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1.
Nutr Metab Cardiovasc Dis ; 31(5): 1445-1453, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33812736

RESUMO

BACKGROUND AND AIMS: How Mediterranean-style diets impact cardiovascular and health outcomes in patients with diabetes and chronic kidney disease (CKD) is not well known. Our aim was to investigate the association between diet quality, using Mediterranean Diet Scores (MDS) and health outcomes. METHODS AND RESULTS: This is a post-hoc analysis of an RCT and longitudinal study investigating patients with diabetes and CKD. MDS was calculated annually. Scores were analyzed for correlation with lipids, HbA1c, serum potassium, health-related quality of life (HRQOL) and depression. 178 diet records from 50 patients who attended two or more visits were included. Mean MDS was moderate (4.1 ± 1.6) and stable over time. Stage 1-2 vs 3-5 CKD had lower raw MDS (3.8 ± 1.5 vs 4.6 ± 1.5, p < 0.001). Having hyperkalemia was associated with a lower raw MDS scores (3.6 ± 1.6 vs 4.2 ± 1.5, p = 0.03) but not energy adjusted MDS. MDS was not associated with HbA1c or lipids. High vs low MDS was associated with improved HRQOL (mental health 84.4 ± 14.3 vs 80.3 ± 17.1, p < 0.05; general health 62.6 ± 21.0 vs 56.3 ± 19.8, p < 0.001) and fewer depressive symptoms (9.1 ± 7.4 vs 11.7 ± 10.6, p = 0.01). CONCLUSIONS: Low MDS was associated with reduced kidney function and health related quality of life, but not other markers of cardiovascular risk. Further studies are needed to understand the nature and direction of the association between diet quality and disease outcomes in this population.


Assuntos
Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Saudável , Dieta Mediterrânea , Rim/fisiopatologia , Qualidade de Vida , Insuficiência Renal Crônica/dietoterapia , Idoso , Fatores de Risco Cardiometabólico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Nível de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Cooperação do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Tempo
2.
Medicine (Baltimore) ; 100(3): e24318, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546062

RESUMO

RATIONALE: The immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome is a rare disorder that most often manifests in the early stages of life. IPEX syndrome with a late onset, presenting with severe gastritis has rarely been reported. PATIENT CONCERNS: Two male adolescents presented with recurrent vomiting, severe malnutrition, and growth retardation due to severe gastritis. DIAGNOSES: Esophagogastroduodenoscopy of the 2 patients revealed rare presentations of severe gastritis with multiple ulcers and stenosis of the pylorus. Next-generation sequencing revealed 2 novel variants in gene FOXP3 in the patients who were diagnosed with the IPEX syndrome. INTERVENTIONS: Both patients were treated with a high calorie formular enteral nutritional therapy. In addition, the pylorus of patient 1 was enlarged by balloon dilation, while patient 2 was treated with mercaptopurine and low dose prednisone. OUTCOMES: Symptoms and nutritional status of the patients improved after treatment. LESSONS: Chronic severe gastritis with stenosis of the pylorus could be an atypical manifestation of the IPEX syndrome. The use of next-generation sequencing is highly suitable for the diagnosis of atypical IPEX syndromes.


Assuntos
Diabetes Mellitus Tipo 1/congênito , Diarreia/complicações , Diarreia/diagnóstico , Gastrite/etiologia , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças do Sistema Imunitário/congênito , Fatores de Tempo , Adolescente , China , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatologia , Diarreia/fisiopatologia , Fatores de Transcrição Forkhead/genética , Gastrite/fisiopatologia , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Humanos , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/fisiopatologia , Masculino , Desnutrição/etiologia
3.
Chem Biol Interact ; 338: 109427, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33639173

RESUMO

Oxidative stress and inflammation are implicated in the occurrence and progression of diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple diaryl diselenide with anti-hyperglycemic, anti-inflammatory, and antioxidant activities. However, the effects of DPDS on DN are still unclear to date. Herein, we aimed to explore whether DPDS could improve renal dysfunction in streptozotocin (STZ)-induced diabetic rats and its underlying mechanisms. STZ-induced DN rats were administered with DPDS (5 or 15 mg/kg) or metformin (200 mg/kg) once daily by intragastric gavage for 12 weeks. DPDS supplementation significantly improved hyperglycemia, glucose intolerance, dyslipidemia, and the renal pathological abnormalities, concurrent with significantly reduced serum levels of creatinine, urea nitrogen, urine volume, and urinary levels of micro-albumin, ß2-microglobulin and N-acetyl-glucosaminidase activities. Moreover, DPDS effectively promoted the activities of antioxidant enzymes, and reduced the levels of MDA and pro-inflammatory factors in serum and the kidney. Furthermore, DPDS supplementation activated the renal Nrf2/Keap1 signaling pathway, but attenuated the high phosphorylation levels of NFκB, JNK, p38 and ERK1/2. Altogether, the current study indicated for the first time that DPDS ameliorated STZ-induced renal dysfunction in rats, and its mechanism of action may be attributable to suppressing oxidative stress via activating the renal Nrf2/Keap1 signaling pathway and mitigating inflammation by suppressing the renal NFκB/MAPK signaling pathways, suggesting a potential therapeutic approach for DN.


Assuntos
Derivados de Benzeno/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/tratamento farmacológico , Inflamação/tratamento farmacológico , Compostos Organosselênicos/uso terapêutico , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Derivados de Benzeno/farmacologia , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Dislipidemias/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Inflamação/complicações , Inflamação/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/patologia , Rim/fisiopatologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Modelos Biológicos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Estreptozocina
4.
Methods Mol Biol ; 2224: 87-98, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33606208

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease, where insulin-producing ß-cells in the pancreas are inappropriately recognized and destroyed by immune cells. Islet transplantation is the most successful cell-based therapy for T1D individuals who experience frequent and severe life-threatening hypoglycemia. However, this therapy is extremely restricted owing to the limited availability of donor pancreas. In recent years, significant progress has been made in generating ß-cells from stem/progenitor cells using different approaches of in vitro differentiation. The insulin production from such in vitro generated ß-cells is still far less than that observed in islet ß-cells. We employed a novel strategy to improve the efficiency of progenitor cell differentiation by performing partial mouse pancreas resection after transplanting in vitro generated insulin-producing cells under the kidney capsule of these mice. Pancreas resection (pancreatectomy) has been shown to induce regenerative pathways, leading to regeneration of almost the entire resected pancreas over 3-5 weeks in mice. We found that in our method, regenerating mouse pancreas promotes better graft differentiation/maturation and insulin production from transplanted cells. In this chapter, we detail the protocols used for transplantation of in vitro differentiated cells in immunocompromised mice, partial pancreatectomy in host (NOD scid) mice, and assessment of graft function. We believe that our protocols provide a solid platform for further studies aimed at understanding growth/differentiation molecules secreted from regenerating pancreas that promote graft maturation.


Assuntos
Diferenciação Celular/fisiologia , Pâncreas/fisiologia , Animais , Diabetes Mellitus Tipo 1/fisiopatologia , Células Secretoras de Insulina/fisiologia , Transplante das Ilhotas Pancreáticas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pancreatectomia/métodos , Células-Tronco/fisiologia
6.
Acta Diabetol ; 58(6): 779-786, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33587176

RESUMO

AIMS: To compare the annual axial length (AL) changes in myopic children with type 1 diabetes mellitus (T1DM) and those without diabetes. METHODS: There are two groups of myopic children in this retrospective cohort study. Group 1 consisted of myopic children with T1DM (44 eyes of 22 patients). Group 2 comprised age-matched myopic children without diabetes (44 eyes of 22 children). These two groups were compared with regard to their baseline clinical characteristics. A generalized estimating equations (GEE) model was also used to determine the most likely factor that contributed to the results. RESULTS: The average ages of group 1 and group 2 were 14.8 and 14.6 years, respectively. Children in group 1 had significantly slower annual AL changes (0.051 mm/year vs 0.103 mm/year; 50.5% slower, P = 0.011) and shorter baseline AL (23.97 vs 25.19 mm, P < 0.001) than those in group 2. GEE also showed that serum glycated hemoglobin (HbA1c) level (B = -0.023, P = 0.039) was the most important factor in reducing AL elongation in group 1 myopic children. CONCLUSIONS: Long-term higher HbA1c level may reduce AL elongation. A strict blood sugar control strategy in clinical practice is warranted to axial myopia progression in T1DM children.


Assuntos
Comprimento Axial do Olho/patologia , Diabetes Mellitus Tipo 1/sangue , Hemoglobina A Glicada/metabolismo , Miopia/sangue , Adolescente , Comprimento Axial do Olho/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/fisiopatologia , Retinopatia Diabética/sangue , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/fisiopatologia , Progressão da Doença , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Miopia/complicações , Miopia/diagnóstico por imagem , Miopia/fisiopatologia , Refração Ocular/fisiologia , Estudos Retrospectivos
7.
Life Sci ; 272: 119250, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33631174

RESUMO

AIM: Despite CXC chemokine ligand 16 (CXCL16) contributes to the pathogenesis of many inflammatory disorders, the mechanism by which CXCL16 is involved in T1DM remains unclear. In this study, we examined the role of the CXCL16/NF-κΒ p65 signaling pathway in the progression of this disease and the possible protective effect of resveratrol (RES) on streptozotocin (STZ)-induced T1DM. MAIN METHODS: Mice were classified into four groups of 10 animals each. The control group received citrate buffer. The RES group received 50 mg/kg i.p. RES for 12 days beginning on day 4 of citrate buffer. The STZ group received 55 mg/kg i.p. STZ once a day for 5 consecutive days. The fourth group injected with RES (50 mg/kg) for 12 days starting on day 4 of STZ injection. Biochemical, physical and oxidative stress parameters were measured in all groups. Moreover, expression of CXCL16 and CD45 was measured in pancreatic islets and spleen. Additionally, NF-κΒ p65 was investigated in isolated islets. KEY FINDINGS: Our results showed a significant elevation of CXCL16, NF-κΒ p65 and CD45 in islets of diabetic (DM) mice. Intriguingly, RES significantly restored distorted biochemical, physical and oxidative stress parameters after STZ treatment as well as inhibited the expression of CXCL16/NF-κΒ p65 in pancreatic islets. Moreover, RES normalized CXCL16 and CD45 expression in islets and spleen. SIGNIFICANCE: This study demonstrates first evidence that CXCL16/NF-κΒ p65 signaling pathway is associated with macrophage infiltration to pancreatic islet in T1DM and that RES successfully improved T1DM may be at least via inhibiting this pathway.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/metabolismo , Resveratrol/farmacologia , Animais , Quimiocina CXCL16/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Modelos Animais de Doenças , Ilhotas Pancreáticas/efeitos dos fármacos , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Resveratrol/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia , Fator de Transcrição RelA/metabolismo
8.
Am J Physiol Heart Circ Physiol ; 320(4): H1738-H1748, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33635166

RESUMO

Emerging evidence suggests the exercise pressor reflex is exaggerated in early stage type 1 diabetes mellitus (T1DM). Piezo channels may play a role in this exaggeration, as blocking these channels attenuates the exaggerated pressor response to tendon stretch in T1DM rats. However, tendon stretch constitutes a different mechanical and physiological stimuli than that occurring during muscle contraction. Therefore, the purpose of this study was to determine the contribution of Piezo channels in evoking the pressor reflex during an intermittent muscle contraction in T1DM. In unanesthetized decerebrate rats, we compared the pressor and cardioaccelerator responses to intermittent muscle contraction before and after locally injecting grammostola spatulata mechanotoxin 4 (GsMTx-4, 0.25 µM) into the hindlimb vasculature. Although GsMTx-4 has a high potency for Piezo channels, it has also been suggested to block transient receptor potential cation (TRPC) channels. We, therefore, performed additional experiments to control for this possibility by also injecting SKF 96365 (10 µM), a TRPC channel blocker. We found that local injection of GsMTx-4, but not SKF 96365, attenuated the exaggerated peak pressor (ΔMAP before: 33 ± 3 mmHg, after: 22 ± 3 mmHg, P = 0.007) and pressor index (ΔBPi before: 668 ± 91 mmHg·s, after: 418 ± 81 mmHg·s, P = 0.021) response in streptozotocin (STZ) rats (n = 8). GsMTx-4 attenuated the exaggerated early onset pressor and the pressor response over time, which eliminated peak differences as well as those over time between T1DM and healthy controls. These data suggest that Piezo channels are an effective target to normalize the exercise pressor reflex in T1DM.NEW & NOTEWORTHY This is the first study to demonstrate that blocking Piezo channels is effective in ameliorating the exaggerated exercise pressor reflex evoked by intermittent muscle contraction, commonly occurring during physical activity, in T1DM. Thus, these findings suggest Piezo channels may serve as an effective therapeutic target to reduce the acute and prolonged cardiovascular strain that may occur during dynamic exercise in T1DM.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/inervação , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Moduladores de Transporte de Membrana/farmacologia , Contração Muscular , Músculo Esquelético/inervação , Reflexo Anormal/efeitos dos fármacos , Venenos de Aranha/farmacologia , Animais , Sistema Nervoso Autônomo/metabolismo , Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Canais Iônicos/antagonistas & inibidores , Canais Iônicos/metabolismo , Masculino , Condicionamento Físico Animal , Ratos Sprague-Dawley , Fatores de Tempo
9.
Arch Biochem Biophys ; 699: 108763, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460581

RESUMO

MicroRNAs (miRNAs) are small non-coding highly conserved RNA molecules that can act as master regulators of gene expression in a sequence-specific manner either by translation repression or mRNA degradation, influencing a wide range of biologic processes that are essential for the maintenance of cellular homeostasis. Chronic pediatric diseases are the leading cause of death worldwide among children and the recent evidence indicates that aberrant miRNA expression significantly contributes to the development of chronic pediatric diseases. This review focuses on the role of miRNAs in five major chronic pediatric diseases including bronchial asthma, congenital heart diseases, cystic fibrosis, type 1 diabetes mellitus, and epilepsy, and their potential use as novel biomarkers for the diagnosis and prognosis of these disorders.


Assuntos
Asma/fisiopatologia , Fibrose Cística/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Epilepsia/fisiopatologia , Cardiopatias Congênitas/fisiopatologia , MicroRNAs/fisiologia , Asma/diagnóstico , Asma/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Doença Crônica , Fibrose Cística/diagnóstico , Fibrose Cística/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/metabolismo , Epilepsia/diagnóstico , Epilepsia/metabolismo , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/metabolismo , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Pediatria , Prognóstico
10.
BMC Pregnancy Childbirth ; 21(1): 96, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514342

RESUMO

BACKGROUND: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT). METHODS: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome. RESULTS: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes. CONCLUSIONS: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Retardo do Crescimento Fetal/etiologia , Macrossomia Fetal/etiologia , Gráficos de Crescimento , Neonatologia/normas , Adulto , Peso ao Nascer , Diabetes Mellitus Tipo 1/terapia , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal/epidemiologia , Macrossomia Fetal/epidemiologia , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Modelos Logísticos , Masculino , Gravidez , Nascimento Prematuro , Reino Unido
11.
Life Sci ; 268: 119003, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417957

RESUMO

AIMS: This study attempts to elicit whether the level of hyperglycemia in an early stage of diabetic nephropathy changes the renal expression of claudins-2 and -5 and to determine the involvement of glucose-induced oxidative stress. MAIN METHODS: Streptozotocin-induced type-1 and type-2 diabetic (DM1, DM2)-rat models were used. At 14-week old, the rats were placed in metabolic cages to evaluate proteinuria, creatinine clearance, and electrolyte excretion. Proximal tubules and glomeruli were isolated and analyzed by Western blot and immunofluorescence. Renal oxidative stress and metalloproteinase activities were evaluated. KEY FINDINGS: We found that claudin-5 expression in glomeruli and claudin-2 expression in proximal tubules were significantly reduced in DM1 versus DM2 model, paralleling with higher proteinuria and loss of sodium and potassium reabsorption, increased malondialdehyde levels, but lower antioxidant capacity in both models. Enzymatic activity of MMP-2 and-9 was increased in both diabetic groups versus control being higher in DM1 than DM2, suggesting higher claudin's degradation. SIGNIFICANCE: The level of hyperglycemia determines the time-dependent progression to diabetic nephropathy; hyperglycemia-induced oxidative stress parallels an increase in metalloproteinases (MMPs) activities consequently affecting the integrity of claudin-2 and -5 in glomerulus and proximal tubule. Our results suggest that chronic high-glycemia levels in early stages of diabetic nephropathy decrease expression of claudins-2 and -5, increase oxidative stress, and induce MMP-activity faster than chronic middle-glycemia levels.


Assuntos
Claudina-2/metabolismo , Claudina-5/metabolismo , Nefropatias Diabéticas/metabolismo , Hiperglicemia/metabolismo , Rim/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/patologia , Rim/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Estresse Oxidativo , Ratos Wistar , Transportador 2 de Glucose-Sódio/metabolismo , Estreptozocina
12.
Am J Physiol Regul Integr Comp Physiol ; 320(4): R384-R392, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33407019

RESUMO

Heat stress, via its effects on muscle intracellular Ca2+ concentrations ([Ca2+]i), has been invoked as a putative therapeutic countermeasure to type 1 diabetes-induced muscle atrophy. Using a circulation- and neurally intact in vivo muscle preparation, we tested the hypothesis that impaired muscle Ca2+ homeostasis in type 1 diabetic rats is due to attenuated heat stress tolerance mediated via transient receptor potential vanilloid 1 (TRPV1). Male Wistar rats were randomly assigned to one of the following four groups: 1) healthy control 30°C (CONT 30°C); 2) CONT 40°C; 3) diabetes 30°C (DIA 30°C); and 4) DIA 40°C. The temperature of 40°C was selected because it exceeds the TRPV1 activation threshold. Spinotrapezius muscles of Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+ probe Fura-2 AM. [Ca2+]i was estimated over 20 min using fluorescence microscopy (340/380 nm ratio) in quiescent muscle held at the required temperature, using a calibrated heat source applied to the ventral muscle surface. Western blotting was performed to determine the protein expression levels of TRPV1 in spinotrapezius muscle. After 20 min of heat stress, the CONT 40°C condition induced a 12.3 ± 5% [Ca2+]i (P < 0.05) elevation that was markedly absent in the DIA 40°C or other conditions. Thus, no significant differences were found among DIA 40°C, DIA 30°C, and CONT 30°C. TRPV1 protein expression was decreased by 42.0 ± 9% in DIA compared with CONT (P < 0.05) and, unlike CONT, heat stress did not increase TRPV1 phosphorylation. In conclusion, diabetes suppresses TRPV1 protein expression and function and inhibits the elevated myocyte [Ca2+]i evoked normally by heat stress. These results suggest that capsaicin or other therapeutic strategies to increase Ca2+ accumulation via TRPV1 might be more effective than hyperthermic therapy for type 1 diabetic patients.


Assuntos
Cálcio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Transtornos de Estresse por Calor/metabolismo , Músculo Esquelético/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Glicemia/metabolismo , Capsaicina/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Transtornos de Estresse por Calor/fisiopatologia , Homeostase , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiopatologia , Fosforilação , Ratos Wistar , Canais de Cátion TRPV/agonistas , Fatores de Tempo
13.
Acta Obstet Gynecol Scand ; 100(2): 263-271, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32880890

RESUMO

INTRODUCTION: Poor glycemic control in maternal type 1 diabetes mellitus during pregnancy can affect fetal cardiac and placental function. However, studies concerning fetal central hemodynamics have revealed conflicting results. We hypothesized that in pregnancies complicated by maternal type 1 diabetes, fetal cardiovascular and placental hemodynamics are comparable to the control fetuses at near-term gestation. In addition, we investigated the relation between newborn serum biomarkers of cardiac function and fetal cardiovascular and placental hemodynamics. Furthermore, we studied whether maternal diabetes is associated with placental inflammation. MATERIAL AND METHODS: In this prospective case-control study, fetal central and peripheral hemodynamics were assessed by ultrasonography in 33 women with type 1 diabetes and in 67 controls with singleton pregnancies between 34+2 and 40+2 gestational weeks. Newborn umbilical cord serum was collected to analyze cardiac natriuretic peptides (atrial and B-type natriuretic peptides) and troponin T concentrations. Placental tissue samples were obtained for cytokine analyses. RESULTS: Fetal ventricular wall thicknesses were greater and weight-adjusted stroke volumes and cardiac outputs were lower in the type 1 diabetes group than in the control group. Pulsatility in the aortic isthmus and inferior vena cava blood flow velocity waveforms was greater in the type 1 diabetes group fetuses than in the controls. A positive correlation was found between branch pulmonary artery and aortic isthmus pulsatility index values. Umbilical artery pulsatility indices were comparable between the groups. Umbilical cord serum natriuretic peptide and troponin T concentrations were elevated in the type 1 diabetes fetuses. These cardiac biomarkers correlated significantly with cardiovascular hemodynamics. Placental cytokine levels were not different between the groups. CONCLUSIONS: In maternal type 1 diabetes pregnancies, fetal cardiovascular hemodynamics is impaired. Maternal type 1 diabetes does not seem to alter placental vascular impedance or induce placental inflammation.


Assuntos
Débito Cardíaco/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Coração Fetal/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Gravidez em Diabéticas/fisiopatologia , Volume Sistólico/fisiologia , Adulto , Aorta/diagnóstico por imagem , Aorta/fisiologia , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Sangue Fetal/metabolismo , Coração Fetal/diagnóstico por imagem , Humanos , Recém-Nascido , Peptídeo Natriurético Encefálico/sangue , Placenta/metabolismo , Gravidez , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiologia , Fluxo Pulsátil/fisiologia , Troponina T/sangue , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler de Pulso , Ultrassonografia Pré-Natal , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/fisiologia
14.
Expert Opin Drug Saf ; 20(2): 155-169, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33249944

RESUMO

Introduction: The aim of insulin replacement in insulin-deficient people (type 1 diabetes, pancreatic causes of diabetes, long-standing type 2 diabetes) is to approximate the physiologic insulin action profile as closely as possible. However, short-acting human insulins start too slow and act too long, causing postprandial hyperglycemia and delayed hypoglycemia, while the insulin action profile of long-acting human insulins is too variable in duration and strength of action, leading to insufficient basal insulin covering and peak insulin levels after injection causing early nocturnal hypoglycemia. Insulin analogues were designed to overcome these shortcomings. In insulin-resistant people (type 2 diabetes), insulin analogues contribute to more efficient and safer insulin supplementation. Areas covered: In this review, we describe the unmet needs for insulin therapy, the currently available short- and long-acting insulin analogues and some considerations on cardiovascular outcomes, use in special populations, and cost-effectiveness. Finally, we discuss what is new in the field of insulin analogues. Expert opinion: The development of insulin analogues is an important step in diabetes treatment. Despite many patients meeting their glycemic targets with the newest analogues, hypoglycemic episodes remain a major problem. More physiologic insulin regimens, with glucose-sensitive or organ-targeting insulin analogues may be the answer to these issues.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulinas/administração & dosagem , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Resistência à Insulina , Insulinas/efeitos adversos
15.
J Pediatr Endocrinol Metab ; 34(2): 217-223, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33185578

RESUMO

OBJECTIVES: In March 2020, lockdown was imposed in India to combat spread of Coronavirus, which was extended till 31st May. Implementation of lockdown and limited outdoor activities resulted in changes in routines of children with diabetes. The aim of this study was to assess the impact of lockdown on glycemic control, weight and body mass index (BMI) patterns of children with type 1 diabetes (T1DM) from different socio-economic (SE) classes. METHODS: This observational study included 77 children and youth (5-20 years) with T1DM having disease duration of ≥6 months. Demographic data and investigations were recorded at two time points (post lockdown when the children came for follow up, pre lockdown data from medical records). RESULTS: Glycemic control improved (pre lockdown HbA1C 79.4±19.2 vs. post lockdown Hba1C 74.5±16.9 mmol/mol, p<0.05) and there was weight gain post lockdown (pre lockdown weight z-score -0.4±0.8 vs. post lockdown weight z-score -0.2±0.8, p<0.05) without any significant change in BMI and insulin requirements. Improved glycemic was seen in the lower SE group control post lockdown (p<0.05), whereas in higher SE group, it remained unchanged. Children whose parents were at home during lockdown showed an improved glycemic control (p<0.05) as compared to children whose parents continued to work during lockdown (p>0.01). CONCLUSIONS: During coronavirus lockdown, glycemic control was adequately maintained in children with T1DM, highlighting importance of stronger family support system leading to more steady daily routine.


Assuntos
COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/estatística & dados numéricos , Diabetes Mellitus Tipo 1/fisiopatologia , SARS-CoV-2 , Fatores Socioeconômicos , Adolescente , Índice de Massa Corporal , Peso Corporal/fisiologia , COVID-19/epidemiologia , Criança , Pré-Escolar , Controle de Doenças Transmissíveis/métodos , Comorbidade , Diabetes Mellitus Tipo 1/epidemiologia , Exercício Físico/fisiologia , Família/psicologia , Controle Glicêmico/estatística & dados numéricos , Humanos , Índia , Sistemas de Apoio Psicossocial , Quarentena , Adulto Jovem
16.
Microvasc Res ; 133: 104077, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979391

RESUMO

While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D). Our goal was to test the hypothesis that administration of a CB2 agonist (JWH-133) would improve impaired endothelial (eNOS)- and neuronal (nNOS)-dependent dilation of cerebral arterioles during T1D. In vivo diameter of cerebral arterioles in nondiabetic and T1D rats was measured in response to an eNOS-dependent agonist (adenosine 5'-diphosphate; ADP), an nNOS-dependent agonist (N-methyl-d-aspartate; NMDA), and an NOS-independent agonist (nitroglycerin) before and 1 h following JWH-133 (1 mg/kg IP). Dilation of cerebral arterioles to ADP and NMDA was greater in nondiabetic than in T1D rats. Treatment with JWH-133 increased responses of cerebral arterioles to ADP and NMDA in both nondiabetic and T1D rats. Responses of cerebral arterioles to nitroglycerin were similar between nondiabetic and T1D rats, and JWH-133 did not influence responses to nitroglycerin in either group. The restoration in responses to the agonists by JWH-133 could be inhibited by treatment with a specific inhibitor of CB2 receptors (AM-630; 3 mg/kg IP). Thus, activation of CB2 receptors can potentiate reactivity of cerebral arterioles during physiologic and pathophysiologic states. We speculate that treatment with CB2 receptor agonists may have potential therapeutic benefits for the treatment of cerebral vascular diseases via a mechanism that can increase cerebral blood flow.


Assuntos
Arteríolas/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/farmacologia , Canabinoides/farmacologia , Transtornos Cerebrovasculares/prevenção & controle , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Receptor CB2 de Canabinoide/agonistas , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Arteríolas/enzimologia , Encéfalo/irrigação sanguínea , Transtornos Cerebrovasculares/enzimologia , Transtornos Cerebrovasculares/fisiopatologia , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 1/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Sprague-Dawley , Receptor CB2 de Canabinoide/metabolismo , Transdução de Sinais
17.
Diabet Med ; 38(5): e14498, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33314244

RESUMO

AIM: To describe diabetes nurses' perspectives on the impact of the COVID-19 pandemic on people with diabetes and diabetes services across Europe. METHODS: An online survey developed using a rapid Delphi method. The survey was translated into 17 different languages and disseminated electronically in 27 countries via national diabetes nurse networks. RESULTS: Survey responses from 1829 diabetes nurses were included in the analysis. The responses indicated that 28% (n = 504) and 48% (n = 873) of diabetes nurses felt the COVID-19 pandemic had impacted 'a lot' on the physical and psychological risks of people with diabetes, respectively. The following clinical problems were identified as having increased 'a lot': anxiety 82% (n = 1486); diabetes distress 65% (n = 1189); depression 49% (n = 893); acute hyperglycaemia 39% (n = 710) and foot complications 18% (n = 323). Forty-seven percent (n = 771) of respondents identified that the level of care provided to people with diabetes had declined either extremely or quite severely. Self-management support, diabetes education and psychological support were rated by diabetes nurse respondents as having declined extremely or quite severely during the COVID-19 pandemic by 31% (n = 499), 63% (n = 1,027) and 34% (n = 551), respectively. CONCLUSION: The findings show that diabetes nurses across Europe have seen significant increases in both physical and psychological problems in their patient populations during COVID-19. The data also show that clinical diabetes services have been significantly disrupted. As the COVID-19 situation continues, we need to adapt care systems with some urgency to minimise the impact of the pandemic on the diabetes population.


Assuntos
COVID-19 , Atenção à Saúde , Diabetes Mellitus/fisiopatologia , Enfermeiras Especialistas , Angústia Psicológica , Ansiedade/psicologia , Atitude do Pessoal de Saúde , Depressão/psicologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/enfermagem , Diabetes Mellitus/psicologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/enfermagem , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/enfermagem , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/psicologia , Pé Diabético/fisiopatologia , Europa (Continente) , Humanos , Hiperglicemia/metabolismo , SARS-CoV-2 , Autogestão , Inquéritos e Questionários
18.
J Ethnopharmacol ; 265: 113210, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32795501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: One of the commonly prescribed 'anti-diabetic' polyherbal mixtures by European herbalists is made of Rubus fruticosus and Vaccinium myrtillus leaves, Potentilla erecta roots, Geum urbanum aerial parts and Phaseolus vulgaris pods. AIM OF THE STUDY: This study aimed to evaluate the phytochemical composition, antioxidant capacity, potential toxicity, hypoglycemic, hypolipidemic, nephroprotective and hepatoprotective activities of this polyherbal mixture decoction. MATERIALS AND METHODS: The phytochemical composition was evaluated using HPLC-UV. The antioxidant activity was assessed using the DPPH test. Potential toxicity was evaluated using the acute and sub-chronic oral toxicity method. Diabetes was induced in Wistar female rats with a single intraperitoneal injection of alloxan monohydrate (150 mg/kg). The animals whose blood glucose was >20 mmol/L for 14 consecutive days were considered diabetic. For the next 14 days, D-10 and D-20 groups were treated with the polyherbal mixture (10 and 20 g of dry plant material/kg, respectively). I and M were control groups treated with insulin glargine (13 IU/kg) and metformin (150 mg/kg), respectively. Healthy control (HC) and diabetic control (DC) groups were treated with water. The blood glucose level was measured on days 14, 21 and 28. Lipid profile analysis was done on day 28. Pancreas, kidney and liver histopathology was evaluated using the H&E and Masson's trichrome staining. The liver tissue was additionally tested for PAS-positive cells. RESULTS: The HPLC-UV analysis revealed the presence of quinic, gallic and caftaric acid, arbutin, rutin, trifolin, astragalin, hyperoside, isoquercetin and quercitrin. The antioxidant activity of the extract was higher than the reference's one (p < 0.01). Treatment with the polyherbal mixture (10 and 20 g/kg) has shown no toxic effects. No major decline in blood sugar was recorded in I and M groups compared to the DC one (22.86 ±â€¯2.58, 28.5 ±â€¯0.42 and 27.82 ±â€¯0.9 mmol/L, respectively). The polyherbal mixture lowered the blood glucose level to the normal value (8.64 ±â€¯4.09, 5.26 ±â€¯1.3 and 6.76 ±â€¯1.54 mmol/L in D-10, D-20 and HC groups, respectively). Furthermore, it decreased the levels of total cholesterol, triglycerides, VLDL, LDL, atherogenic and cardiovascular risk indices (p < 0.001) compared to the DC group. In addition, the extract restored histopathological changes of the pancreas, kidneys and liver to the healthy animal level. CONCLUSION: Treatment with the polyherbal mixture extract was more effective than the standard drugs (insulin and metformin) in the amelioration of hyperglycemia, hyperlipidemia, and histopathological changes of the pancreas, kidney and liver tissue.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Hipolipemiantes/isolamento & purificação , Insulina/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Metformina/farmacologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Plantas Medicinais/química , Ratos , Ratos Wistar
19.
Res Nurs Health ; 44(1): 187-200, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33368403

RESUMO

This meta-analysis aimed to examine the effects of mobile-health-based (mHealth) interventions on improving glycemic stability and quality of life (QOL) in patients with type 1 diabetes (T1D). Various databases, including PubMed, Embase, CINAHL, Cochrane Library, ProQuest, Chinese Electronic Periodical Services, and China Knowledge Resource Integrated, were used to search for relevant articles. A fixed-effects model or random-effects model was used to examine the overall effect. Various methods, including Egger's test, Begg's test, and trim-and-fill, were adopted to examine publication bias. In total, 26 studies were recruited. Results of the random-effects model showed that the use of mHealth-based interventions significantly decreased glycated hemoglobin (HbA1c) (mean difference = -0.37, 95% confidence interval (CI) = -0.53 to -0.22, p < .001), and improved life satisfaction (Hedges' g = 0.30, 95% CI = 0.10 to 0.50, p = .003), worry of diabetes (Hedges' g = -0.25, 95% CI = -0.41 to 0.08, p = .004), and mental health (Hedges' g = 0.36, 95% CI = 0.08 to 0.64, p = .012). Both adults and youths with T1D can benefit from mHealth-based interventions to improve HbA1c (Hedges' g = -0.44, p = .002 vs. -0.30, p = .003). The effect of mHealth-based interventions on improving QOL in both adults and youths could not be examined due to only one study published in adults with T1D. Moreover, those studies that included the function of feedback from professionals showed a significant effect of decreasing HbA1c compared to those without that function (Hedges' g = -0.48 vs. -0.16, p = .019). Mobile devices are convenient, instantaneous, and easy to use to communicate. Applying mHealth-based interventions with the function of feedback from professionals can be considered an alternative healthcare service to achieve optimal glycemic stability in adults and youths with T1D.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Controle Glicêmico/normas , Qualidade de Vida/psicologia , Telemedicina/normas , Adolescente , Adulto , China , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobina A Glicada/análise , Controle Glicêmico/psicologia , Humanos , Melhoria de Qualidade , Telemedicina/métodos
20.
Sci Rep ; 10(1): 22367, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353965

RESUMO

To investigate bone health and body composition in young women with long-duration type 1 diabetes (T1D) in relation to matched controls. Twenty-three Swedish women, age 19.2-27.9 years, with a T1D duration of 10 years or more were recruited from the Swedish National Diabetes Registry (NDR). An age-, gender- and geography-matched control group was recruited. Bone mass and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Data was retrieved from the NDR and SWEDIABKIDS registries. T1D individuals had a mean diabetes duration of 19 years. T1D individuals had reduced lean mass (40.0 ± 6.1 kg vs. 43.9 ± 4.9 kg) and were shorter (1.66 ± 0.06 m vs. 1.71 ± 0.06 m) although comparable BMI. Subjects with T1D had lower muscle area (P = 0.0045). No differences were observed for fractures; physical activity; total, lumbar spine or femur areal bone mineral density. The cortical bone strength strain index was lower for TD1 patients (1875 ± 399 mm3 vs. 2277 ± 332 mm3). In conclusion, young women with long-term diabetes duration showed reduced cortical bone strength, decreased periosteal circumference, endosteal circumference and altered body composition. These factors contribute to the health burden of TD1, which warrants further attention for advancing bone health in women with T1D.


Assuntos
Peso Corporal , Densidade Óssea , Osso Cortical , Diabetes Mellitus Tipo 1 , Sistema de Registros , Absorciometria de Fóton , Adulto , Osso Cortical/diagnóstico por imagem , Osso Cortical/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico por imagem , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Seio Sagital Superior , Suécia
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