RESUMO
This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.
Assuntos
Demência , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Idoso , Pessoa de Meia-Idade , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes , Incidência , Comportamento de Redução do Risco , Demência/epidemiologia , Demência/prevenção & controleRESUMO
AIMS/HYPOTHESIS: We aimed to determine whether the use of glucagon-like peptide-1 receptor agonists (GLP-1RA) in individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus decreases the risk of new-onset adverse cardiovascular events (CVEs) and mortality rate compared with other glucose-lowering drugs in a real setting at a population level. METHODS: We conducted a population-based propensity-matched retrospective cohort study using TriNetX. The cohort comprised patients over 20 years old who were newly treated with glucose-lowering drugs between 1 January 2013 and 31 December 2021, and followed until 30 September 2022. New users of GLP-1RAs were matched based on age, demographics, comorbidities and medication use by using 1:1 propensity matching with other glucose-lowering drugs. The primary outcome was the new onset of adverse CVEs, including heart failure, composite incidence of major adverse cardiovascular events (MACE; defined as unstable angina, myocardial infarction, or coronary artery procedures or surgeries) and composite cerebrovascular events (defined as the first occurrence of stroke, transient ischaemic attack, cerebral infarction, carotid intervention or surgery), and the secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate HRs. RESULTS: The study involved 2,835,398 patients with both NAFLD and type 2 diabetes. When compared with the sodium-glucose cotransporter 2 (SGLT2) inhibitors group, the GLP-1RAs group showed no evidence of a difference in terms of new-onset heart failure (HR 0.97; 95% CI 0.93, 1.01), MACE (HR 0.95; 95% CI 0.90, 1.01) and cerebrovascular events (HR 0.99; 95% CI 0.94, 1.03). Furthermore, the two groups had no evidence of a difference in mortality rate (HR 1.06; 95% CI 0.97, 1.15). Similar results were observed across sensitivity analyses. Compared with other second- or third-line glucose-lowering medications, the GLP-1RAs demonstrated a lower rate of adverse CVEs, including heart failure (HR 0.88; 95% CI 0.85, 0.92), MACE (HR 0.89; 95% CI 0.85, 0.94), cerebrovascular events (HR 0.93; 95% CI 0.89, 0.96) and all-cause mortality rate (HR 0.70; 95% CI 0.66, 0.75). CONCLUSIONS/INTERPRETATION: In individuals with NAFLD and type 2 diabetes, GLP-1RAs are associated with lower incidences of adverse CVEs and all-cause mortality compared with metformin or other second- and third-line glucose-lowering medications. However, there was no significant difference in adverse CVEs or all-cause mortality when compared with those taking SGLT2 inhibitors.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Hipoglicemiantes/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Glucose , Estudos Retrospectivos , Estudos de Coortes , Resultado do Tratamento , Insuficiência Cardíaca/complicações , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistasRESUMO
Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Obesidade/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Exercício Físico , Insulina/metabolismoRESUMO
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases employing abnormal levels of insulin. Enhancing the insulin production is greatly aided by the regulatory mechanisms of the Fractalkine receptor (CX3CR1) system in islet ß-cell function. However, elements including a high-fat diet, obesity, and ageing negatively impact the expression of CX3CR1 in islets. CX3CL1/CX3CR1 receptor-ligand complex is now recognized as a novel therapeutic target. It suggests that T2DM-related ß-cell dysfunction may result from lower amount of these proteins. We analyzed the differential expression of CX3CR1 gene samples taken from persons with T2DM using data obtained from the Gene Expression Omnibus database. Homology modeling enabled us to generate the three-dimensional structure of CX3CR1 and a possible binding pocket. The optimized CX3CR1 structure was subjected to rigorous screening against a massive library of 693 million drug-like molecules from the ZINC15 database. This screening process led to the identification of three compounds with strong binding affinity at the identified binding pocket of CX3CR1. To further evaluate the potential of these compounds, molecular dynamics simulations were conducted over a 50 ns time scale to assess the stability of the protein-ligand complexes. These simulations revealed that ZINC000032506419 emerged as the most promising drug-like compound among the three potent molecules. The discovery of ZINC000032506419 holds exciting promise as a potential therapeutic agent for T2D and other related metabolic disorders. These findings pave the way for the development of effective medications to address the complexities of T2DM and its associated metabolic diseases.
Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Descoberta de Drogas , Insulina , LigantesRESUMO
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played an important role in the pathogenesis of T2DM. Prospective studies on the link between immunoglobulins concentrations and the risk of T2DM in adults are limited. We developed a cohort study including 7,093 adults without T2DM history. The incidence of T2DM was 16.45 per 1,000 person-years. Compared with the lowest quartiles, the hazard ratios (95% confidence intervals) of T2DM for the highest quartiles of IgG, IgE, IgM and IgA were 0.64 (0.48-0.85), 0.94 (0.72-1.23), 0.68 (0.50-0.92) and 1.62 (1.24-2.11) (P for trend was < 0.01, 0.84, 0.02 and < 0.0001), respectively, suggesting that serum IgG and IgM concentrations were inversely associated with the incidence of T2DM, and IgA levels were positively associated with the risk of T2DM in a general adult population.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto , Incidência , Fatores de Risco , Imunoglobulinas/sangue , Idoso , Estudos de CoortesRESUMO
Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Peptídeos Semelhantes ao Glucagon , Glucose , Fragmentos Fc das Imunoglobulinas , Dinâmica Mitocondrial , Proteínas Recombinantes de Fusão , Sirtuína 1 , Animais , Camundongos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Fragmentos Fc das Imunoglobulinas/farmacologia , Isquemia/metabolismo , Isquemia/tratamento farmacológico , Isquemia/patologia , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/metabolismoRESUMO
Gut microbiota function has numerous effects on humans and the diet humans consume has emerged as a pivotal determinant of gut microbiota function. Here, a new concept that gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) trained human gut Akkermansia muciniphila (A. muciniphila) can reverse high-fat diet-induced type 2 diabetes (T2DM) in mice. Oral administration of OMVs released from GaELNs trained A. muciniphila can traffick to the brain where they are taken up by microglial cells, resulting in inhibition of high-fat diet-induced brain inflammation. GaELNs treatment increases the levels of OMV Amuc-1100, P9, and phosphatidylcholines. Increasing the levels of Amuc-1100 and P9 leads to increasing the GLP-1 plasma level. Increasing the levels of phosphatidylcholines is required for inhibition of cGas and STING-mediated inflammation and GLP-1R crosstalk with the insulin pathway that leads to increasing expression of Insulin Receptor Substrate (IRS1 and IRS2) on OMV targeted cells. These findings reveal a molecular mechanism whereby OMVs from plant nanoparticle-trained gut bacteria regulate genes expressed in the brain, and have implications for the treatment of brain dysfunction caused by a metabolic syndrome.
Assuntos
Eixo Encéfalo-Intestino , Diabetes Mellitus Tipo 2 , Exossomos , Alho , Microbioma Gastrointestinal , Nanopartículas , Diabetes Mellitus Tipo 2/metabolismo , Alho/química , Animais , Nanopartículas/química , Exossomos/metabolismo , Camundongos , Akkermansia , Humanos , Masculino , Dieta Hiperlipídica , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/patologiaRESUMO
PURPOSE: To assess the correlation between primary open-angle glaucoma (POAG) and the risk of developing diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). DESIGN: A retrospective cohort study leveraging the global patient database of TriNetX Research Network. PARTICIPANTS: The study included 44 359 patients with diabetes mellitus (DM) with POAG and 4 393 300 patients with DM without any glaucoma ≥ 18 years of age. Propensity score matching harmonized the cohorts to 39 680 patients each, covering diagnoses from January 1, 2005, to January 1, 2023. METHODS: We analyzed data using specific International Classification of Diseases, 10th Revision (ICD-10) codes for DM and glaucoma. We matched the cohorts using propensity score matching, adjusting for age, sex, race/ethnicity, blood markers, relevant medical history, and ophthalmic service use. MAIN OUTCOME MEASURES: The primary outcome was the first-time occurrence of DR, including nonproliferative DR (NPDR) and proliferative DR (PDR), in patients with DM with and without glaucoma at 1-, 5-, and 10-year intervals from their individual index dates. RESULTS: At 10 years, patients with T1DM with POAG exhibited a heightened risk for any DR (adjusted risk ratios [RRs], 4.12; 95% confidence interval [CI], 3.05-5.57, P < 0.0001) and PDR (RR, 7.02; 95% CI, 3.62-13.61, P < 0.0001). Patients with T2DM and POAG also faced an increased 10-year risk for any DR (RR, 2.47; 95% CI, 2.28-2.68, P < 0.0001) and PDR (RR, 3.82; 95% CI, 3.09-4.70, P < 0.0001). The combined association of POAG on DR risk in those with T1DM and T2DM at 10 years was found to be significantly higher among patients with POAG (5.45%) compared with those without glaucoma (2.12%) (adjusted hazard ratio [aHR], 2.33; 95% CI, 2.14-2.53). The cumulative incidence of DR was significantly higher in the POAG group compared with nonglaucoma counterparts after a decade (log-rank P < 0.001). CONCLUSIONS: Our findings underscore a substantial association between POAG and DR development in both T1DM and T2DM patients, emphasizing the need for vigilant screening and comprehensive management in glaucomatous patients with DM to mitigate the risk of DR. Future research should delve into elucidating the causal mechanisms driving these observed associations. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Assuntos
Bases de Dados Factuais , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Glaucoma de Ângulo Aberto , Humanos , Glaucoma de Ângulo Aberto/epidemiologia , Glaucoma de Ângulo Aberto/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/diagnóstico , Feminino , Masculino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Adulto , Incidência , Pressão Intraocular/fisiologiaRESUMO
BACKGROUND: The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus. METHOD: Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13). RESULTS: At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group. CONCLUSION: Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide.
Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Biomarcadores , Diabetes Mellitus Tipo 2 , Incretinas , Liraglutida , Obesidade , Estado Pré-Diabético , Receptores de Superfície Celular , Comportamento de Redução do Risco , Redução de Peso , Humanos , Liraglutida/uso terapêutico , Liraglutida/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Redução de Peso/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Feminino , Obesidade/diagnóstico , Obesidade/sangue , Obesidade/terapia , Biomarcadores/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/terapia , Estado Pré-Diabético/tratamento farmacológico , Receptores de Superfície Celular/sangue , Resultado do Tratamento , Antígenos CD/sangue , Incretinas/uso terapêutico , Incretinas/efeitos adversos , Incretinas/sangue , Adulto , Estudos de Casos e Controles , Fatores de Tempo , Regulação para Baixo , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , IdosoRESUMO
BACKGROUND: Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM. METHODS: Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models. RESULTS: This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear doseâresponse relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05). CONCLUSIONS: T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.
Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Diabetes Mellitus Tipo 2 , Humanos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Espessura Intima-Media Carotídea , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.g. diabetes), autoimmune diseases, nervous system-related diseases, digestive system-related diseases, and even tumours. Aldo-keto reductase 1B10 (AKR1B10) is an important player in the development and progression of multiple diseases, such as tumours and inflammatory diseases. AKR1B10 is upregulated in solid tumours, such as hepatocellular carcinoma (HCC), non-small cell lung carcinoma, and breast cancer, and is a reliable serum marker. However, information on the role of AKR1B10 in inflammation is limited. In this study, we summarized the role of AKR1B10 in inflammatory diseases, including its expression, functional contribution to inflammatory responses, and regulation of signalling pathways related to inflammation. We also discussed the role of AKR1B10 in glucose and lipid metabolism and oxidative stress. This study provides novel information and increases the understanding of clinical inflammatory diseases.
Assuntos
Aldo-Ceto Redutases , Inflamação , Humanos , Inflamação/imunologia , Aldo-Ceto Redutases/metabolismo , Animais , Estresse Oxidativo , Transdução de Sinais , Metabolismo dos Lipídeos , Glucose/metabolismoRESUMO
AIMS: Type 2 diabetes mellitus (T2DM) commonly combines with dyslipidemia, and both are known as the risk factors of cardiovascular events and aggravate the arteriosclerosis progression. In this study, we investigated the relationship between follicle-stimulating hormone (FSH) and lipid profiles in male T2DM patients. MATERIALS AND METHODS: We collected clinical data of male T2DM patients in the Chinese Han population hospitalised from January 2018 to June 2020. A total of 963 patients with a mean age of 58.89 ± 12.25 years old were enroled in this study. RESULTS: The results showed that the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL)-C levels were decreased gradually from the highest quartile groups (Q4) to Q1 group relevant to luteinising hormone and FSH, and no significant difference was observed in high-density lipoprotein-C levels among Q4-Q1 groups. Sub-groups analysis showed that, with the increased FSH level, TC, TG, and LDL-C levels were increased in the elder group (40-59 years old) than those in the younger group (20-39 years old). Spearman's analysis revealed a positive correlation between FSH and the levels of TC, TG, and LDL-C (r = 0.354, r = 0.336, r = 0.312, p < 0.001, respectively). The effect of FSH is independent of the changes in total testosterone level. Multivariate analysis found that increased FSH levels (≥9.26 mIU/mL) and decreased total testosterone levels (<13.30 nmol/L) were positively correlated with high TC, TG, and LDL-Cemia (OR = 4.014, 1.565, 1.602, 1.660, 2.127, 1.322, respectively, p < 0.05). CONCLUSIONS: Our data suggest that high serum FSH level in male T2DM patients could be a potential independent risk factor correlated with the elevated TC, TG, and LDL-C.
Assuntos
Diabetes Mellitus Tipo 2 , Dislipidemias , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Adulto Jovem , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , LDL-Colesterol , Triglicerídeos , Hormônio Foliculoestimulante , Dislipidemias/complicações , Testosterona , HDL-ColesterolRESUMO
Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.
Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Fragmentos Fc das Imunoglobulinas , Incretinas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Estudos Longitudinais , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Feminino , Pessoa de Meia-Idade , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Masculino , Densidade Óssea/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Idoso , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Incretinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes de Fusão/farmacologia , Doenças Ósseas Metabólicas/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
INTRODUCTION: There are growing concerns on how to prevent, slow down and induce remission of type 2 diabetes mellitus (T2DM). Recent evidence has found diet and lifestyle interventions can cause remission of T2DM, however, there are challenges for diverse groups such as British Pakistanis who are four times more at risk of T2DM. There is a need to understand the food behaviours of different generational groups to develop culturally appropriate strategies to support diabetes prevention programmes. AIMS: This study explores beliefs about healthy eating and food practices related to T2DM among British Pakistanis to understand the challenges they face in implementing healthy diets. METHOD: We carried out 26 semi-structured qualitative interviews via telephone and face-to-face. The sample included T2DM British Pakistanis living in Bradford (UK), aged between 18 and 71 with a mean age of 50 (SD = 17.04). Among the participants, 14 were women (54%) and 12 were men (46%), with interviews conducted in both English (76%) and Urdu (24%). Participants were grouped under three generation groups based on age (first generation 65+; second generation 40-64; younger generation 18-39 years). There was no biological link between the generational groups, and they were not part of the same family. Data were analysed using qualitative reflexive thematic analysis. RESULTS: Findings were categorised into three themes: knowledge and awareness of diabetes symptoms; social and family context of food practices and making sense of healthy eating. The family was the fundamental unit of understanding food-related health behaviours. Eating traditional food was perceived as healthy and deemed practical for first generations who were the initial members of their family to settle in the UK as well as the second generations who had parents born in Pakistan. Younger British Pakistanis were born in the UK and reported that they struggled to eat alternative foods within the home and manage their T2DM. CONCLUSION: These findings improve our understanding of how three generations of British Pakistanis with T2DM negotiate healthy diets. There is a need for culturally tailored diet modifications and interventions, where different generational needs can be specifically targeted to adopt healthier diets which should be shared and encouraged.
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Diabetes Mellitus Tipo 2 , População do Sul da Ásia , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta Saudável , Dieta , Povo Asiático , Pesquisa QualitativaRESUMO
INTRODUCTION: The role of dapagliflozin on erectile dysfunction (ED), a condition widely affecting patients with type 2 diabetes mellitus (T2DM), has not yet been studied. AIM: The aim of the study was to evaluate the effects of dapagliflozin alone or in combination with tadalafil on ED in patients with T2DM. METHODS: This was an open-label, non-randomized pilot study involving 30 Caucasian male patients with T2DM and severe ED. They were equally divided into three groups, assigned to treatment with tadalafil 5 mg/day (Group 1), tadalafil 5 mg/day plus dapagliflozin 10 mg/day (Group 2) and dapagliflozin 10 mg/day (Group 3) for 3 months. The presence and the severity of ED were evaluated at enrolment and after treatment, by the International Index of Erectile Function 5-item (IIEF-5) questionnaire and the dynamic penile echo colour Doppler ultrasound (PCDU) examination. RESULTS: At the end of treatment, the three groups showed a significant improvement in IIEF-5 score, by 294%, 375% and 197%, in Groups 1, 2 and 3, respectively. PCDU evaluation showed a significant increase in peak systolic velocity by 178.9%, 339% and 153%; acceleration time was significantly shortened in Group 2 (-26.2%) and was significantly lower than in Group 1 and 3 (-7.2% and -6.6%), while no significant difference was found in end-diastolic velocity after treatment. The greatest rates of improvement were observed in Group 2 for all the end points. CONCLUSIONS: Dapagliflozin improves ED in patients with T2DM and enhances the efficacy of tadalafil. Further studies are needed to confirm our results explain the mechanism(s) by which dapagliflozin exerts its effects on ED.
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Diabetes Mellitus Tipo 2 , Disfunção Erétil , Humanos , Masculino , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/etiologia , Tadalafila/uso terapêutico , Projetos Piloto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Carbolinas , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: This review aims to collect all the data regarding imeglimin and present it as one of the options for managing diabetes. RECENT FINDINGS: It is a new drug that has recently been approved as an oral anti-diabetic drug, either as monotherapy or in combination with other oral antidiabetic drugs including insulin, with modest HbA1c reduction, and a fairly safe profile. Imeglimin was first approved in 2021 in Japan and China and is available in India from October 2022. Imeglimin is the first compound in a new class of oral anti-diabetic medications known as "glimins" that include a tetrahydrotriazine ring. Glimins act by amplifying glucose-stimulated insulin secretion (GSIS) and preserving ß-cell mass, leading to augmented insulin secretion. Furthermore, It also intensifies insulin action by inhibiting of hepatic glucose output and recovery of altered insulin signalling in both hepatocytes (liver) and myocytes (skeletal muscle). This is a unique mode of action than has been demonstrated to be distinct from other classes of drugs, as it targets both insulin secretion and insulin resistance by correcting the mitochondrial dysfunction. Imeglimin has been studied in various phase III trials which have equivocally shown it to be effective in lowering glucose levels and improving pancreatic function and its recommended dose set at 1000 mg bid.
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Diabetes Mellitus Tipo 2 , Triazinas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , GlucoseRESUMO
BACKGROUND: Gestational diabetes mellitus affects up to 10% of pregnancies and is classified into subtypes gestational diabetes subtype A1 (GDMA1) (managed by lifestyle modifications) and gestational diabetes subtype A2 (GDMA2) (requiring medication). However, whether these subtypes are distinct clinical entities or more reflective of an extended spectrum of normal pregnancy endocrine physiology remains unclear. OBJECTIVE: Integrated bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomics harbors the potential to reveal disease gene signatures in subsets of cells and tissue microenvironments. We aimed to combine these high-resolution technologies with rigorous classification of diabetes subtypes in pregnancy. We hypothesized that differences between preexisting type 2 and gestational diabetes subtypes would be associated with altered gene expression profiles in specific placental cell populations. STUDY DESIGN: In a large case-cohort design, we compared validated cases of GDMA1, GDMA2, and type 2 diabetes mellitus (T2DM) to healthy controls by bulk RNA-seq (n=54). Quantitative analyses with reverse transcription and quantitative PCR of presumptive genes of significant interest were undertaken in an independent and nonoverlapping validation cohort of similarly well-characterized cases and controls (n=122). Additional integrated analyses of term placental single-cell, single-nuclei, and spatial transcriptomics data enabled us to determine the cellular subpopulations and niches that aligned with the GDMA1, GDMA2, and T2DM gene expression signatures at higher resolution and with greater confidence. RESULTS: Dimensional reduction of the bulk RNA-seq data revealed that the most common source of placental gene expression variation was the diabetic disease subtype. Relative to controls, we found 2052 unique and significantly differentially expressed genes (-2
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Type 2 diabetes mellitus (T2DM) is one of the metabolic diseases with the highest morbidity rates in the world. Probiotics have positive health impacts on human health and a considerable amount of research has demonstrated their beneficial effects in treating T2DM. However, probiotic intervention in T2DM has complex mechanisms because the pathogenesis of T2DM is complex. This review summarized the mechanisms of probiotic intervention in diabetes from the perspective of diabetes pathogenesis. First, the objectives of probiotic intervention in diabetes aimed at the intestinal tract reparative effects, pancreatic function, host metabolism and self-recovery were comprehensively reviewed. Next, we concluded the clinical application status of ingested probiotics in patients with T2DM, and an obvious imbalance exists between theoretical probiotic research and clinical applications. Finally, we summarized the emerging research on probiotic interventions in T2DM and analyzed the literature in this regard, including next-generation probiotics; suggestions for probiotics consumption with the aim of diabetic complications; as well as the association between novel mechanisms of diabetes remission with the potential for probiotic intervention. In conclusion, this review sheds light on the potential role of probiotics, from proposed mechanisms to prospects in relieving T2DM.
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Obesity has increased dramatically worldwide. Being overweight or obese can lead to various conditions, including dyslipidaemia, hypertension, glucose intolerance and metabolic syndrome (MetS), which may further lead to type 2 diabetes mellitus (T2DM). Previous studies have identified a link between ß-cell dysfunction and the severity of MetS, with multiple organs and tissues affected. Identifying the associations between pancreatic ß-cell dysfunction and organs is critical. Research has focused on the interaction between the liver, gut and pancreatic ß-cells. However, the mechanisms and related core targets are still not perfectly elucidated. The aims of this review were to summarize the mechanisms of ß-cell dysfunction and to explore the potential pathogenic pathways and targets that connect the liver, gut, adipose tissue, muscle, and brain to pancreatic ß-cell dysfunction.
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AIM: To determine the association of the presence of diabetes and, among persons with diabetes, the age at type 2 diabetes mellitus (T2DM) onset, BMI and the interactive effect with the subsequent thyroid cancer risk. MATERIALS AND METHODS: We conducted a population register-based longitudinal cohort study in Shanghai, including 428 568 persons with new-onset T2DM matched with the general population. The risk of thyroid cancer among subgroups was calculated based on standardized incidence ratio (SIR), hazard ratio (HR) and Cox proportional hazards models. RESULTS: In total, 1142 thyroid cancer cases were identified during 8 years of follow-up, with an incidence rate of 59.01/100 000 person-years and a higher risk (SIR = 1.21) compared with the general population. The earlier age at T2DM onset and higher BMI were associated with an increasing risk of thyroid cancer independently (onset age <50, SIR: 1.46; BMI ≥30.0 kg/m2, SIR: 1.93), with the highest risk in patients with both BMI ≥30.0 kg/m2 and onset age <50 years (SIR = 3.91, HR = 3.04). Among patients with T2DM onset age <60 years, SIR increased with higher BMI, while there were no trends when onset age ≥60 years. Among patients with BMI ≥25.0 kg/m2, SIR increased with an earlier onset age, whereas no trends were shown in the BMI <24.9 kg/m2 groups. Obese (BMI ≥30.0 kg/m2) patients had a significantly higher HR of thyroid cancer only when T2DM onset age <60 years. CONCLUSIONS: Both earlier age of T2DM onset (<50 years) and higher BMI (≥30 kg/m2) contributed to the higher risk of thyroid cancer. Patients with young-onset T2DM and obesity are considered more vulnerable to thyroid cancer development.