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1.
Eur J Med Res ; 29(1): 497, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39407333

RESUMO

Type 2 diabetes (T2D) is associated with insulin resistance and progressive dysfunction of ß-pancreatic cells, leading to persistent hyperglycemia. Macrophages play a crucial role in this context, influencing both the development and progression of insulin resistance. These innate immune cells respond to inflammatory stimuli and reprogram their metabolism, directly impacting the pathophysiology of T2D. Macrophages are highly plastic and can adopt either pro-inflammatory or pro-resolutive phenotypic profiles. In T2D, pro-inflammatory macrophages, which rely on glycolysis, exacerbate insulin resistance through increased production of pro-inflammatory cytokines and nitric oxide. In contrast, pro-resolutive macrophages, which prioritize fatty acid metabolism, have different effects on glucose homeostasis. Metaflammation, a chronic low-grade inflammation, is induced by pro-inflammatory macrophages and significantly contributes to the progression of T2D, creating an environment conducive to metabolic dysfunction. This review aims to clarify the contribution of macrophages to the progression of T2D by detailing how their inflammatory responses and metabolic reprogramming influence insulin resistance and the disease's pathophysiology. The review seeks to deepen the understanding of the biochemical and metabolic mechanisms involved, offering broader insights into the impact on the quality of life for millions of patients worldwide.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Macrófagos , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Inflamação/metabolismo , Animais , Reprogramação Celular , Reprogramação Metabólica
2.
J Periodontol ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39189666

RESUMO

BACKGROUND: Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility. METHODS: A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA. RESULTS: Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic ß cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur. CONCLUSIONS: LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic ß-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture. PLAIN LANGUAGE SUMMARY: In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.

3.
JMIR Res Protoc ; 13: e49105, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506891

RESUMO

BACKGROUND: Diabetes mellitus is a chronic disease that is growing worldwide. It is estimated that 15.7 million people aged between 20 and 79 years live with diabetes in Brazil, and the majority of cases are type 2 diabetes (T2D). To successfully manage diabetes, the patient needs to develop self-care activities. However, there is limited understanding of what self-care activities are performed by people with T2D in Brazil. OBJECTIVE: This study aims to identify and map studies that evaluate self-care activities in T2D in Brazil. METHODS: This is a scoping review protocol structured according to the methodological guidelines of the Joanna Briggs Institute. Six databases and gray literature were used. The process of searching, identifying, and evaluating the papers was carried out by 2 independent reviewers, guided by the assumptions established by the Joanna Briggs Institute. We sought to answer the following guiding question: How are self-care activities for people with T2D evaluated in Brazil? We included papers and publications in any language, from public and private domains, and with different methodological approaches. RESULTS: Initial database searches produced a total of 681 results. These papers will be critically analyzed, and relevant information will be extracted. Quantitative and qualitative results of the papers reviewed will be presented to respond to the study's objective. We intend to publish the scoping review in the first half of 2024. CONCLUSIONS: The protocol for this scoping review will evaluate the main self-care activities carried out by adults and older people with T2D in Brazil. The results may help identify knowledge gaps and contribute to future research and diabetes education interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49105.

4.
Heliyon ; 10(3): e25537, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38356516

RESUMO

Background: Type 2 diabetes (T2D) is a complex metabolic ailment marked by a global high prevalence and significant attention in primary healthcare settings due to its elevated morbidity and mortality rates. The pathophysiological mechanisms underlying the onset and progression of this disease remain subjects of ongoing investigation. Recent evidence underscores the pivotal role of the intricate intercellular communication network, wherein cell-derived vesicles, commonly referred to as extracellular vesicles (EVs), emerge as dynamic regulators of diabetes-related complications. Given that the protein cargo carried by EVs is contingent upon the metabolic conditions of the originating cells, particular proteins may serve as informative indicators for the risk of activating or inhibiting signaling pathways crucial to the progression of T2D complications. Methods: In this study, we conducted a systematic review to analyze the published evidence on the proteome of EVs from the plasma or serum of patients with T2D, both with and without complications (PROSPERO: CRD42023431464). Results: Nine eligible articles were systematically identified from the databases, and the proteins featured in these articles underwent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We identified changes in the level of 426 proteins, with CST6, CD55, HBA1, S100A8, and S100A9 reported to have high levels, while FGL1 exhibited low levels. Conclusion: These proteins are implicated in pathophysiological mechanisms such as inflammation, complement, and platelet activation, suggesting their potential as risk markers for T2D development and progression. Further studies are required to explore this topic in greater detail.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38092990

RESUMO

Major depressive disorder (MDD) and type 2 diabetes (T2D) are complex disorders whose comorbidity can be due to hypercortisolism and may be explained by dysfunction of the corticotropin-releasing hormone receptor 1 (CRHR1) and cortisol feedback within the hypothalamic-pituitary-adrenal axis (HPA axis). To investigate the role of the CRHR1 gene in familial T2D, MDD, and MDD-T2D comorbidity, we tested 152 CRHR1 single-nucleotide-polymorphisms (SNPs), via 2-point parametric linkage and linkage disequilibrium (LD; i.e., association) analyses using 4 models, in 212 peninsular families with T2D and MDD. We detected linkage/LD/association to/with MDD and T2D with 122 (116 novel) SNPs. MDD and T2D had 4 and 3 disorder-specific novel risk LD blocks, respectively, whose risk variants reciprocally confirm one another. Comorbidity was conferred by 3 novel independent SNPs. In silico analyses reported novel functional changes, including the binding site of glucocorticoid receptor-alpha [GR-α] on CRHR1 for transcription regulation. This is the first report of CRHR1 pleiotropic linkage/LD/association with peninsular familial MDD and T2D. CRHR1 contribution to MDD is stronger than to T2D and may antecede T2D onset. Our findings suggest a new molecular-based clinical entity of MDD-T2D and should be replicated in other ethnic groups.

6.
Biomolecules ; 13(12)2023 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-38136661

RESUMO

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. OBJECTIVE: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-ß/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-ß/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. RESULTS: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-ß/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. CONCLUSIONS: PPAR-γ2 rs1801282 and PPAR-ß/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved.


Assuntos
Diabetes Mellitus Tipo 2 , PPAR delta , PPAR beta , Adulto , Humanos , PPAR gama/genética , PPAR delta/genética , Diabetes Mellitus Tipo 2/genética , PPAR beta/genética , Hemoglobinas Glicadas/genética , Polimorfismo de Nucleotídeo Único , Biomarcadores , Glucose
7.
Biomolecules ; 11(12)2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34944461

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D. METHODS: Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR. RESULTS: NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1ß, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ. CONCLUSIONS: Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.


Assuntos
Leucócitos Mononucleares , Nitrocompostos , Tiazóis , Adulto , Diabetes Mellitus Tipo 2 , Humanos , MicroRNAs
8.
Curr Hypertens Rev ; 17(2): 85-93, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33823781

RESUMO

The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Volume Sistólico
9.
Vaccines (Basel) ; 9(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572702

RESUMO

In December 2019, a novel coronavirus known as SARS-CoV-2 was first detected in Wuhan, China, causing outbreaks of the coronavirus disease COVID-19 that has now spread globally. For this reason, The World Health Organization (WHO) declared COVID-19 a public health emergency in March 2020. People living with pre-existing conditions such as obesity, cardiovascular diseases, type 2 diabetes (T2D), and chronic kidney and lung diseases, are prone to develop severe forms of disease with fatal outcomes. Metabolic diseases such as obesity and T2D alter the balance of innate and adaptive responses. Both diseases share common features characterized by augmented adiposity associated with a chronic systemic low-grade inflammation, senescence, immunoglobulin glycation, and abnormalities in the number and function of adaptive immune cells. In obese and T2D patients infected by SARS-CoV-2, where immune cells are already hampered, this response appears to be stronger. In this review, we describe the abnormalities of the immune system, and summarize clinical findings of COVID-19 patients with pre-existing conditions such as obesity and T2D as this group is at greater risk of suffering severe and fatal clinical outcomes.

10.
J Cell Mol Med ; 25(5): 2505-2516, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33591627

RESUMO

This study aimed to investigate the relationship between red cell distribution width (RDW) and erythrocyte osmotic stability in non-diabetic and diabetic individuals in both sexes. The study sample (N = 122) was constituted by 53 type 2 diabetics (DM) and 69 non-diabetics (ND), being 21 and 22 men in each group, respectively. The osmotic stability of erythrocytes was obtained by the variation in saline concentration (dX) capable of determining hypoosmotic lysis. Higher RDW values and lower serum iron concentrations were found in the diabetic group when compared to the non-diabetic volunteers. In the group of diabetic women, RDW was positively correlated with the reticulocyte index, and both RDW and dX were negatively correlated with iron, haemoglobin, transferrin saturation index, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. In all the groups studied, RDW was positively correlated with dX, especially in the diabetic group, where the correlation was the strongest. RDW elevation in both women and men with type 2 diabetes mellitus was associated with decreased serum iron indicators. Furthermore, RDW has a similar meaning to dX, as small erythrocytes have less haemoglobin, resulting in both an increase of RDW and dX.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Índices de Eritrócitos , Fragilidade Osmótica , Idoso , Biomarcadores/sangue , Contagem de Células Sanguíneas , Diabetes Mellitus Tipo 2/metabolismo , Eritrócitos/metabolismo , Feminino , Hemoglobinas/metabolismo , Humanos , Ferro/metabolismo , Cinética , Masculino , Pessoa de Meia-Idade
11.
Arch. endocrinol. metab. (Online) ; 65(1): 24-31, Jan.-Feb. 2021. graf
Artigo em Inglês | LILACS | ID: biblio-1152892

RESUMO

ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.


Assuntos
Humanos , Resistência à Insulina , Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia , Polipeptídeo Inibidor Gástrico/metabolismo , Incretinas , Ácidos Graxos não Esterificados , Secreção de Insulina , Insulina/metabolismo
12.
Arch Endocrinol Metab ; 65(1): 24-31, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33320449

RESUMO

Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and ß-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional ß-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of ß-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Ácidos Graxos não Esterificados , Polipeptídeo Inibidor Gástrico/metabolismo , Humanos , Incretinas , Insulina/metabolismo , Secreção de Insulina
13.
Biomed Chromatogr ; 34(12): e4956, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32706910

RESUMO

Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice.


Assuntos
Cromatografia Gasosa/métodos , Diabetes Mellitus Tipo 2/metabolismo , Nariz Eletrônico , Metabolômica/métodos , Compostos Orgânicos Voláteis/urina , Adulto , Idoso , Biomarcadores/urina , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Projetos Piloto
14.
BMC Med Genet ; 21(Suppl 2): 132, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32580712

RESUMO

BACKGROUND: Hispanic/Latino (HL) populations bear a disproportionately high burden of type 2 diabetes (T2D). The ability to predict T2D genetic risk using polygenic risk scores (PRS) offers great promise for improved screening and prevention. However, there are a number of complications related to the accurate inference of genetic risk across HL populations with distinct ancestry profiles. We investigated how ancestry affects the inference of T2D genetic risk using PRS in diverse HL populations from Colombia and the United States (US). In Colombia, we compared T2D genetic risk for the Mestizo population of Antioquia to the Afro-Colombian population of Chocó, and in the US, we compared European-American versus Mexican-American populations. METHODS: Whole genome sequences and genotypes from the 1000 Genomes Project and the ChocoGen Research Project were used for genetic ancestry inference and for T2D polygenic risk score (PRS) calculation. Continental ancestry fractions for HL genomes were inferred via comparison with African, European, and Native American reference genomes, and PRS were calculated using T2D risk variants taken from multiple genome-wide association studies (GWAS) conducted on cohorts with diverse ancestries. A correction for ancestry bias in T2D risk inference based on the frequencies of ancestral versus derived alleles was developed and applied to PRS calculations in the HL populations studied here. RESULTS: T2D genetic risk in Colombian and US HL populations is positively correlated with African and Native American ancestry and negatively correlated with European ancestry. The Afro-Colombian population of Chocó has higher predicted T2D risk than Antioquia, and the Mexican-American population has higher predicted risk than the European-American population. The inferred relative risk of T2D is robust to differences in the ancestry of the GWAS cohorts used for variant discovery. For trans-ethnic GWAS, population-specific variants and variants with same direction effects across populations yield consistent results. Nevertheless, the control for bias in T2D risk prediction confirms that explicit consideration of genetic ancestry can yield more reliable cross-population genetic risk inferences. CONCLUSIONS: T2D associations that replicate across populations provide for more reliable risk inference, and modeling population-specific frequencies of ancestral and derived risk alleles can help control for biases in PRS estimation.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Hispânico ou Latino/genética , População Branca/genética , Colômbia , Diabetes Mellitus Tipo 2/epidemiologia , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Fatores de Risco , Estados Unidos
15.
Prev Med ; 137: 106141, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32454057

RESUMO

Little is known about how health-related behaviours cluster across different populations and how lifestyle clusters are associated with type 2 diabetes (T2D) risk. We investigated lifestyle clusters and their association with T2D in a multi-ethnic population. 4396 Dutch, 2850 South-Asian Surinamese, 3814 African Surinamese, 2034 Ghanaian, 3328 Turkish, and 3661 Moroccan origin participants of the HELIUS study were included (2011-2015). K-medoids cluster analyses were used to identify lifestyle clusters. Logistic and cox regression analyses were performed to investigate the association of clusters with prevalent and incident T2D, respectively. Pooled analysis revealed three clusters: a 'healthy', 'somewhat healthy', and 'unhealthy' cluster. Most ethnic groups were unequally distributed: Dutch participants were mostly present in the 'healthy' cluster, Turkish and Moroccan participants in the 'somewhat healthy' cluster, while the Surinamese and Ghanaian participants were equally distributed across clusters. When stratified for ethnicity, analysis revealed three clusters per ethnic group. While the 'healthy' and 'somewhat healthy' clusters were similar to those of the pooled analysis, we observed considerable differences in the ethnic-specific 'unhealthy' clusters. Fruit consumption (3-4 days/week) was the only behaviour that was consistent across all ethnic-specific 'unhealthy' clusters. The pooled 'unhealthy' cluster was positively associated with prediabetes (OR: 1.34, 95%CI 1.21-1.48) and incident T2D (OR: 1.23, 95%CI 0.89-1.69), and negatively associated with prevalent T2D (OR: 0.80, 95%CI 0.69-0.93). Results were similar for most, but not all, ethnic-specific clusters. This illustrates that targeting multiple behaviours is relevant in prevention of T2D but that ethnic differences in lifestyle clusters should be taken into account.


Assuntos
Diabetes Mellitus Tipo 2 , Etnicidade , Estilo de Vida , Povo Asiático , Diabetes Mellitus Tipo 2/epidemiologia , Gana , Humanos , Países Baixos/epidemiologia , Fatores de Risco , Suriname/epidemiologia
16.
J Immigr Minor Health ; 22(2): 399-409, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31227973

RESUMO

Type 2 diabetes (T2D) is a complex, lifelong condition that is disproportionately prevalent among minority populations. Haitian immigrants (HIs) living in the US with T2D have unique factors that influence diagnosis, treatment, and self-management. The purpose of this integrative review was to provide a synthesis of the research on T2D in the HI population. In a systematic literature search, 14 studies met the inclusion criteria. Three themes were identified: risk factors for less self-management and/or worse metabolic control; protective factors for better self-management and/or metabolic control; and mixed results. HIs had higher HbA1c, yet better self-management, different genetic profiles, and lower levels of vitamin D and hemoglobin concentration compared to other ethnic groups. HIs also reported better dietary quality, less healthcare utilization, and higher perceived emotional/psychological stress compared to other ethnic groups. This study has implications for practice for integrating the unique cultural factors when assessing and intervening with HIs.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Emigrantes e Imigrantes , Feminino , Haiti/etnologia , Humanos , Masculino , Grupos Minoritários , Prevalência , Estados Unidos/epidemiologia
17.
Data Brief ; 28: 104866, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31872004

RESUMO

Maya communities have been shown to exhibit type 2 diabetes (T2D) with high prevalence compared with Mexican mestizo populations. Furthermore, some variants associated with the risk for T2D have been described. In this study, we describe the results of a pilot genome wide association study (GWAS) using 817,823 single nucleotide polymorphisms (SNPs) to identify candidate variants for replication in future studies. Herein, we present the GWAS study data, which were divided into three parts: first, 1289 ancestry informative markers (AIMs) were selected for Latino populations containing European, African, and Native American SNPs obtained from the literature; second, a GWAS hypothesis free to select candidate genes associated with T2D was performed, which identified 24 candidate genes; and third, 39 SNPs previously associated with T2D or related traits were replicated. This article is associated with the original article published in "Gene" under the title "Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population".

18.
J Endocrinol ; 241(1): 59-70, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878016

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1ß), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.


Assuntos
Gluconeogênese , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Condicionamento Físico Animal/métodos , Animais , Glicemia/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica , Glucose/metabolismo , Resistência à Insulina , Lipogênese/genética , Fígado/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/etiologia , Obesidade/fisiopatologia , Oxirredução
19.
J Clin Transl Endocrinol ; 15: 76-80, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30788219

RESUMO

OBJECTIVE: To assess oral antihyperglycemic agents (OAHA) and/or statin treatment initiation in patients with type 2 diabetes (T2D) and time from diagnosis to both types of treatment initiation and intensification. RESEARCH DESIGN AND METHODS: We reviewed 662 retrospective medical records of patients with T2D diagnosed by 31 general practitioner or specialist sites across Mexico, Argentina, and Brazil. Demographic and clinical information was abstracted from patients' medical records and summarized using descriptive statistics. Between-group differences were assessed with Student's t-test for continuous variables and Fisher's exact test for categorical variables. The starting time of each therapy (OAHA and statins, separately) was assessed using Kaplan-Meier estimates. RESULTS: At diagnosis, patients' mean age was 53 years; 44% had hypertension, 42% were obese, and 23% had dyslipidemia. During the 2-year follow-up, 95% of patients received OAHAs but only 29% of those eligible for statins received this prescription. Mean ±â€¯SD and median (Q1, Q3) time to first OAHA was 59 ±â€¯141 days and 1 (1, 31) day, respectively, and 230 ±â€¯232 days and 132 (30, 406) days, respectively, for a statin. During follow-up, 51-53% of patients with HbA1c/FPG values above target did not intensify hyperglycemia treatment. CONCLUSION: Dyslipidemia treatment in patients with T2D was delayed despite its known deleterious effect on atherosclerosis development and ß-cell mass/function. Anti-hyperglycemic treatment was not intensified when targets were not attained. This prescriptive inertia needs to be corrected because attainment of HbA1c treatment goals becomes more difficult, favoring the development of diabetes complications.

20.
Ann Transl Med ; 7(22): 656, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31930057

RESUMO

BACKGROUND: Depression in patients with type 2 diabetes (T2D) is often undiagnosed and remains untreated, leading to poor therapy adherence and ill health-related outcomes. We evaluated the effect of vortioxetine versus sertraline in the treatment of depression, distress and metabolic control in subjects with T2D and depression. METHODS: Participants were selected from the Clinic for Diabetes, diagnosed with depression when the score was ≥14 in the Hamilton Depression Rating Scale, and verified by a psychiatrist in agreement with the DSM-5 instrument (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). The criteria for recruitment also included glycosylated hemoglobin ≥7.5%, 18 to 60 years of age, and written informed consent. Pharmacological treatment for depression was assigned randomly: vortioxetine (10 mg/day) or sertraline (75 mg/day) for 8 weeks. Biochemical parameters, anthropometric measures and depression symptoms were evaluated after antidepressant treatment. This was a randomized singled-blind study. RESULTS: Subjects that met the inclusion criteria were 50, of which only 21 patients with T2D and depression finished the treatment. Vortioxetine and sertraline showed partial remission of depression. Vortioxetine showed a major effect size in glycosylated hemoglobin and a moderate effect size on weight loss, fasting plasma glucose (FPG), cholesterol and triacylglycerol levels. On the other hand, patients treated with sertraline presented a slight increase in body weight, body mass index (BMI), and in all biochemical markers. CONCLUSIONS: Vortioxetine may ameliorate depressive symptoms and metabolic control in patients with T2D and depression. Trial registration number: NCT03978286.

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