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1.
Rev. Nutr. (Online) ; 36: e220103, 2023. tab, graf
Article in English | LILACS | ID: biblio-1521589

ABSTRACT

ABSTRACT Objective: This study aimed to evaluate the effect of baru nuts supplementation on body composition and metabolic profile in adults with type 2 diabetes. Methods: This is a randomized, placebo-controlled, crossover trial with 30 adults with type 2 diabetes. The assay had two periods of 12 weeks each, with a washout period of 12 weeks between treatments. The subjects were randomized and received the two treatments in alternate periods: supplementation of 30g baru nuts or placebo. Anthropometry, body composition, blood pressure, blood sampling, food intake, and physical activity data were analyzed. Results: Baru nut intake reduced waist circumference (p=0.032), compared to placebo group. In the intra-group analysis, baru nut intake reduced total cholesterol (p=0.012) and LDL-c (p=0.017). Conclusion: The daily intake of baru nuts improved abdominal adiposity. Therefore, these nuts should be included in the diet to improve the health status of adults with type 2 diabetes.


RESUMO: Objetivo: Avaliar o efeito da suplementação com amêndoa de baru sobre a composição corporal e perfil metabólico de adultos com diabetes Mellitus tipo 2. Métodos: Este é um estudo randomizado, placebo-controlado, crossover com 30 adultos com diabetes Mellitus tipo 2. O ensaio clínico foi dividido em dois períodos de 12 semanas cada, com um washout de 12 semanas entre os tratamentos. Os sujeitos foram randomizados e receberam dois tratamentos em períodos alternativos: suplementação com 30 g de amêndoa de baru ou placebo. Foram coletados dados referentes à antropometria, composição corporal, pressão arterial, amostras de sangue, ingestão de alimentos e práticas de atividade física. Resultados: A ingestão de amêndoa de baru reduziu a circunferência da cintura (p=0,032), em comparação com o grupo placebo. Na análise intragrupo, a ingestão de amêndoa de baru também reduziu o colesterol total (p=0,012) e LDL-c (p=0,017). Conclusão: A ingestão diária de amêndoa de baru melhorou a adiposidade abdominal, portanto, deve ser incluída na dieta para a melhora do estado de saúde de adultos com diabetes Mellitus tipo 2.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Young Adult , Body Composition , Dipteryx , Diabetes Mellitus, Type 2/metabolism , Placebos/therapeutic use , Cholesterol , Cross-Over Studies , Abdominal Circumference , Arterial Pressure
2.
China Journal of Chinese Materia Medica ; (24): 525-533, 2023.
Article in Chinese | WPRIM | ID: wpr-970489

ABSTRACT

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.


Subject(s)
Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Gastrointestinal Microbiome , RNA, Ribosomal, 16S , Diabetes Mellitus, Type 2/metabolism , Occludin/pharmacology , Claudin-1/metabolism , Intestinal Mucosa , Liver , Triglycerides/metabolism , Diet, High-Fat , Homeostasis , Mice, Inbred C57BL
3.
Frontiers of Medicine ; (4): 388-431, 2023.
Article in English | WPRIM | ID: wpr-982588

ABSTRACT

Metformin has been used for the treatment of type II diabetes mellitus for decades due to its safety, low cost, and outstanding hypoglycemic effect clinically. The mechanisms underlying these benefits are complex and still not fully understood. Inhibition of mitochondrial respiratory-chain complex I is the most described downstream mechanism of metformin, leading to reduced ATP production and activation of AMP-activated protein kinase (AMPK). Meanwhile, many novel targets of metformin have been gradually discovered. In recent years, multiple pre-clinical and clinical studies are committed to extend the indications of metformin in addition to diabetes. Herein, we summarized the benefits of metformin in four types of diseases, including metabolic associated diseases, cancer, aging and age-related diseases, neurological disorders. We comprehensively discussed the pharmacokinetic properties and the mechanisms of action, treatment strategies, the clinical application, the potential risk of metformin in various diseases. This review provides a brief summary of the benefits and concerns of metformin, aiming to interest scientists to consider and explore the common and specific mechanisms and guiding for the further research. Although there have been countless studies of metformin, longitudinal research in each field is still much warranted.


Subject(s)
Humans , Metformin/pharmacokinetics , Diabetes Mellitus, Type 2/metabolism , Hypoglycemic Agents/pharmacology , AMP-Activated Protein Kinases/metabolism , Aging
4.
Journal of Central South University(Medical Sciences) ; (12): 663-670, 2023.
Article in English | WPRIM | ID: wpr-982335

ABSTRACT

OBJECTIVES@#Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy.@*METHODS@#The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels.@*RESULTS@#Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05).@*CONCLUSIONS@#p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.


Subject(s)
Animals , Humans , Mice , Carboxymethylcellulose Sodium/pharmacology , Diabetes Mellitus, Type 2/metabolism , Endothelium, Vascular/metabolism , Glucose/metabolism , Human Umbilical Vein Endothelial Cells , Mice, Inbred C57BL , Nitric Oxide/metabolism , Nitric Oxide Synthase Type III/metabolism , Phosphorylation , Pyruvate Kinase/metabolism , Vasodilation
5.
International Journal of Oral Science ; (4): 6-6, 2023.
Article in English | WPRIM | ID: wpr-971593

ABSTRACT

The failure rate of dental implantation in patients with well-controlled type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients. This due, in part, to the impaired function of bone marrow mesenchymal stem cells (BMSCs) from the jawbone marrow of T2DM patients (DM-BMSCs), limiting implant osseointegration. RNA N6-methyladenine (m6A) is important for BMSC function and diabetes regulation. However, it remains unclear how to best regulate m6A modifications in DM-BMSCs to enhance function. Based on the "m6A site methylation stoichiometry" of m6A single nucleotide arrays, we identified 834 differential m6A-methylated genes in DM-BMSCs compared with normal-BMSCs (N-BMSCs), including 43 and 790 m6A hypermethylated and hypomethylated genes, respectively, and 1 gene containing hyper- and hypomethylated m6A sites. Differential m6A hypermethylated sites were primarily distributed in the coding sequence, while hypomethylated sites were mainly in the 3'-untranslated region. The largest and smallest proportions of m6A-methylated genes were on chromosome 1 and 21, respectively. MazF-PCR and real-time RT-PCR results for the validation of erythrocyte membrane protein band 4.1 like 3, activity-dependent neuroprotector homeobox (ADNP), growth differentiation factor 11 (GDF11), and regulator of G protein signalling 2 agree with m6A single nucleotide array results; ADNP and GDF11 mRNA expression decreased in DM-BMSCs. Furthermore, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that most of these genes were enriched in metabolic processes. This study reveals the differential m6A sites of DM-BMSCs compared with N-BMSCs and identifies candidate target genes to enhance BMSC function and improve implantation success in T2DM patients.


Subject(s)
Humans , Bone Marrow/metabolism , Bone Morphogenetic Proteins/metabolism , Dental Implants/adverse effects , Diabetes Mellitus, Type 2/metabolism , Growth Differentiation Factors/metabolism , Mesenchymal Stem Cells/metabolism , RNA/metabolism , RNA Processing, Post-Transcriptional
6.
Chinese Medical Journal ; (24): 922-932, 2023.
Article in English | WPRIM | ID: wpr-980843

ABSTRACT

BACKGROUND@#Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear.@*METHODS@#In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress.@*RESULTS@#Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment.@*CONCLUSION@#Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.


Subject(s)
Rats , Mice , Animals , Reactive Oxygen Species/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin Resistance , Insulin , Insulin-Secreting Cells/metabolism , Apoptosis , Stress, Physiological , Transcription Factors/metabolism , Palmitates/pharmacology , Obesity/metabolism
7.
Journal of Southern Medical University ; (12): 641-648, 2022.
Article in Chinese | WPRIM | ID: wpr-936358

ABSTRACT

OBJECTIVE@#To investigate the effect of dihydromyricetin (DHM) on cardiac insufficiency in diabetic rats and explore the underlying mechanism.@*METHOD@#Twenty-four male SD rats were randomized equally into normal control group, type 2 diabetes (T2DM) group fed on a high-glucose and high-fat diet for 6 weeks with low-dose streptozotocin (STZ) injection, metformin (MET) group with daily intragastric administration of MET (150 mg/kg) for 8 weeks after T2DM modeling, and dihydromyricetin (DHM) group with daily intragastric administration of DHM (250 mg/kg) for 8 weeks after modeling. The levels of fasting blood glucose, low density lipoprotein (LDL-C), triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL-C) and glycosylated hemoglobin (HbA1c) of the rats were measured, and plasma levels of insulin and high mobility group protein-1 (HMGB1) were detected with ELISA. The cardiac function of the rats was assessed using color echocardiography, ECG was measured using a biological signal acquisition system, and myocardial pathology was observed with HE staining. The protein expressions of HMGB1, nuclear factor-κB (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in the myocardial tissue were detected using Western blotting.@*RESULTS@#Compared with the control group, the rats in T2DM group showed significant anomalies in cardiac function after modeling with significantly increased plasma HMGB1 level and expressions of HMGB1, NF-κB p65 and p-NF-κB p65 proteins in the myocardial tissue (P < 0.05 or 0.01). Treatment with DHM significantly improved the indexes of cardiac function of the diabetic rats (P < 0.05 or 0.01), decreased plasma HMGB1 level and down-regulated the protein expressions of HMGB1 and p-NF-κB p65 in the myocardial tissue (P < 0.05 or 0.01).@*CONCLUSION@#DHM treatment can improve cardiac function in diabetic rats possibly by down-regulation of HMGB1 and phospho-NF-κB p65 expressions in the myocardium.


Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Flavonols , HMGB1 Protein , Heart Failure , Metformin/therapeutic use , NF-kappa B/metabolism , Rats, Sprague-Dawley
8.
Rev. costarric. cardiol ; 23(1)jun. 2021.
Article in Spanish | LILACS, SaludCR | ID: biblio-1389031

ABSTRACT

Resumen Los receptores del cotransportador de sodio-glucosa han demostrado una gran relevancia en la función miocárdica. Los receptores tipo 1 se encuentran en el miocardio en valores bajos, sin embargo, se elevan en patologías cardiacas por medio de distintos mecanismos moleculares. Por otra parte, los receptores tipo 2 están ausentes en el miocardio. Los fármacos que inhiben este receptor tienen beneficio cardiovascular evidente en estudios clínicos y experimentales, principalmente en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca, en los que se ha demostrado una reducción de la mortalidad por causas cardiovasculares y reducción en hospitalización por insuficiencia cardiaca. Existen interrogantes sobre el mecanismo de acción directo de este grupo antihiperglicemiantes sobre el cardiomiocito y se han desarrollado hipótesis y teorías para explicar este efecto. El objetivo de este artículo es revisar y analizar los diferentes mecanismos metabólicos, estructurales, funcionales y mitocondriales en un contexto molecular de los inhibidores del cotransportador sodio-glucosa tipo 2. La acción fisiopatológica del receptor tipo 1 en el miocardio también es importante y se encuentran en desarrollo estudios clínicos para establecer el efecto de su inhibición a nivel cardíaco.


Abstract Sodium-glucose cotransporter receptors have demonstrated relevance in myocardial function. Type 1 receptors are found in the myocardium in low values, however, they are elevated in cardiac pathologies by means of different molecular mechanisms. On the other hand, type 2 receptors are absent in the myocardium. The drugs that inhibit this receptor have been shown to have a cardiovascular benefit demonstrated in clinical and experimental studies, mainly in patients with type 2 diabetes mellitus and heart failure, presenting a reduction in mortality due to cardiovascular causes and a reduction in hospitalization due to heart failure. Due to the above, many questions arise about the mechanism of direct action of this antihyperglycemic group on cardiomyocyte, which is why they have been developed from hypotheses and theories to clarify this action by medicines. The objective of this article is to analyze the different metabolic, structural, functional and mitochondrial mechanisms in a molecular context of the inhibitors of the sodium-glucose cotransporter type 2. On the other hand, to analyze the pathophysiological action of the type 1 receptor in the myocardium, since that future clinical studies will be developed to establish the effect with its inhibition at the cardiac level.


Subject(s)
Humans , Sodium-Glucose Transport Proteins/metabolism , Sodium-Glucose Transporter 2 Inhibitors/pharmacokinetics , Myocardium/metabolism , Diabetes Mellitus, Type 2/metabolism , Sodium-Glucose Transporter 2 Inhibitors/metabolism
9.
Braz. j. med. biol. res ; 54(8): e10782, 2021. tab, graf
Article in English | LILACS | ID: biblio-1249333

ABSTRACT

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.


Subject(s)
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
10.
China Journal of Chinese Materia Medica ; (24): 3643-3649, 2021.
Article in Chinese | WPRIM | ID: wpr-888017

ABSTRACT

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.


Subject(s)
Animals , Rats , Diabetes Mellitus, Type 2/metabolism , Glucose/metabolism , Glycosylation , Insulin/metabolism , Insulin-Secreting Cells/metabolism , Iridoids
11.
Rev. Assoc. Med. Bras. (1992) ; 66(3): 334-337, Mar. 2020. tab
Article in English | SES-SP, LILACS | ID: biblio-1136205

ABSTRACT

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.


Subject(s)
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 , Cross-Sectional Studies , Retrospective Studies , Drug Therapy, Combination , Insulin Glargine/administration & dosage , Mexico , Middle Aged
12.
Clinics ; 75: e1277, 2020. tab, graf
Article in English | LILACS | ID: biblio-1055881

ABSTRACT

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.


Subject(s)
Humans , Gastrointestinal Tract/microbiology , Diabetes Mellitus, Type 2/microbiology , Microbiota/physiology , Gastrointestinal Microbiome , Ecosystem , Gastrointestinal Tract/metabolism , Diabetes Mellitus, Type 2/metabolism
13.
Rev. Col. Bras. Cir ; 47: e20202394, 2020. tab, graf
Article in Portuguese | LILACS | ID: biblio-1136585

ABSTRACT

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.


Subject(s)
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
14.
An. bras. dermatol ; 94(5): 561-566, Sept.-Oct. 2019. tab, graf
Article in English | LILACS | ID: biblio-1054858

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Oxidative Stress , Diabetic Angiopathies/metabolism , Erythema/metabolism , Facial Dermatoses/metabolism , Reference Values , Spectrophotometry , Glycated Hemoglobin/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
15.
Arq. gastroenterol ; 56(3): 270-275, July-Sept. 2019. tab
Article in English | LILACS | ID: biblio-1038708

ABSTRACT

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.


Subject(s)
Humans , Male , Female , Adult , Aged , Insulin Resistance/physiology , Dyslipidemias/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Triglycerides/blood , Glycated Hemoglobin/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
16.
Rev. méd. Chile ; 147(8): 965-976, ago. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058631

ABSTRACT

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.


Subject(s)
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
17.
Rev. Assoc. Med. Bras. (1992) ; 65(8): 1042-1047, Aug. 2019. tab
Article in English | LILACS | ID: biblio-1041049

ABSTRACT

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.


Subject(s)
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
18.
Arch. endocrinol. metab. (Online) ; 63(3): 222-227, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011165

ABSTRACT

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.


Subject(s)
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
19.
Rev. méd. Chile ; 147(4): 480-489, abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1014250

ABSTRACT

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.


Subject(s)
Humans , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/prevention & control , Resistance Training/methods , Physical Conditioning, Human/methods , Time Factors , Glycated Hemoglobin/analysis , Reproducibility of Results , Treatment Outcome , Diabetes Mellitus, Type 2/metabolism , Physical Conditioning, Human/physiology
20.
Rev. Assoc. Med. Bras. (1992) ; 65(1): 70-86, Jan. 2019. tab, graf
Article in English | LILACS | ID: biblio-985001

ABSTRACT

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.


Subject(s)
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
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