : ISRCTN52164803 and https://eudract.ema.europa.eu : EudraCT2009-015396-27.
Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Adulto , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicemia , Automonitorização da Glicemia , Hipoglicemia/tratamento farmacológico , Insulina/uso terapêutico , Conscientização , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , AtitudeRESUMO
BACKGROUND: Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta-cell death and beta-cell function in pancreas donors after brain death. METHODS: In pancreas donors after brain death, we compared clinical and biochemical data in 'insulin-treated' and 'not insulin-treated donors' (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated. RESULTS: Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p = .016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p = .046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p = .035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p = .05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)]. CONCLUSIONS: In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.
Assuntos
Ácidos Nucleicos Livres , Hiperglicemia , Transplante das Ilhotas Pancreáticas , MicroRNAs , Humanos , Peptídeo C , Morte Encefálica , Insulina/genética , Doadores de Tecidos , Morte CelularRESUMO
Associations between islet graft function and well-being in islet transplant recipients requiring exogenous insulin remain unclear. This cross-sectional analysis compared person-reported outcome measures in 15 adults with type 1 diabetes whose islet transplants were classified according to Igls criteria as "Good" (n = 5), "Marginal" (n = 4) and "Failed" (n = 6) graft function. At a mean of 6.2 years post-first islet transplant, 90% reduction in severe hypoglycaemia was maintained in all groups, with HbA1c (mean ± SD mmol/mol) 49 ± 4 in recipients with "Good" function; 56 ± 5 ("Marginal"); and 69 ± 25 ("Failed"). Self-reported impaired awareness of hypoglycaemia persisted in all groups but those with "Good" function were more likely to experience symptoms during hypoglycaemia. "Marginal" function was associated with greater fear of hypoglycaemia (HFS-II score: "Marginal": 113 [95, 119]; "Failed": 63 [42, 93] (p = 0.082); "Good": 33 [29, 61]) and severe anxiety (GAD7: "Marginal"): 21 [17, 21]; "Failed": 6 [6, 6] "Good": 6 [3, 11]; (p = 0.079)), diabetes distress and low mood. Despite clear evidence of ongoing clinical benefit, Igls criteria 'Marginal' function is associated with sub-optimal well-being, including greater fear of hypoglycaemia and severe anxiety. This study provides person-reported validation that "Good" and "Marginal" graft function are differentiated by general and diabetes-specific subjective well-being, suggesting those with "Marginal" function may benefit from further intervention, including re-transplantation.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Transplante das Ilhotas Pancreáticas , Adulto , Humanos , Estudos Transversais , Estado Funcional , Diabetes Mellitus Tipo 1/cirurgia , Diabetes Mellitus Tipo 1/complicações , Hipoglicemia/complicações , Medidas de Resultados Relatados pelo PacienteRESUMO
The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress. This opinion paper emphasizes the importance of addressing bottlenecks in the development and academic research access to ATMPs by implementing several key strategies. These include the establishment of streamlined regulatory processes, securing increased funding for ATMP research, fostering collaborations and partnerships, setting up centralized ATMP facilities, and actively engaging with patient groups. Advocacy at the policy level is essential to provide support for the development and accessibility of ATMPs, thereby driving advancements in transplantation and enhancing patient outcomes. By adopting these strategies, the field of transplantation can pave the way for the introduction of innovative and efficacious ATMP therapies, while simultaneously fostering a nurturing environment for academic research.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Engenharia Tecidual , Humanos , Terapia GenéticaRESUMO
The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3-8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291-15 417] vs. 6442 [5156-7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta -0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.
Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Peptídeo C , Diabetes Mellitus Tipo 1/cirurgia , Sobrevivência de Enxerto , Humanos , InsulinaRESUMO
AIMS: Many individuals with type 1 diabetes retain residual ß-cell function, with increased endogenous insulin secretion associated with reduced hyperglycaemia, hypoglycaemia and glycaemic variability. However, it is unknown when these improvements occur during the day. Dysglycaemia is common in overnight and postprandial periods and associated with diabetes complications. Therefore, this study aimed to determine the influence of residual ß-cell function upon nocturnal and postprandial glycaemic control in established type 1 diabetes. METHODS: Under free-living conditions, 66 participants wore a blinded continuous glucose monitor (CGM), kept a food diary, and completed a stimulated urine C-peptide creatinine (UCPCR) test. Nocturnal, and postprandial CGM outcomes (participant means and discrete event analysis) were compared between UCPCR groups: undetectable (Cpepund ), low (Cpeplow : 0.001-0.19 nmol/mmol) and high (Cpephigh : ≥0.2 nmol/mmol). RESULTS: Greater ß-cell function was associated with incremental improvements in glycaemia. Cpephigh spent significantly greater time in normoglycaemia than Cpepund overnight (76 ± 20% vs. 58 ± 20%, p = 0.005) and 0-300 mins postprandially (68 ± 22% vs. 51 ± 22%, p = 0.045), while also having reducing nocturnal variability (SD 1.12 ± 0.41 vs. 1.52 ± 0.43 mmol/L, p = 0.010). Analysis of individual events, controlling for diabetes duration, BMI, basal insulin, use of a continuous or flash glucose monitor and (for postprandial) meal type, carbohydrate and bolus insulin intake, replicated the group findings, additionally demonstrating Cpepund had increased hyperglycaemia versus Cpeplow overnight and increased postprandial hypoglycaemic events compared with Cpephigh . For all participants, breakfast had a significantly higher incremental area under the curve than lunch and dinner. CONCLUSIONS: Residual ß-cell function is associated with improved nocturnal and postprandial glycaemic control. These data may be of clinical importance for identifying specific periods and individuals where further glycaemic management strategies would be beneficial.
Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Glicemia/análise , Estudos Cross-Over , Diabetes Mellitus Tipo 1/tratamento farmacológico , Progressão da Doença , Humanos , Hiperglicemia/prevenção & controle , Insulina , Período Pós-PrandialRESUMO
Background: Automated dispensing cabinets have the potential to create technology-induced errors that can arise during controlled substance medication dispensing. Despite enhancements made to the medication use process, the impact of ADC functionality on technology-induced controlled substance discrepancies have yet to be described. Objective: To evaluate the impact of ADC functionality expansion on technology-induced errors such as controlled substance discrepancies created during "blind inventory counts" and cassette dispensing errors. Methods: This quasi-experimental study was conducted over 18 months that evaluated the expanded use of dispensing cassettes within 8 ADCs at the University of Chicago Medicine. Unit-dose controlled substances with high usage were directed for inventory reassignment to cassettes. Controlled substance dispenses, blind inventory counts discrepancies and cassette dispensing errors were evaluated before and after cassette expansion. ADC discrepancy and Cassette Dispensing Error rates were calculated using 1-week segments across the study period. Results: Of the 64 040 dispenses during the study period, the proportion of cassette dispenses increased from 16% to 72% after cassette expansion. Controlled substance discrepancies decreased from 11 to 7 discrepancies for every 1000 dispenses (P < .0001). After cassette expansion, cassette dispensing errors increased to roughly 28 errors for every 1000 dispenses (P < .0001). Conclusion: Expansion of ADC functionality created opportunities for reduced technology-induced controlled substance discrepancy rates at the expense of increased cassette dispensing errors.
RESUMO
BACKGROUND: Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation. Oxidative damage to mitochondria is an early event in IR injury. Therefore, the uptake, safety, and efficacy of the mitochondria-targeted antioxidant MitoQ were investigated in models of transplant IR injury. METHODS: MitoQ uptake by warm and cooled pairs of pig and declined human kidneys was measured when preserved in cold static storage or by hypothermic machine perfusion. Pairs of pigs' kidneys were exposed to defined periods of warm and cold ischaemia, flushed and stored at 4°C with or without MitoQ (50 nmol/l to 250 µmol/l), followed by reperfusion with oxygenated autologous blood in an ex vivo normothermic perfusion (EVNP). Pairs of declined human kidneys were flushed and stored with or without MitoQ (5-100 µmol/l) at 4°C for 6 h and underwent EVNP with ABO group-matched blood. RESULTS: Stable and concentration-dependent uptake of MitoQ was demonstrated for up to 24 h in pig and human kidneys. Total blood flow and urine output were significantly greater in pig kidneys treated with 50 µmol/l MitoQ compared with controls (P = 0.006 and P = 0.007 respectively). In proof-of-concept experiments, blood flow after 1 h of EVNP was significantly greater in human kidneys treated with 50 µmol/l MitoQ than in controls (P ≤ 0.001). Total urine output was numerically higher in the 50-µmol/l MitoQ group compared with the control, but the difference did not reach statistical significance (P = 0.054). CONCLUSION: Mitochondria-targeted antioxidant MitoQ can be administered to ischaemic kidneys simply and effectively during cold storage, and may improve outcomes after transplantation.
Assuntos
Transplante de Rim/efeitos adversos , Rim/irrigação sanguínea , Preservação de Órgãos/métodos , Compostos Organofosforados/farmacologia , Traumatismo por Reperfusão/terapia , Ubiquinona/análogos & derivados , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Humanos , Suínos , Ubiquinona/farmacologiaRESUMO
Insulin is routinely used to manage hyperglycaemia in organ donors and during the peri-transplant period in islet transplant recipients. However, it is unknown whether donor insulin use (DIU) predicts beta-cell dysfunction after islet transplantation. We reviewed data from the UK Transplant Registry and the UK Islet Transplant Consortium; all first-time transplants during 2008-2016 were included. Linear regression models determined associations between DIU, median and coefficient of variation (CV) peri-transplant glucose levels and 3-month islet graft function. In 91 islet cell transplant recipients, DIU was associated with lower islet function assessed by BETA-2 scores (ß [SE] -3.5 [1.5], P = .02), higher 3-month post-transplant HbA1c levels (5.4 [2.6] mmol/mol, P = .04) and lower fasting C-peptide levels (-107.9 [46.1] pmol/l, P = .02). Glucose at 10 512 time points was recorded during the first 5 days peri-transplant: the median (IQR) daily glucose level was 7.9 (7.0-8.9) mmol/L and glucose CV was 28% (21%-35%). Neither median glucose levels nor glucose CV predicted outcomes post-transplantation. Data on DIU predicts beta-cell dysfunction 3 months after islet transplantation and could help improve donor selection and transplant outcomes.
Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Transplante das Ilhotas Pancreáticas , Glicemia , Peptídeo C , Glucose , Humanos , Insulina , Doadores de TecidosRESUMO
ß-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of ß-cell replacement therapy. There was consensus that ß-cell replacement therapy could be considered as a treatment for ß-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA1c ) and the occurrence of severe hypoglycemia. Optimal ß-cell graft function is defined by near-normal glycemic control [HbA1c ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good ß-cell graft function requires HbA1c < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal ß-cell graft function is defined by failure to achieve HbA1c < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed ß-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.
Assuntos
Diabetes Mellitus/cirurgia , Transplante das Ilhotas Pancreáticas , Avaliação de Resultados em Cuidados de Saúde , Glicemia , Diabetes Mellitus/sangue , Hemoglobinas Glicadas/metabolismo , HumanosRESUMO
Equine piroplasmosis (EP), caused by two parasitic organisms, Theileria equi and Babesia caballi, is a tick-borne disease of recent concern in horses in the U.S.A. Outbreaks of EP have been detected in Florida, Missouri, Kansas and Texas. In 2009, EP transmission in Texas occurred through the adults of two tick species, Amblyomma mixtum [formerly known as Amblyomma cajennense (Fabricius, 1787)] Koch (Ixodida: Ixodidae) and Dermacentor variabilis (Say) (Ixodida: Ixodidae), the American dog tick (ADT). In this study, we developed a continent-scale map for the distribution of the EP vector species D. variabilis, using a presence-only modelling approach to assess the habitat preferences of this tick. We used identification records from our tick geodatabase of locations in which the presence of the ADT had been noted. The potential distribution of the ADT in the U.S.A. was estimated from environmental factors using the maximum entropy approach based on localities in which there is a high probability of occurrence according to habitat suitability. Elevation and temperature were found to be biologically significant environmental variables influencing the presence of this tick species. Properly designed and constructed probability surfaces using maximum entropy offer one useful approach to the mapping of distribution ranges of tick species based on suitable habitat in the U.S.A.
Assuntos
Distribuição Animal , Vetores Aracnídeos/fisiologia , Dermacentor/fisiologia , Meio Ambiente , Animais , Vetores Aracnídeos/crescimento & desenvolvimento , Mudança Climática , Dermacentor/crescimento & desenvolvimento , Feminino , Larva/crescimento & desenvolvimento , Larva/fisiologia , Masculino , Modelos Biológicos , Ninfa/crescimento & desenvolvimento , Ninfa/fisiologia , Parasitologia , Estados UnidosRESUMO
BACKGROUND: Emergency pediatric situations are stressful for all involved. Variation in weight, physiology, and anatomy can be substantial and errors in calculating drugs and fluids can be catastrophic. OBJECTIVES: To evaluate the reliability of information resources that anesthetic trainees might use when faced with common pediatric emergencies. METHODS: Anesthetic trainees from a single UK deanery were recruited and timed while they identified 18 predetermined pieces of information from three Advanced Pediatric Life Support (APLS) scenarios. The two most popular smartphone applications identified from a previous survey, PaedsED (PaedsED. iED limited, Version 1.0.8, Updated March 2011. ©2009) and Anapaed (AnaPaed. Thierry Girard, Version 1.4.2, Updated Nov 2, 2012. ©Thierry Girard), the British National Formulary for Children (cBNF) and trainee's inherent knowledge were compared with a local, check-list style, handbook of pediatric emergency algorithms - Pediatric Anesthetic Emergency Data sheets (PAEDs). RESULTS: Twenty anesthetic trainees were recruited. The fastest source of information was the trainees own knowledge (median 61 s, IQR 51-83 s). Second fastest was PAEDs (80, [59-110] s), followed by PaedsED (84, [65-111]). The most accurate source overall was PaedsED (100, [83-100]) although the accuracy varied between scenarios. The handbook was rated as the most popular resource by the trainees. CONCLUSION: Although fastest, trainees own knowledge is inaccurate, highlighting the need for additional, rapidly accessible, information. Of the two smartphone applications, PaedsED proved to be fast, accurate, and more popular, while Anapaed was accurate but slow to use. The PAEDs handbook, with its checklist-style format, was also fast, accurate and rated the most popular information source.
Assuntos
Anestesia , Anestesiologia/normas , Serviços Médicos de Emergência , Armazenamento e Recuperação da Informação/métodos , Aplicações da Informática Médica , Pediatria/normas , Algoritmos , Anestesiologia/educação , Criança , Feminino , Humanos , Lactente , Masculino , Fichas de Dados de Segurança de Materiais , Pediatria/educação , SmartphoneRESUMO
CF-related diabetes (CFRD) is a prevalent comorbidity in people with Cystic Fibrosis (CF), significantly impacting morbidity and mortality rates. This review article critically evaluates the current understanding of CFRD molecular mechanisms, including the role of CFTR protein, oxidative stress, unfolded protein response (UPR) and intracellular communication. CFRD manifests from a complex interplay between exocrine pancreatic damage and intrinsic endocrine dysfunction, further complicated by the deleterious effects of misfolded CFTR protein on insulin secretion and action. Studies indicate that ER stress and subsequent UPR activation play critical roles in both exocrine and endocrine pancreatic cell dysfunction, contributing to ß-cell loss and insulin insufficiency. Additionally, oxidative stress and altered calcium flux, exacerbated by CFTR dysfunction, impair ß-cell survival and function, highlighting the significance of antioxidant pathways in CFRD pathogenesis. Emerging evidence underscores the importance of exosomal microRNAs (miRNAs) in mediating inflammatory and stress responses, offering novel insights into CFRD's molecular landscape. Despite insulin therapy remaining the cornerstone of CFRD management, the variability in response to CFTR modulators underscores the need for personalized treatment approaches. The review advocates for further research into non-CFTR therapeutic targets, emphasizing the need to address the multifaceted pathophysiology of CFRD. Understanding the intricate mechanisms underlying CFRD will pave the way for innovative treatments, moving beyond insulin therapy to target the disease's root causes and improve the quality of life for individuals with CF.
RESUMO
BACKGROUND: Severe hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia. METHODS: Preventing Hypoglycemia in Type 2 diabetes (PHT2) is a two-arm, parallel, randomized controlled trial. Participants are eligible if they are adults with T2D receiving care at an integrated group practice in Washington state and have experienced one or more episodes of severe hypoglycemia in the prior 12 months or have impaired awareness of hypoglycemia (Gold score ≥ 4). Participants are randomized to proactive nurse care management with or without my hypo compass, an evidence-based, psychoeducational intervention combining group and individual self-management training. For this study, my hypo compass was adapted to be suitable for adults with T2D and from an in-person to a virtual intervention over videoconference and telephone. The primary outcome is any self-reported severe hypoglycemia in the 12 months following the start of the intervention. Secondary outcomes include biochemical measures of hypoglycemia, self-reported hypoglycemia awareness, fear of hypoglycemia, and emergency department visits and hospitalizations for severe hypoglycemia. The study includes a process evaluation to assess implementation fidelity and clarify the causal pathway. CONCLUSION: The PHT2 trial will compare the effectiveness of two approaches for reducing severe hypoglycemia in adults with T2D. TRIAL REGISTRATION: clinicaltrials.gov, # NCT04863872.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Adulto , Humanos , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversosRESUMO
Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment. Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI). Results: Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia. Conclusions: The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.
Assuntos
Fibrose Cística , Hipoglicemia , Adulto , Humanos , Glucagon , Estudos Transversais , Proinsulina , Fibrose Cística/complicações , GlucoseRESUMO
BACKGROUND: Medication discrepancies at nursing home intake increase the risk of drug-related adverse events. Measuring discrepancy incidence rates and locating the origins of discrepancies can assist in identifying information exchange deficits for high-risk medications. OBJECTIVE: To determine class-specific discrepancy rates, to determine discordance between medication lists, and to explore patient and system-level factors associated with medication discrepancies discovered between the first and second medication reconciliations conducted at nursing home intake. METHODS: Medication discrepancy data were prospectively collected from four long-term care facilities over a 9-month period. Medication discrepancies were defined as mismatched prescribing orders between at least two medication history lists. Discrepancy locations were defined as the pairs or triads of facilities between which medication history lists were discordant. Unadjusted logistic regressions were used to identify medication classes with the highest discrepancy rates and patient factors significantly associated with any medication discrepancy. RESULTS: 40.8% of newly admitted or re-admitted residents and 6.3% of medications reviewed had at least one medication discrepancy discovered during the second medication reconciliation conducted at nursing home intake. Residents prescribed fewer than 14 medications were at less risk of discrepancies. Residents with Charlson Comorbidity Index of 5, COPD, HF, anemia or HTN were at greater risk of discrepancies. Respiratory and analgesic medications were twice as likely as other medication classes to be discrepant (OR = 2.2, 95% CI 1.2-4.4; OR = 2.2, 95% CI 1.3-3.5). Most discrepancies occurred between hospital and nursing home lists (44.9%), or between the hospital, nursing home, and community pharmacy lists (39.3%) CONCLUSIONS: Given the higher risk of discrepancies within respiratory or analgesics, transitions of care teams need to prioritize residents with respiratory conditions or pain. Although re-admitted residents' increased discrepancy risk is likely due to poorer health status, miscommunications across the nursing home, hospital and community pharmacy require further research to clarify system failures.