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1.
BMC Endocr Disord ; 24(1): 102, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956584

RESUMO

BACKGROUND: Lipodystrophy is characterized by progressive loss of adipose tissue and consequential metabolic abnormalities. With new treatments emerging for lipodystrophy, there is a growing need to understand the prevalence of specific comorbidities that may be commonly associated with lipodystrophy to contextualize the natural history of lipodystrophy without any disease modifying therapy. OBJECTIVE: To examine the risk of specific clinical characteristics in people living with lipodystrophy (LD) in 2018-2019 compared with the general US population, among the commercially insured US population. METHODS: A retrospective cohort study was conducted using the 2018-2019 Clinformatics® Data Mart database. An adult LD cohort (age ≥ 18 years) with at least ≥ 1 inpatient or ≥ 2 outpatient LD diagnoses was created. The LD cohort included non-HIV-associated LD (non-HIV-LD) and HIV-associated LD (HIV-LD) subgroups and compared against age- and sex-matched control groups with a 1:4 ratio from the general population with neither an LD or an HIV diagnosis using odds ratios (ORs) with 95% confidence intervals. RESULTS: We identified 546 individuals with non-HIV-LD (mean age, 60.3 ± 14.9 years; female, 67.6%) and 334 individuals with HIV-LD (mean age, 59.2 ± 8.3 years; female, 15.0%) in 2018-2019. Compared with the general population, individuals with non-HIV-LD had higher risks (odds ratio [95% confidence interval]) for hyperlipidemia (3.32 [2.71-4.09]), hypertension (3.58 [2.89-4.44]), diabetes mellitus (4.72 [3.85-5.79]), kidney disease (2.78 [2.19-3.53]), liver fibrosis or cirrhosis (4.06 [1.66-9.95]), cancer (2.20 [1.59-3.01]), and serious infections resulting in hospitalization (3.00 [2.19-4.10]). Compared with individuals with HIV, those with HIV-LD have higher odds of hypertension (1.47 [1.13-1.92]), hyperlipidemia (2.46 [1.86-3.28]), and diabetes (1.37 [1.04-1.79]). CONCLUSIONS: LD imposes a substantial burden on affected individuals due to a high prevalence of metabolic comorbidities and other complications as compared with the general non-LD population. Future longitudinal follow-up studies investigating the causality between LD and observed comorbidities are warranted.


Assuntos
Lipodistrofia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevalência , Adulto , Estados Unidos/epidemiologia , Lipodistrofia/epidemiologia , Bases de Dados Factuais , Idoso , Comorbidade , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Adulto Jovem , Seguimentos
2.
Biomolecules ; 13(9)2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37759688

RESUMO

Clozapine is listed as one of the most effective antipsychotics and has been approved for treating treatment-resistant schizophrenia (TRS); however, several type A and B adverse reactions, including weight gain, metabolic complications, cardiotoxicity, convulsions, and discontinuation syndromes, exist. The critical mechanisms of clinical efficacy for schizophrenia, TRS, and adverse reactions of clozapine have not been elucidated. Recently, the GABA isomer L-ß-aminoisobutyric acid (L-BAIBA), a protective myokine in the peripheral organs, was identified as a candidate novel transmission modulator in the central nervous system (CNS). L-BAIBA activates adenosine monophosphate-activated protein kinase (AMPK) signalling in both the peripheral organs and CNS. Activated AMPK signalling in peripheral organs is an established major target for treating insulin-resistant diabetes, whereas activated AMPK signalling in the hypothalamus contributes to the pathophysiology of weight gain and metabolic disturbances. Clozapine increases L-BAIBA synthesis in the hypothalamus. In addition, the various functions of L-BAIBA in the CNS have recently been elucidated, including as an activator of GABA-B and group-III metabotropic glutamate (III-mGlu) receptors. Considering the expressions of GABA-B and III-mGlu receptors (localised in the presynaptic regions), the activation of GABA-B and III-mGlu receptors can explain the distinct therapeutic advantages of clozapine in schizophrenia or TRS associated with N-methyl-D-aspartate (NMDA) receptor disturbance compared with other atypical antipsychotics via the inhibition of the persistent tonic hyperactivation of thalamocortical glutamatergic transmission in the prefrontal cortex. L-BAIBA has also been identified as a gliotransmitter, and a detailed exploration of the function of L-BAIBA in tripartite synaptic transmission can further elucidate the pathophysiology of effectiveness for treating TRS and/or specific adverse reactions of clozapine.


Assuntos
Antipsicóticos , Clozapina , Receptores de Glutamato Metabotrópico , Clozapina/efeitos adversos , Proteínas Quinases Ativadas por AMP , Antipsicóticos/efeitos adversos , Resultado do Tratamento , Ácido gama-Aminobutírico
3.
Front Endocrinol (Lausanne) ; 13: 917402, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873001

RESUMO

Background: Obesity has been a growing problem in young patients leading to serious metabolic complications. There are many studies supporting the idea, that obesity should be considered as a chronic inflammation closely associated with immune system alterations. Th17 subpopulation is strongly involved in this process. The aim of our study was to evaluate circulating Th17 cells in overweight and obese children and explore the relationships between Th17 subset and metabolic parameters. Methods: We evaluated peripheral Th17 cells in fresh peripheral blood samples from 27 overweight and obese and 15 normal-weight children. Th17 cells were identified by flow cytometry using monoclonal antibody and intracellular IL-17A staining. Th17 cells were defined as CD3+CD4+CD196+IL-17Aic+. The analysis involved anthropometric and metabolic parameters measured at baseline and three months after the change of lifestyle and diet. We evaluated the relationship between metabolic parameters and Th17 cells. Results: In overweight and obese children we found significantly higher Th17 cells percentage compared to normal weight controls (median 0.097% (0.044 - 0.289) vs 0.041% (0.023 - 0.099), p = 0.048). The percentage of Th17 cells decreased statistically significantly in children who reduced weight after the intervention (0.210% (0.143 - 0.315) vs 0.039% (0.028 - 0.106), p = 0.004). In this group we also noticed statistically significant reduction of TC and LDL-C concentration (p = 0.01, p = 0.04, respectively). Conclusions: Obesity in children is associated with increased percentage of peripheral Th17 cells. Weight reduction leads to significant decrease of circulating Th17 cells and improvement of lipid parameters. This significant reduction of proinflammatory Th17 cells is a promising finding suggesting that obesity-induced inflammation in children could be relatively easily reversible.


Assuntos
Sobrepeso , Obesidade Infantil , Criança , Humanos , Inflamação , Interleucina-17 , Sobrepeso/complicações , Sobrepeso/metabolismo , Obesidade Infantil/complicações , Células Th17/metabolismo , Redução de Peso
4.
Cell Metab ; 34(3): 424-440.e7, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35150639

RESUMO

Coronavirus disease 2019 (COVID-19) represents a systemic disease that may cause severe metabolic complications in multiple tissues including liver, kidney, and cardiovascular system. However, the underlying mechanisms and optimal treatment remain elusive. Our study shows that impairment of ACE2 pathway is a key factor linking virus infection to its secondary metabolic sequelae. By using structure-based high-throughput virtual screening and connectivity map database, followed with experimental validations, we identify imatinib, methazolamide, and harpagoside as direct enzymatic activators of ACE2. Imatinib and methazolamide remarkably improve metabolic perturbations in vivo in an ACE2-dependent manner under the insulin-resistant state and SARS-CoV-2-infected state. Moreover, viral entry is directly inhibited by these three compounds due to allosteric inhibition of ACE2 binding to spike protein on SARS-CoV-2. Taken together, our study shows that enzymatic activation of ACE2 via imatinib, methazolamide, or harpagoside may be a conceptually new strategy to treat metabolic sequelae of COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Mesilato de Imatinib/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Metazolamida/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/complicações , COVID-19/metabolismo , COVID-19/virologia , Células Cultivadas , Chlorocebus aethiops , Regulação para Baixo/efeitos dos fármacos , Células HEK293 , Células Endoteliais da Veia Umbilical Humana , Humanos , Mesilato de Imatinib/farmacologia , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/virologia , Metazolamida/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Camundongos Transgênicos , SARS-CoV-2/fisiologia , Células Vero , Internalização do Vírus/efeitos dos fármacos
5.
Mayo Clin Proc Innov Qual Outcomes ; 5(3): 675-681, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34195559

RESUMO

Hypoglycemia and acute metabolic complications (AMCs; ketoacidosis, hyperosmolarity, and coma) are glycemic outcomes that have high cost and high morbidity; these outcomes must be taken into consideration when choosing initial second-line therapy after metformin. We conducted a retrospective cohort study analyzing national administrative data from adults with type 2 diabetes mellitus who started a second-line diabetes medication (sulfonylureas [SFUs], thiazolidinediones [TZDs], glucagon-like peptide 1 [GLP-1] agonists, dipeptidyl peptidase 4 [DPP-4] inhibitors, basal insulin, or sodium-glucose contransporter 2 [SGLT-2] inhibitors) between April 1, 2011 and September 30, 2015 (N=43,288) and compared rates of hypoglycemia and AMCs. Most patients (24,506 [56.6%]) were prescribed sulfonylurea as second-line treatment, followed by DPP-4 inhibitors (7953 [18.4%]), GLP-1 agonists (3854 [8.9%]), basal insulin (2542 [5.9%]), SGLT-2 inhibitors (2537 [5.9%), and TZDs (1896 [4.4%]). Baseline rates of hypoglycemia varied more than 5-fold across initial second-line antidiabetic medication classes, and rates of AMCs varied 7-fold. Compared with patients taking an SFU, lower adjusted rates of hypoglycemia were associated with taking a DPP-4 inhibitor (63% lower rate; incidence rate ratio [IRR], 0.37; 95% CI, 0.25 to 0.57), SGLT-2 inhibitor (54% lower; IRR, 0.46; 95% CI, 0.22 to 0.94), or TZD (79% lower; IRR, 0.21; 95% CI, 0.08 to 0.56) but not a glucagon-like peptide 1 agonist or basal insulin. For AMCs, only initiation of a DPP-4 inhibitor (43% lower rate; IRR, 0.57; 95% CI, 0.41 to 0.81) was associated with a lower adjusted rate compared with SFU. Use of SGLT-2 inhibitors was not associated with a substantially increased rate of acute metabolic complications compared with SFU. Special attention still needs to be paid to glycemic outcomes when choosing a second-line diabetes therapy following metformin.

6.
Nutrients ; 13(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199741

RESUMO

(1) Background: Recent evidence reported a reduced tolerance of macronutrient parenteral intakes in subjects in critically ill conditions. We designed a prospective cohort study to evaluate the effects of hyperglycemia (HG) related to parenteral nutrition (PN) on neurodevelopment (NDV) in survived preterm newborns. (2) Methods: Enrolled newborns with gestational age < 32 weeks or birth weight < 1500 g, were divided in two cohorts: (A) exposed to moderate or severe HG (glucose blood level > 180 mg/dL) in the first week of life; (B) not exposed to HG. We considered as the primary outcome the rate of preterm newborns survived without NDV delay at 24 months of life, evaluated with Bayley Scales of Infants Development III edition. (3) Results: We analyzed 108 (A 32 vs. B 76) at 24 months of life. Newborns in cohort A showed a higher rate of cognitive and motor delay (A 44% vs. B 22 %, p = 0.024; A 38% vs. B 8%, p < 0.001). When adjusting for background characteristics, HG remained a risk factor for motor delay. (4) Conclusions: High nutritional intakes through PN soon after birth increase the risk of HG. The consequences of this severe metabolic complication affect long-term NDV and survival in preterm newborns.


Assuntos
Hiperglicemia/etiologia , Nutrição Parenteral Total , Nutrição Parenteral , Adulto , Peso ao Nascer , Glicemia , Desenvolvimento Infantil , Estudos de Coortes , Idade Gestacional , Humanos , Hiperglicemia/mortalidade , Recém-Nascido , Doenças do Recém-Nascido , Modelos Logísticos , Idade Materna , Análise Multivariada , Transtornos do Neurodesenvolvimento/etiologia , Estudos Prospectivos
7.
Clin Nutr ESPEN ; 43: 448-455, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34024554

RESUMO

BACKGROUND: Chronic respiratory disease (CRD) is an airflow limitation that represents a wide array of serious diseases. The aim of this study is to examine the influence of vitamin C deficiency on metabolic health-related quality in individuals with and without chronic respiratory disease in the Gaza Strip. METHODS: A matched case-control study including 52 cases of CRD and 52 controls of healthy participants were matched by age, sex, body mass index (BMI) and waist circumferences (WC). The study was conducted at the Ministry of Health secondary health-care centers in Gaza strip, Palestine. The biochemical data included Protein Carbonyl (PC), high sensitivity C reactive protein (CRP), vitamin C, fasting blood glucose (FBG) and markers of the lipid profile. RESULTS: By the qualitative estimation of vitamin C consumption, there was a significantly lower consumption of foods that are rich in vitamin C by CRD patients than the matched controls. By comparing the results between both groups, CRD patients had significantly lower plasma concentrations of vitamins C than the control group (18.43 ± 11.93 µgm/ml vs. 24.06 ± 11.19 µgm/ml, P = 0.025), but significantly higher in PC (3.86 ± 4.21 µgm/ml vs. 2.11 ± 0.97 µgm/ml, P = 0.005), CRP (5.98 ± 8.84 mg/l vs. 1.87 ± 1.96 mg/l, P = 0.001), and FBG (102.46 ± 15.09 mg/dl vs. 95.92 ± 10.88 mg/dl, P = 0.017). The results revealed that CRD patients had significantly lower blood oxygen saturation than the control group (96.36 ± 3.81 vs. 98.51 ± 0.75, P < 0.001), whereas no significant differences were observed regarding the lipid profiles markers. CONCLUSION: CRD patients have lower levels of vitamin C in their plasma and their diet than do healthy matched people; they also have higher oxidative stress and inflammatory markers than healthy people, which are risk factors for predicting metabolic complications.


Assuntos
Deficiência de Ácido Ascórbico , Adulto , Ácido Ascórbico , Deficiência de Ácido Ascórbico/complicações , Deficiência de Ácido Ascórbico/epidemiologia , Proteína C-Reativa , Estudos de Casos e Controles , Humanos , Israel , Circunferência da Cintura
8.
Clin Nutr ESPEN ; 41: 275-280, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33487276

RESUMO

BACKGROUND & AIMS: Hyperglycemia is among the common complications of parenteral nutrition (PN) and is often associated with increased mortality despite being treatable. Studies of parenteral nutrition causing hyperglycemia are limited and even available studies lack methodological conduct. This study aimed to evaluate the prevalence, predictors and management of PN-associated hyperglycemia (PN-AH). METHODS: A retrospective study was conducted at a tertiary hospital. Patients ≥ 18 years old who received parenteral nutrition from 2015 to 2018 were conveniently selected. The demographic data, diagnosis, clinically relevant data, blood glucose readings and management of hyperglycemia were gathered from electronic medical records. RESULTS: Among 300 patients included in the study, 140 (46.7%) reported the PN-AH events. Multivariate logistic regression analysis showed female sex, Malay ethnicity, underlying type 2 diabetes mellitus, liver impairment, elevated pre-PN glucose level > 180 mg/dL and ICU admission were independently associated with hyperglycemia (p < 0.05 for all variables). Furthermore, factors such as ICU admission, underlying diabetes mellitus and hyperglycemia before starting PN, cause earlier development of PN-AH. More frequent monitoring of PN was observed in the ICU, guided by a protocol, as compared to the non-ICU setting. CONCLUSION: The prevalence of PN-AH is a significant complication to require medical attention. The predictors such as female gender, Malay ethnicity, underlying Diabetes Mellitus, liver impairment, hyperglycemia before starting PN, and ICU admission should be applied in clinical settings to improve the detection of PN-AH. A guideline outlining the risk factors, monitoring strategies and treatment plans should be developed to improve the detection and management of PN-AH.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Adolescente , Feminino , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Hiperglicemia/etiologia , Nutrição Parenteral/efeitos adversos , Prevalência , Estudos Retrospectivos
9.
JHEP Rep ; 2(6): 100192, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33163950

RESUMO

Non-alcoholic fatty liver disease (NAFLD), specifically its progressive form non-alcoholic steatohepatitis (NASH), represents the fastest growing indication for liver transplantation in Western countries. Diabetes mellitus, morbid obesity and cardiovascular disease are frequently present in patients with NAFLD who are candidates for liver transplantation. These factors require specific evaluation, including a detailed pre-surgical risk stratification, in order to improve outcomes after liver transplantation. Moreover, in the post-transplantation setting, the incidence of cardiovascular events and metabolic complications can be amplified by immunosuppressive therapy, which is a well-known driver of metabolic alterations. Indeed, patients with NASH are more prone to developing early post-transplant complications and, in the long-term, de novo malignancy and cardiovascular events, corresponding to higher mortality rates. Therefore, a tailored multidisciplinary approach is required for these patients, both before and after liver transplantation. Appropriate candidate selection, lifestyle modifications and specific assessment in the pre-transplant setting, as well as pharmacological strategies, adjustment of immunosuppression and a healthy lifestyle in the post-transplant setting, play a key role in correct management.

10.
J Diabetes Metab Disord ; 19(1): 319-325, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32550182

RESUMO

BACKGROUND: Acromegaly is a rare chronic disabling disorder, in which growth hormone (GH) excess is associated with a range of clinical features and systemic complications. The present study aims to evaluate the association between pretreatment basal GH levels as well as GH levels after oral glucose tolerance test (OGTT) and cardio-metabolic comorbidities, including diabetes mellitus (DM), left ventricular hypertrophy (LVH) and hypertension (HTN) in patients with active acromegaly. METHODS: A retrospective study of the medical records regarding 113 patients with acromegaly registered at two main centers of Iran Pituitary Tumor Registry during 2011-2018. RESULTS: The mean age of the patients was 42.76 ± 11.6 (range: 21-72) years. Mean GH level at baseline was 21 ng/ml while nadir GH levels at 60 and 120 min after glucose were 6.95 and 9.05 ng/ml, respectively. There was a negative correlation between age and basal serum GH level (r= -0.196, p = 0.038). Hypertension and diabetes mellitus were detected in 26.8% and 19.7% of the patients. A positive correlation was detected between serum GH values and systolic blood pressure. There was not any significant difference in basal GH and GH post OGTT regarding DM, Diastolic blood pressure and LVH. CONCLUSIONS: Our findings suggest that pretreatment basal GH levels are higher in younger patients with acromegaly. Furthermore, higher GH values (0, 60 and 120 min) during OGTT are associated with higher systolic blood pressure. A comprehensive evaluation of this population regarding comorbidities should be performed.

11.
Microorganisms ; 8(6)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521616

RESUMO

An unexpected increase in weight gain has recently been reported in the course of integrase strand transfer inhibitors (INSTI) treatment. The possibility of this effect in people who are perinatally infected with HIV (PHIV) and thus exposed to lifelong therapy needs to be explored. This is a retrospective multicenter case-control study. Adults with PHIV followed between 2010 and 2019 in two outpatient services in Northern Italy were included if they had at least two weight measures in two successive years of observation. Patients were considered as cases if they were switched to INSTI (INSTI group), or controls if they were never exposed to INSTI (non-INSTI group). The date of the switch in cases was considered to be the baseline (T0), while it was randomly selected in controls. Mixed effect models were used to assess the weight changes in INSTI and non-INSTI groups. A total of 66 participants, 50.0% women, 92.4% Caucasian, were included. Median follow-up was 9 years (range 2-10): 4 years (range 1-8) before and 3 (range 1-9) after-T0. Mean age at the last study visit was 27.3 (±4.8) years, and mean CD4+ T-cells were 820.8 (±323.6) cells/mm3. Forty-five patients were switched to INSTI during the study, while 21 remained in the non-INSTI group. The INSTI group experienced a mean increase (pre-post T0) in bodyweight of 0.28 kg/year (95% CI - 0.29; 0.85, p = 0.338), while in the non-INSTI group, the mean increase was 0.36 kg/year (95% CI - 0.47; 1.20, p = 0.391), without a significant difference between groups (p for interaction between time and treatment regimen = 0.868). Among patients on INSTI, the weight gain after T0 was higher than pre-T0, amounting to +0.28 kg/year (95% CI - 0.29; 0.85), although this difference did not reach significance (p = 0.337). PHIV switched to an INSTI-based regimen did not experience an excessive weight gain compared to those who were treated with a non-INSTI based regimen in our cohort.

12.
Int J Infect Dis ; 92: 71-77, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31884172

RESUMO

OBJECTIVE: To evaluate the evolution of weight and lipid profiles before and after switch to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) among virally suppressed HIV-positive patients. METHODS: Patients switching to E/C/F/TAF between March and July 2018 were included. Weight, lipid profile (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), and glycated hemoglobin (HbA1c) levels at 48 weeks before and after the switch were analyzed using generalized estimating equations in order to identify the associated factors. RESULTS: A total of 693 patients were included, and a weight gain was noted after the switch at weeks 12 (mean +0.63 kg), 24 (+1.25), 36 (+1.58), and 48 (+1.75) (all p < 0.0001). The weight change after the switch was significantly greater than that observed within the preceding 48-week period before the switch (+1.75 kg vs +0.54, p < 0.0001) and was correlated with switch to E/C/F/TAF (coefficient 0.29), later clinic visit (0.15), baseline weight (0.99), diabetes mellitus (coefficient -0.96), and age (-0.02) (all p < 0.01). At week 48, significant increases were observed for TG (mean +62.93 mg/dl), TC (+22.30), LDL-C (+9.70), HDL-C (+3.65) (all p < 0.01), and HbA1c (+0.08%) (p < 0.05), but not TC/HDL-C ratio (+0.12, p = 0.38). CONCLUSIONS: Virally suppressed HIV-positive patients gained a moderate amount of weight and had significant increases in lipid levels after switching to E/C/F/TAF.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Dislipidemias/etiologia , Soropositividade para HIV/complicações , Aumento de Peso , Adenina/efeitos adversos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Alanina , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Cobicistat/efeitos adversos , Cobicistat/uso terapêutico , Emtricitabina/efeitos adversos , Emtricitabina/uso terapêutico , Feminino , Soropositividade para HIV/sangue , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/virologia , Humanos , Lipídeos , Masculino , Pessoa de Meia-Idade , Quinolonas/efeitos adversos , Quinolonas/uso terapêutico , Estudos Retrospectivos , Tenofovir/análogos & derivados
13.
Zhonghua Nan Ke Xue ; 24(3): 277-281, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30161317

RESUMO

Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Glicemia/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Colesterol/sangue , Humanos , Masculino , Neoplasias da Próstata/sangue
14.
J Vet Emerg Crit Care (San Antonio) ; 28(3): 274-278, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29687945

RESUMO

OBJECTIVE: To report a case of severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog. CASE SUMMARY: A female neutered Rat Terrier was presented for an acute onset of seizure-like episodes, weakness, and vomiting approximately 14 hours after ingestion of 198 mg/kg of metformin. The dog was found to be laterally recumbent, paddling, and unresponsive shortly before presentation. On physical exam, the dog was in hypovolemic shock and hypothermic. Blood work revealed severe lactic acidosis and hypoglycemia. The dog was volume resuscitated with intravenous crystalloids and dextrose, followed by a continuous infusion of intravenous fluids and dextrose, as well as administration of isotonic sodium bicarbonate. Repeat blood work showed minimal improvement of the hyperlactatemia for 3 hours despite resolution of hypovolemia and hypoglycemia followed by gradual improvement over the next 9 hours of hospitalization. High performance liquid chromatography/tandem mass spectrometry analysis showed markedly increased plasma metformin concentrations at 3.9 µg/mL. The dog was discharged from the hospital within 24 hours and showed no recurrence of clinical signs one year following discharge. NEW OR UNIQUE INFORMATION PROVIDED: Metformin-associated lactic acidosis and hypoglycemia is a severe complication in human patients, but has not been reported in veterinary medicine. Aggressive treatment with supportive care including IV fluids and dextrose administration resulted in resolution of the clinical signs in this patient. Metformin toxicosis should be considered in dogs with severe hyperlactatemia and hypoglycemia of unknown etiology.


Assuntos
Acidose Láctica/veterinária , Doenças do Cão/tratamento farmacológico , Glucose/uso terapêutico , Hipoglicemia/veterinária , Hipoglicemiantes/toxicidade , Metformina/toxicidade , Acidose Láctica/induzido quimicamente , Acidose Láctica/tratamento farmacológico , Animais , Cães , Feminino , Glucose/administração & dosagem , Hipoglicemia/induzido quimicamente , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/sangue , Infusões Intravenosas/veterinária , Metformina/sangue , Intoxicação/tratamento farmacológico , Intoxicação/veterinária
15.
National Journal of Andrology ; (12): 277-281, 2018.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-689763

RESUMO

Androgen deprivation therapy (ADT) is one of the dominant treatment options for advanced prostate cancer, which has been certified to significantly improve the overall survival of prostate cancer patients. However, it sometimes can also produce severe adverse effects on body metabolism. This review summarizes the adverse effects of ADT on body composition, the levels of cholesterol and blood glucose, and the cardiovascular system, and the intervention management of these metabolic complications as well.


Assuntos
Humanos , Masculino , Antagonistas de Androgênios , Glicemia , Composição Corporal , Sistema Cardiovascular , Colesterol , Sangue , Neoplasias da Próstata , Sangue , Tratamento Farmacológico
16.
J Korean Med Sci ; 32(8): 1268-1274, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28665062

RESUMO

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.


Assuntos
Infecções por HIV/diagnóstico , Síndrome Metabólica/diagnóstico , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirretrovirais/uso terapêutico , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Dislipidemias/diagnóstico , Dislipidemias/etiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hospitais , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Prevalência , Inibidores de Proteases/uso terapêutico , República da Coreia/epidemiologia , Fatores de Risco , Adulto Jovem
17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-210876

RESUMO

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.


Assuntos
Humanos , Masculino , Ásia , Pressão Sanguínea , Índice de Massa Corporal , Colesterol , Estudos de Coortes , Estudos Transversais , Diagnóstico , Dislipidemias , Jejum , Glucose , Infecções por HIV , HIV , Incidência , Coreia (Geográfico) , Lipoproteínas , Metaboloma , Análise Multivariada , Obesidade Abdominal , Prevalência , Inibidores de Proteases , Fatores de Risco , Triglicerídeos
18.
J Clin Diagn Res ; 10(10): OC06-OC10, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27891368

RESUMO

INTRODUCTION: Gestational diabetes is defined as various degrees of glucose intolerance diagnosed or detected for the first time during pregnancy and is the most common metabolic complication of pregnancy. Early diagnosis and adequate treatment are important to prevent complications. Pre-eclampsia, polyhydramnios, fetalmacrosomia, and operative delivery are some of the complications seen in pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). AIM: The present study was designed to determine whether there was an association between Mean Platelet Volume (MPV) in predicting poor fetal outcome, insulin resistance, neonatal Apgar scores and gestational age for women with GDM. MATERIALS AND METHODS: In this retrospective study, we enrolled 101 pregnant women with GDM together with a group of 138 healthy controls. MPV, insulin and homeostatic model assessment (HOMA-IR) values were measured at 24-28 weeks of the pregnancy. An independent samples t-test was used to compare MPV values. Multivariate linear regression models were used to establish relations between MPV values, HOMA-IR, insulin levels and Apgar score. RESULTS: There was a significant positive correlation between MPV values, HOMA-IR and Insulin levels and a negative correlation with Apgar score at 1 min and 5 min in the GDM group (r=0.227, p=0.02; r=0.206, p=0.03; r=-0.485, p<0.001; and r=-0.399, p<0.001, respectively). In the multivariate logistic regression analysis, a high MPV value was most consistently associated with a low Apgar 1 min score (ß=-0.387, p=0.003) in the GDM group. An MPV of >8.0 fL had a sensitivity of 82% and a specificity of 75% for the prediction of GDM. CONCLUSION: We investigated the potential of MPV values in predicting low Apgar scores and insulin resistance in women with GDM.

19.
Appl Physiol Nutr Metab ; 41(6): 640-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27218680

RESUMO

Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders.


Assuntos
Dieta Hiperlipídica , Proteína Amiloide A Sérica/metabolismo , Reação de Fase Aguda , Amiloidose/sangue , Amiloidose/complicações , Animais , Artrite/sangue , Artrite/complicações , Glicemia/metabolismo , Doença de Crohn/sangue , Doença de Crohn/complicações , Modelos Animais de Doenças , Feminino , Insulina/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Camundongos Transgênicos , Obesidade/sangue , Obesidade/complicações , Proteína Amiloide A Sérica/genética , Fator de Necrose Tumoral alfa/sangue , Regulação para Cima
20.
Intern Med J ; 46(2): 141-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25732203

RESUMO

Androgen deprivation therapy (ADT) is a standard systemic treatment for men with prostate cancer. Men on ADT may be elderly and have comorbidities that are exacerbated by ADT, such as cardiovascular disease, diabetes, obesity, sedentary lifestyle and osteoporosis. Studies on managing the impacts of ADT have focused on men with non-metastatic disease, where ADT is given for a limited duration. However, some men with advanced or metastatic prostate cancer will achieve long-term survival with palliative ADT and therefore also risk morbidity from prolonged ADT. Furthermore, ADT is continued during the use of other survival-prolonging therapies for men with advanced disease, and there is a general trend to use ADT earlier in the disease course. As survival improves, management of the metabolic effects of ADT becomes important for maintaining both quality and quantity of life. This review will outline the current data, offer perspectives for management of ADT complications in men with advanced prostate cancer and discuss avenues for further research.


Assuntos
Androgênios/deficiência , Antineoplásicos Hormonais/uso terapêutico , Gerenciamento Clínico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Antineoplásicos Hormonais/farmacologia , Humanos , Masculino , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo
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