RESUMEN
OBJECTIVE: This study investigates the association between a new insulin resistance indicator, the triglyceride-glucose (TyG) index, and the risk of macrosomia. DESIGN: This is a prospective cohort study. METHODS: This study included 1332 women who delivered at Peking University International Hospital between October 2017 and August 2019. Participants were divided equally into three groups based on the TyG index. Logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the relationship between the TyG index and macrosomia and conducted subgroup analyses. The TyG index's ability to predict macrosomia was assessed using the receiver operating characteristic (ROC) curve. RESULTS: Multivariable logistic regression analysis revealed that the TyG index is an independent risk factor for macrosomia (Odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.30, p < .05). RCS analysis indicates that the risk of macrosomia increases with the rise of the TyG index (p for nonlinearity <.001) when the TyG index is >6.53. Subgroup analysis showed a synergistic additive interaction between the TyG index and gestational diabetes mellitus (GDM) of macrosomia. The area under the ROC curve for the predictive model was 0.733 (95% CI 0.684, 0.781), with a sensitivity of 76.4% and specificity of 66.9%. Incorporating the TyG index alongside traditional risk factors notably enhances macrosomia prediction (p < .05). CONCLUSIONS: The TyG index independently predicts macrosomia, and exhibits an additive interaction with GDM in its occurrence. Integrating the TyG index with traditional risk factors improves the prediction of macrosomia. TRIAL REGISTRY: Clinical trials. gov [NCT02966405].
RESUMEN
Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Quimioterapia Combinada , Receptor del Péptido 1 Similar al Glucagón , Hipoglucemiantes , Insulina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/administración & dosificación , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Receptor del Péptido 1 Similar al Glucagón/agonistas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacología , Insulina/administración & dosificación , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Hemoglobina Glucada/metabolismo , Resultado del Tratamiento , Administración Oral , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Receptor del Péptido 1 Similar al Glucagón , Hiperglucemia , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Femenino , Masculino , Persona de Mediana Edad , Receptor del Péptido 1 Similar al Glucagón/agonistas , Estudios Retrospectivos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Hiperglucemia/epidemiología , Hiperglucemia/inducido químicamente , Anciano , Enfermedades Cardiovasculares/epidemiología , Glucemia/metabolismo , Glucemia/análisis , Glucemia/efectos de los fármacos , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Hipoglucemiantes/uso terapéutico , Adulto , Estudios de Seguimiento , Control Glucémico , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
AIMS: To explore the correlation between visceral adipose tissue and albuminuria, and whether there is interaction between visceral adipose tissue and diabetes on albuminuria. METHODS: The study subjects were adult subjects (age ≥ 18 years) from the National Health and Nutrition Examination Surveys (NHANES) database of the USA in 2017-2018. Visceral fat area (VFA) was measured by dual-energy X-ray absorptiometry (DXA). Subjects were divided into three groups according to VFA: low (VFA 0-60cm2), medium (VFA 60-120 cm2) and high (VFA ≥ 120 cm2). Albuminuria was defined as urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. The statistical analysis software used is STATA 17.0. RESULTS: Data pertaining to 2965 participants (2706 without albuminuria) were included in the analysis. High VFA is an independent risk factor for albuminuria (OR 1.367, 95% CI 1.023-1.827). In the low-VFA group, there is no significant association between diabetes and albuminuria (OR 1.415, 95% CI 0.145-13.849). In the medium-VFA group, diabetes is an independent risk factor for albuminuria (OR 2.217, 95% CI 1.095-4.488). In the high-VFA group, diabetes is also an independent risk factor for albuminuria (OR 5.150, 95% CI 3.150-8.421). There is an additive interaction between high VFA (VFA ≥ 120 cm2) and diabetes on the effect of albuminuria (RERI 3.757, 95% CI 0.927-6.587, p = 0.009), while no multiplication interaction (OR 1.881, 95% CI 0.997-1.023, p = 0.141). CONCLUSIONS: High VFA may represent an independent risk factor for albuminuria. The amount of visceral fat may affect the effect of diabetes on albuminuria. The higher the visceral fat, the stronger the correlation between diabetes and albuminuria should be present. We suppose an additive interaction between VFA and diabetes on the effect of albuminuria.
Asunto(s)
Albuminuria , Diabetes Mellitus , Grasa Intraabdominal , Humanos , Albuminuria/epidemiología , Albuminuria/etiología , Masculino , Femenino , Grasa Intraabdominal/fisiopatología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Encuestas Nutricionales , Adiposidad , Estudios Transversales , Anciano , Absorciometría de FotónRESUMEN
AIMS: This study aimed to investigate the association between long-term use of antibiotics during childhood and the risk of type 2 diabetes mellitus (T2DM) using a prospective cohort from the UK Biobank. METHODS: Participants in the UK Biobank who completed the online survey for digestive health were included in this prospective cohort study. A Cox regression model adjusted for sociodemographic characteristics, general health factors, mental health, lifestyle factors, comorbidities, and medication use was used to estimate the hazard ratio (HR) and confidence interval (CI) of the association between long-term use of antibiotics in the childhood and incident T2DM. RESULTS: The final analyses included 152,992 participants and 22,133 of them received long-term/recurrent antibiotics as children or teenagers. During the follow-up, 3370 and 681 incident T2DM cases occurred in the non-exposed and exposed groups respectively. Long-term use of antibiotics in childhood was associated with an increased risk of T2DM, with an HR of 1.16 (95 % CI, 1.07-1.27) after adjusting for potential confounders. Results in the subgroup analyses and sensitivity analyses were highly consistent with the primary analyses. CONCLUSIONS: Long-term use of antibiotics in childhood is associated with the risk of T2DM in middle and old age in the UK Biobank population.
Asunto(s)
Diabetes Mellitus Tipo 2 , Niño , Humanos , Adolescente , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Estudios Prospectivos , Bancos de Muestras Biológicas , Biobanco del Reino Unido , Estilo de Vida , Factores de Riesgo , Reino Unido/epidemiologíaRESUMEN
OBJECTIVE: To investigate the effects of metabolic associated fatty liver disease (MAFLD) on chronic kidney disease (CKD) and abnormal albuminuria and the interaction between MAFLD and diabetes on abnormal albuminuria. METHODS: Data of participants in the American 2017-2018 National Health and Nutrition Examination Survey were analyzed. Hepatic steatosis was defined as median controlled attenuation parameter ≥248 dB/m, which was measured by ultrasound transient elastography. MAFLD was defined by evidence of hepatic steatosis on ultrasound in addition to any metabolic dysregulation. Hepatic fibrosis was detected by FibroScan and quantified by parameter of stiffness (E). Hepatic fibrosis was defined as E ≥ 9.7 kPa. As component of CKD, reduced estimated glomerular filtration rate (eGFR) was defined as<60 mL/min/1.73 m2 and abnormal albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: Data pertaining to 5119 participants were included in the analysis, with 40.6% hepatic normal, 52.1% MAFLD, and 7.2% hepatic fibrosis. Multivariable regression analyses showed that for abnormal albuminuria, the odds ratio (OR) was 0.82 (0.65-1.04) for MAFLD group and 1.73 (1.14.-,2.63) for hepatic fibrosis group, both taking the hepatic healthy group as reference. As for reduced eGFR, the OR was 0.68 (0.51-0.92) for MAFLD group and 0.93 (0.56-1.53) for hepatic fibrosis group. Diabetes was significantly related to greater risk of abnormal albuminuria (3.04 [2.70-3.42]) and reduced eGFR (1.53 [1.33-1.77]). With regard to the prevalence of abnormal albuminuria, the OR was 1.64 (1.03-2.60) for those with hepatic fibrosis only, 3.30 (2.80-3.89) for those with diabetes only, and 5.05 (3.30-7.72) for those with both two conditions. But there were neither additive interaction (relative excess risk due to interaction 0.56 [-1.41-.53], p = .577) nor multiplicative interaction (OR 0.81 [0.45-1.47], p = .492) between hepatic fibrosis and diabetes on the prevalence of abnormal albuminuria. CONCLUSION: MAFLD with hepatic fibrosis is an independent risk factor for abnormal albuminuria, but it does not have interaction with diabetes on abnormal albuminuria.
Asunto(s)
Diabetes Mellitus , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Humanos , Albuminuria/etiología , Encuestas Nutricionales , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Cirrosis HepáticaRESUMEN
Introduction: DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. Methods: A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients "ß" to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. Results: Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m2, 24 h UTP ≥ 3 g, and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. Conclusion: The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment.
Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Nefropatías Diabéticas/patología , Diagnóstico Diferencial , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Biopsia/efectos adversosRESUMEN
BACKGROUND AND AIMS: Vascular calcification (VC) is regarded as an independent risk factor for cardiovascular events in type 2 diabetic patients. Glucose transporter 1 (GLUT1) involves VC. Intermedin/Adrenomedullin-2 (IMD/ADM2) is a cardiovascular protective peptide that can inhibit multiple disease-associated VC. However, the role and mechanism of IMD in diabetic VC remain unclear. Here, we investigated whether IMD inhibits diabetic VC by inhibiting GLUT1. METHODS AND RESULTS: It was found that plasma IMD concentration was significantly decreased in type 2 diabetic patients and in fructose-induced diabetic rats compared with that in controls. Plasma IMD content was inversely correlated with fasting blood glucose level and VC severity. IMD alleviated VC in fructose-induced diabetic rats. Deficiency of Adm2 aggravated and Adm2 overexpression attenuated VC in high-fat diet-induced diabetic mice. In vitro, IMD mitigated high glucose-induced calcification of vascular smooth muscle cells (VSMCs). Mechanistically, IMD reduced advanced glycation end products (AGEs) content and the level of receptor for AGEs (RAGE). IMD decreased glucose transporter 1 (GLUT1) levels. The inhibitory effect of IMD on RAGE protein level was blocked by GLUT1 knockdown. GLUT1 knockdown abolished the effect of IMD on alleviating VSMC calcification. IMD receptor antagonist IMD17-47 and cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) inhibitor H89 abolished the inhibitory effects of IMD on GLUT1 and VSMC calcification. CONCLUSIONS: These findings revealed that IMD exerted its anti-calcification effect by inhibiting GLUT1, providing a novel therapeutic target for diabetic VC.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hormonas Peptídicas , Calcificación Vascular , Animales , Humanos , Ratones , Ratas , Adrenomedulina/metabolismo , AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Fructosa/efectos adversos , Fructosa/metabolismo , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Miocitos del Músculo Liso/metabolismo , Hormonas Peptídicas/farmacología , Transducción de Señal , Calcificación Vascular/metabolismoRESUMEN
Objective: This study aimed to investigate the effect of sarcopenia, osteoporosis, and osteosarcopenia on spine fracture in patients with prediabetes. Methods: We collected and analyzed the data from the U.S. National Health and Nutrition Examination Surveys during the period from 2009 to 2018. Bone mineral density and the skeletal muscle mass index (SMI) were measured with dual-energy X-ray absorptiometry (DXA). The diagnosis of spine fracture was based on DXA and history. Results: People with prediabetes were more likely to develop sarcopenia than normal glucose tolerance subjects (OR 1.33, 95% CI 1.07-1.66), while there was no significant increase of osteoporosis in prediabetes (OR 0.91, 95% CI 0.78-1.05). The SMI was independently associated with osteoporosis in prediabetes adults (OR 0.65, 95% CI 0.50-0.85). Both sarcopenia and osteoporosis were positively associated with spine fracture in prediabetes (OR 4.44, 95% CI 1.76-11.21, and OR 2.90, 95% CI 1.85-4.56, respectively). The risk of spine fracture was substantially higher in the presence of osteosarcopenia (OR 6.63; 95% CI, 1.34-32.94) than in the presence of sarcopenia or osteoporosis alone in prediabetes. Conclusion: In adults with prediabetes, both sarcopenia and osteoporosis are risk factors for spine fracture, and the combination of sarcopenia and osteoporosis further increases the prevalence of spine fracture.
Asunto(s)
Osteoporosis , Estado Prediabético , Sarcopenia , Fracturas de la Columna Vertebral , Humanos , Adulto , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Sarcopenia/diagnóstico , Fracturas de la Columna Vertebral/etiología , Estado Prediabético/complicaciones , Estado Prediabético/epidemiología , Osteoporosis/complicaciones , Osteoporosis/epidemiología , Densidad Ósea/fisiologíaRESUMEN
AIMS/INTRODUCTION: Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as an important complication of type 2 diabetes mellitus. The aims of the preset study was to investigate the cognitive protection of incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors, in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: PubMed, EMBASE, Cochrane library, Web of Science and PsycINFO were searched from the inception through 17 January 2023 for randomized controlled trials and cohort studies on the association between incretin-based therapies and cognitive function. A total of 15 studies were finally included in our systematic review, and eight of which were incorporated into our meta-analysis. RESULTS: Pooled results showed that the Mini-Mental State Examination score in incretin-based therapy groups was increased by 1.20 compared with the control group (weighted mean difference 1.20, 95% confidence interval 0.39-2.01). The results of eight studies assessed by the Newcastle Ottawa Quality Assessment Scale and the Cochrane Collaboration's tool, and the quality of the eight studies were at a relatively high level. Egger's regression did not show significant publication bias. CONCLUSIONS: Current evidence shows that incretin-based therapies might be more effective, when compared with the other hypoglycemic drugs, for cognitive improvement in patients with type 2 diabetes mellitus.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Incretinas/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Hipoglucemiantes/efectos adversos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Cognición , Receptor del Péptido 1 Similar al Glucagón/agonistasRESUMEN
Objective: To investigate the association between adipose distribution and hepatic steatosis in American adults and to assess whether this association varies among different blood glucose states. Methods: Data from the American National Health and Nutrition Examination Survey (NHANES) 2017-2018 were analyzed. The subjects were divided into three groups: diabetes, prediabetes and normal glucose tolerance (NGT). Hepatic steatosis was quantified by median controlled attenuation parameter (CAP), which was measured by ultrasound transient elastography. Total abdominal fat volume, visceral adipose tissue (VAT) volume, total percent fat, trunk percent fat, android percent fat and android to gynoid ratio (AGR) was measured by dual-energy X-ray absorptiometry (DXA). Results: Data pertaining to 2986 participants (1581 with hepatic steatosis) were included in the analysis. In the NGT group, the proportion of S0 (<5% of the hepatocytes with fatty infiltration) was 58.9%, and 25.2% for S3 (≥66% of the hepatocytes with fatty infiltration). In contrast, the proportion of S0 was 11.1%, while S3 accounts for as high as 68.7% in the diabetes group. In the NGT group, all parameters of fat distribution revealed a positive relation with the occurrence of hepatic steatosis (p<0.05) except total percent fat (p=0.872) after adjusting for confounding factors. In the prediabetes group, VAT volume, trunk percent fat, android percent fat and AGR had significant influence on hepatic steatosis (p<0.05). As for diabetes, only AGR remained significantly correlated with hepatic steatosis (p=0.004). Conclusion: For NGT individuals, high level of total abdominal fat volume, VAT volume, trunk percent fat, android percent fat and AGR all can be used to predict hepatic steatosis. For diabetes, only AGR can predict hepatic steatosis among the surveyed parameters of adipose distribution.
RESUMEN
Aim: This study aims to investigate the association between the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the risk of fracture among patients with type 2 diabetes mellitus. Methods: Medline, Embase, Cochrane Library, and Clinical-Trials.gov databases were searched for randomized controlled trials (RCTs). Network meta-analysis was performed for total fracture and a series of secondary outcomes. Results: A total of 177 RCTs (n = 165,081) involving the risk of fracture were identified (a median follow-up of 26 weeks). DPP-4i, GLP-1 RAs, and SGLT-2i did not increase total fracture risk compared with insulin (odds ratio: 0.86, 95% confidence interval: 0.39-1.90; 1.05, 0.54-2.04; 0.88, and 0.39-1.97, respectively), metformin (1.41, 0.48-4.19; 1.72, 0.55-5.38; 1.44, 0.48-4.30), sulfonylureas (0.77, 0.50-1.20; 0.94, 0.55-1.62; 0.79, 0.48-1.31), thiazolidinediones (0.82, 0.27-2.44; 1.00, 0.32-3.10; 0.83, 0.27-2.57), α-glucosidase inhibitor (4.92, 0.23-103.83; 5.99, 0.28-130.37; 5.01, 0.23-107.48), and placebo (1.04, 0.84-1.29; 1.27, 0.88-1.83; 1.06, 0.81-1.39). Conclusions: The use of DPP-4i, GLP-1 RAs, or SGLT-2i is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients.
RESUMEN
BACKGROUND: Macrosomia is closely associated with poor maternal and fetal outcome. But there is short of studies on the risk of macrosomia in early pregnancy. The purpose of this study is to establish a nomogram for predicting macrosomia in the first trimester. METHODS: A case-control study involving 1549 pregnant women was performed. According to the birth weight of newborn, the subjects were divided into macrosomia group and non-macrosomia group. The risk factors for macrosomia in early pregnancy were analyzed by multivariate logistic regression. A nomogram was used to predict the risk of macrosomia. RESULTS: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed that prepregnancy overweight (OR: 2.13 95% CI: 1.18-3.83)/obesity (OR: 3.54, 95% CI: 1.56-8.04), multiparity (OR:1.88, 95% CI: 1.16-3.04), the history of macrosomia (OR: 36.97, 95% CI: 19.90-68.67), the history of GDM/DM (OR: 2.29, 95% CI: 1.31-3.98), the high levels of HbA1c (OR: 1.76, 95% CI: 1.00-3.10) and TC (OR: 1.36, 95% CI: 1.00-1.84) in the first trimester were the risk factors of macrosomia. The area under ROC (the receiver operating characteristic) curve of the nomogram model was 0.807 (95% CI: 0.755-0.859). The sensitivity and specificity of the model were 0.716 and 0.777, respectively. CONCLUSION: The nomogram model provides an effective mothed for clinicians to predict macrosomia in the first trimester.
Asunto(s)
Diabetes Gestacional , Enfermedades del Recién Nacido , Peso al Nacer , Estudios de Casos y Controles , Diabetes Gestacional/epidemiología , Femenino , Macrosomía Fetal/epidemiología , Macrosomía Fetal/etiología , Humanos , Recién Nacido , Nomogramas , Embarazo , Factores de Riesgo , Aumento de PesoRESUMEN
Intermedin (IMD), a paracrine/autocrine peptide, protects against cardiac fibrosis. However, the underlying mechanism remains poorly understood. Previous study reports that activation of nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to cardiac fibrosis. In this study, we aimed to investigate whether IMD mitigated cardiac fibrosis by inhibiting NLRP3. Cardiac fibrosis was induced by angiotensin II (Ang II) infusion for 2 weeks in rats. Western blot, real-time PCR, histological staining, immunofluorescence assay, RNA sequencing, echocardiography, and hemodynamics were used to detect the role and the mechanism of IMD in cardiac fibrosis. Ang II infusion resulted in rat cardiac fibrosis, shown as over-deposition of myocardial interstitial collagen and cardiac dysfunction. Importantly, NLRP3 activation and endoplasmic reticulum stress (ERS) were found in Ang II-treated rat myocardium. Ang II infusion decreased the expression of IMD and increased the expression of the receptor system of IMD in the fibrotic rat myocardium. IMD treatment attenuated the cardiac fibrosis and improved cardiac function. In addition, IMD inhibited the upregulation of NLRP3 markers and ERS markers induced by Ang II. In vitro, IMD knockdown by small interfering RNA significantly promoted the Ang II-induced cardiac fibroblast and NLRP3 activation. Moreover, silencing of inositol requiring enzyme 1 α (IRE1α) blocked the effects of IMD inhibiting fibroblast and NLRP3 activation. Pre-incubation with PKA pathway inhibitor H89 blocked the effects of IMD on the anti-ERS, anti-NLRP3, and anti-fibrotic response. In conclusion, IMD alleviated cardiac fibrosis by inhibiting NLRP3 inflammasome activation through suppressing IRE1α via the cAMP/PKA pathway.
Asunto(s)
Adrenomedulina , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Neuropéptidos , Adrenomedulina/genética , Adrenomedulina/metabolismo , Angiotensina II/farmacología , Animales , Células Cultivadas , Endorribonucleasas , Fibrosis , Inflamasomas/metabolismo , Complejos Multienzimáticos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Neuropéptidos/genética , Neuropéptidos/metabolismo , Proteínas Serina-Treonina Quinasas , RatasRESUMEN
PURPOSE: To determine the impact of type 2 diabetes mellitus (T2DM) on visual functions, identify different modifiers as risk or protective factors, and find out how these factors affect patients' visual symptoms and visual functions as a whole. METHODS: We performed an online survey among 1030 participants (400 patients, 630 non-patients). Demographic features and severity of disease were documented, while visual functions were evaluated using National Eye Institute Visual Functioning questionnaire-25 (NEI VFQ-25). Independent t-test, analysis of variance, linear and nonlinear regression models were used to assess all data. RESULTS: Scores other than color vision among T2DM patients were significantly lower compared with non-T2DM participants. There was significant difference after stratification of age and education, but no significant difference between different genders was observed. Parameters including duration of T2DM, fasting plasma glucose (FPG) and glycosylated hemoglobin A1c (HbA1c) negatively impacted on the scores, with 20 years' of diabetic duration, 10 mmol/L of FPG, 7.5% of HbA1c being potential cut-off points. Poorer best corrected visual acuity (BCVA) and diagnosis of diabetic retinopathy were risk factors, while they simultaneously produced mediation effect, contributing 5%-78% of effect in the deterioration of visual functions caused by longer diabetic duration and higher blood glucose. CONCLUSION: Significant visual impairments and faster deterioration in visual functions were seen in T2DM patients, with older age, lower educational level, longer diabetic duration, poorer blood glucose administration, limited BCVA, and the presence of diabetic retinopathy identified as risk factors. Average BCVA and diabetic retinopathy also yielded mediation effect as diabetic duration lengthened and blood glucose elevated.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Trastornos de la Visión , Glucemia , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/etiología , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Encuestas y Cuestionarios , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/etiologíaRESUMEN
BACKGROUND: Time in range (TIR) refers to the time an individual spends within their target glucose range, which now has been popularized as an important metric to classify glycemic management and also recognized as an important outcome of current diabetes therapies. This study aimed to investigate the association between TIR and the severity of the urinary albumin excretion rate (UAER) in patients with type 2 diabetes mellitus (T2DM). METHODS: We retrospectively analyzed the data of 1014 inpatients with T2DM at the Department of Endocrinology and Metabolism of Peking University International Hospital, China. TIR was defined as the percentage of blood glucose within the target range of 3.90-10.00âmmol/L. Urine samples for assessment of UAER were collected for 3 consecutive days from the start of hospitalization. RESULTS: The TIR values for patients with normal urine levels of albumin, microalbuminuria, and macroalbuminuria were 70%â±â20%, 50%â±â20%, and 30%â±â20%, respectively (all P â < â0.001). The patients were stratified according to quartiles of TIR as follows: quartile (Q) 1, <55%; Q2, 55%-72%; Q3, 73%-83%; and Q4, >83%. The incidences of microalbuminuria in Q1, Q2, Q3, and Q4 were 41.1%, 21.6%, 7.1%, and 5.5% (all P â<â0.001), respectively. The respective incidences of macroalbuminuria were 24.2%, 1.1%, 1.4%, and 0% (all P â<â0.001). In multinomial logistic regression analyses, TIR was significantly correlated with microalbuminuria (odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.52-0.65, P â<â0.001) and macroalbuminuria (OR 0.26, 95% CI: 0.18-0.38, P â<â0.001) after adjusting for age, sex, body mass index, diabetes duration, systolic blood pressure, and levels of triglycerides, glycosylated hemoglobin A1c, and creatinine. CONCLUSION: The proportion of blood glucose in TIR is closely related to the severity of UAER in patients with T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2 , Albúminas , Albuminuria/orina , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Pacientes Internos , Estudios RetrospectivosRESUMEN
Objective: We aimed to explore the role and possible mechanism of leptin in lower-extremity artery calcification in patients with type 2 diabetes mellitus (T2DM). Methods: We recruited 59 male patients with T2DM and 39 non-diabetic male participants. All participants underwent computed tomography scan of lower-extremity arteries. The calcification scores (CSs) were analyzed by standardized software. Plasma leptin level was determined by radioimmunoassay kits. Human vascular smooth muscle cells (VSMCs) calcification model was established by beta-glycerophosphate and calcium chlorideinduction. Calcium deposition and mineralization were measured by the o-cresolphthalein complexone method and Alizarin Red staining. The mRNA expression of bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and osteopontin (OPN) was determined by quantitative RT-PCR. The protein levels of BMP2, Runx2, α-smooth muscle actin (α-SMA) and (p)-Akt was determined by Western-blot analysis, and α-SMA was also measured by immunofluorescence analysis. Results: Compared with controls, patients with T2DM showed higher median calcification score in lower-extremity artery [286.50 (IQR 83.41, 1082.00) vs 68.66 (3.41, 141.30), p<0.01]. Plasma leptin level was higher in patients with calcification score ≥300 than ≥100 (252.67 ± 98.57 vs 189.38 ± 44.19 pg/ml, p<0.05). Compared with calcification medium, intracellular calcium content was significantly increased in VSMCs treated by leptin (200, 400 and 800 ng/ml) combined with calcification medium [11.99 ± 3.63, 15.18 ± 4.55, and 24.14 ± 5.85 mg/ml, respectively, vs 7.27 ± 1.54 mg/ml, all p<0.01]. Compared with calcification medium, Alizarin Red staining showed calcium disposition was more obvious, and the mRNA level of BMP2, Runx2 and OCN was significantly increased, and immunofluorescence and Western blot analysis showed that the expression of α-SMA was downregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium, respectively. Compared with calcification medium, the protein level of BMP2 and Runx2 was upregulated in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Moreover, blocking PI3K/Akt signaling pathway can decrease the protein expression of BMP2 and Runx2 in VSMCs treated by leptin (400 ng/ml) combined with calcification medium. Conclusions: Leptin promoted lower-extremity artery calcification of T2DM by upregulating the expression of BMP2 and Runx2, and regulating phenotypic switch of VSMCs via PI3K/Akt signaling pathway.
Asunto(s)
Diabetes Mellitus Tipo 2 , Leptina/sangre , Calcificación Vascular/sangre , Adulto , Anciano , Arterias/efectos de los fármacos , Arterias/metabolismo , Arterias/patología , Arteriosclerosis/sangre , Arteriosclerosis/etiología , Estudios de Casos y Controles , Células Cultivadas , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Humanos , Leptina/farmacología , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Proyectos Piloto , Calcificación Vascular/diagnóstico , Calcificación Vascular/etiologíaRESUMEN
PURPOSE: To evaluate the effects of serum thyroid hormone levels on advanced liver fibrosis in cases with NAFLD (non-alcoholic fatty liver disease) and T2DM (type 2 diabetes mellitus). PATIENTS AND METHODS: A total of 1422 cases with T2DM who were admitted to Peking University International Hospital between December 2014 and October 2019 were retrospectively analyzed. Standard anthropometry as well as clinical and laboratory evaluation were performed on all patients. Abdominal ultrasonography was performed to diagnose NAFLD. NFS (NAFLD fibrosis score) was used to identify advanced fibrosis in patients with T2DM and NAFLD. RESULTS: In cases with T2DM and NAFLD, the serum FT3 level in cases with advanced fibrosis was lower than that in those without advanced fibrosis (4.79±0.89 vs 4.28±1.19, P < 0.05), and significant difference was not found in serum levels of FT4 and TSH between cases with advanced fibrosis and those without advanced fibrosis (P > 0.05). The incidence of advanced fibrosis declined as the rise of serum FT3 levels (P trend < 0.05). Besides, FT3 (OR, 0.492; 95% CI, 0.384-0.631) was noted as a factor influencing advanced fibrosis in cases with T2DM and NAFLD (P< 0.05). CONCLUSION: In cases with T2DM and NAFLD, the incidence of advanced fibrosis is negatively correlated with serum FT3 levels, and a low FT3 level is an independent risk factor of advanced fibrosis.
RESUMEN
This study was aimed at exploring the predictive value of first-trimester glycosylated hemoglobin (HbA1c) levels in the diagnosis of gestational diabetes mellitus (GDM). A total of 744 pregnant women registered at the Peking University International Hospital between March 2017 and March 2019 were included in this study. Data on personal characteristics and biochemical indicators of the pregnant women were collected during the first trimester. The International Association of Diabetes and Pregnancy Study Groups has adopted specific diagnostic criteria as the gold standard for the diagnosis of GDM. Receiver operating characteristic (ROC) curve statistics were used to assess the predictive value of first-trimester HbA1c levels in the diagnosis of GDM. HbA1c levels in the first trimester were significantly higher in the GDM group than in the non-GDM group (5.23% ± 0.29% vs. 5.06 ± 0.28%, P < 0.05). The first-trimester HbA1c level was an independent risk factor for gestational diabetes. The area under the ROC curve (AUC) of HbA1c for GDM was 0.655 (95% confidence interval 0.620-0.689, P < 0.001). The positive likelihood ratio was the highest at HbA1c = 5.9%, sensitivity was 2.78, and specificity was 99.83%. There was no statistical difference in AUC between fasting blood glucose and HbA1c (P = 0.407). First-trimester HbA1c levels can be used to predict GDM. The risk of GDM was significantly increased in pregnant women with first-trimester HbA1c levels > 5.9%. There was no statistical difference between first-trimester HbA1c and fasting blood glucose levels in predicting GDM.