RESUMO
AIMS: To assess the impact of social deprivation, demographics and centre on HbA1c outcomes with continuous subcutaneous insulin infusion (CSII) in adults with Type 1 diabetes. METHODS: Demographic data, postcode-derived English Index of Multiple Deprivation data and 12-month average HbA1c (mmol/mol) pre- and post-CSII were collated from three diabetes centres in the north west of England, University Hospital of South Manchester (UHSM), Salford Royal Foundation Hospital (SRFT) and Manchester Royal Infirmary (MRI). Univariable and multivariable regression models explored relationships between demographics, Index of Multiple Deprivation, centre and HbA1c outcomes. RESULTS: Data were available for 693 (78%) individuals (UHSM, n = 90; SRFT, n = 112; and MRI, n = 491) of whom 59% were women. Median age at CSII start was 39 (IQR 29.5-49.0) years and median diabetes duration was 20 (11-29) years. Median Index of Multiple Deprivation was 15 193 (6313-25 727). Overall median HbA1c improved from 69 to 64 mmol/mol (8.5% to 8.0%) within the first year of CSII. In multivariable analysis, higher pre-CSII HbA1c was significantly associated with higher deprivation (P = 0.036), being female (P < 0.001), and centre (MRI; P = 0.005). Following pre-CSII HbA1c adjustment, post-CSII HbA1c or HbA1c change were not related to demographic factors and deprivation, but remained significantly related to the centre; UHSM and SRFT had larger reductions in HbA1c with CSII compared with MRI [median -7.0 (-0.6%) vs. -6.0 (-0.55%) vs. -4.5 (-0.45%) mmol/mol; P = 0.005]. CONCLUSIONS: Higher pre-CSII HbA1c levels were associated with higher deprivation and being female. CSII improves HbA1c irrespective of social deprivation and demographics. Significant differences in HbA1c improvements were observed between centres. Further work is warranted to explain these differences and minimize variation in clinical outcomes with CSII.
Assuntos
Carência Cultural , Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas/metabolismo , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Sistemas de Infusão de Insulina , Insulina/administração & dosagem , Adulto , Glicemia/metabolismo , Demografia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Inglaterra/epidemiologia , Feminino , Geografia , Hemoglobinas Glicadas/análise , Humanos , Infusões Subcutâneas , Masculino , Pessoa de Meia-Idade , Distância Psicológica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
CONTEXT: Acromegaly increases cardiovascular morbidity. We tested the hypothesis that increased arterial stiffness together with left ventricular hypertrophy may be a contributory factor. PATIENTS AND DESIGN: Fifty-six patients (40 males, 54 ± 13 yr; 25 active disease, 31 in remission) and 46 healthy controls (30 males, 52 ± 13 yr) underwent measurements of aortic pulse wave velocity (PWV), carotid Doppler (IMT), echocardiography, and cardiovascular risk factors. RESULTS: Mean serum IGF-I was 323 ± 286 ng/ml (sd score 1.8 ± 1.9) in all patients. Age, body mass index, diastolic blood pressure (BP), and lipid levels were similar comparing patients and controls. Systolic BP (130.8 ± 19.9 vs. 122 ± 14 mm Hg controls, P < 0.01) and PWV (11.7 ± 3.8 vs. 9.7 ± 2.8 m/sec, 95% confidence interval -3.4 to -0.7, P <0.01) were higher in patients than controls. Regression analysis revealed age, presence of acromegaly, systolic BP, and body mass index, inversely, as significantly and independently associated with PWV. No difference in carotid IMT was seen (0.8 ± 0.2 patients vs. 0.7 ± 0.2 mm controls, P = 0.5) or between active/controlled disease. In the subset of participants with echocardiography (n = 32), left ventricular mass was higher by a mean of 38.2 g (95% confidence interval -80.9 to +4.6, P = 0.08). CONCLUSION: In summary, patients with acromegaly had independently and significantly increased aortic PWV as evidence of arterial stiffening but unaltered carotid IMT compared with controls, also influenced by age and systolic BP. Premature cardiovascular disease in patients with acromegaly is likely related to pressure-related arterial and left ventricular stiffening rather than atherosclerotic disease.
Assuntos
Acromegalia/patologia , Artérias/patologia , Artérias Carótidas/patologia , Acromegalia/diagnóstico por imagem , Adulto , Idoso , Artérias/diagnóstico por imagem , Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Artérias Carótidas/diagnóstico por imagem , Estudos Transversais , Feminino , Fibrinogênio/metabolismo , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Decúbito Dorsal/fisiologia , UltrassonografiaRESUMO
BACKGROUND: Exenatide is an incretin mimetic licensed for treatment of Type 2 diabetes poorly controlled despite maximally tolerated doses of oral therapy. Similar in structure to the natural incretin hormone glucagon-like peptide 1 (GLP-1), it helps restore underlying pathophysiological abnormalities. CASE REPORT: We report the successful use of exenatide, combined with insulin, in a 66-year-old woman initially diagnosed with Type 2 diabetes in 1989 but now exhibiting a Type 1 phenotype. Diet, lifestyle advice and oral glucose-lowering agents were commenced but persisting poor control necessitated insulin therapy in 2005. She later presented twice in diabetic ketoacidosis, suggesting conversion to a Type 1 phenotype (postprandial C-peptide < 94 pmol/l). Despite differing insulin regimens, control remained poor with frequent hyperglycaemic and hypoglycaemic excursions, severely impairing quality of life. Whilst an inpatient in 2007 [glycated haemoglobin (HbA(1c)) 10.2%, body mass index (BMI) 31.5 kg/m(2)] exenatide was commenced in an attempt to stabilize glycaemic control. Dramatic improvements were seen and continued. Eight months later, HbA(1c) had fallen by 2% with an 8-kg weight loss and 10-unit reduction in daily insulin dose. Quality of life dramatically improved. C-peptide remains undetectable. CONCLUSIONS: This patient with features of both Type 1 and Type 2 diabetes benefited greatly from exenatide with insulin therapy. The improvement seen in glycaemic control could not be attributable to enhanced insulin secretion but could be as a result of a combination of the other incretin effects (postprandial glucagon suppression, delayed gastric emptying and weight loss secondary to increased satiety) all improving insulin sensitivity, reducing insulin dose and smoothing control.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Sobrepeso/complicações , Peptídeos/uso terapêutico , Peçonhas/uso terapêutico , Idoso , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 2/complicações , Exenatida , Feminino , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: The decision to commence lifelong glucocorticoid replacement therapy is often based on a cortisol stimulation test. We investigated the relationship between the peak cortisol response to insulin-induced hypoglycemia and daily cortisol production rate (CPR) to ascertain whether provocative tests are accurate in indicating the need to initiate lifelong glucocorticoid replacement. PATIENTS AND METHODS: Ten patients (five male; mean age, 44 +/- 13 yr) with pituitary disease and with demonstrably suboptimal peak cortisol response (350-500 nmol/liter) to insulin-induced hypoglycemia, underwent CPR measurement by isotope dilution using gas chromatography-mass spectrometry and 24-h urinary free cortisol (UFC). RESULTS: The median baseline and peak cortisol attained with hypoglycemia were 284 (164-323) and 473.5 (366-494) nmol/liter, respectively. A strong positive correlation was seen between peak stimulated cortisol and CPR (adjusted for body surface area) (r = 0.75; P = 0.02), and in all patients CPR [4.6 (2.9-15.1) mg/d x m(2)] was within the reference range (2.1-12 mg/d x m(2)) or elevated (one patient). A wide range was found for 24-h UFC [116.5 (20.5-265.9) nmol/liter] in this group of patients, and this parameter lacked significant correlation with either serum cortisol concentration or CPR. CONCLUSION: This is the first study to demonstrate a significant correlation between CPR and peak cortisol values during hypoglycemic challenge. An inadequate cortisol response to hypoglycemia suggests the need for glucocorticoid cover at times of stress, but these data indicate that a suboptimal peak cortisol does not equate to a low CPR and should not be an automatic indication for lifelong glucocorticoid replacement therapy. UFC bears no relation to serum cortisol or CPR and is therefore unhelpful in assessment of such patients.
Assuntos
Hidrocortisona/biossíntese , Hidrocortisona/sangue , Doenças da Hipófise/sangue , Adulto , Glicemia/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Terapia de Reposição Hormonal , Humanos , Hipoglicemia/sangue , Hipoglicemia/induzido quimicamente , Hipoglicemiantes , Insulina , Cinética , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnósticoRESUMO
BACKGROUND: The prevalence of gallstones (GS) is increased in acromegaly and further increased by somatostatin analogue (SA) therapy. The incidence is reported at 10-63%, but they are often asymptomatic and rarely require definitive management. Evidence suggests discontinuation of SA may precipitate acute biliary problems. OBJECTIVE: To determine the frequency of symptomatic gallstones in patients treated with SA. DESIGN: Retrospective analysis of prospectively followed patients in our centre. RESULTS: Fifty patients (30 male, mean age 54 +/- 16 years) were on treatment with SA on 1 January 2003. Fifteen (11 male, mean age 50 +/- 17 years) have since discontinued SA with three proceeding to develop acute cholecystitis and two, biliary colic necessitating cholecystectomy. Three of the five had abnormal liver enzymes at or within 3 months of symptomatic presentation. Two of the remaining 35 patients experienced biliary colic necessitating cholecystectomy. These data indicate a highly significant increase in acute biliary problems on discontinuing SA (5 in 27.67 patient 'off-treatment' years vs. 2 in 299 patient treatment years, chi(2), P < 0.0001). All seven patients experiencing problems were male (P = 0.01). CONCLUSION: This analysis demonstrates the high incidence of symptomatic GS following SA withdrawal, particularly in men. Although liver enzymes were raised no common abnormality was evident to aid as a predictor of future symptoms. We recommend all patients due to stop SA be forewarned of the risk of acute biliary problems. Further work is required to confirm if there is a gender-related difference in the incidence of acute biliary problems on discontinuing SA therapy.
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Acromegalia/complicações , Antineoplásicos Hormonais/uso terapêutico , Cálculos Biliares/etiologia , Octreotida/uso terapêutico , Receptores da Somatotropina/antagonistas & inibidores , Acromegalia/tratamento farmacológico , Adulto , Idoso , Distribuição de Qui-Quadrado , Feminino , Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos Cíclicos/uso terapêutico , Estudos Retrospectivos , Risco , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Suspensão de TratamentoRESUMO
INTRODUCTION: Pegvisomant use in acromegaly negates the use of GH levels to monitor disease activity. To achieve antagonism, plasma concentrations must be approximately 1000-fold greater than GH which with the high homology between the peptides makes GH measurement a challenge when pegvisomant is present. OBJECTIVE: We investigated the effect of pegvisomant on GH measured using commercially available assays. METHODS: Pooled serum samples with GH concentrations <0.38, 3.85 and 7.69 microg/l were spiked with increasing pegvisomant concentrations (9000-494 000 microg/l). Samples were analysed by the Nichols Advantage, DPC Immulite 2000, Diasorin IRMA, Beckman Access Dxl, Tosoh AIA and Wallac Delfia assays. RESULTS: With baseline GH <0.38 microg/l measured levels were <0.38 in all assays except Nichols, Diasorin and Beckman where GH peaked at 1.5, 9.6 and 17.7 micarog/l respectively at low pegvisomant concentrations, falling thereafter. With the other two samples, measured GH levels progressively fell with increasing pegvisomant concentrations, except the Beckman assay where an increase (30.8 microg/l) was seen at a pegvisomant concentration of 9000 microg/l; and Diasorin and Tosoh where smaller increases were seen at lower pegvisomant concentrations, levels gradually falling thereafter. CONCLUSION: The presence of pegvisomant resulted in artefactually low measured GH in most assays. We speculate this fall is due to assay antibody-binding pegvisomant, reducing the amount of available antibody to bind actual GH thereby producing less sandwich formation: the 'high-dose hook' effect. In most assays, this effect is modest and results in lower GH, but the level of interference makes them unsuitable for studies on the influence of pegvisomant on GH neuroregulation.
Assuntos
Hormônio do Crescimento Humano/análogos & derivados , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/química , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in activation of the matrix metalloproteinase (MMP) system; the latter is implicated in atherosclerosis and cardiovascular disease. Patients with acromegaly have reduced life expectancy primarily due to cardiac disease. AIM: This study assessed plasma MMPs and VEGF levels in patients with active acromegaly (IGF-I > 130% upper limit of normal), and on treatment with pegvisomant. SUBJECTS AND METHODS: Twenty patients [nine female, mean age 56.1 +/- 13.8 yr (mean +/- sd)] were studied at baseline and on pegvisomant therapy and compared with data from 25 healthy volunteers (12 female; 56.6 +/- 14.2 yr). Plasma MMP-2, MMP-9, and VEGF levels were measured. RESULTS: Serum IGF-I fell from a baseline (mean +/- sd) level of 620.1 +/- 209.3 ng/ml to 237.5 +/- 118.5 ng/ml on pegvisomant (doses 10-60 mg; P < 0.001). MMP-2 levels at baseline were significantly higher in patients compared with healthy controls (380.7 +/- 204.8 vs. 207.4 +/- 62.6 ng/ml; P < 0.001), but with treatment a significant reduction in MMP-2 [380.7 +/- 204.8 vs. 203.0 +/- 77.4 ng/ml; P < 0.001] and VEGF (283.4 +/- 233.6 vs. 229.1 +/- 157.4 pg/ml; P = 0.008) was noted. There was no significant difference in MMP-9 levels between patients and controls at baseline (797.5 +/- 142.1 vs. 788.3 +/- 218.0 ng/ml; P = 0.87) or between baseline and posttreatment levels (797.5 +/- 142.1 vs. 780.0 +/- 214 ng/ml; P = 0.76). CONCLUSIONS: Our novel data demonstrate that treatment of acromegaly with pegvisomant leads to reductions in MMP-2 and VEGF concentrations. Further studies are required to determine the significance of these findings with relation to cardiac disease.
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Acromegalia/sangue , Acromegalia/tratamento farmacológico , Hormônio do Crescimento Humano/análogos & derivados , Metaloproteinase 2 da Matriz/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Índice de Massa Corporal , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To investigate the efficacy of the Neuropen, a new clinical device that assesses both pain and pressure perception, to evaluate peripheral nerve function in diabetic patients compared with standard clinical testing methods. METHODS: Peripheral nerve function was assessed in 124 diabetic patients attending a multidisciplinary diabetes clinic, using (i) the modified Neuropathy Disability Score (NDS), derived from assessment of vibration, pinprick (pain), temperature sensation plus ankle reflexes, and (ii) vibration perception threshold (VPT) measured at the hallux. Patients were stratified into various neuropathic groups according to their NDS score. In addition, nerve function was assessed using the Neuropen, a device combining a 10-g monofilament and a weighted Neurotip. Inability to feel sensation on either or both feet for each test of the Neuropen (i.e. the monofilament or the Neurotip) was defined as an abnormal response. RESULTS: The sensitivity of the Neuropen to detect neuropathy compared with the NDS (score > or = 6/10) was high using either an abnormal monofilament response (87.8%), an abnormal Neurotip response (91.8%) or a combination of the two (82.0%). Neuropen specificity improved, however, when the combination of abnormal monofilament and abnormal Neurotip responses was used (68%), rather than the individual tests (57% and 41%, respectively). CONCLUSIONS: The Neuropen is a sensitive device for assessing nerve function and may provide an inexpensive alternative screening method to identify patients with moderate to severe neuropathy.