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1.
J Biochem Mol Toxicol ; 37(11): e23463, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37566541

RESUMO

Eupafolin is a phyto compound of flavone that exerts anti-inflammatory, antioxidant, and antiproliferative properties. The main purpose of this study is to examine the antidiabetic effect of eupafolin on nicotinamide-streptozotocin (STZ)-induced Type 2 diabetes (T2D) rats. After nicotinamide (120 mg/kg) treatment, STZ (60 mg/kg) was administrated intravenously to induce T2D. Rats with fasting blood glucose (FBG) > 200 mg/dL are chosen for the study 7 days after T2D induction. The eupafolin treatment was continued for another 15 days. FBG and an oral glucose tolerance test (OGTT) were measured on the 21st day after T2D induction. The blood lipid, serum insulin, and homeostatic model assessment (HOMA-IR) were determined. In liver homogenate, oxidative stress indicators were measured. In addition, the effect of eupafolin on the expression of the proteins InsR, insulin receptor substrate (IRS)-2, GLUT4, PPARγ, and phosphatidylinositol 3-kinase (PI3K)/Akt was investigated using a western blot. As measured by OGTT and HOMA-IR, eupafolin treatment reduced FBG and insulin resistance (IR). Furthermore, when compared to diabetic rats, liver antioxidant enzymes were dramatically normalized. The level of glycogen in the liver of diabetic rats was increased by eupafolin treatment. In T2D rats, eupafolin dramatically increased the InsR, IRS-2, GLUT4, and PPARγ. Further, the eupafolin treatment activated the PI3K/Akt signaling in T2D rats. These findings imply that the antidiabetic mechanism of eupafolin may be related to the activation of the PPARγ and the PI3K/Akt signaling pathway in T2D rats. As a result, the flavonoid eupafolin could be an antidiabetic medication for T2D after a comprehensive clinical investigation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Flavonas , Resistência à Insulina , Ratos , Animais , Hipoglicemiantes/química , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , PPAR gama/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Antioxidantes/farmacologia , Transdução de Sinais , Flavonas/farmacologia , Niacinamida/farmacologia , Glicemia/metabolismo , Insulina
2.
Ren Fail ; 45(1): 2221130, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37403637

RESUMO

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.


Assuntos
Anemia , Falência Renal Crônica , Humanos , Masculino , Feminino , Fator de Crescimento Insulin-Like I , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Estudos Transversais , Diálise Renal/efeitos adversos , Anemia/tratamento farmacológico , Hemoglobinas
3.
Br J Clin Pharmacol ; 88(6): 2718-2726, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34907592

RESUMO

AIM: To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow-up study and to investigate its potential mechanisms. METHODS: A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population-based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin-like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time-varying effect of incident PPI use on T2DM during follow-up. RESULTS: Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment-insulin resistance (0.100, 95% CI 0.056, 0.145) and C-reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (-0.009 mmol/L, 95% CI -0.014, -0.004) and IGF-1 (-0.805 nmoL/L, 95% CI -1.015, -0.595). After adjustment for risk factors such as physical activity and body mass index/waist-to-hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36-2.10). The effect was dose-dependent with the highest risk (HR 1.88, 95% CI 1.29-2.75) in those on more than one defined daily dose. CONCLUSION: New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.


Assuntos
Diabetes Mellitus Tipo 2 , Estudos de Coortes , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Seguimentos , Humanos , Magnésio , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Risco
4.
Gynecol Endocrinol ; 38(6): 503-507, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35536048

RESUMO

Gestational diabetes mellitus is a frequently diagnosed glucose metabolic disorder during pregnancy. Diabetes mellitus has been found to pose important health risks to the developing fetus, mother, and offspring. Here, we investigated the protective effects of S14G-humanin, a potent humanin analogue, against maternal and neonatal adverse outcomes in mice with diabetes mellitus. The results show that S14G-humanin administration reduced the blood glucose levels and elevated the serum insulin levels in diabetes mellitus mice. The parameters of serum lipid metabolism including low-density lipoprotein, total cholesterol, and high-density lipoprotein in diabetes mellitus mice were also decreased after S14G-humanin administration. Intervention with S14G-humanin also increased the fetus alive ratio and fetal length, as well as decreased fetal and placenta weights. In addition, we demonstrate that S14G-humanin elevated the activity of the anti-oxidative enzymes catalase, glutathione peroxidase, and superoxide dismutase and reduced the inflammatory cytokines levels in the placentas of diabetes mellitus mice. The significantly increased endoplasmic reticulum stress in the placentas of diabetes mellitus mice was also attenuated by S14G-humanin administration. Taken together, S14G-humanin exerted protective roles in improving maternal and neonatal outcomes. Our findings indicate that S14G-humanin might be an effective intervention approach for women with diabetes mellitus.


Assuntos
Diabetes Gestacional , Animais , Citocinas , Diabetes Gestacional/tratamento farmacológico , Feminino , Humanos , Camundongos , Peptídeos , Placenta , Gravidez
5.
Phytother Res ; 35(9): 5053-5067, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33893683

RESUMO

The aim of this study was to perform a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the effect of grapes/grape products supplementation on glycemic indices in adults. Our systematic search to find relevant RCTs was performed up to February 2020 using PubMed, Scopus, ISI Web of Science, Cochrane Library, and Google Scholar. Based on the heterogeneity between included studies, a random effects or a fixed model was applied in the meta-analysis, and results were expressed as weighted mean differences (WMD) with 95% confidence intervals (CI). Twenty-nine clinical trials (1,297 participants) fulfilled the eligibility criteria of the present meta-analysis. Overall, the grapes/grape products supplementation significantly reduced homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.54, 95% CI: -0.91, -0.17, p = . 004) but did not affect fasting insulin levels (WMD: -0.90 µIU/ml, 95% CI: -1.04, 2.84, p = .362) and hemoglobin A1C (Hb1Ac) percentage (WMD: 0.00%, 95% CI: -0.10, 0.11, p = . 916) in the main analyses. In addition, changes to fasting blood glucose (FBG) levels were in favor of the control group (WMD: 1.19 mg/dl, 95% CI: 0.05, 2.34, p = .041). We found that giving grapes/grape products to adults might have beneficial effects on the HOMA-IR. Further, large-scale RCTs with longer duration are required to confirm these results.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Preparações de Plantas/uso terapêutico , Vitis , Adulto , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Humanos , Insulina , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitis/química
6.
Int J Food Sci Nutr ; 66(8): 950-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26600067

RESUMO

BACKGROUND: In this study, we aimed to investigate the association of dietary phytochemical index (DPI) with insulin resistance, ß-cell dysfunction, and insulin sensitivity. METHODS: This longitudinal study was conducted on 1141 participants of the Tehran Lipid and Glucose Study. Dietary data were collected using a validated semi-quantitative FFQ with 168 food items at baseline and DPI was calculated. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up. RESULTS: After 3-years of follow-up, the risk of hyperinsulinemia significantly decreased by 65 (OR = 0.35, 95% CI = 0.21-0.60) and 86% (OR = 0.14, 0.07-0.29), in the third and fourth quartile categories of DPI, respectively. The occurrence of insulin resistance and insulin insensitivity in participants with higher DPI was significantly lower than the others (OR = 0.48, 95% CI = 0.25-0.93 and OR = 0.11, 95% CI = 0.05-0.24, respectively). CONCLUSION: Higher consumption of phytochemical-rich foods may have protective effects against development of insulin resistance.


Assuntos
Dieta , Resistência à Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Compostos Fitoquímicos/administração & dosagem , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Ingestão de Energia , Feminino , Seguimentos , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/dietoterapia , Insulina/sangue , Células Secretoras de Insulina/patologia , Irã (Geográfico) , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários
7.
West Indian Med J ; 65(1): 13-17, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-26716795

RESUMO

OBJECTIVE: This study evaluated the ability of 0.8% neem leaf extract (NLE) to treat diabetes mellitus by assessing its effects on blood glucose, insulin levels and islet morphology in streptozotocin (STZ)-induced diabetic Sprague-Dawley rats. METHODS: Diabetes was induced in two to three-day old rat pups by STZ intraperitoneally (60 mg/kg), followed by a further 40 mg/kg dose 12-23 weeks later. The diabetic treated (DT) rats received 0.8% w/v NLE in tap water while diabetic control (DC) and normal control (NC) rats received water ad libitum. Body weight, water and chow consumption, and blood glucose were evaluated weekly. Blood and pancreas were collected at the end of the study to evaluate serum insulin and islet histology, respectively. RESULTS: Neem leaf extract (0.8%) improved weight gain and beta cell regeneration but did not reduce blood glucose. Serum insulin increased slightly in the treated group and three-fold in the DC group (p < 0.05). CONCLUSION: The results suggest that NLE has beta cell regenerating potential.

8.
Pharm Biol ; 53(12): 1803-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25885938

RESUMO

CONTEXT: Salvianolic acids are the most abundant water-soluble compounds extracted from the herb Salvia miltiorrhiza L. (Lamiaceae) with antioxidant and protective effects. OBJECTIVE: This study evaluates the antidiabetic effect of salvianolic acid B (Sal B) in multiple low-dose streptozotocin (MLDS)-induced diabetes in rat. MATERIALS AND METHODS: Rats were divided into control, Sal B40-treated control, diabetic, Sal B20-, and Sal B40-treated diabetic groups. Sal B was daily administered at doses of 20 or 40 mg/kg (i.p.), started on third day post-STZ injection for 3 weeks. Serum glucose and insulin level and some oxidative stress markers in pancreas were measured in addition to the oral glucose tolerance test (OGTT), histological assessment, and apoptosis determination. RESULTS: After 3 weeks, treatment of diabetic rats with Sal B20 and Sal B40 caused a significant decrease of the serum glucose (p < 0.05-0.01) and improvement of OGTT. Meanwhile, serum insulin was significantly higher in Sal B20- and Sal B40-treated diabetics (p < 0.01) and treatment of diabetics with Sal B40 significantly lowered malondialdehyde (MDA) (p < 0.05), raised glutathione (GSH) (p < 0.05), and activity of catalase (p < 0.01) with no significant change of nitrite. Furthermore, the number of pancreatic islets (p < 0.05) and their area (p < 0.01) was significantly higher and apoptosis reactivity was significantly lower (p < 0.05) in the Sal B40-treated diabetic group versus diabetics. DISCUSSION AND CONCLUSION: Three-week treatment of diabetic rats with Sal B exhibited antidiabetic activity which is partly exerted via attenuation of oxidative stress and apoptosis and augmentation of antioxidant system.


Assuntos
Benzofuranos/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Animais , Benzofuranos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Hipoglicemiantes/farmacologia , Masculino , Ratos , Ratos Wistar
9.
J Stroke Cerebrovasc Dis ; 23(3): e163-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24139410

RESUMO

BACKGROUND: Although elevated serum C-peptide level as an indicator of insulin resistance increases the obesity-associated risk of cardiovascular disease among diabetic patients, evidence indicating that serum C-peptide level is associated with stroke in nondiabetic subjects is limited. The aim of this study is to evaluate the association between serum C-peptide level and ever stroke in nondiabetic subjects and investigated the associations of serum C-peptide level with body fat distribution and stroke events among nondiabetic subjects. METHODS: This study was a population-based cross-sectional study that included 7030 participants aged 12-85 years. Body fat distribution was determined by dual-energy X-ray absorptiometry. Serum C-peptide level was measured using the radioimmunoassay method. The association between serum C-peptide level and body fat distribution was evaluated by multiple linear regression models. Logistic regression analysis was performed to calculate the odds ratio (OR) of serum C-peptide level being associated with ever stroke. RESULTS: A total of 103 nondiabetic subjects reported having a stroke. Logistic regression analysis revealed a high-serum C-peptide level significantly associated with ever stroke among nondiabetic subjects (OR: 3.71, 95% confidence interval: 1.78-7.75). Meanwhile, in multiple linear regression analysis, serum C-peptide level was positively associated with total and regional fat distribution among nondiabetic subjects. CONCLUSION: The serum C-peptide level is strongly associated with the ever stroke in nondiabetic subjects and significantly associated with total and regional body fat distribution.


Assuntos
Adiposidade , Peptídeo C/sangue , Obesidade/complicações , Acidente Vascular Cerebral/etiologia , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/análise , Criança , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Razão de Chances , Radioimunoensaio , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Estados Unidos , Regulação para Cima , Adulto Jovem
10.
JTCVS Open ; 17: 172-182, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38420553

RESUMO

Objective: This study aimed to determine the maximum safe dose of intranasal insulin administration during cardiac surgery. Methods: This open-label, Phase 1, single-center, dose-escalation clinical trial recruited patients scheduled to undergo elective cardiac surgery or major vascular surgery requiring cardiopulmonary bypass between February and September 2021. They were grouped into 5 dose-escalation cohorts and administered 0, 40, 80, 160, and 240 IU insulin (n = 6 in each group) via a metered nasal dispenser after the induction of general anesthesia. Blood samples were collected at 10-minute intervals for the first 60 minutes and at 30-minute intervals thereafter. Hypoglycemia was defined as a blood glucose level <70 mg/dL. Patient recruitment was terminated after hypoglycemia was observed in 2 patients in any of the groups. Results: In total, 27 of 29 enrolled patients were administered intranasal insulin or saline. Hypoglycemia was not observed after the administration of intranasal insulin in the 0, 40, 80, or 160 IU groups; however, it was observed in 2 of 3 patients in the 240 IU group. The serum insulin concentration was elevated in the 160-IU group, but the C-peptide concentration was not elevated in any of the groups. Conclusions: The administration of up to 160 IU intranasal insulin did not induce clinically significant hypoglycemia. However, 160 IU intranasal insulin should be administered cautiously because insulin can enter the systemic circulation in a dose-dependent manner.

11.
Cureus ; 16(4): e58270, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38623323

RESUMO

Insulin autoimmune syndrome (IAS) or Hirata disease is a rare condition presenting as recurrent hypoglycemia, and associated with elevated insulin levels in the presence of insulin autoantibodies (IAAs) in patients who were never exposed to exogenous insulin and with no evidence of pancreatic abnormalities. IAS is much more frequent in East Asians, especially the Japanese population, compared to the lower incidence in Caucasians. However, it can be associated with other autoimmune diseases or drug use like methimazole and alpha-lipoic acid (ALA). We report a case of a 47-year-old Caucasian male presenting with a 12-month history of worsening episodes of fasting and post-prandial hypoglycemia associated with symptoms of dizziness, tremors, palpitations, and unconsciousness associated with hypoglycemia. Symptoms resolved with the administration of carbohydrate-containing foods, establishing Whipple's triad. At an outside facility, he had initial labs that showed elevated insulin levels (141 µU/ml) with normal glucose, C-peptide, and proinsulin levels, but there was no availability of an IAA lab assay. Given his symptoms, severity, and frequency of hypoglycemia, he was admitted to the hospital for a 72-hour fast, which showed the lowest glucose level of 64 mg/dl with inappropriately high insulin of 22.2 µU/ml, low C-peptide of 0.57 ng/ml, and undetectable proinsulin of <1.6 pmol/L, but with IAA being >50 U/ml (0.0-0.4 U/ml). He was treated with intensive dietary counseling with a low-carbohydrate diet and prednisone 20 mg twice daily initially. Additionally, he could not tolerate octreotide, diazoxide, and acarbose due to side effects. He is currently on prednisone 10 mg daily and nifedipine with no further hypoglycemic episodes, but still has a high IAA of >50 U/ml and serum insulin levels of 70-112 µU/ml. Our case highlights the importance of recognizing hypoglycemia and checking for IAA levels as first-line diagnostic tests, in the absence of which there could be a delay in diagnosis and leading to unnecessary lab and imaging testing. Our case is unique since it happened in a Caucasian without any prior exposure to a triggering factor and has not undergone self-remission yet, which happens in most of IAS cases.

12.
Diabetes Res Clin Pract ; 207: 111057, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38104901

RESUMO

BACKGROUND: Handgrip strength (HGS) is a surrogate marker of whole body strength that has been observed to correlate inversely with the metabolic syndrome (MetS). In this study, we examined whether HGS in young, healthy individuals, was associated with surrogate endpoints of the MetS. A secondary goal was to examine whether absolute HGS (absHGS) or relative HGS (relHGS) was a stronger predictor of MetS. METHOD: 834 subjects (577 women), aged 18-26, were recruited. Surrogate endpoints for MetS were waist circumference, HDL, fasting glucose, fasting insulin, triglycerides, and systolic and diastolic blood pressure (BP). We also examined the association between HGS and body fat percentage, HOMA-IR, CRP, orosomucoid and apolipoprotein A-1 and apolipoprotein B. The associations were examined using multivariable linear regression. RESULTS: AbsHGS and relHGS were each associated with several surrogate endpoints of the metabolic syndrome, with RelHGS being statistically significantly associated with a greater number of the variables - all except fasting glucose and diastolic BP. CONCLUSION: RelHGS correlates with components of the MetS even in young, healthy populations. It is a better predictor of MetS components than absHGS. As a cheap and easy to use biomarker, relHGS holds merit as a screening tool for metabolic dysfunction even in preclinical contexts.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Adulto , Humanos , Feminino , Síndrome Metabólica/complicações , Força da Mão , Triglicerídeos , Biomarcadores , Glucose , Tecido Adiposo/metabolismo , Glicemia/metabolismo
13.
Technol Health Care ; 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37599547

RESUMO

BACKGROUND: Mild cognitive impairment (MCI) is a mild memory or cognitive impairment. OBJECTIVE: To explore the relationship between serum klotho (K1) protein and insulin-like growth factor-1 and mild cognitive impairment in the elderly in order to provide accurate and appropriate indicators for clinical diagnosis and treatment of MCI. METHODS: This randomized stratified study adopted a multistage cluster sampling method. 161 elderly patients with mild cognitive impairment were included as the MCI group, and 161 healthy people matched with the MCI group in gender, age and education were selected as the control group. RESULTS: The levels of serum K1 protein and insulin-like growth factor-1 in the MCI group were lower than those in the control group (P< 0.05). Both IGF-1 and K1 had predictive value for MCI (P< 0.05). The area under the curve (AUC) of IGF-1 for predicting MCI was 0.859 (95% CI: 0.790∼0.929), and the AUC of K1 for predicting MCI was 0.793 (95% CI: 0.694∼0.892). The value of joint prediction of the two indicators was the highest, with an AUC of 0.939 (95% CI: 0.896-0.993). CONCLUSION: High serum K1 and insulin-like growth factor-1 are the protective factors of cognitive impairment in MCI patients. Both IGF-1 and serum K1 proteins have predictive value for MCI, and the combination of the two indicators has the highest predictive value.

14.
Clin Pharmacol Drug Dev ; 12(11): 1089-1098, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37300344

RESUMO

To investigate the bioequivalence of miglitol orally disintegrating tablets in healthy Chinese volunteers based on pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Additionally, the safety profile was estimated. Two randomized, open-label, single-dose, crossover trials were conducted under fasting conditions. In the PD trial (CTR20191811), 45 healthy volunteers were randomly divided into 3 groups in a 1:1:1 ratio and administered sucrose alone or coadministered with 50 mg of miglitol orally disintegrating tablet test or reference formulation/sucrose. In the PK trial (CTR20191696), 24 healthy volunteers were randomized (1:1) to receive the test or reference formulation (50 mg). Blood samples were collected at 15 and 17 sampling points per cycle in the PD and PK trials, respectively. Plasma miglitol and serum glucose concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry method. Serum insulin concentrations were measured using electrochemiluminescent immunoassay. Statistical analyses for the PD and PK parameters were subsequently performed. The volunteers' physical indicators were monitored and documented during the entire study to estimate drug safety. The PD and PK parameters of the two formulations were similar. The main PD and PK end points were both within the prespecified range of 80%-125%. The incidences of treatment-emergent adverse events (TEAEs) and drug-related TEAEs were similar between the test and reference formulation groups, and no serious TEAEs or deaths occurred during the 2 trials. These 2 formulations were demonstrated to be bioequivalent and well tolerated in healthy Chinese volunteers under fasting condition.


Assuntos
1-Desoxinojirimicina , Humanos , Área Sob a Curva , População do Leste Asiático , Jejum , Voluntários Saudáveis , Sacarose , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/farmacocinética
15.
Front Vet Sci ; 10: 1018230, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051514

RESUMO

Introduction: Accurate quantitative analysis of equine insulin in blood samples is critical for assessing hyperinsulinemia in horses. Although there are various laboratory methods for evaluating equine serum insulin, different immunoassays show significant discrepancies between the determined insulin concentrations and are often not comparable. The aim of this study was to evaluate the Immulite® 1000 chemiluminescent immunoassay (CLIA) to establish independent laboratory and assay-specific cut values to provide an accurate diagnosis of hyperinsulinemia in horses. Thus, the analytical and clinical performance of Immulite® 1000 CLIA in terms of precision (intra- and inter-assay coefficient of variance, CV) and recovery upon dilution were evaluated and compared with radioimmunoassay (RIA), which has been previously validated for use in horses. Material and methods: Archived serum samples (n = 106) from six Quarter horse mares enrolled in the glucose phase of a Frequently Sampled Insulin and Glucose Test (FSIGT) study were used to measure blood insulin. Results: The Immulite® 1000 CLIA had good precision with acceptable intra- and inter-assay CVs, adequate recovery on dilution, and a strong correlation with the RIA (r = 0.974, P < 0.0001), with constant bias resulting in consistently lower values. Discussion: On this basis, the Immulite® 1000 Insulin Assay is valid for measuring equine serum insulin for diagnostic and monitoring purposes when cut values are appropriately adjusted.

16.
Cureus ; 15(11): e48514, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38074057

RESUMO

Insulinomas are a rare cause of recurrent hypoglycemia in non-diabetic patients. Diagnosis requires hypoglycemia (plasma glucose <50 mg/dL), neuroglycopenic symptoms, and prompt relief of symptoms following the administration of glucose, known as Whipple's triad. The gold standard diagnostic tests are measuring insulin, C-peptide, and glucose during a 72-hour fast. In the preoperative period and in patients with unresectable or metastatic tumors, medical management with diazoxide and octreotide can be considered for recurrent hypoglycemia. We present a case of insulinoma in a 37-year-old woman who initially presented after a seizure-related motor vehicle accident. Upon admission, her initial glucose level was 32 mg/dL, indicating a likely hypoglycemic seizure. During her hospitalization, she had recurrent episodes of fasting and postprandial hypoglycemia, ranging from 32-70 mg/dL. She exhibited the characteristics of Whipple's triad when values dropped below 50 mg/dL. These episodes necessitated continuous infusions of 10% dextrose. Tests for insulin autoantibodies, sulfonylurea screens, and thyroid function yielded unremarkable results. A 72-hour fasting test was initiated to investigate potential endogenous causes of excessive insulin production. Laboratory results from a venous glucose level of 46 mg/dL indicated a notable rise in C peptide and insulin levels, alongside beta hydroxybutyrate suppression, all of which fulfilled the diagnostic criteria for insulinoma. An abdominal magnetic resonance imaging (MRI) unveiled a 1.3 cm mass in the pancreatic tail. This case emphasizes the importance of employing a focused approach when evaluating non-diabetic individuals displaying hypoglycemia with positive Whipple's triad. This targeted method not only enables early detection of this rare condition but also assists in eliminating other common causes of recurrent hypoglycemia in non-diabetic individuals. Moreover, in addition to this diagnosis being rare, it is important to note that patients with insulinomas typically do not exhibit a glucose level low enough to induce seizures during their initial presentation.

17.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(9): 1509-1514, 2023 Sep 20.
Artigo em Zh | MEDLINE | ID: mdl-37814865

RESUMO

OBJECTIVE: To investigate the value of C-peptide-based insulin resistance index in evaluating the correlation between insulin resistance and serum uric acid (Ua) level in subjects undergoing health examination. METHODS: The data of 46 017 subjects undergoing health examination were retrospectively collected from the Second Medical Center of PLA General Hospital from January, 2017 to December, 2021. The subjects were divided into Ua≤420 µmol/L group and Ua>420 µmol/L group for comparison of HOMA insulin resistance index (HOMA2-IR) and HOMA insulin resistance-C peptide (HOMA2 IR-CP). The correlations of HOMA2-IR and HOMA2 IR-CP with Ua level were analyzed using Pearson correlation analysis and linear regression analysis. Hierarchical interaction analysis was conducted to assess the differences in the association between insulin resistance index and Ua level in different subgroups. The ROC curve was used to evaluate the predictive ability of insulin resistance index for an increased Ua level. RESULTS: The levels of HOMA2-IR and HOMA2 IR-CP were significantly lower in Ua≤420 µmol/L group than in Ua>420 µmol/L group. Univariate Pearson correlation analysis showed a weak correlation of HOMA2-IR with Ua (r=0.262, P<0.001) and moderate correlation of HOMA2 IR-CP with Ua (r=0.409, P<0.001). Multivariate linear regression analysis, after adjustment for confounding factors, demonstrated that HOMA2-IR (R2=0.445, P<0.001) and HOMA2 IR-CP (R2=0.461, P<0.001) were both factors affecting Ua level. Hierarchical interaction analysis showed that the association of insulin resistance index with Ua level varied significantly with gender, age, and glucose metabolism (P<0.001). ROC curve showed that the areas under the curve predicted an increased Ua level by HOMA2-IR and HOMA2 IR-CP were 0.662 and 0.722, respectively. CONCLUSIONS: HOMA2 IR-CP is a more accurate indicator for assessing the correlation between insulin resistance and Ua level.


Assuntos
Resistência à Insulina , Insulina , Humanos , Peptídeo C , Ácido Úrico , Estudos Retrospectivos
18.
J Cosmet Dermatol ; 22(4): 1392-1399, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36606389

RESUMO

BACKGROUND: Prevalence of adult patients with acne is increasing and women comprise majority of the cases. There is lack of data on biochemical and hormonal abnormalities in adult female acne (AFA). AIMS: To evaluate biochemical and hormonal parameters in 60 patients of AFA. METHODS: A cross-sectional observational study conducted from November 2018 to March 2020 in Dermatology outpatient department of a tertiary care hospital in North India. Adult females (age > 25 years) with a clinical diagnosis of acne were included in the study. RESULTS: 60 cases of AFA were included. The age ranged between 26-41 years with mean age at presentation being 29.45 years. 53.3% patients had persistent acne while 46.7% had late-onset acne. 50% patients had history of premenstrual flare-up of their acne. Raised FBG was found in 25% patients. 10% had raised serum insulin levels. HOMA-IR index was deranged in 55% patients. At least one lipid alteration was reported in 91.6% of patients. In hormonal parameters, raised TT was present in 6.7%, LH in 3.3%, FSH in 18.3%, prolactin in 3.3%, and TSH in 15%. No association was found between acne severity and biochemical and hormonal parameters. CONCLUSIONS: Our study highlighted the importance of measuring lipid profile in AFA and calculating HOMA-IR index for measuring insulin resistance rather than simply measuring serum insulin levels. In our study, additional parameter deranged in significant number of patients was FBG. Hence, we recommend routine screening of lipid profile, FBG and calculation of HOMA-IR index in AFA.


Assuntos
Acne Vulgar , Resistência à Insulina , Insulinas , Adulto , Humanos , Feminino , Estudos Transversais , Acne Vulgar/epidemiologia , Lipídeos
19.
Indian J Dermatol ; 68(4): 377-384, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822394

RESUMO

Background: Psoriasis is a chronic, immune mediated inflammatory condition of the skin and imbalance in inflammatory mediators could result in insulin resistance, metabolic syndrome and facilitate the occurrence and progression of Non-alcoholic fatty liver disease (NAFLD). Objectives: Primary objectives: To study the frequency of NAFLD in cases of chronic plaque psoriasis and controlsTo study the interleukin levels in cases of chronic plaque psoriasis and controls. Secondary objectives: To study the BMI, lipid profile, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin in cases and controlsTo study the association of age, duration of psoriasis, PASI (psoriasis area severity index), BSA (body surface area) involved, BMI (body mass index), lipid profile, obesity, waist circumference, FBS (fasting blood sugar), PPBS (post prandial blood sugar) and serum insulin levels with NAFLD in patients of chronic plaque psoriasisTo correlate serum levels of IL1-ß, IL6 and TNF-α with NAFLD in patients of chronic plaque psoriasis. Methods: 50 clinically diagnosed cases of chronic plaque psoriasis with age ≥ 18years, diseases duration ≥ 6 months and 30 age and sex matched controls were recruited. PASI, BSA of cases was calculated and BMI, BP, WC of all subjects was measured. Serum lipid profile, FBS, PPBS, insulin level, IL1- ß , IL6, TNF- α , high frequency B-mode ultrasound, LFT and fibroscan were done in all subjects. Results: 28(56.0%) cases and 2(6.6%) controls had NAFLD with statistically significant difference. Significantly elevated WC, serum insulin, deranged lipid profile, fatty liver, transaminitis, fibroscan score, liver fibrosis, NAFLD and interleukins were found in cases vs controls. There was a significant association of NAFLD in psoriatic patients with increasing duration of psoriasis, BMI ≥23 Kg/m2, high WC, increasing BSA involved, deranged lipid profile, raised total cholesterol levels and increasing number of risk factors. Nonsignificant but positive association of NAFLD in cases was found with high levels of IL1 - ß, IL - 6, TNF-α, FBS and increasing PASI. Conclusion: Significantly increased interleukin levels and their weak positive correlation with the severity of psoriasis (PASI, BSA) in patients of chronic plaque psoriasis explains the possible role of inflammation in the causation of psoriasis. Screening may be considered in psoriatic patients with increasing duration of psoriasis, high WC, high BSA involved, high BMI, obesity, dyslipidemia and insulin resistance. Limitations: Small sample size. Conflict of Intrest: NONE.

20.
J Diabetes Metab Disord ; 21(2): 1369-1375, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36404867

RESUMO

Background: One of the most common metabolic diseases, Type 2 Diabetes Mellitus (T2DM), is caused by a combination of two basic factors: insufficient insulin secretion by pancreatic -cells or a failure of insulin-sensitive tissues to respond adequately to insulin. The aim of this paper was to assess the diagnostic accuracy of serum nesfatin-1 in type 2 diabetes mellitus (T2DM). Methods: Sixty patients with T2DM were recruited from (Baquba Teaching Hospital) in Iraq during the period (from November 2021 - March 2022). T2DM group was classified into 30 newly diagnosis patients (without treatment) and 30 ongoing diabetic patients (with treatment) for comparison, as well 30 healthy individuals were included as a control. The ELISA Kit was used to measure serum nesfatin-1 and serum insulin, fasting serum glucose, and lipid profile test were measured through spectrophotometric, instead of HbA1c was determined using HPLC method. Results: The concentration of serum nesfatin-1 in the T2DM group was significantly lower than that of the healthy subjects (p < 0.05). There was a significant difference in the serum nestafin-1 concentrations between newly diagnosis and ongoing T2DM patients. There were substantial negative connections between serum Nesfatin-1 concentration and HOMA-IR, as well as strong negative correlations between serum nesfatin-1 and serum insulin level. The concentration of serum Nesfatin-1, on the other hand, had no significant association with the anthropometries measurements and biochemical parameters. The area under the curve was excellent (AUC = 0.827, p = 0.0001), with high diagnostic accuracy (86.2) in differentiating newly diagnosis T2DM from the healthy subject group. Conclusion: Nesfatin-1 levels in the sera of diabetic patients was shown to be lower and nesfatin-1 levels were shown to be significantly linked to newly diagnosed patients.

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