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2.
BMC Endocr Disord ; 22(1): 256, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273168

RESUMO

BACKGROUND: Growth differentiation factor 15 (GDF15) was newly discovered to be a promising target of metformin. The study was aimed to investigate the relationship between GDF15 and glycemic control after metformin treatment in patients with type 2 diabetes mellitus. METHODS: The study was a post-hoc analysis of AIM (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed Insulin compared to Metformin) study. The participants were randomly assigned to 12 weeks of metformin (MET) or acarbose (ACA) treatment combined with insulin. Serum GDF15 levels of 51 subjects from MET group and 53 subjects from ACA group were measured at baseline and after a 12-week treatment. Fasting plasma glucose (FPG), 2-h postprandial plasma glucose (2-h PG) and glycated hemoglobin A1c (HbA1c) were measured at baseline and endpoint. RESULTS: After a 12-week treatment, serum GDF15 levels significantly increased in MET group [baseline vs. endpoint, 936.70 (741.00, 1205.40) pg/mL vs. 1265.20 (1027.90, 1634.00) pg/mL, P < 0.001], but not in ACA group [baseline vs. endpoint, 920.60 (701.45, 1332.55) pg/mL vs. 893.80 (663.25, 1284.05) pg/mL, P = 0.944]. However, there were no significant differences of glycemic control parameters (ΔFPG, Δ2-h PG and ΔHbA1c) between subgroups of MET group divided by median of ΔGDF15 (all P > 0.05). Spearman correlation coefficient and analysis of covariance after adjustment for baseline HbA1c levels showed that ΔGDF15 was not correlated with ΔFPG, Δ2-h PG and ΔHbA1c (all P > 0.05). CONCLUSION: Serum GDF15 levels were significantly elevated after metformin treatment in patients with type 2 diabetes mellitus. However, the increase was not an indicator of the glucose-lowering effect of metformin. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02438397 . Registered 8 May 2015.


Assuntos
Diabetes Mellitus Tipo 2 , Fator 15 de Diferenciação de Crescimento , Hipoglicemiantes , Metformina , Humanos , Acarbose/uso terapêutico , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/análise , Controle Glicêmico , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/metabolismo , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico
3.
N Engl J Med ; 387(12): 1063-1074, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36129996

RESUMO

BACKGROUND: The comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain. METHODS: In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%. RESULTS: A total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P<0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups. CONCLUSIONS: All four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Hemoglobina A Glicada , Hipoglicemiantes , Glicemia/análise , Pesquisa Comparativa da Efetividade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Quimioterapia Combinada , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Liraglutida/efeitos adversos , Liraglutida/uso terapêutico , Metformina/efeitos adversos , Metformina/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico , Resultado do Tratamento
5.
Front Public Health ; 10: 882686, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045734

RESUMO

Aims: To evaluate the correlation of nesfatin-1, GSH and SOD levels with ß-cell insulin secretion and their influence on insulin secretion in the development of type 2 diabetes mellitus (T2DM). Materials and methods: 75 patients with T2DM, 67 with prediabetes and 37 heathy participants were recruited in this study. Serum levels of nesfatin-1, GSH and SOD were quantified and statistically analyzed. Results: The levels of nesfatin-1, GSH and SOD in T2DM were significantly decreased (P < 0.001) compared to either in prediabetes or in healthy control, and significant reduction of these biomarkers was also observed in prediabetes when compared to the control (P < 0.001). Circulating nesfatin-1, GSH and SOD were not only strongly correlated with ß-cell insulin secretion, but also exerted remarkable influence on the secretion. Conclusion: Serum nesfatin-1, GSH and SOD are important factors involving insulin secretion in the development of T2DM, which may help provide new ideas for forthcoming investigations on the roles of these factors in pathogenesis of T2DM, as well as for active prediction and prevention of prediabetes before it develops into overt T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Glutationa/metabolismo , Nucleobindinas/metabolismo , Estado Pré-Diabético , Superóxido Dismutase-1/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Glutationa/sangue , Humanos , Secreção de Insulina , Nucleobindinas/sangue , Estado Pré-Diabético/sangue , Estado Pré-Diabético/metabolismo , Superóxido Dismutase , Superóxido Dismutase-1/sangue
6.
Front Endocrinol (Lausanne) ; 13: 899008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957835

RESUMO

Aim: The association between gamma-glutamyl transferase (GGT) and type 2 diabetes mellitus (T2DM) is controversial. In this study, we investigated the association between GGT and the risk of T2DM using real-world data, Mendelian randomization (MR) analysis, and literature mining. Methods: A cross-sectional study enrolled 3,048 participants (>40 years) from a community in Northeastern China was conducted. A generalized additive model was used to examine the relation between GGT and T2DM. A two-sample MR was performed to investigate the causal effect of GGT (61,089 individuals, mostly of European ancestry) on T2DM (29,193 cases and 182,573 controls of European ancestry). Results: GGT was related to glucose metabolism indicators, such as fasting plasma glucose and glycosylated hemoglobin (P < 0.05). The odds ratios (ORs) [95% confidence interval (95% CI), P] for T2DM across the GGT categories (14-16, 17-20, 21-25, 26-35, ≥36) were 1.14 [(0.88-1.47), P = 0.330], 1.55 [(1.22-1.98), P < 0.001], 1.87 [(1.47-2.28), P < 0.001], 1.97 [(1.55-2.52), P < 0.001], and 2.29 [(1.78-2.94), P < 0.001] versus GGT ≤ 13 category after adjusting for potential confounding factors. A generalized additive model identified a non-linear correlation between GGT and T2DM and indicated that the risk of T2DM almost levelled out when GGT exceeded 34 IU/L. The MR analysis showed that the odds of having T2DM for a one-time increase in genetically determined GGT was 0.998 [(0.995-1.002), P = 0.34]. Conclusions: Our analysis of observational study suggested that GGT, its increment, within a certain range, is indicative of the development of T2DM. However, MR analysis provided no evidence that GGT is a linear causal factor of T2DM. Further investigation is required to determine if GGT exerts a non-linear causal effect on T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Análise da Randomização Mendeliana , gama-Glutamiltransferase , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Hemoglobina A Glicada/análise , Humanos , gama-Glutamiltransferase/metabolismo
7.
J Med Life ; 15(6): 792-796, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35928354

RESUMO

Serum creatinine level begins to increase after a decrease in glomerular filtration rate (GFR) by 50% and more, so the question emerged about a more accurate method of determining GFR. The study aimed to determine the role of renal damage markers in the diagnosis of early-stage renal disease in patients with latent autoimmune diabetes in adults (LADA). We included 84 patients with diabetes mellitus (DM) and chronic kidney disease (CKD) caused by diabetic kidney disease (DKD), as well as 25 representatives of the control group. Patients were divided into three groups - 43 people with LADA, 21 with type 1 diabetes mellitus (T1DM), and 20 patients with type 2 diabetes mellitus (T2DM). GFR was assessed using six formulas after establishing the category of GFR and albuminuria. The GFR rate estimated by the CKD-EPI formula in patients with LADA and DKD did not significantly differ from that of CKD-EPI cysC, slightly different from MDRD GFR (10.6% higher, respectively) but 21.9% lower compared to CG formula. In patients with LADA and T1DM, GFR was higher in cases with existing albuminuria, regardless of the formulas used. Thus, the non albuminuria phenotype is accompanied by a greater degree of renal impairment, which indicates the need to determine serum cystatin C in the early stages of LADA. Cystatin C levels are the most accurate, early, and independent predictor of the development and progression of CKD in patients with DM, including LADA.


Assuntos
Cistatina C , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Autoimune Latente em Adultos , Insuficiência Renal Crônica , Biomarcadores/sangue , Creatinina/sangue , Cistatina C/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Taxa de Filtração Glomerular , Humanos , Rim , Diabetes Autoimune Latente em Adultos/sangue , Diabetes Autoimune Latente em Adultos/complicações , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações
8.
Inflammopharmacology ; 30(5): 1843-1851, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35974263

RESUMO

BACKGROUND: Inflammation is a prominent clinical manifestation in type 2 diabetes mellitus (T2DM) patients, often associated with insulin resistance, metabolic dysregulation, and other complications. AIM OF THE STUDY: The present study has been designed to check the serum levels of PAR-1 and correlate with various clinical manifestations and inflammatory cytokines levels in type 2 diabetic subjects. MATERIAL AND METHODS: The study population was divided into two groups, healthy volunteers (n = 15): normal glycated hemoglobin (HbA1c) (4.26 ± 0.55) and type 2 diabetic subjects (n = 30): HbA1c levels (7.80 ± 2.41). The serum levels of PAR-1 (ELISA method) were studied in both groups and correlated with demographic parameters age, weight, body mass index (BMI), and conventional inflammation biomarkers like C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumour necrosis factor-alpha (TNF-α). RESULTS: The demographic variables including the body weight (77.38 ± 10.00 vs. controls 55.26 ± 6.99), BMI (29.39 ± 3.61 vs. controls 25.25 ± 4.01), glycemic index HbA1c (7.80 ± 2.41 vs. controls 4.26 ± 0.55) were found to be statistically increased in T2DM subjects than the healthy control group. The levels of various inflammatory biomarkers and PAR-1 were significantly elevated in T2DM groups in comparison to healthy volunteers. The univariate and multivariate regression analysis revealed that elevated PAR-1 levels positively correlated with increased body weight, BMI, HbA1c, and inflammatory cytokines. CONCLUSION: Our findings indicate that the elevated serum PAR-1 levels serve as an independent predictor of inflammation in T2DM subjects and might have prognostic value for determining T2DM progression.


Assuntos
Diabetes Mellitus Tipo 2 , Receptor PAR-1 , Fator de Necrose Tumoral alfa , Biomarcadores , Glicemia/metabolismo , Peso Corporal , Proteína C-Reativa/análise , Citocinas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Interleucina-6 , Interleucina-8 , Receptor PAR-1/sangue
9.
Nutr. hosp ; 39(4): 916-923, jul. - ago. 2022. tab, graf
Artigo em Inglês | IBECS | ID: ibc-ADZ-862

RESUMO

Objective: to evaluate the lipid metabolism of patients with type 2 diabetes mellitus (T2DM) after very low-carbohydrate ketogenic (VLCK) diet treatment, so as to provide an evidence-based basis for better dietary management and comprehensive treatment of diabetic patients. Methods: PubMed, Cochrane Library, Embase, and Web of Science databases were searched for randomized controlled trial about VLCK diet on lipid metabolism of T2DM up to September 2021. The data were analyzed using the Stata 15.0; standardized mean difference (SMD) was used as effect size. Results: ten articles were included in this meta-analysis. There were no significant differences between the two groups in total cholesterol (SMD = -0.07, 95 % CI: -0.06-0.20, p > 0.05), HDL (SMD = 0.13, 95 % CI: -0.05-0.31, p > 0.05) and LDL (SMD = 0.07, 95 % CI: -0.06-0.20, p > 0.05) levels after treatment. No difference was found in total cholesterol, HDL, and LDL levels between the two groups after 3, 6, and 12 months of treatment (p > 0.05). Triglyceride levels decreased after VLCK diet compared with control (SMD = -0.49, 95 % CI: -0.82 to -0.17, p = 0.003). A marked reduction of triglyceride levels was identified after 3 months of VLCK diet treatment (SMD = -0.69, 95 % CI: -1.00 to -0.38), without significant difference after 6 and 12 months. Conclusion: T2DM patients who receive a VLCK diet to lower blood glucose are not associated with increased levels of total cholesterol and LDL, and decreased levels of HDL. Additionally, this diet can achieve a short-term reduction of triglyceride levels (AU)


Objetivo: evaluar el metabolismo lipídico de los pacientes con diabetes mellitus de tipo 2 (DMT2) tras el tratamiento con una dieta cetogénica muy baja en carbohidratos (VLCK), con el fin de proporcionar una base basada en la evidencia para un mejor manejo dietético y un tratamiento integral de los pacientes diabéticos. Métodos: se buscaron en las bases de datos PubMed, Cochrane Library, Embase y Web of Science ensayos controlados aleatorios sobre los efectos de la dieta VLCK en el metabolismo de los lípidos de la DMT2 hasta septiembre de 2021. Los datos se analizaron con el Stata 15.0. Se utilizó la diferencia de medias estandarizada (DME) como tamaño del efecto. Resultados: se incluyeron diez artículos en este metaanálisis. No hubo diferencias significativas entre los dos grupos en los niveles de colesterol total (DME = -0,07, IC del 95 %: -0,06-0,20, p > 0,05), HDL (DME = 0,13, IC del 95 %: -0,05-0,31, p > 0,05) y LDL (DME = 0,07, IC del 95 %: -0,06-0,20, p > 0,05) después del tratamiento. No se encontraron diferencias en los niveles de colesterol total, HDL y LDL entre los dos grupos después de 3, 6 y 12 meses de tratamiento (p > 0,05). Los niveles de triglicéridos disminuyeron después de la dieta VLCK en comparación con el control (DME = -0,49, IC del 95 %: -0,82 a -0,17, p = 0,003). Se identificó una marcada reducción de los niveles de triglicéridos después de 3 meses de tratamiento con la dieta VLCK (DME = -0,69, IC del 95 %: -1,00 a -0,38), sin diferencias significativas después de 6 y 12 meses. Conclusión: los pacientes con DMT2 que reciben una dieta VLCK para reducir la glucemia no se asocian a un aumento de los niveles de colesterol total y LDL, y a una disminución de los niveles de HDL. Además, esta dieta puede lograr una reducción a corto plazo de los niveles de triglicéridos (AU)


Assuntos
Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Metabolismo dos Lipídeos , Dieta Cetogênica , Glicemia/análise , Triglicerídeos/sangue , Colesterol/sangue , Lipídeos/sangue
10.
Med Arch ; 76(2): 135-139, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35774047

RESUMO

Background: Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia. Objective: The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020. Methods: This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005. Results: The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005). Conclusion: HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator A de Crescimento do Endotélio Vascular , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/patologia , Humanos , Hipóxia/sangue , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Neovascularização Patológica/sangue , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/sangue
11.
Cardiovasc Diabetol ; 21(1): 127, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787704

RESUMO

BACKGROUND: Raised liver function tests (LFTs) have been correlated with multiple metabolic abnormalities and variably associated with cardiorenal outcomes. We sought to systematically test the relationship between LFT levels within the accepted range and major cardiorenal outcomes in a large clinical trial in type 2 diabetes, and the possible impact of placebo-controlled canagliflozin treatment. METHODS: We measured serum alanine aminotransferase (ALT), aspartic aminotransferase (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin concentrations in 10,142 patients, at baseline and repeatedly over follow-up. The relation of LFTs to first hospitalized heart failure (HHF), cardiovascular (CV) and all-cause mortality, and progression of renal impairment was investigated using multivariate proportional-hazards models. RESULTS: In univariate association, ALT was reciprocally predictive, and ALP was positively predictive, of all adjudicated outcomes; γGT also was directly associated with CV-but not renal-outcomes. In multivariate models including all 5 LFTs and 19 potential clinical confounders, ALT was independently associated with lower, and γGT with higher, CV outcomes risk. Canagliflozin treatment significantly reduced ALT, AST, and γGT over time. In a fully adjusted model including updated LFT levels and treatment, γGT was independently associated with CV and all-cause mortality, ALP with renal dysfunction progression, and canagliflozin treatment with significant reduction in HHF and renal risk. CONCLUSIONS: Higher γGT levels are top LFT markers of risk of HHF and death in patients with diabetes and high CV risk, while ALT are protective. Canagliflozin lowers the risk of HHF and renal damage independently of LFTs and potential confounders.


Assuntos
Canagliflozina , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Testes de Função Hepática , Inibidores do Transportador 2 de Sódio-Glicose , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Fígado , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
12.
Sci Rep ; 12(1): 10504, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732646

RESUMO

We sought to examine whether dietary intakes may affect the relationship between ApoB EcoRI and lipid profile, as well as serum inflammatory markers, in patients with type 2 diabetes (T2DM). This current study consisted of 648 diabetic patients. Dietary intake was calculated by a food frequency questionnaire. Biochemical markers (high-density lipoprotein (HDL), total cholesterol (TC), LDL, TG, CRP, IL-18, PGF2α) were measured based on standard protocols. Genotyping of the Apo-B polymorphisms (rs1042031) was conducted by the PCR-RFLP method. The gene-diet interactions were evaluated using GLMs. In comparison to GG homozygotes, A-allele carriers with above the median -CHO intake (≥ 54 percent of total energy) had considerably greater TC and PGF2a concentrations. Furthermore, as compared to GG homozygotes, A-allele carriers with above the median protein intake (≥ 14 percent of total energy) had higher serum levels of TG (P = 0.001), CRP (P = 0.02), TG/HDL (P = 0.005), and LDL/HDL (P = 0.04) ratios. Moreover, A-allele carriers with above the median total fat intake (≥ 35 percent of total calories) had significantly higher TC level (P = 0.04) and LDL/HDL (P = 0.04) ratios compared to GG homozygotes. Furthermore, when compared to GG homozygotes, A-allele carriers who consumed above the median cholesterol (> 196 mg) had greater TG (P = 0.04), TG/HDL (P = 0.01) ratio, and IL-18 (P = 0.02). Furthermore, diabetic patients with the GA, AA genotype who consume above the median cholesterol had lower ghrelin levels (P = 0.01). In terms of LDL/HDL ratio, ApoB EcoRI and dietary intakes of specific fatty acids (≥ 9 percent for SFA and ≥ 12 percent for MUFA) had significant interaction. LDL/HDL ratio is greater in A-allele carriers with above the median SFA intake (P = 0.04), also when they consumed above the median MUFA this association was inverse (P = 0.04). Our study showed that plasma lipid levels in participants carrying the (AA or AG) genotype were found to be more responsive to increasing the percentage of energy derived from dietary fat, CHO, protein, SFA, and cholesterol consumption. Therefore, patients with a higher genetic susceptibility (AA or AG) seemed to have greater metabolic markers with a higher percentage of macronutrient consumption. Also, ApoB EcoRI correlations with metabolic markers might be attenuated with above the median MUFA consumption.


Assuntos
Apolipoproteínas B , Diabetes Mellitus Tipo 2 , Dieta , Nutrientes , Apolipoproteína B-100 , Apolipoproteínas B/genética , Biomarcadores/sangue , Colesterol/sangue , Desoxirribonuclease EcoRI/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Genótipo , Humanos
13.
Nutr Metab Cardiovasc Dis ; 32(8): 1917-1923, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35680486

RESUMO

BACKGROUND AND AIMS: Growth arrest-specific 6 protein (Gas6) has been established to play important roles in various biological processes, but little is currently known on the role of Gas6 signaling in humans. This research explored the association between Gas6 expression and carotid atherosclerosis (AS) in type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: As many as 126 T2DM patients were recruited in this study and classified into two groups based on their carotid intima-media thickness (CIMT). Meanwhile, 50 healthy individuals were recruited for the normal control group (NC). The subgroups were compared in terms of clinical data and Gas6 expression levels. Gas6 levels were decreased in T2DM patients with or without AS compared to NC subjects (9.64 ± 1.41 ng/ml, 11.38 ± 2.08 ng/ml, and 13.64 ± 2.61 ng/ml, respectively) (p < 0.001). The interaction between Gas6 and AS in T2DM was analyzed by logistic regression model and receiver operating characteristic (ROC) curve analysis. Decreased Gas6 expression was an independent risk factor relevant to AS in T2DM (p = 0.027). The area under the ROC curve to estimate the diagnostic value of low Gas6 expression for AS in T2DM was 0.750. The correlation between Gas6 and other parameters was evaluated by Pearson correlation analysis and linear regression model. Body mass index (BMI), hemoglobin A1c (HbA1c) and tumor necrosis factor-α(TNF-α) were independently correlated with Gas6. CONCLUSION: Low Gas6 expression is an independent risk factor for AS in T2DM. Gas6 expression is affected by BMI, HbA1c and TNF-α levels.


Assuntos
Doenças das Artérias Carótidas , Diabetes Mellitus Tipo 2 , Peptídeos e Proteínas de Sinalização Intercelular , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Hemoglobina A Glicada/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue
14.
Iran J Immunol ; 19(2): 193-200, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35767893

RESUMO

BACKGROUND: Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions. OBJECTIVE: To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. METHODS: This study included 387 Caucasians divided into four groups: healthy controls, obese subjects without carbohydrate issues, prediabetic patients, and recently discovered type 2 diabetics. RESULTS: Subject with body mass index ≥30kg/m2 and glycemic disorders showed significantly high levels of IL-18 (249.77 ± 89.96 pg/ml; 259.01 ± 95.70 pg/ml; and 340.98 ± 127.65 pg/ml) compared with that of the control group (219.47 ± 110.53 pg/ml, p < 0.05). IL-18 also had significant positive associations with some anthropometric parameters, liver enzymes, fasting, post-load glucose, insulin, uric acid, and triglycerides while negative with HDL. The circulating IL-18 levels for differentiating subjects with carbohydrate disturbances and those with metabolic syndrome were determined by ROC analysis. The AUC for the disturbances of the carbohydrate metabolism was 0.597 (p = 0.001; 95% CI = 0.539 - 0.654) and for MS AUC was 0.581 (p = 0.021; 95 % CI = 0.516 - 0.647). CONCLUSION: Our data indicate that as the levels of IL-18 are increased the carbohydrate tolerance is deteriorated. However, the significance of IL-18 in the progression of diabetes mellitus and subsequent consequences requires further exploration.


Assuntos
Diabetes Mellitus Tipo 2 , Interleucina-18 , Obesidade , Estado Pré-Diabético , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Interleucina-18/sangue , Obesidade/sangue , Obesidade/diagnóstico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico
15.
Can J Diabetes ; 46(5): 449-456.e3, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35739046

RESUMO

OBJECTIVES: Our aim in this study was to evaluate the efficacy of a Self-Management Multidisciplinary Program (MP) on glycemic management, quality of life and diabetes self-care activities. METHODS: People with type 2 diabetes and glycated hemoglobin (A1C) of >7.5% were randomized to participate in the MP or to usual care (UC). The MP consisted of face-to-face meetings with each health-care provider (nurse, pharmacist, dietitian, physical educator and social worker) to approach diabetes self-management issues. MP topics were tailored toward local habits and culture. Three different modules were offered over 12 weeks. The primary outcome was change in A1C from baseline to 12 months. Diabetes Quality of Life and Summary of Diabetes Self-Care Activities questionnaires were assessed at baseline and at 6 and 12 months. RESULTS: Ninety-six participants were included (mean 59 years of age, 60% women, diabetes duration 16±10 years, 62% of lower middle/low socioeconomic status). Change in A1C at 12 months (UC: 0.52% [95% confidence interval, -1.07 to 0.04]; MP: -0.30% [95% confidence interval, -1.05 to 0.44]; p=0.33) was not different between the groups. There was an increase in satisfaction and a reduction in worry about future effects of diabetes in the MP group, which was not found in the UC group. CONCLUSIONS: A short-term self-management multidisciplinary program improved diabetes-related quality of life but failed to reduce A1C in individuals with longstanding type 2 diabetes and a low socioeconomic status.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Qualidade de Vida , Autocuidado
16.
Neurology ; 99(7): e650-e659, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35654594

RESUMO

BACKGROUND AND OBJECTIVES: Previous studies have highlighted antidiabetic drugs as repurposing candidates for Alzheimer disease (AD), but the disease-modifying effects are still unclear. METHODS: A 2-sample mendelian randomization study design was applied to examine the association between genetic variation in the targets of 4 antidiabetic drug classes and AD risk. Genetic summary statistics for blood glucose were analyzed using UK Biobank data of 326,885 participants, whereas summary statistics for AD were retrieved from previous genome-wide association studies comprising 24,087 clinically diagnosed AD cases and 55,058 controls. Positive control analysis on type 2 diabetes mellitus (T2DM), insulin secretion, insulin resistance, and obesity-related traits was conducted to validate the selection of instrumental variables. RESULTS: In the positive control analysis, genetic variation in sulfonylurea targets was associated with higher insulin secretion, a lower risk of T2DM, and an increment in body mass index, waist circumference, and hip circumference, consistent with drug mechanistic actions and previous trial evidence. In the primary analysis, genetic variation in sulfonylurea targets was associated with a lower risk of AD (odds ratio [OR] = 0.38 per 1 mmol/L decrement in blood glucose, 95% CI 0.19-0.72, p = 0.0034). These results for sulfonylureas were largely unchanged in the sensitivity analysis using a genetic variant, rs757110, that has been validated to modulate the target proteins of sulfonylureas (OR = 0.35 per 1 mmol/L decrement in blood glucose, 95% CI 0.15-0.82, p = 0.016). An association between genetic variations in the glucagon-like peptide 1 (GLP-1) analogue target and a lower risk of AD was also observed (OR = 0.32 per 1 mmol/L decrement in blood glucose, 95% CI 0.13-0.79, p = 0.014). However, this result should be interpreted with caution because the positive control analyses for GLP-1 analogues did not comply with a weight-loss effect as shown in previous clinical trials. Results regarding other drug classes were inconclusive. DISCUSSION: Genetic variation in sulfonylurea targets was associated with a lower risk of AD, and future studies are warranted to clarify the underlying mechanistic pathways between sulfonylureas and AD.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Reposicionamento de Medicamentos , Estudo de Associação Genômica Ampla , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética
17.
Am J Prev Med ; 63(4): 603-610, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35718629

RESUMO

INTRODUCTION: RCTs have found that type 2 diabetes can be prevented among high-risk individuals by metformin medication and evidence-based lifestyle change programs. The purpose of this study is to estimate the use of interventions to prevent type 2 diabetes in real-world clinical practice settings and determine the impact on diabetes-related clinical outcomes. METHODS: The analysis performed in 2020 used 2010‒2018 electronic health record data from 69,434 patients aged ≥18 years at high risk for type 2 diabetes in 2 health systems. The use and impact of prescribed metformin, lifestyle change program, bariatric surgery, and combinations of the 3 were examined. A subanalysis was performed to examine uptake and retention among patients referred to the National Diabetes Prevention Program. RESULTS: Mean HbA1c values declined from before to after intervention for patients who were prescribed metformin (-0.067%; p<0.001) or had bariatric surgery (-0.318%; p<0.001). Among patients referred to the National Diabetes Prevention Program lifestyle change program, the type 2 diabetes postintervention incidence proportion was 14.0% for nonattendees, 12.8% for some attendance, and 7.5% for those who attended ≥4 sessions (p<0.001). Among referred patients to the National Diabetes Prevention Program lifestyle change program, uptake was low (13% for 1‒3 sessions, 15% for ≥4 sessions), especially among males and Hispanic patients. CONCLUSIONS: Findings suggest that metformin and bariatric surgery may improve HbA1c levels and that participation in the National Diabetes Prevention Program may reduce type 2 diabetes incidence. Efforts to increase the use of these interventions may have positive impacts on diabetes-related health outcomes.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Adolescente , Adulto , Cirurgia Bariátrica , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Masculino , Metformina/uso terapêutico
18.
N Engl J Med ; 387(5): 433-443, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35658022

RESUMO

BACKGROUND: The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes. METHODS: In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed. RESULTS: A total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (-0.6 percentage points in the 0.75-mg group and -0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (-18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults. CONCLUSIONS: Treatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.).


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Adolescente , Glicemia/efeitos dos fármacos , Criança , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Fragmentos Fc das Imunoglobulinas/administração & dosagem , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Injeções Subcutâneas , Insulinas/uso terapêutico , Metformina/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento
19.
Sci Rep ; 12(1): 11000, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768559

RESUMO

Although serum uric acid level and systemic inflammation have been highlighted as risk factors for type 2 diabetes mellitus (T2DM), little is known about these associations in the Korean population. Thus, we examined the individual and combined associations of serum uric acid and systemic inflammation (evaluated using high-sensitivity C-reactive protein [hs-CRP] measurement) with the future risk of T2DM. A total of 4152 Korean adults aged 45-76 years without T2DM, cancer, or gout at baseline in 2007-2008 from the Korean Genome and Epidemiology Study were followed up until 2016. Cox proportional hazard models were used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2DM according to sex-specific tertiles of serum uric acid and hs-CRP levels after adjustment for confounders. During the mean follow-up of 7.3 years, 548 participants developed T2DM. High serum uric acid and hs-CRP levels were independently associated with an increased incidence of T2DM. The multivariable-adjusted HRs (95% CIs) for the incidence of T2DM in the highest tertiles of serum uric acid and hs-CRP were 1.54 (1.24-1.93) and 1.90 (1.48-2.43), respectively. High levels of serum uric acid and hs-CRP in combination were associated with an increased incidence of T2DM (HR: 4.69; 95% CI: 2.81-7.84) compared to low levels of serum uric acid and hs-CRP. These findings suggest that the combination of high serum uric acid and hs-CRP levels was significantly associated with an elevated incidence of T2DM; however, their synergistic effects were not observed in middle-aged and elderly Korean adults.


Assuntos
Diabetes Mellitus Tipo 2 , Ácido Úrico , Adulto , Idoso , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Ácido Úrico/sangue
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