Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 135
Braz. j. med. biol. res ; 54(8): e10782, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249333


We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-α). HFCD-fed rats had significantly (P≤0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-α, and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-α levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone.

Animals , Rats , Insulin Resistance , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Carbohydrates/pharmacology , Oxidative Stress , Diet, High-Fat , Pioglitazone/metabolism , Pioglitazone/pharmacology , Insulin/metabolism , Liver/metabolism , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology
Article in Chinese | WPRIM | ID: wpr-888017


Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic β cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic β cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic βcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic β cells.

Animals , Diabetes Mellitus, Type 2/metabolism , Glucose/metabolism , Glycosylation , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Iridoids , Rats
Rev. Assoc. Med. Bras. (1992) ; 66(3): 334-337, Mar. 2020. tab
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1136205


SUMMARY OBJECTIVE To present the results of metabolic control in patients with type 2 Diabetes Mellitus from a private clinic in Northern Mexico, METHODS This cross-sectional study used retrospective data obtained from electronic records from a private outpatient clinic at the end of 2018. Inclusion criteria were a diagnosis of T2DM and age ≥ 18 years. Baseline characteristics (age, gender, drug use) were reported. The achievement of glycated hemoglobin goals was established as <7%. RESULTS A total of 3820 patients were evaluated. Their mean age was 59.86 years (+/-15.01). Of the population, 46.72% were men, and 53.28% were women. Glycated hemoglobin goals were adequate in 1872 (54%) patients. There were 3247 patients (85%) treated with oral medications, of which 1948 (60%) reported glycated hemoglobin less than 7%. Insulin use was reported in 573 (15%) patients, with 115 (20%) reporting glycated hemoglobin less than 7%. The most frequently used basal insulin was glargine in 401 (70%) patients. CONCLUSIONS Our findings are clearly higher than the control rate reported by our national health surveys of 25% with glycated hemoglobin < 7%, but similar to that reported in other countries. The most commonly used therapeutic scheme was the combination of oral hypoglycemic agents. The percentage of cases that include insulin in their treatment was lower. Clinical inertia to insulin initiation and intensification has been defined as an important cause of this problem.

RESUMO OBJETIVO Apresentar os resultados do controle metabólico de pacientes com Diabetes Mellitus tipo 2 em uma clínica privada no norte do México, MÉTODOS Este estudo transversal utilizou dados retrospectivos obtidos em prontuários eletrônicos de um ambulatório privado no final de 2018. Os critérios de inclusão foram o diagnóstico de DM2 e idade ≥ 18 anos. Características basais (idade, sexo, uso de drogas) foram relatadas. A realização de metas de hemoglobina glicada foi estabelecida como <7%. RESULTADOS Um total de 3820 pacientes foram avaliados. A média de idade foi de 59,86 anos (+/- 15,01). Da população, 46,72% eram homens e 53,28% eram mulheres. Objetivos de hemoglobina glicada foram adequados em 1872 (54%) pacientes. Havia 3247 pacientes (85%) tratados com medicamentos orais relatando em 1948 (60%) menos de 7%. O uso de insulina foi relatado em 573 (15%) pacientes, com 115 (20%) relatando menos de 7%. A insulina basal mais utilizada foi a glargina, em 401 (70%) pacientes. CONCLUSÕES Nossos resultados são claramente mais altos do que a taxa de controle relatada por nossos levantamentos nacionais de saúde de 25% com hemoglobina glicada <7%, mas semelhante à relatada em outros países. O esquema terapêutico mais utilizado foi a combinação de hipoglicemiantes orais. A porcentagem de casos que incluem insulina no tratamento foi menor. A inércia clínica à iniciação e intensificação da insulina tem sido definida como uma importante causa desse problema.

Humans , Male , Female , Adult , Aged , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Glycated Hemoglobin A , Cross-Sectional Studies , Retrospective Studies , Drug Therapy, Combination , Insulin Glargine/administration & dosage , Mexico , Middle Aged
Rev. Col. Bras. Cir ; 47: e20202394, 2020. tab, graf
Article in Portuguese | LILACS | ID: biblio-1136585


RESUMO Objetivo: avaliar as diferenças no perfil metabonômico de pacientes que atingiram remissão de diabetes mellitus tipo 2 (DM2) após cirurgia bariátrica em relação aos que apresentaram manutenção ou recidiva dessa condição após a cirurgia. Métodos: Participaram do estudo 33 pacientes obesos diabéticos tipo 2, dos quais 22 tiveram remissão completa da DM2 e 11 tiveram recidiva da DM2 ou não apresentaram remissão da doença no pós-operatório. Amostras de sangue foram coletadas para avaliação dos perfis metabonômicos séricos através de um estudo metabonômico baseado em RMN de 1H. Resultados: o modelo metabonômico para avaliação da recidiva da diabetes apresentou uma acurácia de 93,9%, sensibilidade de 81,8%, especificidade de 100%, valor preditivo positivo (VPP) igual a 100% e valor preditivo negativo (VPN) igual a 91,7%. Conclusão: a cirurgia bariátrica promove efeitos específicos na distribuição dos metabólitos de pacientes que atingiram remissão de DM2, e essa nova distribuição pode ser avaliada através de um modelo metabonômico.

ABSTRACT Purpose: To evaluate the differences in the metabonomic profile of patients who achieved remisison of Type 2 diabetes mellitus (T2DM) after bariatric surgery in relation to those who presented maintenance or recurrence of this condition after surgery. Methods: Thirthy-three patients with obesity and T2D were submitted to bariatric/metabolic surgery, among which, 22 experienced complete remission of T2D, and 11 did not experience remission in the postoperative period. Blood samples were taken in order to assess the serum profiles through a 1H NMR-based metabonomic study. Results: The metabonomic model for the assessment of T2D recurrence presented an accuracy of 93.9%, sensibility of 81.8%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 91.7%. Conclusion: bariatric surgery provide specific effects on the distribution of metabolites in those patients who achieved remission of T2DM, and this new distribution can be assessed through a metabonomic model.

Humans , Male , Female , Obesity, Morbid/surgery , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Bariatric Surgery , Time Factors , Blood Glucose/metabolism , Obesity, Morbid/metabolism , Remission Induction , Biomarkers/metabolism , Weight Loss , Cross-Sectional Studies , Predictive Value of Tests , Sensitivity and Specificity , Treatment Outcome , Middle Aged
Clinics ; 75: e1277, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055881


The gut microbiota is a group of over 38 trillion bacterial cells in the human microbiota that plays an important role in the regulation of human metabolism through its symbiotic relationship with the host. Changes in the gut microbial ecosystem are associated with increased susceptibility to metabolic disease in humans. However, the composition of the gut microbiota in those with type 2 diabetes mellitus and in the pathogenesis of metabolic diseases is not well understood. This article reviews the relationship between environmental factors and the gut microbiota in individuals with type 2 diabetes mellitus. Finally, we discuss the goal of treating type 2 diabetes mellitus by modifying the gut microbiota and the challenges that remain in this area.

Humans , Gastrointestinal Tract/microbiology , Diabetes Mellitus, Type 2/microbiology , Microbiota/physiology , Gastrointestinal Microbiome , Ecosystem , Gastrointestinal Tract/metabolism , Diabetes Mellitus, Type 2/metabolism
An. bras. dermatol ; 94(5): 561-566, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054858


Abstract Background Rubeosis faciei diabeticorum is a persistent facial erythema in patients with diabetes mellitus. The actual pathogenesis has not been studied. However, it is speculated to be a cutaneous diabetic microangiopathy. Objective Examine the correlation between the severity of facial erythema and the possible causes of microvascular diabetic complications, namely oxidative stress, hyperglycemia, and cutaneous accumulation of advanced glycation end-products . Methods Patients diagnosed with Type 2 diabetes mellitus (n = 32) were enrolled in the study. The facial erythema index was measured using the Mexameter MX18; cutaneous accumulation of advanced glycation end-products was estimated by measuring skin auto fluorescence with the AGE Reader (DiagnOptics Technologies B.V. - Groningen, Netherlands). Glycated haemoglobin, total antioxidant status, and malondialdehyde were measured in blood by TBARS assay. The correlation between the selected variables was assessed by Spearman's rank test; p ≤ 0.05 was considered statistically significant. Results There was a statistically significant correlation between total antioxidant status and the facial erythema index (ρ = 0.398, p = 0.024). Malondialdehyde, skin autofluorescence, glycated haemoglobin, body mass index, duration of diabetes, and age did not demonstrate statistically significant correlation with the facial erythema index. Study limitations This is an observational study. Elevation of total antioxidant status could have been caused by several factors that might have also influenced the development of rubeosis faciei, including hyperbilirubinemia and hyperuricemia. Conclusions The results contradicted expectations. Total antioxidant status correlated positively with facial erythema index; however, there was no correlation with oxidative stress and skin autofluorescence. Further investigations should be conducted to reveal the cause of total antioxidant status elevation in patients with rubeosis faciei.

Humans , Male , Female , Adult , Middle Aged , Aged , Oxidative Stress , Diabetic Angiopathies/metabolism , Erythema/metabolism , Facial Dermatoses/metabolism , Reference Values , Spectrophotometry , Glycated Hemoglobin A/analysis , Body Mass Index , Statistics, Nonparametric , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetic Angiopathies/complications , Erythema/etiology , Facial Dermatoses/etiology , Fluorescence , Malondialdehyde/blood , Antioxidants/analysis
Arq. gastroenterol ; 56(3): 270-275, July-Sept. 2019. tab
Article in English | LILACS | ID: biblio-1038708


ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

RESUMO CONTEXTO: Os fatores de risco metabólicos da doença hepática gordurosa não alcoólica (DHGNA) em abstêmios não diabéticos, que constituem um grupo distinto, não são bem definidos. OBJETIVO: Identificar os fatores de risco metabólicos da DHGNA em indivíduos não diabéticos e que não consumam álcool. MÉTODOS: Em um estudo transversal, o efeito dos parâmetros metabólicos (IMC, níveis de lipídios individuais, HbA1c, Homa IR e os componentes da síndrome metabólica) de 150 abstêmios não diabéticos consecutivos (90 com tolerância à glicose normal e 60 pré-diabéticos) em sua NFS (parâmetro de gravidade quantificável da DHGNA) foram estudados por análise de regressão linear. Um estudo similar em separado foi feito nos grupos normais da tolerância da glicose e do pré-diabetes. Esses parâmetros foram comparados com os de 75 abstêmios diabéticos pareados com DHGNA. Para analisar ainda mais a diferença entre a tolerância à glicose normal foi realizada a regressão logística binária dos fatores tomando pré-diabetes e diabetes como variável de desfecho, nos grupos diabéticos e pré-diabéticos. RESULTADOS: Todos os parâmetros metabólicos foram significativamente maiores nos diabéticos comparados aos não diabéticos e em pré-diabéticos comparados àqueles com tolerância normal à glicose, exceto HDL. Os índices TG, HDL e IMC previram significativamente o NFS no geral nos grupos de tolerância normal (R2 ajustado 68,7%, P=0,000) e de glicose normal (R2 ajustado 73,2%, P=0,000), enquanto o IMC, TG, LDL e HbA1c predisseram em pré-diabéticos (R2 ajustado 89%, P=0,000). A síndrome metabólica foi associada significativamente com o NFS nos grupos totais e pré-diabéticos. O TG elevado (odds ratio 1,08), o LDL (odds ratio 1,03) e a HbA1c (odds ratio 11,54) foram positivamente associados ao pré-diabetes em comparação com o grupo normal de tolerância à glicose. CONCLUSÃO: Em abstêmios não diabéticos as dislipidemias são os principais contribuintes para o desenvolvimento da DHGNA.

Humans , Male , Female , Adult , Aged , Insulin Resistance/physiology , Dyslipidemias/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Triglycerides/blood , Glycated Hemoglobin A/analysis , Body Mass Index , Cross-Sectional Studies , Risk Factors , Metabolic Syndrome/metabolism , Diabetes Mellitus, Type 2/metabolism , Dyslipidemias/blood , Non-alcoholic Fatty Liver Disease/etiology , Middle Aged , Obesity/metabolism
Rev. méd. Chile ; 147(8): 965-976, ago. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058631


Background: Type 2 diabetes etiology has a strong genetic component. More than 20 genetic variants have been associated with diabetes and other metabolic markers. However, the polymorphism rs7903146 of the TCF7L2 gene has shown the strongest association. Aim: To investigate the association of TCF7L2 (rs7903146) genotype with adiposity and metabolic markers in the Chilean adult population. Material and Methods: The association of TCF7L2 (rs7093146) with adiposity and metabolic markers was studied in 301 participants. The outcomes of the study were adiposity markers (body weight, body mass index (BMI), fat mass and waist circumference) and metabolic markers (blood glucose, insulin, HOMA-IR, lipid profile, high sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT) and leptin). Results: There was an association between the polymorphism TCF7L2 genotype and fasting blood glucose. The latter increased by 4.86 mg/dl per each copy of the risk allele [(95% confidence intervals (CI): 0.48; 9.24), p = 0.03] in the unadjusted adjusted model. However, this association was slightly attenuated in the fully adjusted model [4.38 mg/dl (95% IC: 0.16; 8.60), p = 0.04)]. There were no associations between the TCF7L2 genotype and any other metabolic or adiposity outcome. Conclusions: These findings confirm the association between the TCF7L2 (rs7903146) and fasting glucose in the Chilean population. However, further studies are needed to confirm the association between the TCF7L2 and diabetes risk in the Chilean population.

Humans , Male , Female , Adult , Middle Aged , Young Adult , Polymorphism, Single Nucleotide , Diabetes Mellitus, Type 2/genetics , Adiposity/genetics , Transcription Factor 7-Like 2 Protein/genetics , Reference Values , Blood Glucose/genetics , Genetic Markers , Linear Models , Chile , Anthropometry , Nutritional Status , Cross-Sectional Studies , Risk Factors , Diabetes Mellitus, Type 2/metabolism , Alleles , Adiposity/ethnology , Genetic Association Studies , Gene Frequency , Genotype
Rev. Assoc. Med. Bras. (1992) ; 65(8): 1042-1047, Aug. 2019. tab
Article in English | LILACS | ID: biblio-1041049


SUMMARY BACKGROUND We investigated the serum annexin V and anti-annexin V levels and their relationship with metabolic parameters in patients recently diagnosed type 2 diabetic. METHODS A total of 143 patients recently diagnosed type 2 diabetes and 133 control subjects were included in the study. Body mass index (BMI), hs-CRP, HOMA-IR, carotid intima-media thickness, and serum levels of annexin V and anti-annexin V were investigated. RESULTS HOMA-IR, serum hs-CRP, and carotid intima-media thickness were found to be statistically significant. The Pearson correlation analysis revealed a statistically significant positive relationship between the carotid intima-media thickness and the annexin V level (r=0.29, p=0.006*). A statistically significant positive relationship was also detected between the Annexin V level and level of serum hs-CRP (r=0.29 p=0.006*). CONCLUSION A positive relationship was observed between the carotid intima-media thickness and annexin V at the end of our investigation. In this regard, we also believe that serum levels of annexin V may be increased for cardiovascular protection in the elevation of carotid intima-media thickness.

RESUMO OBJETIVO Investigar os níveis séricos de anexina V e antianexina V e sua relação com os parâmetros metabólicos em pacientes diabéticos tipo 2 recém-diagnosticados. MÉTODOS Foram incluídos no estudo 143 pacientes e 133 controles com diabetes tipo 2 recém-diagnosticado. O índice de massa corporal (IMC), PCR-as, Homa-IR, espessura íntima média carotídea e níveis séricos de anexina V e antianexina V foram investigados. RESULTADOS O Homa-IR, a PCR-s do soro e a espessura média da carótida foram estatisticamente significantes. A análise de correlação de Pearson revelou uma relação positiva estatisticamente significante entre a espessura média da carótida e anexina V (r=0,29; p=0,006 *). Foi também detectada uma relação positiva estatisticamente significativa entre o nível de anexina V e o nível sérico de PCR-as (r=0,29, p=0,006*). CONCLUSÃO Também foi observada uma relação positiva entre a espessura média da carótida e anexina V no final da nossa investigação. A esse respeito, também pensamos que os níveis séricos de anexina V podem ser aumentados para proteção cardiovascular na elevação da espessura média da carótida.

Humans , Male , Female , Adult , Aged , Autoantibodies/blood , Annexin A5/blood , Diabetes Mellitus, Type 2/blood , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Annexin A5/immunology , Annexin A5/metabolism , Diabetes Mellitus, Type 2/metabolism , Carotid Intima-Media Thickness , Homeostasis , Middle Aged
Arch. endocrinol. metab. (Online) ; 63(3): 222-227, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011165


ABSTRACT Objective Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet β-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. Subjects and methods We conducted a cross-sectional study to compare islet β-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. Results We found that compared with that in normal controls, HOMA-β in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-β in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). Conclusions There were obvious decreases in HOMA-β and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.

Humans , Adult , Middle Aged , Aged , Insulin Resistance , Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/metabolism , Homeostasis/physiology , Time Factors , Blood Glucose/analysis , Body Mass Index , Case-Control Studies , Cross-Sectional Studies , Islets of Langerhans/metabolism , Diabetes Mellitus, Type 2/physiopathology , Glucose Tolerance Test , Models, Biological
Rev. méd. Chile ; 147(4): 480-489, abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1014250


Physical training is recommended in several studies and guidelines for the control of type 2 diabetes mellitus (DM2) and its complications. We performed a systematic review about the effects of aerobic training (AT), resistance (RT) or the combination of both (AT/ RT), on glycated hemoglobin (HbA1c) in patients with DM2. Therefore, we included 15 clinical trials with at least 12 weeks duration about training program or recommendations of physical exercise, that evaluated the reduction in HbA1c levels in patients with DM2. Information was obtained on training modality (AT, RT or AT / RT), training parameters, duration and weekly training frequency. The results showed increases in peak or maximal oxygen uptake, exercise tolerance time and muscle strength, depending on the type of training, and a reduction in HbA1c levels. We conclude that exercise training is associated with reductions of HbA1c in patients with DM2. Thus, it can be a complementary tool in the management of these patients.

Humans , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/prevention & control , Resistance Training/methods , Physical Conditioning, Human/methods , Time Factors , Glycated Hemoglobin A/analysis , Reproducibility of Results , Treatment Outcome , Diabetes Mellitus, Type 2/metabolism , Physical Conditioning, Human/physiology
Rev. Assoc. Med. Bras. (1992) ; 65(1): 70-86, Jan. 2019. tab, graf
Article in English | LILACS | ID: biblio-985001


SUMMARY The prevalence of type 2 diabetes mellitus (T2DM) in the elderly grew sharply over the last decade. Reduced insulin sensitivity and secretory capacity, weight gain, sarcopenia, and elevated adiposity are all common metabolic and body changes in the aging population that favor an increased risk of hypoglycemia, frailty syndrome, falls, and cognitive dysfunction. First line antidiabetic therapy is frequently not safe in older individuals because of its high risk of hypoglycemia and prevalent co-morbid diseases, such as chronic kidney disease, osteoporosis, cardiovascular disease, and obesity. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new class of antidiabetic therapy that inhibits glucose and sodium reabsorption on renal proximal convoluted tubule. Its effect is well demonstrated in various clinical scenarios in the younger population. This review and metanalysis describe particularities of the SGLT2i on the elderly, with mechanistic insights of the potential benefit and remaining challenges about the use of these drugs in this important age group. Further, we will present a meta-analysis of the main effects of SGLT2i reported in post-hoc studies in which the median age of the subgroups analyzed was over 60 years. Despite the absence of specific clinical trials for this population, our findings suggest that SGLT2i therapy on older individuals is effective to lower glucose and maintain its effect on systolic blood pressure and body weight.

RESUMO A prevalência da diabetes mellitus tipo 2 em idosos cresceu muito na última década. A redução na sensibilidade à insulina e na capacidade secretora, ganho de peso, sarcopenia e adiposidade elevada são todas alterações metabólicas e corporais comuns entre a população idosa. Essas mudanças críticas favorecem o aumento no risco de hipoglicemia, síndrome de fragilidade, quedas e disfunções cognitivas. A primeira linha de tratamento contra a diabete muitas vezes não é segura para indivíduos mais velhos devido ao alto risco de hipoglicemia e a prevalência de comorbidades patogênicas, como doença renal crônica, osteoporose, doença cardiovascular e obesidade. Os inibidores do cotransportador sódio-glicose 2 (SGLT2) são uma nova classe de tratamento contra a diabete que inibe reabsorção de glicose e sódio na parte convoluta do túbulo proximal. Seu efeito é claramente demonstrado em diversos cenários clínicos em populações mais jovens. Esta revisão e meta-análise descreve as particularidades dos SGLT2 na população idosa, abordando os mecanismos dos potenciais benefícios e desafios ainda presentes do uso destes medicamentos nesse grupo etário tão importante. Além disso, apresentaremos uma meta-análise dos principais efeitos dos SGLT2 encontrados em estudos post-hoc nos quais a idade média dos subgrupos analisados foi acima de 60 anos. Apesar da ausência de ensaios clínicos que incluem essa população, os dados encontrados sugerem que o tratamento com SGLT2 em idosos é eficaz para diminuir os níveis de glicose e tem efeitos na pressão arterial sistólica e no peso corporal.

Humans , Aged , Aged, 80 and over , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hypoglycemic Agents/therapeutic use , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/drug therapy , Risk Factors , Frail Elderly , Diabetes Mellitus, Type 2/metabolism , Insulin/metabolism , Middle Aged
Braz. j. med. biol. res ; 52(6): e8344, 2019. graf
Article in English | LILACS | ID: biblio-1001533


Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

Humans , Male , Female , Middle Aged , Insulin Resistance/physiology , MicroRNAs/metabolism , Diabetes Mellitus, Type 2/physiopathology , Insulin-Secreting Cells/physiology , Apoptosis , MicroRNAs/genetics , Cell Proliferation , Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/metabolism , Adiponectin/genetics , Adiponectin/metabolism , Real-Time Polymerase Chain Reaction , Flow Cytometry
Rev. Assoc. Med. Bras. (1992) ; 64(7): 586-589, July 2018. tab
Article in English | LILACS | ID: biblio-1041015


SUMMARY INTRODUCTION: The impact of type 2 diabetes mellitus raises interest in understanding its evolutionary-genetic basis, to unveil yet unknown pathways that may have immediate medical relevance. The HNF1β gene (hepatocyte nuclear factor-1 beta) is a transcription factor expressed in tissues such as liver, kidney, genital tract and pancreas that is known to be essential for insulin secretion and glucose balance. We tested the association of allelic variants produced by the HNF1β gene (rs4430796) variation with the clinical and biochemical profile of elderly Brazilian outpatients with metabolic disorders. MATERIAL AND METHODS: Anthropometry, blood pressure, glycaemia, lipemia and other parameters were assessed in 184 Brazilians aged 60 or older in clinical care settings. Alleles were determined by amplification of the polymorphic site by real time polymerase chain reaction. RESULTS: Analysing variables across the genotypes, a statistically significant difference was noticed in the allele frequencies among diabetic patients, with 30.8% of the A homozygous bearing the condition compared to a prevalence of 12.2% between G homozygotes. CONCLUSION: Our results corroborate the possible protective property of the GG genotype from the rs4430796 variation (already presented in the literature) against occurrence of diabetes mellitus, which appears applicable to elderly individuals as well, even in the context of multiple metabolic disorders so typical in older Brazilians.

Humans , Male , Female , Aged , Genetic Predisposition to Disease/genetics , Diabetes Mellitus, Type 2/genetics , Hepatocyte Nuclear Factor 1-beta/genetics , Brazil , Polymorphism, Single Nucleotide , Diabetes Mellitus, Type 2/metabolism , Alleles , Hepatocyte Nuclear Factor 1-beta/metabolism , Gene Frequency , Genotype
Acta cir. bras ; 33(6): 542-550, June 2018. tab, graf
Article in English | LILACS | ID: biblio-949355


Abstract Purpose: To evaluate the effects of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) on the content of triglyceride (TG), as well as on the gene and protein expressions of adiponectin receptor 2 (AdipoR2), p38 mitogen-activated protein kinase (P38MAPK), and lipoprotein lipase (LPL) in the liver of rats with type 2 diabetes mellitus (T2DM) so as to provide theoretical basis for exploring the mechanism by which 1,25(OH)2D3 regulates TG. Methods: Wistar rats were divided into four groups (n=25), with different treatments and detected the gene and protein expressions of AdipoR2, p38MAPK, and LPL in the liver tissue by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Meanwhile, the content of TG in the liver tissue was detected by the Enzyme-linked immunosorbent assay. Results: The expression of AdipoR2, p38MAPK, LPL gene and protein in the liver of VitD intervention group was significantly higher than that in T2DM group (P <0.05), while the TG content was significantly lower than that in T2DM group (P <0.05). Conclusion: 1,25(OH)2D3 can decrease the content of TG in the liver, and its mechanism may be achieved by upregulating the expressions of AdipoR2, p38MAPK, and LPL in the liver.

Animals , Male , Triglycerides/blood , Calcitriol/pharmacology , Diabetes Mellitus, Type 2/metabolism , Liver/drug effects , Liver/metabolism , Reference Values , Blood Glucose/analysis , Body Weight , Enzyme-Linked Immunosorbent Assay , Gene Expression , Up-Regulation , Blotting, Western , Reproducibility of Results , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , p38 Mitogen-Activated Protein Kinases/analysis , p38 Mitogen-Activated Protein Kinases/drug effects , Diabetes Mellitus, Type 2/prevention & control , Receptors, Adiponectin/analysis , Receptors, Adiponectin/drug effects , Lipoprotein Lipase/analysis , Lipoprotein Lipase/drug effects
Rev. méd. Chile ; 146(6): 693-701, jun. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-961449


Background: There is a wide interindividual variability in the response to a period of exercise training. The science have reported that a minimum of participants could be non-responders for improving different health-related outcomes after training. Aim: To compare the effects of a 6-weeks exercise program on body composition, cardiovascular and metabolic outcomes patients with type 2 diabetes and hypertension. Material and Methods: Data from 23 trained subjects were used in a secondary analysis of the response to exercise. Of these, 14 were considered adherent to training and nine as non-adherent. Body mass, height, waist circumference, four skinfolds and their sum, blood pressure and plasma triglyceride levels were assessed before and after the training period. Results: Among adherent participants, significant reductions were observed in the sum of four skinfolds (30 ± 7 to 27 ± 6 mm, p ≤ 0.05), systolic blood pressure (133 ± 18 to 127 ± 20 mmHg; p ≤ 0.05) and plasma triglycerides (125 ± 58 to 102 ± 34 mg/dL; p ≤ 0.05). No changes were observed in weight or diastolic blood pressure. Among non-adherent participants, no changes of measured parameters were observed. Among adherent participants, 57% were considered as non-responders for waist circumference, 7% for the sum of skinfold thickness, 50% for systolic blood pressure, 64% for diastolic blood pressure and 57% for plasma triglycerides. Conclusions: Participants with a good adherence to a 6-weeks exercise training program experienced overall improvement in body composition, blood pressure and plasma triglycerides. The prevalence of non-responders varied considerably among measured outcomes.

Humans , Male , Female , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/prevention & control , Exercise Therapy/methods , High-Intensity Interval Training/methods , Hypertension/metabolism , Hypertension/prevention & control , Time Factors , Triglycerides/blood , Blood Pressure/physiology , Body Composition/physiology , Anthropometry , Reproducibility of Results , Risk Factors , Patient Compliance , Treatment Outcome , Statistics, Nonparametric
Medicina (B.Aires) ; 78(2): 91-98, abr. 2018. ilus
Article in Spanish | LILACS | ID: biblio-954956


En la diabetes mellitus tipo 2 el aumento en la producción de quilomicrón en el estado post-prandial se asocia a mayor riesgo cardiovascular. La evidencia actual posiciona al enterocito como actor principal en la dislipemia de la diabetes mellitus tipo 2 debido a que aumenta la producción de apolipoproteína B-48 en respuesta a una elevación de ácidos grasos libres y glucosa. El metabolismo del quilomicrón se encuentra regulado por múltiples factores independientes además de la ingesta de grasa alimentaria. Entre estos factores se destacan las hormonas intestinales, como el péptido similar al glucagón tipo 1 que disminuye la producción de apolipoproteína B-48 y el péptido similar al glucagón tipo 2 que la aumenta. Por otro lado, la insulina inhibe de forma aguda la producción de quilomicrón en el sujeto sano mientras que en la diabetes mellitus tipo 2, este efecto está ausente. La comprensión de los factores reguladores emergentes de la secreción de quilomicrón permite vislumbrar nuevos mecanismos de control en su metabolismo y aportar estrategias terapéuticas focalizadas en la hiperlipidemia posprandial en la diabetes mellitus tipo 2 con la reducción del riesgo cardiovascular.

In type 2 diabetes mellitus there is an overproduction of chylomicron in the postprandial state that is associated with increased cardiovascular risk. Current evidence points out a leading role of enterocyte in dyslipidemia of type 2 diabetes mellitus, since it increases the production of apolipoprotein B-48 in response to a raise in plasma free fatty acids and glucose. The chylomicron metabolism is regulated by many factors apart from ingested fat, including hormonal and metabolic elements. More recently, studies about the role of gut hormones, have demonstrated that glucagon-like peptide-1 decreases the production of apolipoprotein B-48 and glucagon-like peptide-2 enhances it. Insulin acutely inhibits intestinal chylomicron production in healthy humans, whereas this acute inhibitory effect on apolipoprotein B-48 production is blunted in type 2 diabetes mellitus. Understanding these emerging regulators of intestinal chylomicron secretion may offer new mechanisms of control for its metabolism and provide novel therapeutic strategies focalized in type 2 diabetes mellitus postprandial hyperlipidemia with the reduction of cardiovascular disease risk.

Humans , Chylomicrons/metabolism , Enterocytes/metabolism , Diabetes Mellitus, Type 2/metabolism , Dyslipidemias/metabolism , Triglycerides/metabolism , Insulin Resistance , Postprandial Period , Diabetes Mellitus, Type 2/complications , Dyslipidemias/complications , Glucagon-Like Peptide 1/metabolism
Braz. dent. j ; 28(6): 675-678, Nov.-Dec. 2017. graf
Article in English | LILACS | ID: biblio-888702


Abstract Cell-derived microparticles (MPs) have been described as vital contributors to the inflammatory process. However, its role in the periodontal disease pathogenesis remains unclear. Therefore, we aimed to detect the presence neutrophil (CD66b+) and platelet (CD41b+) derived microparticles in gingival crevicular fluid from individuals having periodontitis aggravated by type 2 diabetes. Twelve patients (56.2 ±7.2 yrs) with severe form of chronic periodontitis aggravated by type 2 diabetes were included. Clinical and metabolic data were gathered. Gingival crevicular fluid was collected using filter strips from deep and shallow sites. MPs were detected by flow cytometry according to their size (< 1 µm) and the expression of surface markers (CD66b for neutrophil-derived MPs and CD41b for platelet-derived MPs). All samples were positive for the antibodies. Median levels of CD66b+ MPs and CD41b+ MPs were, respectively, 3,677.0 (2,553.2 - 9,059.8) MP/µL and 520.7 (432.9 - 766.1) MP/µL in deep sites. In shallow sites, the corresponding values were 2,644.9 (1,451.5 - 3,858.9) MP/µL and 371.2 (287.2 - 692.7) MP/µL. There was no significant difference between deep and shallow sites (p>0.05). In conclusion, this study reported the presence of neutrophil and platelet derived microparticles in gingival crevicular fluid from individuals having severe periodontitis and type 2 diabetes.

Resumo As micropartículas derivadas de células (MPs) têm sido descritas como contribuintes vitais para o processo inflamatório. No entanto, seu papel na patogênese da doença periodontal permanece obscuro. Por isso, nosso objetivo foi detectar a presença de micropartículas derivadas de neutrófilos (CD66b +) e plaquetas (CD41b +) no fluido gengival de indivíduos com periodontite e diabetes tipo 2. Doze pacientes (56,2 ± 7,2 anos) com periodontite crônica severa e diabetes tipo 2 foram incluídos no estudo. Foram coletados dados clínicos e metabólicos. O fluido gengival foi coletado usando tiras de filtro de papel em sítios rasos e profundos. As MPs foram detectadas por citometria de fluxo de acordo com o seu tamanho (<1 μm) e pela expressão de marcadores de superfície (CD66b para MPs derivadas de neutrófilos e CD41b para MPs derivadas de plaquetas). Todas as amostras foram positivas para os anticorpos. Os níveis médios de CD66b + MPs e CD41b + MPs foram, respectivamente, 3.677.0 (2,553.2 - 9,059.8) MP/μL e 520.7 (432.9 - 766.1) MP/μL nos sítios profundos. Nos sítios rasos, os valores correspondentes foram 2,644.9 (1,451.5 - 3,858.9) MP/μL e 371.2 (287.2 - 692.7) MP/μL. Não houve diferença significativa entre os sítios rasos e profundos (p>0.05). Concluindo, o presente estudo reportou a presença de micropartículas derivadas de neutrófilos e plaquetas no fluido gengival de pacientes com periodontite e com diabetes tipo 2 .

Humans , Male , Female , Middle Aged , Cell-Derived Microparticles/metabolism , Diabetes Mellitus, Type 2/metabolism , Gingival Crevicular Fluid/metabolism , Periodontitis/metabolism , Antigens, CD/immunology , Cell-Derived Microparticles/immunology , Diabetes Mellitus, Type 2/complications , Flow Cytometry , Periodontitis/complications