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1.
Nature ; 579(7798): 279-283, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32132708

RESUMEN

Although it is well-established that reductions in the ratio of insulin to glucagon in the portal vein have a major role in the dysregulation of hepatic glucose metabolism in type-2 diabetes1-3, the mechanisms by which glucagon affects hepatic glucose production and mitochondrial oxidation are poorly understood. Here we show that glucagon stimulates hepatic gluconeogenesis by increasing the activity of hepatic adipose triglyceride lipase, intrahepatic lipolysis, hepatic acetyl-CoA content and pyruvate carboxylase flux, while also increasing mitochondrial fat oxidation-all of which are mediated by stimulation of the inositol triphosphate receptor 1 (INSP3R1). In rats and mice, chronic physiological increases in plasma glucagon concentrations increased mitochondrial oxidation of fat in the liver and reversed diet-induced hepatic steatosis and insulin resistance. However, these effects of chronic glucagon treatment-reversing hepatic steatosis and glucose intolerance-were abrogated in Insp3r1 (also known as Itpr1)-knockout mice. These results provide insights into glucagon biology and suggest that INSP3R1 may represent a target for therapies that aim to reverse nonalcoholic fatty liver disease and type-2 diabetes.


Asunto(s)
Glucagón/farmacología , Gluconeogénesis/efectos de los fármacos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Hígado/efectos de los fármacos , Acetilcoenzima A/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Diabetes Mellitus Tipo 2/fisiopatología , Activación Enzimática/efectos de los fármacos , Glucagón/sangre , Receptores de Inositol 1,4,5-Trifosfato/genética , Lipasa/metabolismo , Lipólisis/efectos de los fármacos , Lipólisis/genética , Ratones Noqueados , Mitocondrias/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Oxidación-Reducción/efectos de los fármacos
2.
Medicine (Baltimore) ; 99(12): e19562, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32195965

RESUMEN

It has been established that prediabetes can causes significant comorbidities, particularly in the elderly. The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. In this study, we enrolled older women to investigate their relationships with prediabetes.Five thousand four hundred eighty-two nonobese, nondiabetic women were included. They were divided into normal glucose tolerance and prediabetes groups. Receiver operating characteristic curve was performed to investigate the effects on whether to have prediabetes for each factors. Two models were built: Model 1: FPIS + SPIS, and Model 2: model 1 + GE. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models.The aROC curve of GE was significantly higher than the diagonal line followed by SPIS and FPIS accordingly. The aROC curve of Model 1 (0.611) was not different from GE. However, Model 2 improved significantly up to 0.663. Based on this model, an equation was built (-0.003 × GE - 212.6 × SPIS - 17.9 × insulin resistance + 4.8). If the calculated value is equal or higher than 0 (≥0), then the subject has higher chance to have prediabetes (sensitivity = 0.607, specificity = 0.635).Among the 4 factors, GE is the most important contributor for prediabetes in older women. By building a model composed of FPIS, SPIS, and GE, the aROC curve increased significantly. The equation built from this model could predict prediabetes precisely.


Asunto(s)
Grupo de Ascendencia Continental Asiática/etnología , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Secreción de Insulina/fisiología , Estado Prediabético/epidemiología , Anciano , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Persona de Mediana Edad , Estado Prediabético/fisiopatología , Prevalencia , Sensibilidad y Especificidad , Taiwán/epidemiología
3.
Medicine (Baltimore) ; 99(10): e19378, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32150083

RESUMEN

BACKGROUND: Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction. The relationship between metformin therapy and cognitive function in patients with T2D is unknown. Therefore, we determined the relationship between metformin therapy and cognitive function in patients with T2D using a meta-analysis. METHODS: We systematically searched the Cochrane library, PubMed, and Embase to identify studies showing correlations, and we calculated hazard ratios (HRs). RESULTS: We identified 10 studies including 254,679 participants. Metformin significantly reduced the occurrence of cognitive dysfunction in patients with T2D (HR 0.90; 95% CI [0.88, 0.92]). Compared with other hypoglycemic drugs, sulfonylureas also improved cognitive dysfunction (HR 0.92; 95% CI [0.88, 0.95]). Thiazolidinediones gave no statistically significant improvement in cognitive dysfunction (HR 0.97; 95% CI [0.87, 1.07]). The use of insulin aggravated cognitive dysfunction (HR 1.34; 95% CI [1.24, 1.43]). In the subgroup analysis of various regions controlling for age, gender, education, diabetes course, complications, metformin administration and dosage, and follow-up time, metformin significantly improved cognitive dysfunction in patients in the Americas and Europe (HR 0.69; 95% CI [0.63, 0.74]), (HR 0.71; 95% CI [0.66, 0.76], respectively), while metformin did not significantly improve cognitive dysfunction in Asian patients (HR 0.99; 95% CI [0.96, 1.01]). CONCLUSIONS: Metformin significantly improved cognitive dysfunction in patients with T2D. Sulfonylureas also improved cognitive dysfunction. Thiazolidinediones had no significant effect on cognitive dysfunction. The use of insulin aggravated cognitive dysfunction. Metformin improved cognitive dysfunction more significantly in patients in the Americas and Europe than in Asia.


Asunto(s)
Disfunción Cognitiva/etiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Metformina/efectos adversos , Disfunción Cognitiva/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Metformina/uso terapéutico
4.
Medicine (Baltimore) ; 99(8): e19235, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080125

RESUMEN

Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients.A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups.Irisin level showed a tendency to increase in prediabetes group compared to normal group (P < .1) but showed a significant decrease when comparing diabetes from prediabetes group (P < .001). IL-13 decreased in diabetes group compared to prediabetes and normal group (P < .001, P < .05, respectively). FSTL-1 of diabetes group was lower than that of prediabetes group (P < .05), and fractalkine was higher in diabetes group compared to that of prediabetes and normal group (P < .01, P < .01, respectively).Irisin, IL-13, and FSTL-1 levels were reduced in diabetes group compared to normal or prediabetes group while fractalkine showed a progressive increase from normal to diabetes group. Further studies are warranted to study the roles of various myokine in diabetes through a larger prospective study.


Asunto(s)
Citocinas/biosíntesis , Diabetes Mellitus Tipo 2/fisiopatología , Fibronectinas/biosíntesis , Proteínas Relacionadas con la Folistatina/biosíntesis , Estado Prediabético/fisiopatología , Adulto , Anciano , Quimiocina CX3CL1/biosíntesis , Estudios Transversales , Femenino , Intolerancia a la Glucosa/fisiopatología , Hemoglobina A Glucada , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
5.
Diab Vasc Dis Res ; 17(1): 1479164120903044, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32037878

RESUMEN

Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.


Asunto(s)
Coagulación Sanguínea , Vasos Coronarios/metabolismo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/etiología , Células Endoteliales/metabolismo , Fibrina/metabolismo , Microcirculación , Trombosis/etiología , Adulto , Estudios de Casos y Controles , Células Cultivadas , Vasos Coronarios/fisiopatología , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Flujo Sanguíneo Regional , Trombosis/sangre , Trombosis/fisiopatología , Factores de Tiempo
6.
Life Sci ; 243: 117285, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31926241

RESUMEN

Vaspin, an insulin-sensitizing adipokine, has been associated with type 2 diabetes (T2D). The present study aimed to investigate the distribution of genotypes and high-risk alleles of vaspin genetic variants (rs77060950 G/T and rs2236242 A/T), in Gujarat subpopulation (India). Genomic DNA isolated from PBMCs was used to genotype vaspin polymorphisms by PCR-RFLP and ARMS-PCR from 502 controls and 478 patients. RNA isolated from visceral adipose tissue (VAT) of 22 controls and 20 patients was used to assess vaspin transcript levels by qPCR while the vaspin titre of the subjects was assayed using ELISA. Phenotypic characteristics of Fasting Blood Glucose (FBG), BMI and plasma lipid profile were estimated and analyzed for the genotype-phenotype correlation. We identified a significant association of rs2236242 A/T with T2D as the TT genotype conferred a 3.087-fold increased risk. The TT genotype showed association with increased FBG, BMI and Triglycerides levels. Increased GA, GT and TA haplotype frequencies, decreased VAT transcript and vaspin protein levels in T2D patients was observed, which were further negatively correlated with FBG and BMI. In conclusion, rs2274907 A/T polymorphism is strongly associated with reduced vaspin transcript and protein levels, and related metabolic alterations that may play a role in the advancement of T2D.


Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Intrones , Polimorfismo de Nucleótido Simple , Serpinas/genética , Diabetes Mellitus Tipo 2/genética , Genotipo , Humanos , ARN Mensajero/genética , Serpinas/sangre , Serpinas/metabolismo
7.
Intern Med ; 59(1): 45-53, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31902908

RESUMEN

Objective Exercise therapy is used for glycemic control in type 2 diabetes mellitus (T2DM). We evaluated the effects of intensive health guidance using the Internet of things (IoT) among Japanese company workers with early T2DM. Methods Fifty-three men (mean age: 54 years) with glycated hemoglobin (HbA1c) levels of >6.5% were enrolled in a 6-month exercise therapy program between August 2016 and January 2017. They used activity meters, scales, and sphygmomanometers connected to the Internet by Bluetooth. These devices automatically and continuously recorded daily information, and the participants simultaneously received health guidance from a public health nurse twice a month. Results The number of daily steps significantly increased, whereas the amount of physical activity increased but was not significant. The mean decrease (±SD) in HbA1c levels after 3 and 6 months was estimated to be -0.40% (±0.45, p<0.0001) and -0.19% (±0.55, p=0.033), respectively, by a linear mixed model that included baseline HbA1c levels and age as covariates. The program failed to improve the body mass index and blood pressure of the participants. The percentage of active stage (action and maintenance stage) in stage of health behavior significantly increased from 48% to 68% (p=0.011). Conclusion Intensive lifestyle intervention using a wearable monitoring system and remote health guidance improved diabetic control in middle-aged company workers.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Ejercicio/fisiología , Conductas Relacionadas con la Salud/fisiología , Estilo de Vida , Monitoreo Fisiológico/métodos , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad
8.
Medicine (Baltimore) ; 99(2): e18708, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914078

RESUMEN

Sarcopenia is a geriatric syndrome and it impairs physical function. Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of sarcopenia. The purpose of this study is to explore characteristics of general information and metabolic factors of sarcopenia in patients with T2DM in the northeast of China, and provide information for the prevention and treatment of sarcopenia in clinical practice.Patients with T2DM aged ≥65 were recruited in Changchun from March 2017 to February 2018. Questionnaires of general information, physical examination, laboratory and imaging examination were conducted. The patients were assigned into sarcopenia group and non-sarcopenia group according to the diagnostic criteria proposed by Asian working group for sarcopenia (AWGS), and the differences between 2 groups were analyzed.A total of 132 participants were included in this study, of which, 38 (28.8%) were diagnosed with sarcopenia. 94 (71.2%) were with no sarcopenia. Logistic regression analysis showed that age (OR: 1.182, 95%CI: 1.038-1.346), trunk fat mass (TFM) (OR: 1.499, 95%CI: 1.146-1.960) and free thyroxine (FT4) (OR: 1.342, 95%CI: 1.102-1.635) were independent risk factors for sarcopenia. BMI (body mass index) (OR: 0.365, 95%CI: 0.236-0.661), exercise (OR: 0.016, 95%CI: 0.001-0.169), female (OR: 0.000, 95%CI: 0.00-0.012), metformin (OR: 0.159, 95%CI: 0.026-0.967) and TSM (trunk skeletal muscle mass) (OR: 0.395, 95%CI: 0.236-0.661) were protective factors for sarcopenia.Sarcopenia in patients with T2DM is associated with increased age, increased TFM and increased FT4 level. Regular exercise, female, metformin administrations, high BMI and increased TSM are associated with lower risk of sarcopenia.


Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Sarcopenia/epidemiología , Sarcopenia/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Composición Corporal/fisiología , Índice de Masa Corporal , China/epidemiología , Estudios Transversales , Ejercicio/fisiología , Femenino , Humanos , Modelos Logísticos , Masculino , Metformina/uso terapéutico , Músculo Esquelético/fisiopatología , Factores de Riesgo , Factores Sexuales , Tiroxina/sangre
9.
Mymensingh Med J ; 29(1): 209-214, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31915360

RESUMEN

Most of the mortalities among Diabetic Nephropathy patients are cardiovascular, if we identify the risk factor, measures can be taken to prevent it. Hence an objective was set to evaluate the association between carotid artery intima media thickness (CIMT) with eGFR in patients of CKD stage III, IV and V among patients with type 2 diabetes mellitus; also, correlation with age, BMI, lipid profile. This cross-sectional, observational study was performed in 70 patients in different stages of CKD in Diabetic Patients selected by Inclusion Criteria (Diabetic nephropathy patients with stages III, IV, V and exclusion Criteria (Acute kidney injury, History of carotid surgery, Patients of MI and stroke). This study was performed in Department of Nephrology, Dhaka Medical College in collaboration with the Department of Radiology and Imaging, laboratory of Department of Biochemistry and Department of Microbiology at Dhaka Medical College Hospital (By standard method in laboratory) from 1st January 2016 to 31st December 2016. eGFR was measured by MDRD formula and the CIMT was measured using an ultrasonographic examination. The mean CIMT was 0.9±0.21mm, and 62.9% of the subjects showed IMT thickening (≥1mm). The carotid IMT elevated significantly with the stage progression of CKD (Overall eGFR mean 28.8±14.5mL/min/1.73m² in CIMT<1mm with range from 6 to 54 and 9.1±9.0mL/min/1.73m² in CIMT ≥1mm with range from 3 to 32 (p=0.001). The eGFR was significantly lower in the patients with CIMT thickening than those without CIMT thickening. eGFR was also significantly associated with CKD stages (p=0.001), serum creatinine (p=0.001), BMI (r = -0.330, p=0.005), and negatively associated with age group, duration of hypertension, smoking. However, the CIMT was not significantly different among the patients at different stages of diabetic nephropathy (r = -0.172, p=156) and age group. It has been concluded that the mean CIMT was markedly high in patients with CKD compared to normal expected value. This study showed a relationship between the CIMT and the renal parameters as eGFR and the stages of diabetic nephropathy with a confirm association between the CIMT and diabetic macroangiopathy.


Asunto(s)
Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus/patología , Riñón/fisiopatología , Insuficiencia Renal Crónica/fisiopatología , Bangladesh/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Tasa de Filtración Glomerular , Humanos , Insuficiencia Renal Crónica/epidemiología
10.
Expert Opin Investig Drugs ; 29(2): 191-196, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31928475

RESUMEN

Introduction: NASH and type 2 diabetes (T2D) are clinical definitions that overlap and result from metabolic dysfunction caused by over-nutrition relative to metabolic need. This volume details drug development programs aimed at specific NASH pathology with a focus on liver outcomes; this commentary suggests a metabolic approach that should not be overlooked based on a new understanding of insulin sensitizers.Areas covered: The overlap of NASH and T2D with respect to metabolic syndrome is discussed in the context of new understandings of insulin sensitizers. Adverse clinical outcomes in subjects with advanced NAFLD (e.g. NASH) and advanced metabolic dysfunction (e.g., T2D) are primarily due to cardiovascular issues. Clinical evidence suggests that insulin resistance and hyperinsulinemia predict adverse cardiovascular outcomes. NALFD/NASH significantly contributes to insulin resistance and hyperinsulinemia. A new insulin sensitizer that targets the newly identified mitochondrial pyruvate carrier could provide an approach.Expert opinion: A metabolic approach is needed for the treatment of NASH. Clinical studies are underway to determine whether a new insulin sensitizer that targets pyruvate metabolism can impact NASH, T2D, and cardiovascular disease. A broader view of metabolic disease may provide a more assessable way to track therapeutic benefit.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Desarrollo de Medicamentos , Humanos , Resistencia a la Insulina , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/fisiopatología , Afecciones Crónicas Múltiples , Enfermedad del Hígado Graso no Alcohólico/fisiopatología
11.
J Appl Oral Sci ; 28: e20190248, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31939522

RESUMEN

OBJECTIVE: The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes (T2D) and periodontitis. To evaluate the effect of scaling and root planing (SRP) on the metabolic control and systemic inflammation of patients with type 2 diabetes (T2D). METHODOLOGY: A literature search was conducted using the MEDLINE database via PubMed and the Cochrane Central Register of Controlled Trials, from their oldest records up to July 2018. Only randomized clinical trials (RCT) were considered eligible for evaluating the effect of periodontal treatment on markers of metabolic control [glycated hemoglobin (HbA1C)] and systemic inflammation [C-reactive protein (CRP)] in patients with T2D. The quality of the studies was evaluated using the Cochrane Collaboration risk assessment tool. Meta-analyses were performed for HbA1c and CRP using random effects models. The size of the overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. Heterogeneity was assessed using the Q-statistic method (x2 and I²). The level of significance was established at p<0.05. RESULTS: Nine RCT were included. SRP was effective in reducing HbA1c [DM=0.56 (0.36-0.75); p<0.01] and CRP [DM=1.89 (1.70-2.08); p<0.01]. No heterogeneity was detected (I2=0%, p>0.05). CONCLUSIONS: SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.


Asunto(s)
Raspado Dental/métodos , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/fisiopatología , Periodontitis/fisiopatología , Periodontitis/terapia , Aplanamiento de la Raíz/métodos , Proteína C-Reactiva/análisis , Hemoglobina A Glucada/análisis , Humanos , Sesgo de Publicación , Resultado del Tratamiento
12.
Expert Opin Ther Pat ; 30(1): 27-38, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31771391

RESUMEN

Introduction: The activation of free fatty acid receptor 1 (FFAR1) induces insulin secretion in a glucose-dependent manner, and thereby is considered as an attractive anti-diabetic target. The clinical studies provided a lot of evidence that FFAR1 agonists improved glucose control in T2DM without the risk of hypoglycemia. The field of FFAR1 agonists is extremely competitive with many patent applications filed in recent years identifying potent candidates.Area covered: The present review summarizes patent applications (2016-2019) filing for FFAR1 modulators, including FFAR1 partial/full agonists, atypical agonists, and multiple target agonists, along with in vitro and in vivo evaluation.Expert opinion: The clinical studies of FFAR1 agonists have proved their potential for the improvement of glucose control. However, there are a few issues still to be solved in this field since TAK-875 terminated in Phase III studies due to liver toxicity. The biggest challenge on the development of FFAR1 agonists may not be the identification of a highly potent compound, but finding out the exact mechanisms of hepatotoxicity and avoid it. Moreover, the further exploration of chemical spaces on FFAR1 full agonists and multi-targeted agonists, as well as corresponding clinical studies, will be expected and might open up new directions in this field.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Receptores Acoplados a Proteínas G/agonistas , Animales , Benzofuranos/efectos adversos , Benzofuranos/farmacología , Diabetes Mellitus Tipo 2/fisiopatología , Desarrollo de Medicamentos , Humanos , Hipoglucemiantes/efectos adversos , Insulina/metabolismo , Secreción de Insulina/efectos de los fármacos , Patentes como Asunto , Receptores Acoplados a Proteínas G/metabolismo , Sulfonas/efectos adversos , Sulfonas/farmacología
13.
Curr Diabetes Rev ; 16(2): 137-142, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31362677

RESUMEN

BACKGROUND: Smoking is an established predictor of type 2 diabetes. However, the link between smoking cessation and diabetes progression remains a subject of scholarly investigation. OBJECTIVE: The objective of this systematic review is to establish the link between smoking cessation and diabetes. DATA SOURCES: The study utilized conference abstracts and peer-reviewed journals that reported randomized controlled trials smoking cessation interventions for diabetes patients. RESULTS: Results from the review were inconclusive on the link between smoking cessation and diabetes. On one hand, several researchers have confirmed a positive correlation between smoking cessation and decreased risk of diabetes. On the other hand, some researchers have demonstrated that immediate withdrawal of nicotine resulted in increased risk of diabetes; however, this risk reduces with time. CONCLUSION: The result of this review did not estblish a clear relationship between smoking cessation and diabates. LIMITATIONS: Compared to other studies examining the implication of smoking on chronic diseases, this study identified a very small number of trials evaluating the effect of smoking cessation on diabetes. The small number of studies implies that the results may not be suitable for generalization. IMPLICATION: Results from the review can help in the development of a tailored intervention for effective management of diabetes in smoking patients.


Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Cese del Hábito de Fumar , Fumar/efectos adversos , Diabetes Mellitus Tipo 2/terapia , Progresión de la Enfermedad , Humanos , Nicotina/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo
14.
Food Chem Toxicol ; 135: 110965, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31743741

RESUMEN

Perilla oil (PerO), a natural oil with a high unsaturated fatty acid content derived from the mature seeds of Perilla frutescens, is a homology of medicine and food. The type 2 diabetes mellitus (T2DM) model was successfully established using a high-fat and high-sugar diet combined with a single low-dose of streptozocin (STZ). PerO intervention reduced the levels of fasting blood glucose and the level, size and accumulation of lipid droplets, increased the insulin level and diminished the body weight loss. PerO pretreatment markedly promoted the serum levels of alanine transaminase (ALT) and aspartate transaminase alanine (AST) and inhibited the levels of glucose (GLU), glucose-6-phosphate dehydrogenase (G6PD), triglycerides (TGs) and total cholesterol (TC). Moreover, PerO treatment enhanced the expression of phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) and activated the expression of glucose transporter 4 (Glut4) and phospho-AKT serine/threonine kinase (p-AS160) in the liver. Additionally, PerO treatment distinctly decreased the abundance of Aerococcus and facilitated the richness of Alloprevotella in the intestine, as well as accelerated the restoration of the gut microflora diversity. Thus, PerO regulates intestinal microbiota and alleviates insulin resistance through the PI3K/AKT signaling pathway in type-2 diabetic KKAy mice and may be a potential functional food for diabetic treatment.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina/fisiología , Transducción de Señal/efectos de los fármacos , Ácido alfa-Linolénico/uso terapéutico , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/fisiopatología , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratones Endogámicos C57BL , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Perilla/química , Fosfatidilinositol 3-Quinasa/metabolismo , Aceites Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Estreptozocina
15.
J Orthop Res ; 38(1): 13-22, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31166037

RESUMEN

Over 300,000 tendon repairs are performed annually in the United States to repair damage to tendons as a result of either acute trauma or chronic tendinopathy. Individuals with type II diabetes mellitus (T2DM) are four times more likely to experience tendinopathy, and up to five times more likely to experience a tendon tear or rupture than non-diabetics. As nearly 10% of the US population is diabetic, with an additional 33% pre-diabetic, this is a particularly problematic health care challenge. Tendon healing in general is challenging and often unsatisfactory due to the formation of mechanically inferior scar-tissue rather than regeneration of native tendon structure. In T2DM tendons, there is evidence of an amplified scar tissue response, which may be associated with the increased the risk of rupture or impaired restoration of range of motion. Despite the dramatic effect of T2DM on tendon function and outcomes following injury, there are few therapies available to promote improved healing in these patients. Several recent studies have enhanced our understanding of the pro-inflammatory environment of T2DM healing and have assessed potential treatment approaches to mitigate pathological progression in pre-clinical models of diabetic tendinopathy. This review discusses the current state of knowledge of diabetic tendon healing from molecular to mechanical disruptions and identifies promising approaches and critical knowledge gaps as the field moves toward identification of novel therapeutic strategies to maintain or restore tendon function in diabetic patients. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:13-22, 2020.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Homeostasis , Traumatismos de los Tendones/fisiopatología , Tendones/fisiopatología , Cicatrización de Heridas , Animales , Diabetes Mellitus Tipo 2/fisiopatología , Modelos Animales de Enfermedad , Humanos , Tendinopatía/etiología , Tendones/citología
16.
Adv Exp Med Biol ; 1131: 943-963, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31646540

RESUMEN

Insulin secretion in humans is usually induced by mixed meals, which upon ingestion, increase the plasma concentration of glucose, fatty acids, amino acids, and incretins like glucagon-like peptide 1. Beta-cells can stay in the off-mode, ready-mode or on-mode; the mode-switching being determined by the open state probability of the ATP-sensitive potassium channels, and the activity of enzymes like glucokinase, and glutamate dehydrogenase. Mitochondrial metabolism is critical for insulin secretion. A sound understanding of the intermediary metabolism, electrophysiology, and cell signaling is essential for comprehension of the entire spectrum of the stimulus-secretion coupling. Depolarization brought about by inhibition of the ATP sensitive potassium channel, together with the inward depolarizing currents through the transient receptor potential (TRP) channels, leads to electrical activities, opening of the voltage-gated calcium channels, and exocytosis of insulin. Calcium- and cAMP-signaling elicited by depolarization, and activation of G-protein-coupled receptors, including the free fatty acid receptors, are intricately connected in the form of networks at different levels. Activation of the glucagon-like peptide 1 receptor augments insulin secretion by amplifying calcium signals by calcium induced calcium release (CICR). In the treatment of type 2 diabetes, use of the sulfonylureas that act on the ATP sensitive potassium channel, damages the beta cells, which eventually fail; these drugs do not improve the cardiovascular outcomes. In contrast, drugs acting through the glucagon-like peptide-1 receptor protect the beta-cells, and improve cardiovascular outcomes. The use of the glucagon-like peptide 1 receptor agonists is increasing and that of sulfonylurea is decreasing. A better understanding of the stimulus-secretion coupling may lead to the discovery of other molecular targets for development of drugs for the prevention and treatment of type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Calcio/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Glucosa , Humanos , Insulina , Células Secretoras de Insulina/enzimología , Células Secretoras de Insulina/patología
17.
J Med Life ; 12(3): 290-295, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31666833

RESUMEN

The purpose of this study is to scrutiny the Dynamics of heart rate variability (HRV) in patients with PICS with 2nd type DM against the background of Taurine (TN) and meldonium (ME). The results of the investigations prove the decrease of the oxidative stress, which is basis of DACN, under the influence of sulfur-containing amino acid taurine (TN), and meldonium (ME) - a competitive inhibitor of gamma-butyrobetaine hydroxylase. Biochemical mechanisms of synergistic action of ME and TN are also described. The results of the studies of 98 patients with PICS and concomitant 2nd type diabetes mellitus were analyzed. They were distributed by simple randomization method into two groups, comparable according to age and sex: the main group (MG) (n = 68): and group of comparison (GoC) (n = 30). HRV was evaluated twice daily at the Cardiosense HMEGG system: at baseline and after 12 weeks of treatment. For the assessment of HRV the frequency and spectral parameters were used. While evaluating the different methods of treatment, their influence on the range of spectral and time indices of HRV was determined (p = 0.001 by the criterion of Kruskall-Wallis). It was learned that the combined application of ME and TN gives a statistically significant (p <0.01) increase of SDNN, HF at night, pNN - on 50% by day (p <0.01, p <0.001 and p <0.01 respectively), and statistically significant decrease in LF at night, compared to GHG.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Frecuencia Cardíaca/fisiología , Metilhidrazinas/uso terapéutico , Infarto del Miocardio/complicaciones , Taurina/uso terapéutico , Anciano , Femenino , Humanos , Masculino , Metilhidrazinas/farmacología , Persona de Mediana Edad , Taurina/farmacología , Factores de Tiempo
18.
Adv Neurobiol ; 23: 363-383, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31667816

RESUMEN

Cognitive dysfunction is one of the comorbidities of diabetes mellitus, but hippocampus-dependent learning and memory, a component of cognitive function, shows particular decline in type 2 diabetes, suggesting an increased risk for dementia and Alzheimer's disease. Cognitive function is related to dysregulated glucose metabolism, which is the typical cause of type 2 diabetes; however, hippocampal glycogen and its metabolite lactate are also crucial for hippocampus-dependent memory function. Type 2 diabetes induced hippocampus-dependent learning and memory dysfunction can be improved by chronic exercise and this improvement may possibly mediate through an adaptation of the astrocyte-neuron lactate shuttle (ANLS). This chapter focuses on the dysregulation of hippocampal glycometabolism in type 2 diabetes examining both existing evidence as well as the potential underlying pathophysiological mechanism responsible for memory dysfunction in type 2 diabetes, and showing for the first time that chronic exercise could be an effective therapy for type-2-diabetes-induced hippocampal memory decline.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Ejercicio/fisiología , Glucógeno/metabolismo , Hipocampo/metabolismo , Memoria Espacial , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/terapia , Terapia por Ejercicio , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Ácido Láctico/metabolismo , Neuronas/metabolismo
19.
Medicine (Baltimore) ; 98(44): e17736, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689819

RESUMEN

To explore associated risk factors and their interactions with type 2 diabetes (T2DM) among the elderly with prediabetes in rural areas in China.A nested case-control study was conducted in a fixed cohort to identify the risk factors for T2DM among the elderly with prediabetes in rural areas of Yiyang City in China. A total of 37 elderly with T2DM were included in the cases group and 111 elderly subjects with prediabetes were matched in the control group. Data related to sociodemographic characteristics, lifestyle behavior, and anthropometric variables were collected by trained staff using standard tools. The risk factors for T2DM were determined using conditional logistic regression analysis, and their additive interactions were also explored.Multivariable conditional logistic regression analysis results showed that overweight/obesity (odds ratio [OR] = 4.80, 95% confidence interval [CI]: 1.20-12.28), family history of diabetes (OR = 3.63, 95% CI: 1.03-12.81), physically inactive (OR = 3.08, 95% CI: 1.14-8.30), high waist-to-hip ratio (WHR) (OR = 3.15, 95% CI: 1.27-7.80), and inadequate diabetes-specific health literacy (DSHL) (OR = 3.92, 95% CI: 1.14-13.48) increased the risk for T2DM. Additive interactions for T2DM were observed between a family history of diabetes and high WHR with a relative excess risk of interaction (RERI) of 10.02 (95% CI: 4.25, 15.78), and between high WHR and overweight or obesity, with an RERI of 3.90 (95% CI: 0.36, 7.44).The independent risk factors for T2DM are overweight or obesity, high WHR, family history of diabetes, physically inactive, and inadequate DSHL. High WHR as a risk factor for T2DM has additive interactions with family history of diabetes and overweight or obesity.


Asunto(s)
Diabetes Mellitus Tipo 2/etiología , Estado Prediabético/etiología , Población Rural/estadística & datos numéricos , Anciano , Antropometría , Estudios de Casos y Controles , China/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Ejercicio , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estado Prediabético/epidemiología , Estado Prediabético/fisiopatología , Riesgo , Factores de Riesgo , Conducta Sedentaria , Relación Cintura-Cadera
20.
Medicine (Baltimore) ; 98(44): e17805, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31689862

RESUMEN

Carotid intima-media thickness (C-IMT) increases in patients with adult type-2 diabetes mellitus (DM) and is used for early detection of macrovascular complications. We aimed to investigate the change of C-IMT in prediabetes and type-2 DM patients compared to subjects with normal glucose metabolism (NGM).A total of 180 individuals (60 subjects with NGM, 60 patients with prediabetes and 60 patients with type-2 DM) were included in this study. Routine laboratory and micro-macrovascular involvement were investigated. Urine albumin-creatinine ratio (ACR) was measured for urinary albuminuria detection. In addition to routine laboratory examination, right-left common and internal C-IMT (CC-IMT and IC-IMT) were measured.Systolic and diastolic blood pressure values were found to be higher in prediabetes and type-2 DM groups than NGM group. The prevalence of nephropathy and presence of CAD were higher in type-2 DM groups than prediabetes. Glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, blood urea nitrogen, creatinine, high sensitive C reactive protein (hs-CRP) levels and urinary ACR were significantly higher in patients within prediabetes and type-2 DM groups than NGM group. Glucose, HbA1c and hs-CRP levels were found to be higher in type-2 DM groups than prediabetes. Estimated glomerular filtration rate and high-density lipoprotein (HDL) cholesterol level was found to be lower in patients within prediabetes and type-2 DM groups than NGM group. Right-left-mean CC-IMT and IC-IMT values were found to be higher in prediabetes and type-2 DM groups than NGM group. Left IC-IMT, left CC-IMT, and mean IC-IMT values were found to be higher in type-2 DM patients compared to prediabetes. LDL and HDL cholesterols, HbA1c, and hs-CRP levels were independently associated with IC-IMT and CC-IMT.C-IMT values were significantly higher in impaired glucose metabolism compared to NGM. C-IMT measurement may be used as part of routine screening of macrovascular complication in patients with prediabetes and newly diagnosed type-2 DM.


Asunto(s)
Grosor Intima-Media Carotídeo , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Angiopatías Diabéticas/diagnóstico , Estado Prediabético/diagnóstico por imagen , Anciano , Glucemia/metabolismo , Presión Sanguínea , Proteína C-Reactiva/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estado Prediabético/sangre , Estado Prediabético/fisiopatología
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