RESUMO
OBJECTIVE: Associations between albuminuria and renal outcomes are inconsistent in patients with type 2 diabetes (T2D). Soluble tumor necrosis factor receptor type 1 (sTNFR1) is involved in declined kidney function and poor renal outcomes but this has not been confirmed among Chinese T2D patients. This study aimed to examine the association of sTNFR1 and renal outcomes in a cohort of these patients. METHODS: Two hundred and eighty-three Chinese T2D patients were enrolled in a prospective observational study which excluded individuals with estimated glomerular filtration rates (eGFR) <30 mL/min/1.73m2. Composite renal outcomes included either or both a >30% decline in eGFR and worsening albuminuria from consecutive tests of blood/urine during a 3.5-year follow-up. RESULTS: Higher sTNFR1 levels were associated with impaired renal outcomes. sTNFR1 levels of ≥979 pg/mL yielded the most sensitivity and specific predictions of renal outcomes according to the receiver operating curve (area under the curve 0.68, P<.001; sensitivity 78.3%, specificity 48.9%). Renal events occurred more frequently in subjects with sTNFR1 ≥979 pg/mL than in others (sTNFR1 <979 pg/mL; 29% versus 10%; P<.001 by log-rank test). The association between sTNFR1 ≥979 pg/mL and renal outcomes remained significant after adjustment for relevant covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18 to 5.02; P = .01) and consistent across subgroups stratified by age, sex, blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system inhibitors. CONCLUSION: Increased sTNFR1 levels were associated with renal outcomes in Chinese T2D subjects, making sTNFR1 a potential biomarker in diabetic kidney disease.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Albuminúria/epidemiologia , Povo Asiático , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Taxa de Filtração Glomerular , Humanos , Rim , Receptores Tipo I de Fatores de Necrose Tumoral , Fatores de RiscoRESUMO
Objective: Upstroke time per cardiac cycle (UTCC) in the lower extremities has been found to be predictive of cardiovascular mortality in the general population. Therefore, the purpose of the study was to test the associations between increasing UTCC and outcomes in patients with type 2 diabetes. Methods: A total of 452 patients with type 2 diabetes (age, 67.5 ± 8.6 years; male, 54%) registered in a share-care program participated in the study at an outpatient clinic in Taipei Veterans General Hospital across a mean of 5.8 years. Primary outcomes were all-cause mortality hospitalization for coronary artery disease, stroke, revascularization, amputation, and diabetic foot syndrome. Secondary end-point outcome was all-cause mortality. Results: Increment of UTCC associations with primary and secondary outcomes were undertaken prior to baseline characteristic adjustments. A UTCC of 20.1% exhibited the greatest area under curve (AUC), sensitivity, and specificity balance to predict composite events in receiver operating curves (AUC, 0.63 [P = .001]; sensitivity, 67.7%; specificity, 54.9%). Sixty-four composite events and 17 deaths were identified from medical records. UTCC ≥20.1% was associated with the occurrence of composite events and an increased risk of mortality. For composite events, an adjusted hazard ratio (HR) of 2.45 and 95% confidence interval (CI) of 1.38 to 4.35 (P = .002) were calculated. For all-cause mortality, an adjusted HR of 1.91 and 95% CI of 0.33 to 10.99 (P = .467) were calculated. Conclusion: Increasing UTCC was associated with cardiovascular outcomes in patients with type 2 diabetes. Therefore, UTCC is advocated as a noninvasive screening tool for ambulatory patients with type 2 diabetes. Abbreviations: CAD = coronary artery disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; HR = hazard ratio; PAD = peripheral artery disease; UTCC = upstroke time per cardiac cycle.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVES: Most patients with Cushing's disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response. DESIGNS: A prospective study of 29 patients with CD. METHODS: Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry. RESULTS: Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients. CONCLUSIONS: We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Desamino Arginina Vasopressina/farmacologia , Hipersecreção Hipofisária de ACTH/metabolismo , Neoplasias Hipofisárias/metabolismo , Receptores de Vasopressinas/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Hormônio Liberador da Corticotropina/farmacologia , Feminino , Imunofluorescência , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Increased interarm systolic blood pressure difference (IASBPD) is associated with cardiovascular prognosis in the general population. This study aimed to evaluate whether IASBPD or ankle brachial index (ABI) is strongly associated with cardiovascular outcomes in patients with type 2 diabetes.Total 446 type 2 diabetes followed up for a mean 5.8 years divided by ABI (<0.9 vs ≥0.9) or IASBPD (<10 vs ≥10 mm Hg). The primary outcome was a composite of all-cause mortality, hospitalization for coronary artery disease, nonfatal stroke, carotid, or peripheral revascularization, amputations, and diabetic foot syndrome. The secondary endpoint was all-cause mortality.Sixty-four composite events and 17 deaths were identified. The primary and secondary outcomes were higher than those in the group with ABIâ<â0.9 vs ABIâ≥â0.9 (32.8% vs 11.6%, Pâ<â.005 for primary outcome; 14.0% vs 2.3%, Pâ<â.005 for all-cause mortality) but IASBPD cannot exhibit a prognostic value. ABIâ<â0.9 was also the dominant risk factor of both endpoints demonstrated by multivariate Cox proportional analysis (composite events: adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.26-4.53; Pâ=â.007; all-cause mortality: adjusted HR, 3.27: 95% CI, 1.91-5.60; Pâ<â.001).The ABI was more associated with cardiovascular outcomes in patients with diabetes than IASBPD.
Assuntos
Índice Tornozelo-Braço , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Idoso , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS) remains a challenging issue for clinical endocrinologists. In this respect, bilateral inferior petrosal sinus sampling (BIPSS) appears to be the most sensitive and specific test. Here, we report our 15-year experience of analyzing the performance of BIPSS, both in the correct diagnosis and in the precise lateralization of tumors in patients with Cushing's disease (CD). METHODS: Between 1992 and 2006, 18 patients with CD (16 females, 2 males; age range, 14-56 years) were admitted to Taipei Veterans General Hospital and subjected to BIPSS plus ovine corticotropin-releasing hormone (oCRH) stimulation. Four of them had previously undergone transsphenoidal hypophysectomy (TSH) and had a recurrence thereafter. BIPSS was performed by inserting a catheter in the right and left inferior petrosal sinus for ACTH assay via a femoral vein puncture. An inferior petrosal sinus/peripheral ACTH ratio (C/P ratio) > or = 2 at baseline > or = 3 after oCRH injection indicated a pituitary origin of ACTH secretion, and an interpetrosal ACTH gradient (IPS ratio) > or = 1.4 at baseline or after oCRH indicated evidence of lateralization. RESULTS: Positive BIPSS results were found in 16 patients at baseline and in 17 patients after oCRH injection. In 17 out of 18 patients, TSH was subsequently carried out and a pituitary source was confirmed on histopathologic examination. The only 1 false-negative test result was noted in a patient who had undergone previous TSH. Thus, the sensitivities of BIPSS for the diagnosis of CD before and after oCRH stimulation were 89% and 94%, respectively. Moreover, using an IPS ratio > or = 1.4 as a criterion, BIPSS correctly lateralized the tumor in 9 of 17 and 10 of 17 patients at baseline and after oCRH stimulation, respectively, including in 2 patients who had a centrally located tumor and who had an IPS ratio < 1.4. Thus, the sensitivities of lateralization of BIPSS were 53% and 59%, respectively. None of the 4 patients who had previous TSH were precisely localized by BIPSS. If these 4 patients were excluded, the sensitivities of BIPSS for localizing in the patients who had not undergone previous operation increased to 70% (9/13) at baseline and 77% (10/13) after oCRH stimulation, respectively. CONCLUSION: BIPSS combined with oCRH stimulation is a safe and reliable examination both in the differential diagnosis of CD and in the correct lateralization of pituitary microadenoma in patients without previous pituitary surgery. Nevertheless, this procedure may provide misleading results in patients who have received previous pituitary surgery.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/diagnóstico , Amostragem do Seio Petroso/métodos , Adolescente , Adulto , Hormônio Liberador da Corticotropina/farmacologia , Síndrome de Cushing/sangue , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Amostragem do Seio Petroso/efeitos adversosRESUMO
Endocan expression has been reported to be associated with aggressive tumor progression and poor outcomes in various cancers, such as breast cancer, renal cell cancer, lung cancer, gastric cancer, and pituitary adenomas. However, the prognostic significance of endocan in neuroendocrine tumors remains unknown. Thus, the aim of this study was to determine the correlation between endocan expression in pancreatic neuroendocrine tumor (PNET) tissues and progression-free survival. This study included 73 patients with confirmed PNETs who were treated in a single tertiary center in north Taiwan between 1992 and 2015. Immunohistochemical endocan expression and microvessel density (MVD) were examined, and the relationships between these parameters and other clinicopathological characteristics were analyzed. The abovementioned patients were divided into groups according to their endocan expression levels (≥1% or <1%) and median MVDs. Negative endocan expression (Pâ=â.002) and a high MVD (Pâ<â.001) were significant and favorable prognostic factors for progression-free survival. However, positive endocan expression was significantly associated with a low MVD (Pâ=â.037) and tumor mitosis (Ki-67 index) (Pâ=â.028). Multivariate Cox regression analysis showed that positive endocan expression (hazard ratio: 4.778, Pâ=â.018) and lymph node involvement (hazard ratio: 5.121, Pâ=â.005) were independent prognostic factors for tumor recurrence.In conclusion, endocan expression was correlated with poor clinical outcomes in PNETs. Our data indicated that endocan expression may be a reliable marker for predicting tumor recurrence in patients with PNETs.
Assuntos
Proteínas de Neoplasias , Recidiva Local de Neoplasia/patologia , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Proteoglicanas , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Intervalo Livre de Doença , Feminino , Expressão Gênica/genética , Humanos , Masculino , Microvasos/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Proteínas de Neoplasias/análise , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Neovascularização Patológica/metabolismo , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Proteoglicanas/análise , Proteoglicanas/genética , Estudos Retrospectivos , Estatística como Assunto , Taiwan/epidemiologiaRESUMO
OBJECTIVE: The association between ankle brachial index (ABI) and outcomes in diabetic subjects is controversial. The purpose of this study was to evaluate whether the ABI is more strongly associated with cardiovascular outcomes comparing with non-high-density lipoprotein cholesterol (non-HDL-c). RESEARCH DESIGN AND METHODS: A total of 452 type 2 diabetic subjects followed up for a mean of 5.8 years were grouped by ABI (<0.9 versus ≥0.9) and non-HDL-c (<100mg/dL versus ≥100mg/dL). Primary outcomes were composite events including all-cause mortality, hospitalization for coronary artery disease, stroke, revascularization, amputation and diabetic foot, and the secondary end point was all-cause mortality. RESULTS: Intergroup differences in percentage of men, duration of diabetes, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, triglycerides and estimated glomerular filtration rate were significant. A total of 64 composite events and 17 deaths were recorded. A higher number of composite events occurred in the group with abnormal ABI but optimal non-HDL-c than in those with suboptimal non-HDL-c but normal ABI (29% versus 11%, P < 0.05). A similar trend was observed in all-cause mortality (11% versus 1%, P < 0.05). The ABI was the dominant risk factor for both end points after adjusting other factors (for composite events, hazard ratio = 0.02, 95% CI: 0.00-0.10, P < 0.001 and for all-cause mortality, hazard ratio = 0.01, 95% CI: 0.00-0.28, P = 0.006). CONCLUSIONS: The ABI was more strongly associated with outcomes in diabetes than non-HDL-c. The ABI should be routinely screened in diabetes even without symptom.
Assuntos
Índice Tornozelo-Braço , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Técnicas de Diagnóstico Cardiovascular/instrumentação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , TaiwanRESUMO
Insulin autoimmune syndrome, characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia, is a rare cause of hypoglycemia. We report a patient with pulmonary tuberculosis who developed recurrent spontaneously post-absorptive hyperinsulinemic hypoglycemia after treatment with anti-tuberculous drugs. Imaging studies of the pancreas were unremarkable, and selective intra-arterial calcium stimulation with hepatic venous sampling for insulin failed to show a gradient, thus almost completely excluding the possibility of occult insulinoma or nesidioblastosis. Examinations of sera, however, disclosed a high titer of polyclonal insulin-binding autoantibodies containing at least 2 classes of binding sites, 1 with high affinity but low capacity, and the other with low affinity but high capacity. An oral glucose tolerance test revealed high serum levels of total insulin associated with relatively low levels of free insulin, but not of C-peptide, suggesting binding of the released insulin to autoantibodies. Regretfully, shortly after the withdrawal of isoniazid, the patient died of respiratory failure unrelated to hypoglycemia, and whether these antibodies were induced by isoniazid remains unknown. We recommend that insulin autoimmune syndrome be one of the differential diagnoses in patients with hyperinsulinemic hypoglycemia.
Assuntos
Doenças Autoimunes/complicações , Coma/etiologia , Diabetes Mellitus Tipo 2/complicações , Hipoglicemia/complicações , Idoso , Antituberculosos/uso terapêutico , Doenças Autoimunes/imunologia , Glicemia/análise , Evolução Fatal , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Anticorpos Anti-Insulina/sangue , Masculino , Síndrome , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
AIMS: Peripheral arterial disease (PAD) could be an additional risk factor for the clinical outcomes in different populations. The purpose of this study was to evaluate the influence of PAD on patients with diabetic kidney disease. METHODS: 362 persons with type 2 diabetes were followed-up for a mean 4.8 years grouped by ankle brachial index (ABI) (<0.9 vs. â§0.9) and albuminuria (with or without). Primary and secondary outcomes were composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation, and diabetic foot) and all-cause mortality. RESULTS: Inter-group differences in duration of diabetes, glycated hemoglobin, creatinine, and estimated glomerular filtration rate were significant. During the follow-up period, 53 composite events were recorded (14.7%) and 13 (3.5%) individuals died. Subjects with albuminuria plus ABI<0.9 had higher risk of composite events than those with albuminuria but normal ABI (p<0.05). The only trend difference between the two groups was in all-cause mortality. Albuminuria plus ABI <0.9 was associated with risk of composite events (hazard ratio [HR] 4.20, 95% confidence interval [CI] 1.77-9.92, p=0.001) and all-cause mortality (HR 17.77, 95% CI 1.93-162.20, p=0.011). CONCLUSIONS: PAD might be an additional risk factor for adverse outcomes in patients with diabetic kidney disease. Further prospective data are required to validate this conclusion.
Assuntos
Índice Tornozelo-Braço , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
The selective intra-arterial calcium stimulation test has greatly facilitated the precise regionalization of insulinomas smaller than 2 cm, which noninvasive techniques (ultrasound [US], computed tomography [CT], magnetic resonance imaging [MRI]) often fail to localize. This study examined not only the role of the test in the localization of insulinomas, but also the responsiveness of 3 beta-cell peptides (insulin, C peptide, and proinsulin) and their relationship to the degree of differentiation of the tumor cells, using percentage decrease of both proinsulin/insulin (P/I) and proinsulin/C peptide (P/C) ratios after stimulation as indices. Ten consecutive surgically proven insulinoma patients each received an injection of calcium into the arteries supplying the pancreas after standard selective angiography and beta-cell peptide levels were measured in samples taken from the right hepatic vein before and 30, 60, 90, 120, and 180 seconds after each injection prior to operation. After surgery, the expressions of the calcium sensing receptor (CaSR) on the resected tumors were assessed by immunohistochemistry. Intra-arterial calcium stimulation with sampling either for insulin or for C peptide correctly predicted the site of insulinoma in 8 of 9 patients or in 7 of 8 patients if the 2 big malignant insulinomas were excluded; thus, the detection rate of this test was 89% and 88%, respectively. Calcium administration stimulated a marked and prompt release of insulin and C peptide simultaneously. Both peaked within 30 to 60 seconds, then declined gradually thereafter, remaining above the baseline at 180 seconds. The magnitude of increase correlated well with the corresponding percentage decrease of P/I and P/C ratios. The response of proinsulin was much less. Immunohistochemistry demonstrated variable membraneous staining for CaSR in normal pancreatic islets and in about 9% of the total normal beta cells, whereas staining in tumor cells was only minimally detectable. We conclude that selective intra-arterial calcium stimulation with hepatic venous sampling either for insulin or for C peptide is a highly sensitive method for the preoperative localization of small insulinomas. Calcium injection stimulates a brisk response of insulin, C peptide, and proinsulin simultaneously and the magnitude of increase of both insulin and C peptide appears to be correlated well with the degree of differentiation of the tumor cells. The exact mechanism by which calcium provokes the release of beta-cell peptides is less clear and whether the CaSR is involved in the mechanism of its action requires further study.
Assuntos
Cálcio , Insulina/sangue , Insulinoma/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adulto , Idoso , Peptídeo C/sangue , Cálcio/administração & dosagem , Cálcio/metabolismo , Diferenciação Celular , Feminino , Humanos , Imuno-Histoquímica , Injeções Intra-Arteriais , Insulinoma/sangue , Insulinoma/patologia , Masculino , Pessoa de Meia-Idade , Pâncreas/irrigação sanguínea , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Proinsulina/sangueRESUMO
OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. METHODS: A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (<0.9 vs. ≥0.9) and baPWV (<1,700 cm/s vs. ≥1,700 cm/s). RESULTS: The outcomes were all-cause mortality and composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation and diabetic foot). Inter-group differences in the smoking rate, duration of diabetes, systolic and pulse blood pressure, anti-platelet drugs, estimated glomerular filtration rate, and urine albumin excretion were significant. During the follow-up period, 17 (3.7%) individuals died and composite events were recorded in 64 cases (14.1%). A low ABI plus high baPWV was found be associated with poor outcomes compared with a normal ABI plus low baPWV (p<0.001). Meanwhile, a low ABI plus high baPWV was associated with an increased risk of all-cause mortality [hazard ratio (HR) 17.01, 95% confidence interval (CI) 1.57-183.73, p=0.019] and composite events (HR 8.53, 95% CI 3.31-21.99, p<0.001). CONCLUSION: In this study, the outcomes of patients with a low ABI plus high baPWV were the worst, while the subjects with a low ABI plus low baPWV or normal ABI exhibited similar outcomes. Therefore, the ABI plus baPWV exhibits a better association with the outcomes of T2DM.
Assuntos
Índice Tornozelo-Braço , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/complicações , Doença Arterial Periférica/complicações , Análise de Onda de Pulso , Idoso , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologiaRESUMO
AIMS: To determine the relationships between cardiovascular autonomic neuropathy (CAN) and autonomic symptoms, clinical parameters and diabetic complications in type 2 diabetes (T2DM). METHODS: The results of autonomic symptoms, clinical parameters, diabetes complications and cardiovascular reflex (CVR) tests of 674 T2DM were analyzed. RESULTS: Significant correlations were found between CAN risk and age (p=0.019), duration of diabetes (p=0.008), HbA1c (p<0.001), systolic blood pressure (p=0.006), nephropathy (p<0.001), retinopathy (p<0.001), and QTc interval (p<0.001), but not BMI and hyperlipidemia. Patients with retinopathy or proteinuria had increase risk of CAN, and proliferative diabetic retinopathy (PDR) was the most significant risk factor (odds ratio: 6.85; 95% CI: 2.32-20.20) for CAN. Eighty-three percent of patients complained of autonomic symptoms; and the more symptoms complained, the higher the prevalence of CAN. Impotence was the only single symptom associated with CAN risk. Additional CAN risks were also observed when patients with multiple symptoms and/or complications in combinations. CONCLUSIONS: Our results implied that patients with multiple symptoms and/or complications in combinations have increased CAN risk, and this may provide additional information for clinicians to identify T2DM at risk of having CAN.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Sistema Nervoso Autônomo/patologia , Complicações do Diabetes , Diabetes Mellitus Tipo 2/epidemiologia , Neuropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
OBJECTIVE: Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease. PATIENTS: Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests. RESULTS: All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation. CONCLUSIONS: Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.
Assuntos
Hiperinsulinismo/diagnóstico , Hipoglicemia/diagnóstico , Nesidioblastose/diagnóstico , Adulto , Idoso , Amiloide/análise , Antígenos de Neoplasias/análise , Biomarcadores/análise , Biomarcadores Tumorais/análise , Peptídeo C/sangue , Proliferação de Células , Diazóxido/uso terapêutico , Jejum , Feminino , Proteínas de Homeodomínio/análise , Humanos , Hiperinsulinismo/metabolismo , Hiperinsulinismo/cirurgia , Hipoglicemia/metabolismo , Hipoglicemia/cirurgia , Imuno-Histoquímica/métodos , Insulina/sangue , Células Secretoras de Insulina/química , Células Secretoras de Insulina/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Lectinas Tipo C/análise , Masculino , Pessoa de Meia-Idade , Nesidioblastose/metabolismo , Nesidioblastose/cirurgia , Pancreatectomia , Proteínas Associadas a Pancreatite , Período Pós-Prandial , Proinsulina/análise , Proinsulina/sangue , Receptores de Detecção de Cálcio/metabolismo , Síndrome , Transativadores/análiseRESUMO
BACKGROUND: Adequate surgical treatment of hypoglycemia caused by benign diffuse islet cell disease (BDICD) is not associated with predictable results. Arterial stimulation and venous sampling (ASVS) has been reported to establish the diagnosis of BDICD, as well as serve as a guide to resection. The purpose of this study is to determine the efficacy of this method for the treatment of benign diffuse islet cell disease. METHODS: We retrospectively reviewed 38 adults with symptomatic hyperinsulinemic hypoglycemia treated by a single surgeon from 1982 to 1998. Nine of them had pathologic evidence of BDICD. We demonstrated the clinical presentations, serum level of fasting blood sugar, insulin and C-peptide before and after operations, pathological results, and outcomes of distal pancreatectomy in 5 patients and ASVS-guided pancreatectomies in 4 patients with BDICD. RESULTS: Five patients (4 females and 1 male) who received distal pancreatectomy (Group 1) were aged from 19 to 75, and were culled from a group of 30 patients with spontaneous hyperinsulinemic hypoglycemia. Two had the multiple endocrine neoplasia (MEN) 1 syndrome. The follow-up was from 7 to 16 years. Three patients (including 1 MEN 1 patient) became diabetic. Another 1 is euglycemic, and the other MEN 1 patient developed recurrent disease. Four patients (2 males and 2 females, Group 2), found in a group of 8 patients with hyperinsulinemic hypoglycemia, had ASVS-guided pancreatectomies. Their ages ranged from 29 to 69 years. The area of the pancreas supplied by the splenic artery was removed in all patients. Follow-up from half to 2 years showed that all the patients had normal fasting levels of glucose, normal levels of insulin and C-peptide, and no more hypoglycemic attacks. CONCLUSIONS: Arterial stimulation venous sampling is a useful guide for pancreatectomy to treat adult patients with BDICD. Data from this small sample of patients suggest that the results may be superior to those obtained by "blind" distal pancreatectomy.