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1.
Diabet Med ; 41(3): e15195, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37562414

RESUMO

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Automonitorização da Glicemia , Satisfação do Paciente , Psicometria , Reprodutibilidade dos Testes , Estudos Retrospectivos , Estudos Prospectivos , Glicemia , Inquéritos e Questionários
2.
Clin Endocrinol (Oxf) ; 98(2): 153-164, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36367077

RESUMO

Adrenal adenomas are incidentally identified in up to 5% of computer tomography scans performed for unrelated indications. A proportion of these adrenal incidentalomas are found to autonomously secrete cortisol based on definitions in current guidelines. Epidemiological studies suggest that chronic exposure to mild glucocorticoid excess from adrenal incidentalomas is associated with significantly increased cardiometabolic risk. However, current management guidelines adopt a conservative approach as no large prospective randomized studies have demonstrated that these patients benefit from surgery. This narrative review examines the epidemiological and mechanistic studies related to three common clinical settings of mild glucocorticoid excess to gain further insight into the potential benefits of treating patients with adrenal incidentaloma and possible autonomous cortisol secretion.


Assuntos
Neoplasias das Glândulas Suprarrenais , Glucocorticoides , Humanos , Glucocorticoides/efeitos adversos , Neoplasias das Glândulas Suprarrenais/complicações , Hidrocortisona/uso terapêutico , Estudos Prospectivos
3.
Clin Endocrinol (Oxf) ; 97(1): 64-71, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35394663

RESUMO

OBJECTIVE: The objective of this study is to assess the relationship between hypothalamic-pituitary-adrenal (HPA) axis activity, vascular function and insulin sensitivity in healthy adults. DESIGN: Open observational study. PATIENTS: Thirty healthy adults were studied at the Endocrine Research Unit, Repatriation General Hospital, Adelaide, SA, Australia. MEASUREMENTS: HPA activity was assessed from the serum cortisol 30 min after 1 µg ACTH1-24 (Novartis Pharmaceuticals). Subjects with a cortisol below (n = 15) and above (n = 15) the median were categorized as low and high responders, respectively. Reactive hyperaemia index (RHI) was measured fasting to estimate endothelial function. Matsuda index was calculated from glucose and insulin concentrations collected fasting and 30 minutely for 2 h after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). The primary endpoint was the difference in RHI between low and high responders. RESULTS: There were no significant differences in age (61 ± 9 vs. 64 ± 7 years, p = .19), body mass index (BMI; 26 ± 3 vs. 24 ± 4 kg/m2 , p = .25) and sex (p = .71) between low and high responders. High responders had a lower RHI (2.1 ± 0.2 vs. 2.6 ± 0.2, p = .04) than low responders and there was a negative association between RHI and peak cortisol post ACTH1-24 (ß = -.56, p < .01). There were no significant differences in Matsuda index (15.0 ± 2.4 vs. 22.7 ± 5.2, p = .19) between high and low responders. CONCLUSION: In healthy adults, endothelial dysfunction is likely to contribute to the association between HPA hyperactivity and increased cardiovascular risk. As insulin sensitivity was not different in high and low responders, endothelial dysfunction is not primarily secondary to insulin resistance.


Assuntos
Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário/metabolismo , Insulina , Sistema Hipófise-Suprarrenal/metabolismo
4.
Nitric Oxide ; 122-123: 47-53, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35367633

RESUMO

BACKGROUND: Arginine metabolites are associated with cardiovascular and all-cause mortality in several patient groups. We investigated whether arginine metabolites are associated with mortality in patients with critical illness and whether associations are independent of other factors affecting prognosis in an Intensive Care Unit (ICU). METHODS: 1155 acutely unwell adult patients admitted to a mixed medical-surgical ICU were studied. Arginine, asymmetric dimethyl-l-arginine (ADMA), monomethyl-l-arginine (MMA), symmetric dimethyl-l-arginine (SDMA) and l-homoarginine were measured in a plasma sample collected at admission to ICU by liquid chromatography tandem mass spectrometry. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. RESULTS: In this cohort, 163 patients (14.1%) died. ADMA (odds ratio = 1.159 (1.033-1.300) per 0.1 µmol/L increment, p = 0.012), homoarginine (odds ratio = 0.963 (0.934-0.992), p = 0.013) and risk of death score (odds ratio = 1.045 (1.037-1.053) per 1% increment, p < 0.001) were independently associated with mortality in ICU patients. The area under the receiver operator characteristic curve for risk of death score, ADMA and homoarginine combined for mortality was greater than for risk of death score alone (0.815 (95% CI 0.790-0.837) vs 0.796 (95% CI 0.781-0.820), p = 0.019). Other arginine metabolites were not independently associated with mortality. CONCLUSIONS: ADMA is positively and homoarginine negatively associated with mortality in ICU patients, independent of other clinical factors. Measuring ADMA and homoarginine may refine models to predict ICU mortality. Reducing ADMA and increasing homoarginine are potential therapeutic targets to reduce mortality in critically ill patients.


Assuntos
Sistema Cardiovascular , Homoarginina , Adulto , Arginina/metabolismo , Biomarcadores/metabolismo , Sistema Cardiovascular/metabolismo , Estudos de Coortes , Estado Terminal , Homoarginina/metabolismo , Humanos
5.
Intern Med J ; 52(11): 1917-1924, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-34343400

RESUMO

BACKGROUND: Cardiovascular disease is a leading cause of death in breast cancer survivors, but the underlying cause is not fully characterised. AIMS: To determine whether insulin sensitivity, cardiovascular risk markers and body composition were perturbed in women treated with chemotherapy for early stage breast cancer and whether perturbations occurred before or after cancer treatment. METHODS: Sixteen women with breast cancer and 17 control subjects were studied. Twelve breast cancer patients returned for a second visit following cancer treatment comprising chemotherapy (n = 2), or chemotherapy and radiotherapy (n = 10). The Matsuda index to estimate insulin sensitivity, fasting lipids, pulse wave velocity (PWV), reactive hyperaemia index (RHI) and body composition by dual energy X-ray absorptiometry were measured. RESULTS: There were no significant differences in age (53 ± 9 vs 54 ± 11 years; P = 0.82) or body mass index (28 ± 7 vs 28 ± 6; P = 0.97) between patients with breast cancer and controls. Patients with breast cancer had higher triglycerides than controls (1.2 ± 0.1 vs 0.8 ± 0.1 mmol/L; P = 0.03), but there were no significant differences in the Matsuda index, PWV and RHI. Following cancer treatment, there was a lower Matsuda index (6.3 ± 1.2 vs 5.2 ± 1.0; P = 0.01), but this was not associated with a significant change in vascular function. Bone mass fell by 3% from 2.27 ± 0.11 to 2.20 ± 0.10 kg after cancer treatment (P = 0.03). CONCLUSIONS: Patients with breast cancer had higher triglycerides before treatment and a reduction in insulin sensitivity and bone mass following cancer treatment. Future larger and longer-term studies should characterise the effect of reduced insulin sensitivity on rates of diabetes, cardiovascular disease, cancer outcomes and fracture. TRIAL REGISTRATION: ACTRN12614001055695.


Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Hipertrigliceridemia , Resistência à Insulina , Rigidez Vascular , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Densidade Óssea , Doenças Cardiovasculares/epidemiologia , Análise de Onda de Pulso , Triglicerídeos
6.
Crit Care Med ; 48(2): e115-e122, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939810

RESUMO

OBJECTIVES: To determine whether relative hyperglycemia was associated with in-hospital mortality in critically ill patients independent of other prognostic variables and whether this association is affected by background glycemia. DESIGN: Prospective observational study. SETTING: Mixed medical-surgical ICU in a metropolitan teaching hospital. PATIENTS: From 2,617 admissions to ICU between January 27, 2016, and March 30, 2017, 1,262 consecutive patients who met inclusion and exclusion criteria were studied. INTERVENTIONS: Glycosylated hemoglobin was used to estimate average glucose concentration over the prior 3 months. Glucose concentration on ICU admission was divided by estimated average glucose concentration to calculate the stress hyperglycemia ratio, an index of relative glycemia. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. MEASUREMENTS AND MAIN RESULTS: In this study, there were 186 deaths (14.7%). Admission glucose was significantly associated with mortality in univariate analysis (odds ratio = 1.08 per mmol/L glucose increment; p < 0.001) but not after adjustment for risk of death score (odds ratio = 1.01; p = 0.338). In contrast, stress hyperglycemia ratio was significantly associated with mortality both in univariate analysis (odds ratio = 1.09 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and after adjustment for risk of death score (odds ratio = 1.03; p = 0.014). Unlike admission glucose concentration, stress hyperglycemia ratio was significantly associated with mortality in patients with glycosylated hemoglobin less than 6.5% (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and glycosylated hemoglobin greater than or equal to 6.5% (48 mmol/mol) (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p = 0.005). CONCLUSIONS: Unlike absolute hyperglycemia, relative hyperglycemia, as assessed by the stress hyperglycemia ratio, independently predicts in-hospital mortality in critically ill patients across the glycemic spectrum. Future studies should investigate whether using measures of relative hyperglycemia to determine individualized glycemic treatment targets improves outcomes in ICU.


Assuntos
Estado Terminal/mortalidade , Mortalidade Hospitalar , Hiperglicemia/epidemiologia , APACHE , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Hemoglobinas Glicadas , Hospitais de Ensino , Humanos , Unidades de Terapia Intensiva , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Eur Respir J ; 54(5)2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31413163

RESUMO

This international randomised controlled trial evaluated whether COPD patients with comorbidities, trained in using patient-tailored multidisease exacerbation action plans, had fewer COPD exacerbation days than usual care (UC).COPD patients (Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification II-IV) with ≥1 comorbidity (ischaemic heart disease, heart failure, diabetes, anxiety, depression) were randomised to a patient-tailored self-management intervention (n=102) or UC (n=99). Daily symptom diaries were completed for 12 months. The primary outcome "COPD exacerbation days per patient per year" was assessed using intention-to-treat analyses.No significant difference was observed in the number of COPD exacerbation days per patient per year (self-management: median 9.6 (interquartile range (IQR) 0.7-31.1); UC: median 15.6 (IQR 3.0-40.3); incidence rate ratio (IRR) 0.87 (95% CI 0.54; 1.39); p=0.546). There was a significantly shorter duration per COPD exacerbation for self-management (self-management: median 8.1 (IQR 4.8-10.1) days; UC: median 9.5 (IQR 7.0-15.1) days; p=0.021), with no between-group differences in the total number of respiratory hospitalisations (IRR 0.76 (95% CI 0.42; 1.35); p=0.348), but a lower probability of ≥1 for respiratory-related hospitalisation compared to UC (relative risk 0.55 (95% CI 0.35; 0.87); p=0.008). No between-group differences were observed in all-cause hospitalisations (IRR 1.07 (95% CI 0.66; 1.72)) or mortality (self-management: n=4 (3.9%); UC: n=7 (7.1%); relative risk 0.55 (95% CI 0.17; 1.84)).Patient-tailored exacerbation action plans for COPD patients with comorbidities did not significantly reduce exacerbation days, but reduced the duration per COPD exacerbation and the risk of having at least one respiratory-related hospitalisation during follow-up, without excess all-cause mortality.


Assuntos
Planejamento de Assistência ao Paciente , Doença Pulmonar Obstrutiva Crônica/terapia , Autogestão , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Método Simples-Cego
8.
Intern Med J ; 48(8): 999-1002, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30133980

RESUMO

Growth hormone (GH) replacement therapy was recently recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for listing on the Pharmaceutical Benefits Scheme for adults with severe GH deficiency and impaired quality of life. This approval was significant for two reasons. First, the application was initiated and coordinated by a health professional working group, who prepared a 'public interest' submission to PBAC. Second, it resulted in a recommendation to subsidise therapy for a rare disease after two prior rejections on the basis of uncertainty about efficacy and cost effectiveness. There are important lessons to learn about the power of professional groups to drive health policy and attain funding for rare diseases.


Assuntos
Análise Custo-Benefício/economia , Terapia de Reposição Hormonal/economia , Hormônio do Crescimento Humano/deficiência , Seguro de Serviços Farmacêuticos/economia , Doenças Raras/tratamento farmacológico , Doenças Raras/economia , Adulto , Análise Custo-Benefício/tendências , Nanismo Hipofisário/tratamento farmacológico , Nanismo Hipofisário/economia , Terapia de Reposição Hormonal/tendências , Humanos , Seguro de Serviços Farmacêuticos/tendências , Doenças Raras/epidemiologia
9.
Cardiovasc Diabetol ; 16(1): 157, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29233143

RESUMO

BACKGROUND: Hyperglycemia is associated with increased morbidity and mortality in patients with an acute myocardial infarction (AMI). We evaluated whether complications after AMI are associated with absolute or relative glycemia. METHODS: A total of 192 patients with AMI were randomized to intensive or conventional insulin therapy. Absolute glycemia was defined as mean blood glucose level (BGL) during the first 24 h following randomization. Relative glycemia was defined by the stress hyperglycaemia ratio (SHR), calculated as mean BGL divided by average glucose concentration over the prior 3 months estimated from glycosylated haemoglobin. The primary endpoint was a "complicated AMI", defined as an AMI complicated by death, congestive cardiac failure, arrhythmia, cardiac arrest, reinfarction, cardiogenic shock, inotrope use or emergency revascularization. RESULTS: There was not a significant association between mean BGL and complicated AMI (odds ratio (OR) 1.05 per mmol/L glucose increment, 95% confidence intervals (CI) 0.93-1.19). In contrast, SHR was positively associated with a complicated myocardial infarction (OR 1.22 per 0.1 SHR increment, 95% CI 1.06-1.42), and individual complications of death (OR 1.55, 95% CI 1.14-2.11), congestive cardiac failure (OR 1.27, 95% CI 1.05-1.54), arrhythmia (OR 1.31, 95% CI 1.12-1.54) and cardiogenic shock (OR 1.42, 95% CI 1.03-1.97). The relationship between SHR and a complicated AMI was independent of diabetic status, intensive insulin therapy, sex and hypoglycemia. CONCLUSIONS: Relative, but not absolute, glycemia during insulin treatment is independently associated with complications after an AMI. Future studies should investigate whether basing therapeutic glycaemic targets on relative glycemia improves patient outcomes.


Assuntos
Glicemia/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Infarto do Miocárdio/complicações , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/mortalidade , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Revascularização Miocárdica , Razão de Chances , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Diabetes Obes Metab ; 19(4): 571-578, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27995731

RESUMO

AIM: Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. MATERIALS AND METHODS: Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. RESULTS: On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P = .02) and the insulin dose was increased over time ( P = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P = .45) or between groups ( P = .24). CONCLUSIONS: There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina Glargina/administração & dosagem , Insulina Isófana/administração & dosagem , Prednisolona/efeitos adversos , Idoso , Glicemia/efeitos dos fármacos , Esquema de Medicação , Feminino , Hospitalização , Humanos , Hiperglicemia/induzido quimicamente , Hipoglicemia/induzido quimicamente , Pacientes Internados , Insulina/administração & dosagem , Insulina Aspart/administração & dosagem , Masculino , Refeições , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Pituitary ; 20(6): 676-682, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28828544

RESUMO

PURPOSE: Internal carotid artery (ICA) aneurysms have rarely been found in association with marked hyperprolactinemia in the absence of prolactinoma; the cause of hyperprolactinemia has never been investigated. We aimed to determine if the observed hyperprolactinemia is due to a vascular-derived or known prolactin secretagogue from the injured ICA, analogous to pregnancy-associated hyperprolactinemia putatively due to placental factors. METHODS: We conducted a case series and literature review of individuals with severe hyperprolactinemia in association with ICA aneurysms. In two affected patients at our institutions, we performed RT-PCR and ELISA of prolactin secretagogues that are produced by vascular tissue and/or upregulated in pregnancy: AGT (encoding angiotensinogen), TAC1 (encoding substance P), HDC (encoding the enzyme responsible for conversion of histidine to histamine), and prolactin-releasing hormone (PRLH). Patient blood samples were compared to pregnancy blood samples (positive controls) and middle-aged male blood samples (negative controls). RESULTS: Two men presented with serum prolactin >100-fold normal associated with cavernous ICA aneurysms and no pituitary adenoma. Aneurysm stenting in one man more than halved his serum prolactin. In both men, dopamine agonist therapy markedly reduced serum prolactin. RT-PCR and ELISA showed no differences between patients and controls in AGT, TAC1 or HDC expression or PRLH titre, respectively. Literature review revealed 11 similar cases. CONCLUSIONS: We propose the term 'vasculogenic hyperprolactinemia' to encompass the hyperprolactinemia associated with ICA aneurysms. This may be mediated by an endothelial factor capable of paracrine stimulation of lactotrophs; however, angiotensin II, substance P, histamine and PRLH appear unlikely to be causative.


Assuntos
Hiperprolactinemia/sangue , Prolactina/sangue , Adulto , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/metabolismo , Artéria Carótida Interna/patologia , Humanos , Masculino
12.
Intern Med J ; 47(12): 1448-1451, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29224198

RESUMO

We report two cases of hypoglycaemia; one with apparently spontaneous hypoglycaemia and one with presumed insulin overdose. In both cases insulin concentration was normal when measured with the Roche immunoassay, but elevated when remeasured with the Advia Centaur immunoassay and a diagnosis of hypoglycaemia secondary to insulin analogue administration was made. These cases highlight that physicians need to understand the binding characteristics of the insulin immunoassay they use.


Assuntos
Overdose de Drogas/sangue , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Insulina/efeitos adversos , Insulina/sangue , Idoso , Overdose de Drogas/diagnóstico , Evolução Fatal , Feminino , Humanos , Hipoglicemia/diagnóstico , Imunoensaio/métodos , Pessoa de Meia-Idade
13.
Clin Endocrinol (Oxf) ; 84(4): 501-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26493042

RESUMO

OBJECTIVE: Postprandial hyperglycaemia is associated with increased arterial stiffness and cardiovascular events. Low-dose prednisolone causes insulin resistance that typically manifests as postprandial hyperglycaemia. We investigated whether prednisolone causes postprandial vascular dysfunction in a cohort of patients with rheumatoid arthritis. DESIGN: An open interventional and cross-sectional study was undertaken. PATIENTS AND MEASUREMENTS: Eighteen subjects with rheumatoid arthritis who had not taken oral glucocorticoids for ≥6 months were studied before and after prednisolone 6 mg/day for 7 days to determine the acute effects of prednisolone. Pre-prednisolone data were compared to 18 subjects with rheumatoid arthritis taking long-term (>6 months) prednisolone (6·5 ± 1·8 mg/day) to assess the chronic effects of prednisolone. Augmentation index (by applanation tonometry) and reactive hyperaemia index (by peripheral artery tonometry) were measured before and after a mixed-meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). Insulin sensitivity was estimated by the Matsuda index and sympathetic nervous system activity from urinary noradrenaline excretion. RESULTS: Matsuda index was lower after acute (2·0 ± 1·0 vs 3·6 ± 1·1, P = 0·01) and chronic (1·9 ± 1·0 vs 3·6 ± 1·1, P = 0·04) prednisolone. Postprandial augmentation index was lower after acute prednisolone (2551 ± 197 vs 2690 ± 272%*min, P ≤ 0·001), but not chronic prednisolone. There were no significant differences in reactive hyperaemia index with acute or chronic prednisolone. Noradrenaline excretion was lower after acute (54 ± 8 vs 93 ± 23 nmol/6 h, P = 0·02), but not chronic, prednisolone. CONCLUSIONS: Prednisolone-induced insulin resistance is not associated with postprandial vascular dysfunction in patients with rheumatoid arthritis. Reduced sympathetic activity may contribute to the reduction in postprandial arterial stiffness with acute prednisolone.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glicemia/análise , Resistência à Insulina/fisiologia , Prednisolona/uso terapêutico , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Estudos Transversais , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hiperglicemia/sangue , Hiperglicemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Prednisolona/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos
14.
Clin Endocrinol (Oxf) ; 85(5): 741-747, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27321736

RESUMO

OBJECTIVE: Glucocorticoids can cause postprandial hyperglycaemia, but the effects on postprandial energy and fat metabolism are uncertain. We investigated the effects of acute and chronic low-dose prednisolone on fasting and postprandial energy expenditure and substrate metabolism. DESIGN: An open interventional and cross-sectional study was undertaken. PATIENTS AND MEASUREMENTS: Eighteen patients who had not taken oral glucocorticoids for ≥6 months were studied before and after 7 days prednisolone (6 mg/day) to assess the acute effects of prednisolone. Baseline data from patients, not on glucocorticoids, were compared with 18 patients on long-term prednisolone (6·5 ± 1·8 mg/day for >6 months) to assess the chronic effects. Energy expenditure and substrate oxidation were measured using indirect calorimetry before and after a mixed meal. Adipocyte insulin resistance index and insulin-mediated suppression of NEFA were calculated from fasting and postprandial insulin and NEFA concentrations. RESULTS: There were no significant differences in resting energy expenditure or diet-induced thermogenesis with prednisolone. Acute (-2·1 ± 6·2 vs -16·3 ± 4·8 mg/min, P = 0·01) and chronic (-1·4 ± 2·8 vs -16·3 ± 4·8 mg/min, P = 0·01) prednisolone attenuated postprandial suppression of fat oxidation. Chronic (31·6 ± 3·8 vs 17·0 ± 3·3, P = 0·007), but not acute, prednisolone increased adipocyte insulin resistance index. However, insulin-mediated suppression of NEFA was not significantly different after acute or chronic prednisolone. CONCLUSIONS: Prednisolone does not alter energy expenditure. However, even at low doses, prednisolone exerts adverse effects on fat metabolism, which could exacerbate insulin resistance and increase cardiovascular risk. Attenuated postprandial suppression of fat oxidation, but not lipolysis, suggests that prednisolone causes greater insulin resistance in skeletal muscle than in adipocytes.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Metabolismo Energético/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Prednisolona/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Idoso , Calorimetria Indireta , Ácidos Graxos não Esterificados/análise , Feminino , Humanos , Resistência à Insulina , Lipólise , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Oxirredução , Prednisolona/administração & dosagem , Termogênese/efeitos dos fármacos
16.
Clin Endocrinol (Oxf) ; 80(3): 328-32, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24111609

RESUMO

CONTEXT: Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. PATIENT: A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. INVESTIGATIONS AND RESULTS: Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. CONCLUSIONS: Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis.


Assuntos
Síndrome de Cushing/diagnóstico , Transtornos Autoinduzidos/diagnóstico , Hipersecreção Hipofisária de ACTH/diagnóstico , Síndrome de Cushing/sangue , Síndrome de Cushing/urina , Diagnóstico Diferencial , Transtornos Autoinduzidos/sangue , Transtornos Autoinduzidos/urina , Feminino , Humanos , Pessoa de Meia-Idade
18.
Diabetes Technol Ther ; 26(1): 76-79, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37943602

RESUMO

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion.


Assuntos
Hiperglicemia , Insulina , Adulto , Humanos , Insulina/uso terapêutico , Glicemia/análise , Automonitorização da Glicemia , Monitoramento Contínuo da Glicose , Prednisolona/uso terapêutico , Estudos Prospectivos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Insulina Regular Humana
19.
J Clin Endocrinol Metab ; 109(3): e1020-e1028, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37967229

RESUMO

CONTEXT: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. OBJECTIVE: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. DESIGN: Cross-sectional study. PATIENTS: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma. METHODS: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. MAIN OUTCOME MEASURE: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma. RESULTS: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. CONCLUSION: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality.


Assuntos
Adenoma , Neoplasias das Glândulas Suprarrenais , Adenoma Adrenocortical , Doenças Cardiovasculares , Adulto , Humanos , Hidrocortisona , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Monitorização Ambulatorial da Pressão Arterial , Fatores de Risco , Neoplasias das Glândulas Suprarrenais/complicações , Adenoma Adrenocortical/complicações , Adenoma/complicações , Glucose , Fatores de Risco de Doenças Cardíacas
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