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World Journal of Diabetes Dec 2023Diabetic kidney disease is one of the common complications of type 2 diabetes (T2D). There are no typical symptoms in the early stage, and the disease will progress to... (Clinical Trial)
Clinical Trial
BACKGROUND
Diabetic kidney disease is one of the common complications of type 2 diabetes (T2D). There are no typical symptoms in the early stage, and the disease will progress to moderate and late stage when albuminuria reaches a high level. Treatment is difficult and the prognosis is poor. At present, the pathogenesis of diabetic kidney disease is still unclear, and it is believed that it is associated with genetic and environmental factors.
AIM
To explore the relationship between the glucokinase regulatory protein () gene rs780094 polymorphism and T2D with albuminuria.
METHODS
We selected 252 patients (126 males and 126 females) with T2D admitted to our hospital from January 2020 to October 2020, and 66 healthy people (44 females and 22 males). According to the urinary albumin/creatinine ratio, the subjects were divided into group I (control), group II (T2D with normoalbuminuria), group III (T2D with microalbuminuria), and group IV (T2D with macroalbuminuria). Additionly, the subjects were divided into group M (normal group) or group N (albuminuria group) according to whether they developed albuminuria. We detected the gene rs780094 polymorphism (C/T) of all subjects, and measured the correlation between gene rs780094 polymorphism (C/T) and T2D with albuminuria.
RESULTS
Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium. Genotype frequency was significantly different among the four groups ( = 0.048, = 7.906). T allele frequency in groups II, III, and IV was significantly higher than that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT + TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.
CONCLUSION
CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individuals carrying susceptible genes to delay the onset of T2D.
PubMed: 38222779
DOI: 10.4239/wjd.v14.i12.1803 -
Renal Failure Dec 2024The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the...
The incidence and mortality of chronic kidney disease (CKD) are increasing globally. Studies have demonstrated the significance of genetic risk factors in the progression of CKD. Telomerase reverse transcriptase () may be implicated in the development of CKD. This study aimed to investigate the correlation between gene variants and susceptibility to CKD in the Chinese population. A total of 507 patients with CKD and 510 healthy controls were recruited for this case-control study. Four candidate loci were identified using the MassARRAY platform. Logistic regression analysis was employed to assess the association between gene variants and the risk of CKD. The false positive reporting probability (FPRP) method was utilized to evaluate the validity of statistically significant associations. The multifactorial dimensionality reduction (MDR) method was used to evaluate the interaction between SNPs and the risk of CKD. Furthermore, discrepancies in the clinical features of subjects with diverse genotypes were evaluated using one-way analysis of variance (ANOVA). Our findings revealed a correlation between rs2735940 and rs4635969 and an increased risk of CKD. Stratification analysis indicated that rs4635969 was related to an increased risk of CKD in different subgroups (age ≤ 50 years and male). MDR analysis indicated that the two-site model (rs2735940 and rs4635969) was the best prediction model. Furthermore, the rs2735940 GG genotype was found to be linked to an increased level of microalbuminuria (MAU) in patients with CKD. Our study is the first to reveal a connection between gene variants and susceptibility to CKD, providing new insights into the field of nephrology.
Topics: Humans; Male; Middle Aged; Case-Control Studies; China; Genetic Association Studies; Genotype; Renal Insufficiency, Chronic; Telomerase
PubMed: 38197421
DOI: 10.1080/0886022X.2023.2300725 -
Obesity Surgery Feb 2024Bariatric surgery has been the most effective treatment modality for morbid obesity that reduces associated comorbidities and improves quality of life. This study aims...
INTRODUCTION
Bariatric surgery has been the most effective treatment modality for morbid obesity that reduces associated comorbidities and improves quality of life. This study aims at evaluating and comparing the impact of two types of bariatric surgery-laparoscopic sleeve gastrectomy (LSG) and one anastomosis gastric bypass (OAGB)-on renal functions and urinary monocyte chemoattractant protein-1 (MPC-1) levels in morbidly obese patients 3 months after surgery.
METHODS
This is a prospective study of 40 morbidly obese patients who underwent bariatric surgery. Two types of bariatric surgery were done-laparoscopic sleeve gastrectomy (LSG) (26 patients) and laparoscopic one anastomosis gastric bypass (OAGB) (14 patients). The outcomes of the two procedures were compared in terms of renal function parameters and the level of urinary MCP-1.
RESULTS
There were no statistically significant differences in the mean postoperative urinary MCP-1 (73.53 ± 21.25, 75.43 ± 26.17, P > 0.5), microalbuminuria (8.83 ± 6.26, 10.02 ± 8.6, P > 0.05), urinary creatinine (109.21 ± 43.22, 99.19 ± 48.65, P > 0.05), MCP1/Cr ratio (0.78 ± 0.36, 1.01 ± 0.70, P > 0.05), eGFR (100.32 ± 9.54, 104.39 ± 9.54, P > 0.05) in the cases who had either LSG operation or OAGB operation.
CONCLUSION
Bariatric surgery improves all indicators of kidney malfunction and reduces the level of urinary MCP-1. Both laparoscopic sleeve gastrectomy (LSG) and laparoscopic one anastomosis gastric bypass (OAGB) cause similar improvement of the renal function and reduction of urinary MCP-1 level.
Topics: Humans; Gastric Bypass; Obesity, Morbid; Prospective Studies; Quality of Life; Chemokine CCL2; Treatment Outcome; Gastrectomy; Kidney; Retrospective Studies; Laparoscopy
PubMed: 38196045
DOI: 10.1007/s11695-023-07033-z -
American Journal of Perinatology May 2024Among children born extremely preterm (EP), the antecedents of chronic kidney disease (CKD), including neonatal acute kidney injury (nAKI), are not well characterized.
OBJECTIVE
Among children born extremely preterm (EP), the antecedents of chronic kidney disease (CKD), including neonatal acute kidney injury (nAKI), are not well characterized.
STUDY DESIGN
This was a retrospective cohort pilot study. Participants ( = 36) were adolescents born before 28 weeks of gestation enrolled at birth into the extremely low gestational age newborn study, between 2002 and 2004, at the University of North Carolina. Participants were stratified by the primary exposure to nAKI, defined using the modified Kidney Disease Improving Global Outcomes nAKI criteria. Baseline serum creatinine (SCr) was defined as the lowest SCr after 48 to 72 postnatal hours. The primary outcome was an abnormal kidney profile during adolescence, defined as having one or more of these outcomes: elevated blood pressure (>120/80 mm Hg), microalbuminuria (urine microalbumin/creatinine >30 µg/g), or an abnormal kidney volume measured by ultrasound (total kidney volume corrected for body surface area <10th%ile for age).
RESULTS
Half of the participants had a history of nAKI. Thirteen had stage 1 nAKI, four had stage 2, and one had stage 3 nAKI. At 15 years of age, 50% were overweight/obese, 31% had elevated blood pressure (BP), 11% had abnormal kidney volumes, and 17% had microalbuminuria. The relative risk for having an abnormal kidney profile during adolescence among participants with a history of nAKI was 0.63 (95% confidence interval: 0.3-1.3, = 0.2).
CONCLUSION
In this sample of adolescents born EP, a history of nAKI was not associated with elevated BP, microalbuminuria, or abnormal kidney volume. Future studies are needed in larger samples to better characterize the relationship between nAKI and CKD in EP-born children.
KEY POINTS
· Extremely preterm birth is associated with acute kidney injury.. · Extremely preterm birth is associated with chronic kidney disease.. · Neonatal acute kidney injury after extremely preterm birth was not associated with kidney outcomes..
Topics: Humans; Acute Kidney Injury; Infant, Extremely Premature; Female; Retrospective Studies; Adolescent; Male; Infant, Newborn; Creatinine; Albuminuria; Pilot Projects; Kidney; Renal Insufficiency, Chronic; Hypertension; Gestational Age; Ultrasonography
PubMed: 38195965
DOI: 10.1055/s-0043-1778038 -
Diabetology & Metabolic Syndrome Jan 2024The Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease,...
The Steno Diabetes Center Copenhagen developed the Steno T1 Risk Engine (ST1RE) to predict cardiovascular events, encompassing fatal and nonfatal ischemic heart disease, ischemic stroke, heart failure, and peripheral arterial disease in type 1 diabetes mellitus(T1DM).The current study investigated the agreement between ST1RE and the Brazilian Society for Endocrinology and Metabology (SBEM) classification. Participants were included in the study if diagnosed with T1DM and had at least one outpatient visit in 2021. Patients with established cardiovascular disease and chronic kidney disease on dialysis were excluded. Clinical parameters were obtained from medical records, such as age, body mass index (BMI), blood pressure, physical activity, current smoking, microvascular target organ damage, levels of low-density lipoprotein cholesterol, creatinine, glycated hemoglobin (HbA1c), and albuminuria.Overall, 92 patients (38 males and 53 females) with an age median (P25; P75) of 33 years (25.5;42.5), BMI of 24.8 + 4.1 kg/m2, and duration of diabetes (mean ± SD) of 23.4 + 9.5 years were evaluated. There were no differences considering the gender for most analyzed variables, but a higher proportion of women exhibited microvascular complications such as microalbuminuria, macroalbuminuria, and retinopathy. Our results show a weak agreement in the 10-year cardiovascular risk estimation between SBEM and ST1RE classifications. According to SBEM criteria, 72.8% of patients were considered high-risk, while only 15.2% of patients received the same classification using ST1RE. The dissimilarities between these two classifications were also evident when age and gender factors were compared. While 60% of patients under 35 years were classified as high risk according to SBEM criteria, only 1.8% received this stratification risk in the ST1RE classification.The results indicate a low agreement between the 10-year cardiovascular event risk classification by SBEM and the classification by ST1RE for type 1 diabetes patients without established cardiovascular disease.
PubMed: 38191429
DOI: 10.1186/s13098-023-01224-5 -
Frontiers in Endocrinology 2023To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4...
OBJECTIVE
To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM).
METHODS
According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively.
RESULTS
To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [β = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [β = -1.633, 95% CI (-2.77, -0.496)] and Tf [β = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, 0.015 and 0.001], and Tf (OR = 0.109 and 0.119, 0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both 0.001) in the MA group.
CONCLUSION
DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.
Topics: Humans; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Ferroptosis; Diabetic Nephropathies; Iron; Transferrin; Ferritins; Albuminuria
PubMed: 38189040
DOI: 10.3389/fendo.2023.1297166 -
BMC Endocrine Disorders Jan 2024Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem...
Effects of conditioned media derived from human Wharton's jelly mesenchymal stem cells on diabetic nephropathy and hepatopathy via modulating TGF-β and apelin signaling pathways in male rats.
BACKGROUND
Diabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton's jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications.
METHODS
Twenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-β) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation.
RESULTS
DM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-β gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-β expression and enhanced apelin expression in the kidney and liver tissues.
CONCLUSION
Human WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-β and apelin signaling pathways.
Topics: Animals; Humans; Male; Rats; Apelin; Culture Media, Conditioned; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Liver Diseases; Mesenchymal Stem Cells; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta; Wharton Jelly
PubMed: 38178017
DOI: 10.1186/s12902-023-01535-8 -
BMC Endocrine Disorders Jan 2024The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC).
METHOD
We carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study.
RESULT
In this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline. Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort.
CONCLUSION
The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population.
Topics: Humans; Middle Aged; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Cholesterol, HDL; Triglycerides; Cholesterol; Lipoproteins, HDL
PubMed: 38167035
DOI: 10.1186/s12902-023-01526-9 -
International Journal of Biological... 2024TGF-β/Smad3 signaling plays a critical role in type 2 diabetes (T2D) and type 2 diabetic nephropathy (T2DN), but treatment by specifically targeting Smad3 remains...
TGF-β/Smad3 signaling plays a critical role in type 2 diabetes (T2D) and type 2 diabetic nephropathy (T2DN), but treatment by specifically targeting Smad3 remains unexplored. To develop a new Smad3-targeted therapy for T2D and T2DN, we treated db/db mice at the pre-diabetic or established diabetic stage with a pharmacological Smad3 inhibitor SIS3. The therapeutic effect and mechanisms of anti-Smad3 treatment on T2D and T2DN were investigated. We found that anti-Smad3 treatment on pre-diabetic db/db mice largely attenuated both T2D and T2DN by markedly reducing blood glucose levels, and inhibiting the elevated serum creatinine, microalbuminuria, and renal fibrosis and inflammation. Unexpectedly, although SIS3 treatment on the established diabetic db/db mice inhibited T2DN but did not significantly improve T2D. Mechanistically, we uncovered that inhibition of T2DN in SIS3-treated db/db mice was associated with effectively restoring the balance of TGF-β/Smad signaling by inhibiting Smad3 while increasing Smad7, thereby suppressing Smad3-mediated renal fibrosis and NF-κB-driven renal inflammation via lncRNA Erbb4-IR and LRN9884-dependent mechanisms. We also revealed that inhibition of islet β cell injury by preventing the loss of islet Pax 6 could be the mechanism through which the pre-diabetic treatment, rather than the late SIS3 treatment on db/db mice significantly improved the T2D phenotype.
Topics: Mice; Animals; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Prediabetic State; Inflammation; Transforming Growth Factor beta; Fibrosis; Smad3 Protein; Kidney
PubMed: 38164169
DOI: 10.7150/ijbs.87820 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical... (Review)
Review
Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and approximately 1/3 of diabetic patients may progress to DKD. A typical early clinical manifestation of DKD is microalbuminuria and patients may present with macroproteinuria accompanied by a decrease in renal function condition as the disease progresses. It is generally believed that the likelihood of a reversal of the disease is reduced after the development of macroproteinuria in patients with DKD, and that eventually some patients' condition may develop into end-stage renal disease (ESRD). Moreover, the thickening of the glomerular basement membrane, mesangial matrix expansion, Kimmelstiel-Wilson (K-W) nodules, and glomerulosclerosis in end-stage diabetes mellitus are typical pathologic changes of DKD. However, some DKD patients, especially those with type 2 diabetes mellitus (T2DM) combined with DKD, may have diverse clinical manifestations, showing variations in disease progression and regression, and manifesting as non-classical types of DKD, such as normoalbuminuric DKD, proteinuria-reduced DKD, and DKD with rapid decline in renal function. In addition, the formation of crescents, a special pathological change, is observed in renal biopsy. However, this issue is currently under-recognized by clinicians and therefore deserves more attention. In order to improve clinicians' understanding of the presentations and pathological changes of non-classical DKD and the level of DKD prevention and treatment in China, we present a preliminary introduction to the clinical phenotypes and pathological changes of non-classical types of DKD in this paper by summarizing the findings of our prior studies as well as domestic and international literature.
Topics: Humans; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Albuminuria; Kidney Failure, Chronic; China; Kidney
PubMed: 38162079
DOI: 10.12182/20231160102