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1.
Life Sci ; 244: 117305, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31953161

RESUMO

Diabetes mellitus (DM) is a complex metabolic disorder involving multiple deleterious molecular pathways and cellular defects leading to disturbance in the biologic milieu. It is currently a global health concern with growing incidence, especially among younger adults. There is an unmet need to find new therapeutic targets for the management of diabetes. Vitamin D is a promising target in the pathophysiology of DM, especially since vitamin D deficiency is common in patients with diabetes compared to people without diabetes. Evidence suggests that it can play significant roles in improving peripheral insulin sensitivity and glucose metabolism, however, the exact pathophysiological mechanism is not clarified yet. In this current study, we have reviewed the evidence on the effect of vitamin D in improving insulin resistance via distinct molecular pathways.


Assuntos
Intolerância à Glucose/prevenção & controle , Homeostase , Deficiência de Vitamina D/complicações , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Animais , Intolerância à Glucose/etiologia , Humanos
2.
Nutrients ; 11(8)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409000

RESUMO

Helicobacter pylori (H. pylori) may be involved in diabetes and other insulin-related processes. This study aimed to investigate the associations between H. pylori infection and the risks of type 2 diabetes, impaired glucose tolerance (IGT), diabetic nephropathy, and poor glycemic control. We retrospectively evaluated 16,091 subjects without diabetes at baseline who underwent repeated health examinations. Subjects were categorized according to whether they were seropositive and seronegative for H. pylori infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The serological results were validated using an independent cohort (n = 42,351) based on a histological diagnosis of H. pylori infection. During 108,614 person-years of follow-up, 1338 subjects (8.3%) developed newly diagnosed diabetes, although the cumulative incidence of diabetes was not significantly related to serological H. pylori status. The multivariate Cox proportional-hazards regression models revealed that H. pylori seropositivity was not significantly associated with diabetes (HR: 1.01, 95% CI: 0.88-1.16; p = 0.854), IGT (HR: 0.98, 95% CI: 0.93-1.04; p = 0.566), diabetic nephropathy (HR: 0.99, 95% CI: 0.82-1.21; p = 0.952), or poor glycemic control (HR: 1.05, 95% CI: 0.90-1.22; p = 0.535). Similarly, histopathological findings of H. pylori infection were not significantly associated with diabetes (p = 0.311), diabetic nephropathy (p = 0.888), or poor glycemic control (p = 0.989). The findings from these large Korean cohorts indicate that there does not appear to be a role for past H. pylori infection in the development of diabetes, IGT, diabetic nephropathy, or poor glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Infecções por Helicobacter , Helicobacter pylori/crescimento & desenvolvimento , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Nefropatias Diabéticas/etiologia , Feminino , Intolerância à Glucose/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Hiperglicemia/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Fatores de Risco
3.
Nutrients ; 11(9)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443365

RESUMO

Development of obesity-associated comorbidities is related to chronic inflammation, which has been linked to gut microbiota dysbiosis. Thus, modulating gut microbiota composition could have positive effects for metabolic disorders, supporting the use of probiotics as potential therapeutics in vivo, which may be enhanced by a microencapsulation technique. Here we investigated the effects of non-encapsulated or pectin-encapsulated probiotic supplementation (Lactobacillus paracasei subsp. paracasei L. casei W8®; L. casei W8) on gut microbiota composition and metabolic profile in high-fat (HF) diet-fed rats. Four male Wistar rat groups (n = 8/group) were fed 10% low-fat, 45% HF, or HF with non-encapsulated or encapsulated L. casei W8 (4 × 107 CFU/g diet) diet for seven weeks. Microbiota composition, intestinal integrity, inflammatory profiles, and glucose tolerance were assessed. Non-encapsulated and pectin-encapsulated probiotic supplementation positively modulated gut microbiota composition in HF-fed male rats. These changes were associated with improvements in gut barrier functions and local and systemic inflammation by non-encapsulated probiotics and improvement in glucose tolerance by encapsulated probiotic treatment. Thus, these findings suggest the potential of using oral non-encapsulated or encapsulated probiotic supplementation to ameliorate obesity-associated metabolic abnormalities.


Assuntos
Glicemia/metabolismo , Dieta Hiperlipídica , Microbioma Gastrointestinal , Intolerância à Glucose/prevenção & controle , Inflamação/prevenção & controle , Intestinos/microbiologia , Lactobacillus/crescimento & desenvolvimento , Probióticos/administração & dosagem , Animais , Modelos Animais de Doenças , Disbiose , Metabolismo Energético , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Intolerância à Glucose/microbiologia , Inflamação/sangue , Inflamação/etiologia , Inflamação/microbiologia , Mediadores da Inflamação/sangue , Insulina/sangue , Masculino , Permeabilidade , Ratos Wistar
4.
Artigo em Inglês | MEDLINE | ID: mdl-31284480

RESUMO

Background: Early-onset diabetes results in longer lifetime hyperglycemic exposure that consequently leads to earlier chronic diabetes complications and premature death. The aim of this study was to quantify the prevalence and risk factors of undiagnosed diabetes and undiagnosed prediabetes in apparently healthy young adults aged <40 years. Methods: This study used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey conducted by the Korean Ministry of Health and Welfare from 2014 to 2017. A total of 4442 apparently healthy young adults enrolled in this study. Multivariate logistic regression analyses were conducted separately to evaluate associated risk factors with undiagnosed diabetes and undiagnosed prediabetes in groups stratified by sex. Results: The prevalence of undiagnosed diabetes and undiagnosed prediabetes was 1.2% and 25.0%, respectively. Obesity (body mass index ≥ 30.0 kg/m2) was a significant risk factor of undiagnosed diabetes regardless of sex (men, odds ratio (OR): 9.808, 95% confidence interval (CI): 1.619-59.412; women, OR: 7.719, 95% CI: 1.332-44.747). Family history of diabetes was significantly associated with undiagnosed diabetes (OR: 3.407, 95% CI: 1.224-9.481) in women only. Increased age, obesity status, and family history of diabetes were significant risk factors for undiagnosed prediabetes. Alcohol consumption was found to be negatively associated with undiagnosed prediabetes in women. Conclusions: Increased attention and implementation of precise strategies for identifying young adults at high risk for undiagnosed diabetes would allow for increased wellbeing as well as reduced healthcare burdens associated with diabetes.


Assuntos
Intolerância à Glucose/epidemiologia , /epidemiologia , Adulto , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/etiologia , Humanos , Masculino , Inquéritos Nutricionais , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , /etiologia , Adulto Jovem
6.
Diabetes Metab Syndr ; 13(2): 1047-1051, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336442

RESUMO

BACKGROUND: The World has seen an emerging trend of diabetes among adolescents and moderately aged people over the last decade. The aim of the study was to identify the risk factors associated with impaired glucose metabolism and the prevalence of impaired glucose metabolism among the adult population of district Srinagar. METHODS: Multi-stage cluster random sampling design was used and from each household, participants were selected using a Kish grid method. Socio-demographic and clinical data were collected. The participants were then subjected to fasting venous blood glucose estimation. RESULTS: Age, waist circumference, hip circumference, weight, and body mass index were all statistically significant between normoglycemic participants and those with impaired glucose metabolism (p < 0.018). On logistic regression, subjects who had a higher BMI were more likely to develop Impaired glucose metabolism (OR = 3.52, OR 95% CI = 1.25-9.87); Moreover, consumption of carbonated drinks, (3-6 times/week OR = 4.40, OR 95% CI = 2.06-9.40; >6 times/week OR = 11.04, OR 95% CI = 0.86-140.66) was found to be a potential risk factor. Participants with a family history of diabetes were more susceptible to develop impaired glucose metabolism (OR = 6.41, OR 95% CI = 3.22-12.78). The risk effect of these factors was even stronger before adjusting for age, sex, family history of diabetes, and BMI in participants. CONCLUSION: Risk factors for impaired glucose metabolism include increasing age, obesity, and higher consumption of carbonated drinks, hypertension, smoking behavior, high-calorie diet intake and positive family history of diabetes.


Assuntos
Biomarcadores/análise , Índice de Massa Corporal , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/etiologia , Obesidade/complicações , Circunferência da Cintura , Adulto , Idoso , Glicemia/análise , Estudos Transversais , Feminino , Seguimentos , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Adulto Jovem
7.
Neurol India ; 67(3): 757-762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347550

RESUMO

Objective: The natural history of glucose intolerance (GI) in patients with acromegaly undergoing surgical treatment has not been fully understood. This study was aimed to unravel the prevalence and predictors of recovery from GI in these patients in a prospective multivariate model. Materials and Methods: Patients with acromegaly treated between 2007 and 2016 were prospectively studied with respect to demographics, clinicoradiological features, comorbidities, and hormonal investigations before surgery and at regular follow-up. The independent predictors of recovery from diabetes were analyzed. Results: There were a total of 151 patients with active acromegaly included in the study. The median baseline growth hormone (GH) and insulin-like growth factor (IGF)-1 levels were 25 and 811 ng/mL, respectively. Diabetes mellitus (DM) and pre-diabetes were noted in 93 (61.6%) and 20 (13.2%) patients, respectively. Following surgical treatment, the median HbA1c decreased significantly from 6.4% to 5.5% (P < 0.001), with 46.8% having complete recovery from DM or pre-diabetes. This glycemic recovery had significant association with both biochemical (P = 0.001) and radiological remission (P = 0.01). The recovery from DM had a greater association with post-operative IGF-1 than GH, especially among those with discordant GH and IGF-1 levels (60% in normal IGF-1 and high GH vs. 20% in high IGF-1 and normal GH). Post-operative IGF-1 had a significant impact on recovery from DM (P = 0.01) independent of age, body mass index, duration of DM, and pre-operative HbA1c. Conclusion: Nearly half of the patients with acromegaly with DM or pre-diabetes had glycemic recovery, influenced by biochemical and radiologic remission. Post-operative IGF-1 appears to be the strongest independent determinant of recovery from DM.


Assuntos
Acromegalia/cirurgia , Complicações do Diabetes/diagnóstico , Acromegalia/complicações , Adolescente , Adulto , Idoso , Criança , Complicações do Diabetes/etiologia , Feminino , Intolerância à Glucose/etiologia , Hormônio do Crescimento Humano/análise , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
8.
Diabetes Metab Syndr ; 13(3): 1971-1973, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31235123

RESUMO

BACKGROUND: Vitamin D deficiency appears to be lower in diabetic patients. Vitamin D may affect glycemic control & diabetic nephropathy. AIM: To assess vitamin D level in type 2 diabetic patients and its relation to their glycemic control and development of nephropathy compared to healthy controls. DESIGN: and Setting: Case control study including 82 participants (41 cases and 41 controls) from Family Medicine Clinic, Cairo University Hospitals. METHOD: Participants fulfilling the inclusion criteria were allocated into two groups, diabetes and control groups. History was taken, examination was done, and blood sample was withdrawn for analysis of Vitamin D levels and HBA1C. From the diabetic group only, serum creatinine was assessed and urine sample was collected for microalbuminuria. The results were analyzed using SPSS program version 21. RESULTS: Vitamin D level was lower in the diabetic group compared to control (65.5% and 56.1%). Vitamin D level was inversely proportionate to HbA1c levels in the diabetic patients (p value 0.000 & r -0.482), as well as to the A/C ratio (p value 0.01 & r -0.396). CONCLUSION: Vitamin D level appeared to be lower in diabetic patients and is associated with poor glycemic control & microalbuminuria.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Intolerância à Glucose/etiologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/sangue , Adulto , Glicemia/análise , Estudos de Casos e Controles , Estudos Transversais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Feminino , Seguimentos , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hemoglobina A Glicada/análise , Índice Glicêmico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Deficiência de Vitamina D/sangue , Vitaminas/sangue
9.
Diabetes Metab Syndr ; 13(3): 2057-2060, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31235136

RESUMO

Patients with Diabetic nephropathy (DN) have an increase in cardiovascular mortality, and since IR may be a contributing factor. Therefore, the aim of this study was to assess the role of pro insulin/insulin ratio as a predictor of insulin resistance in patients with diabetic nephropathy PATIENTS AND METHODS: A Case-control study was conducted in a total of 50 patients who diagnosed with type 2 diabetes mellitus from July 2017 to March 2018. The patients were divided into 2 groups according to presence of diabetic nephropathy. Demographic and clinical data were collected. RESULTS: There is a significant increase in serum pro insulin/insulin ratio in patients with diabetic nephropathy patients compared to patients without diabetic nephropathy An association was found between increase serum pro insulin/insulin ratio and increase predicting of insulin resistance. Cut-off value of serum pro insulin/insulin ratio ≥0.1145 with sensitivity and specificity of 92.3 and 60.3 respectively as a predictor for insulin resistance CONCLUSION: This study demonstrate a strong relationship between insulin resistance and CKD and this relationship was stronger in the presence of obesity. Pro insulin/insulin ratio was found to be a significant predictor for insulin resistance.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/complicações , Intolerância à Glucose/diagnóstico , Resistência à Insulina , Insulina/sangue , Proinsulina/sangue , Glicemia/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Diabetes Metab Syndr ; 13(3): 2208-2213, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31235158

RESUMO

AIMS: Glucose tolerance abnormalities are frequently observed in patients with chronic liver disease (CLD). Insulin resistance (IR) has been suggested to be a major factor responsible for these abnormalities in CLD. However studies relating IR with severity of CLD are scarce in Nigeria. This study assessed insulin resistance and glucose tolerance abnormalities in CLD and their relationship with the severity of CLD in a tertiary hospital in South-West, Nigeria. METHODS: This cross sectional study involved 100 subjects with CLD. Ethical clearance was obtained and informed consent was granted by participants. Participants were interviewed using a structured proforma; physical examination and relevant investigations were performed. Insulin resistance was measured using the homeostasis model assessment (HOMA-IR) Data was analysed using Statistical Package for Social Sciences version 20.0 and p value of <0.05 was considered significant. RESULTS: Mean age of the study participants was 51.9 ±â€¯11.9 years, and mean duration of CLD was 15.9 ±â€¯5.8 months. Glucose tolerance abnormalities were present in 66 subjects (66%) and increased from 16.1% in Child Pugh's class A to 90.0% in class C. HOMA-IR positively correlated with age, body mass index, serum blood glucose, duration and severity of CLD. Increasing age, presence of hepatocellular carcinoma, Child Pugh's class B and class C were associated with glucose tolerance abnormalities. CONCLUSION: Glucose tolerance abnormalities and insulin resistance were highly prevalent among chronic liver disease subjects studied and seemed to parallel the severity of CLD, determined by the Child Pugh's score.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Resistência à Insulina , Hepatopatias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Estudos Transversais , Feminino , Seguimentos , Intolerância à Glucose/epidemiologia , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prognóstico , Fatores de Risco , Adulto Jovem
11.
Nutrients ; 11(6)2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31212845

RESUMO

This study was performed to estimate the possibility of using an ethyl acetate fraction from Aruncus dioicus var. kamtschaticus (EFAD) on metabolic syndrome that is induced by a high-fat diet (HFD). It was demonstrated that EFAD suppresses lipid accumulation and improves insulin resistance (IR) caused by Tumor necrosis factor alpha (TNF-α) in in-vitro experiments using the 3T3-L1 cell. In in-vivo tests, C57BL/6 mice were fed EFAD at 20 and 40 mg/kg body weight (BW) for four weeks after the mice were fed HFD for 15 weeks to induce obesity. EFAD significantly suppressed the elevation of BW and improved impaired glucose tolerance in obese mice. Additionally, this study showed that EFAD has an ameliorating effect on obesity-induced cognitive disorder with behavioral tests. The effect of EFAD on peripheral-IR improvement was confirmed by serum analysis and western blotting in peripheral tissues. Additionally, EFAD showed an ameliorating effect on HFD-induced oxidative stress, impaired cholinergic system and mitochondrial dysfunction, which are interrelated symptoms of neurodegeneration, such as Alzheimer's disease and central nervous system (CNS)-IR in brain tissue. Furthermore, we confirmed that EFAD improves CNS-IR by confirming the IR-related factors in brain tissue. Consequently, this study suggests the possibility of using EFAD for the prevention of neurodegeneration by improving metabolic syndrome that is caused by HFD.


Assuntos
Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Obesidade/psicologia , Extratos Vegetais/farmacologia , Células 3T3-L1 , Animais , Peso Corporal/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/etiologia , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia
12.
Am J Physiol Endocrinol Metab ; 317(2): E362-E373, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237447

RESUMO

Skeletal muscle insulin resistance manifests shortly after high-fat feeding, yet mechanisms are not known. Here we set out to determine whether excess skeletal muscle membrane cholesterol and cytoskeletal derangement known to compromise glucose transporter (GLUT)4 regulation occurs early after high-fat feeding. We fed 6-wk-old male C57BL/6NJ mice either a low-fat (LF, 10% kcal) or a high-fat (HF, 45% kcal) diet for 1 wk. This HF feeding challenge was associated with an increase, albeit slight, in body mass, glucose intolerance, and hyperinsulinemia. Liver analyses did not reveal signs of hepatic insulin resistance; however, skeletal muscle immunoblots of triad-enriched regions containing transverse tubule membrane showed a marked loss of stimulated GLUT4 recruitment. An increase in cholesterol was also found in these fractions from HF-fed mice. These derangements were associated with a marked loss of cortical filamentous actin (F-actin) that is essential for GLUT4 regulation and known to be compromised by increases in membrane cholesterol. Both the withdrawal of the HF diet and two subcutaneous injections of the cholesterol-lowering agent methyl-ß-cyclodextrin at 3 and 6 days during the 1-wk HF feeding intervention completely mitigated cholesterol accumulation, cortical F-actin loss, and GLUT4 dysregulation. Moreover, these beneficial membrane/cytoskeletal changes occurred concomitant with a full restoration of metabolic responses. These results identify skeletal muscle membrane cholesterol accumulation as an early, reversible, feature of insulin resistance and suggest cortical F-actin loss as an early derangement of skeletal muscle insulin resistance.


Assuntos
Membrana Celular/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/etiologia , Resistência à Insulina , Músculo Esquelético/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Colesterol/farmacologia , Dieta Ocidental/efeitos adversos , Gorduras na Dieta/farmacologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/prevenção & controle , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Hiperinsulinismo/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
13.
Am J Physiol Endocrinol Metab ; 317(2): E399-E410, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237448

RESUMO

Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor farnesoid X receptor (FXR) has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA), improves insulin sensitivity in patients with type 2 diabetes with nonalcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high-fat diet (HFD; 60% kcal from fat) for 4 wk before and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in nonpregnant and pregnant HFD-fed mice (by 22.4%, P < 0.05 and 36.4%, P < 0.001, respectively) and reduced the impact of pregnancy on insulin resistance but did not change glucose tolerance. In nonpregnant HFD-fed mice, OCA ameliorated weight gain, reduced mRNA expression of inflammatory markers in white adipose tissue, and reduced plasma glucagon-like peptide 1 concentrations (by 62.7%, P < 0.01). However, these effects were not evident in pregnant mice. OCA administration can normalize plasma cholesterol levels in a mouse model of GDM. However, the absence of several of the effects of OCA in pregnant mice indicates that the agonistic action of OCA is not sufficient to overcome many metabolic consequences of the pregnancy-associated reduction in FXR activity.


Assuntos
Glicemia/efeitos dos fármacos , Ácido Quenodesoxicólico/análogos & derivados , Diabetes Gestacional/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Animais , Glicemia/metabolismo , Ácido Quenodesoxicólico/uso terapêutico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Dislipidemias/complicações , Dislipidemias/metabolismo , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/metabolismo
14.
BMC Endocr Disord ; 19(1): 44, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053128

RESUMO

Gestational Diabetes Mellitus (GDM) is the most common metabolic disorder in pregnancy, and it is associated with increased risk of morbidity in maternal-fetal outcomes. GDM is also associated with a higher risk to develop diabetes in the future. Diabetes-related autoantibodies (AABs) have been detected in a small percentage (usually less than 10%) of women with gestational diabetes. The prevalence in gestational diabetes of these autoimmune markers of type 1 diabetes (T1D) has been assessed in many studies, together with the risk of progression of AABs-positive GDM towards impaired glucose regulation (IFG or IGT) and overt diabetes after pregancy. The question whether it is necessary to test for T1D autoantibodies in all pregnancies with GDM is still debated. Here we examine the epidemiology of T1D autoantibodies in GDM, their clinical relevance in term of future risk of diabetes or impaired glucose regulation and in term of maternal-fetal outcomes, and discuss when it may be the most appropriate time to search for T1D autoantibodies in women with gestational diabetes.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Gestacional/sangue , Intolerância à Glucose/diagnóstico , Autoanticorpos/imunologia , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/imunologia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/etiologia , Teste de Tolerância a Glucose , Humanos , Gravidez , Prognóstico
15.
Nutrients ; 11(6)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141900

RESUMO

Animal experimentation has a long history in the study of metabolic syndrome-related disorders. However, no consensus exists on the best models to study these syndromes. Knowing that different diets can precipitate different metabolic disease phenotypes, herein we characterized several hypercaloric rat models of obesity and type 2 diabetes, comparing each with a genetic model, with the aim of identifying the most appropriate model of metabolic disease. The effect of hypercaloric diets (high fat (HF), high sucrose (HSu), high fat plus high sucrose (HFHSu) and high fat plus streptozotocin (HF+STZ) during different exposure times (HF 3 weeks, HF 19 weeks, HSu 4 weeks, HSu 16 weeks, HFHSu 25 weeks, HF3 weeks + STZ) were compared with the Zucker fatty rat. Each model was evaluated for weight gain, fat mass, fasting plasma glucose, insulin and C-peptide, insulin sensitivity, glucose tolerance, lipid profile and liver lipid deposition, blood pressure, and autonomic nervous system function. All animal models presented with insulin resistance and dyslipidemia except the HF+STZ and HSu 4 weeks, which argues against the use of these models as metabolic syndrome models. Of the remaining animal models, a higher weight gain was exhibited by the Zucker fatty rat and wild type rats submitted to a HF diet for 19 weeks. We conclude that the latter model presents a phenotype most consistent with that observed in humans with metabolic disease, exhibiting the majority of the phenotypic features and comorbidities associated with type 2 diabetes in humans.


Assuntos
Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica , Sacarose na Dieta , Intolerância à Glucose/etiologia , Resistência à Insulina , Síndrome Metabólica/etiologia , Obesidade/etiologia , Ganho de Peso , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Dislipidemias/sangue , Dislipidemias/etiologia , Dislipidemias/fisiopatologia , Ingestão de Energia , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Insulina/sangue , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Obesidade/sangue , Obesidade/fisiopatologia , Fenótipo , Ratos Wistar , Ratos Zucker
16.
PLoS One ; 14(5): e0216728, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071174

RESUMO

Gestational diabetes mellitus (GDM) is today universally diagnosed during late pregnancy. Treating hyperglycaemia during pregnancy reduces the risk of complications, the effect of interventions is however limited due to the late diagnosis. It is thus important to identify biomarkers reaching a high precision for GDM development in early pregnancy. Here we aim to investigate soluble CD163 (sCD163) and soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) in early pregnancy GDM and their association to the development of later glucose intolerance. In this case-control study, women diagnosed with GDM in early pregnancy (n = 70) at Lund University Hospital, Lund, Sweden in 2011-2015 were age- and BMI matched to pregnant volunteers without diabetes (n = 70) recruited in early pregnancy from maternal health care centres in 2014-2015. Plasma levels of sCD163 and sTWEAK were analysed using commercial ELISA. Plasma levels of sCD163 did not differ between patients with and without GDM in early pregnancy (p = 0.86), plasma levels of sTWEAK however was decreased in women with GDM (0.71 [0.4-1.75] ng/ml) compared to controls (1.38 [0.63-4.86] ng/ml; p = 0.003). Women with sTWEAK levels in the lowest tertile had an increased risk of GDM in early pregnancy (p = 0.014). Neither sCD163 nor sTWEAK were associated with later glucose intolerance in women with GDM. This study reports decreased levels of sTWEAK in women with early pregnancy GDM, independent of age and BMI. Neither sCD163 nor sTWEAK were found to be associated to later glucose intolerance.


Assuntos
Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Citocina TWEAK/sangue , Diabetes Gestacional/sangue , Intolerância à Glucose/sangue , Receptores de Superfície Celular/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Intolerância à Glucose/etiologia , Humanos , Pessoa de Meia-Idade , Gravidez , Primeiro Trimestre da Gravidez/sangue , Fatores de Risco , Solubilidade , Suécia , Adulto Jovem
17.
J Pediatr Endocrinol Metab ; 32(5): 537-541, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31075084

RESUMO

Hematopoietic stem cell transplantation (HSCT) has been newly identified as an etiology underlying acquired lipodystrophy (ALD). We report about two children with leukemia who underwent HSCT and later manifested aberrant fat distributions consistent with acquired partial lipodystrophy (APL). Both patients manifested graft-versus-host disease (GVHD), suggesting that GVHD may trigger lipodystrophy. The patients exhibited diabetic blood glucose patterns in the oral glucose tolerance test (OGTT) with high homeostasis model assessment ratios (HOMA-Rs), hypertriglyceridemia, fatty liver, and decreased serum leptin and adiponectin levels. Both patients were diagnosed with APL with metabolic disease. A review of the data of patients with ALD after HSCT revealed common clinical features, including aberrant fat distribution, impaired glucose tolerance (IGT) or diabetes and dyslipidemia. Based on previous reports and our two cases, we speculate that GVHD in the adipose tissue supports the development of ALD after HSCT. In conclusion, children may develop APL after HSCT. Therefore, evaluations of fat distribution and metabolic disease may be important during the long-term follow-up of these patients.


Assuntos
Fígado Gorduroso/etiologia , Intolerância à Glucose/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hipertrigliceridemia/etiologia , Leucemia Mieloide Aguda/terapia , Lipodistrofia/etiologia , Doenças Metabólicas/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Fígado Gorduroso/patologia , Feminino , Intolerância à Glucose/patologia , Humanos , Hipertrigliceridemia/patologia , Lactente , Leucemia Mieloide Aguda/patologia , Lipodistrofia/patologia , Doenças Metabólicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico
18.
Cells ; 8(4)2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018536

RESUMO

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder accompanied by high blood glucose, insulin resistance, and relative insulin deficiency. Endoplasmic reticulum (ER) stress induced by high glucose and free fatty acids has been suggested as one of the main causes of ß-cell dysfunction and death in T2DM. Stem cell-derived insulin-secreting cells were recently suggested as a novel therapy for diabetes. In the present study, we demonstrate the therapeutic potential of tonsil-derived mesenchymal stem cells (TMSCs) to treat high-fat diet (HFD)-induced T2DM. To explore whether TMSC administration can alleviate T2DM, TMSCs were intraperitoneally injected in HFD-induced T2DM mice once every 2 weeks. TMSC injection markedly improved glucose tolerance and glucose-stimulated insulin secretion and prevented HFD-induced pancreatic ß-cell hypertrophy and cell death. In addition, TMSC injection relieved the ER-stress response and preserved gene expression related to glucose sensing and insulin secretion. Moreover, administration of TMSC-derived conditioned medium induced similar therapeutic outcomes, suggesting paracrine effects. Finally, proteomic analysis revealed high secretion of insulin-like growth factor-binding protein 5 by TMSCs, and its expression was critical for the protective effects of TMSCs against HFD-induced glucose intolerance and ER-stress response in pancreatic islets. TMSC administration can alleviate HFD-induced-T2DM via preserving pancreatic islets and their function. These results provide novel evidence of TMSCs as an ER-stress modulator that may be a novel, alternative cell therapy for T2DM.


Assuntos
Intolerância à Glucose/metabolismo , Intolerância à Glucose/terapia , Células-Tronco Mesenquimais/metabolismo , Animais , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Glucose/metabolismo , Intolerância à Glucose/etiologia , Humanos , Hiperglicemia/complicações , Insulina/genética , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina , Ilhotas Pancreáticas/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Tonsila Palatina/metabolismo , Tonsila Palatina/fisiologia
19.
Presse Med ; 48(3 Pt 2): e125-e145, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30878333

RESUMO

The correct diagnosis of a patient presenting with a solid pancreatic mass requires a careful diagnostic work-up, since many differential diagnoses are possible that completely alter the following treatments. In our chapter, we have discussed the clinical approach to the problem in a sort of diagnostic flow-chart. Firstly, we analysed the different potential presentations of a solid pancreatic mass, which can be both asymptomatic or symptomatic, and the differential diagnosis based on the symptoms of presentation. Then we focused on the various imaging techniques commonly used in the diagnostic work-up, stressing on the different presentations according to the type of disease, and the operative procedures that can supplement this part. Lastly, we discussed the best diagnostic work up that should be followed to fully understand the characteristics of each disease, which is of paramount importance to choose the adequate treatment plan, with special attention to pancreatic adenocarcinoma and its many treatment strategies such as chemotherapy, surgery, or medical therapy. In patients presenting with a solid pancreatic mass it is crucial to reach a definitive diagnosis using a well determined diagnostic work-up to better characterize the lesion, since the best treatment varies widely according not only to the type of disease but also to its features.


Assuntos
Neoplasias Pancreáticas/diagnóstico , Dor Abdominal/etiologia , Adenocarcinoma/diagnóstico , Ampola Hepatopancreática/patologia , Biomarcadores Tumorais/análise , Carcinoma de Células Acinares/diagnóstico , Diabetes Mellitus/etiologia , Diagnóstico Diferencial , Diagnóstico por Imagem , Drenagem , Endoscopia do Sistema Digestório , Intolerância à Glucose/etiologia , Humanos , Icterícia/etiologia , Laparoscopia , Náusea/etiologia , Estadiamento de Neoplasias/métodos , Tumores Neuroendócrinos/diagnóstico , Cuidados Paliativos , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Pancreatite/diagnóstico , Seleção de Pacientes , Vômito/etiologia
20.
Amino Acids ; 51(4): 727-738, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30830312

RESUMO

Obesity in fathers leads to DNA damage and epigenetic changes in sperm that may carry potential risk factors for metabolic diseases to the next generation. Taurine (TAU) supplementation has demonstrated benefits against testicular dysfunction and pancreatic islet impairments induced by obesity, but it is not known if these protective actions prevent the propagation of metabolic disruptions to the next generation; as such, we hypothesized that paternal obesity may increase the probability of endocrine pancreatic dysfunction in offspring, and that this could be prevented by TAU supplementation in male progenitors. To test this, male C57Bl/6 mice were fed on a control diet (CTL) or a high-fat diet (HFD) without or with 5% TAU in their drinking water (CTAU and HTAU) for 4 months. Subsequently, all groups of mice were mated with CTL females, and the F1 offspring were identified as: CTL-F1, CTAU-F1, HFD-F1, and HTAU-F1. HFD-fed mice were normoglycemic, but glucose intolerant and their islets hypersecreted insulin. However, at 90 days of age, HFD-F1 offspring displayed normal glucose homeostasis and adiposity, but reduced glucose-induced insulin release. HFD-F1 islets also exhibited ß- and α-cell hypotrophy, and lower δ-cell number per islet. Paternal TAU supplementation prevented the decrease in glucose-induced insulin secretion and normalized ß-cell size and δ-cell number, and increased α-cell size/islet in HTAU-F1 mice. In conclusion, HFD consumption by male founders decreases ß-cell secretion and islet-cell distribution in their offspring. TAU attenuates the deleterious effects of paternal obesity on insulin secretion and islet-cell morphology in F1 offspring.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Sistema Endócrino/efeitos dos fármacos , Intolerância à Glucose/tratamento farmacológico , Ilhotas Pancreáticas/efeitos dos fármacos , Pancreatopatias/tratamento farmacológico , Taurina/administração & dosagem , Animais , Sistema Endócrino/fisiopatologia , Intolerância à Glucose/etiologia , Intolerância à Glucose/patologia , Homeostase , Secreção de Insulina , Ilhotas Pancreáticas/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/fisiopatologia , Pancreatopatias/etiologia , Pancreatopatias/patologia
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