Risk Of Diabetic Nephropathy Research Articles

Adiponectin Can Be an Early Predictable Marker for Type 2 Diabetes Mellitus and Nephropathy.

BackgroundSeveral studies have examined serum adiponectin concentrations in prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other types of diabetes associated with the risk of T2DM and diabetic nephropathy (DN); however, the results to date are inconclusive. An aim of the current study is to determine whether adiponectin is a useful marker for the earlier development of T2DM and DN.MethodologyThis cross-sectional study included 400 subjects. Among the subjects, 100 were prediabetes subjects, 200 were T2DM patients, and the remaining 100 were healthy controls. The biochemical and clinical parameters of all patients were analyzed and the data were recorded.ResultsThe mean levels of adiponectin were significantly lower in prediabetic subjects than in healthy controls (3.22 ± 0.98, 5.36 ± 2.24, p = 0.0001**). Furthermore, the levels of adiponectin were significantly higher in both the groups of T2DM patients when compared to healthy controls (19.85 ± 3.31, 11.83 ± 3.01, and 5.36 ± 2.24, p = 0.0001**). In both diabetic groups, adiponectin was positively correlated with body mass index, glycated hemoglobin, insulin, homeostasis model assessment of insulin resistance, and microalbuminuria, while negatively correlated with estimated glomerular filtration rate. Interestingly, adiponectin had a reversed correlation in the prediabetic group.ConclusionBased on the results, the present study suggests that significantly decreased levels of serum adiponectin in prediabetic subjects might be used as a variable marker for T2DM. Moreover, adiponectin may useful for detecting the early onset of nephropathy, compared to microalbumin, as its concentration was significantly elevated in patients who were newly diagnosed with T2DM without nephropathy.

Predicting diabetic nephropathy in type 2 diabetic patients using machine learning algorithms.

Global healthcare centers today are challenged by the dramatic increase in the prevalence of diabetes. Also, complications from diabetes are a major cause of deaths worldwide. One of the most frequent microvascular complications in diabetic patients is diabetic nephropathy (DN) which is the leading cause of death and end-stage renal disease (ESRD). Despite the different risk factors for DN identified in previous research, machine learning (ML) methods can help determine the importance of the predictors and prioritize them. The main focus of this investigation is on predicting the incidence of DN in type 2 diabetic mellitus (T2DM) patients using ML algorithms. Demographic information, laboratory results, and examinations on 6235 patients with T2DM covering a period of 10years (2011-2020) were extracted from the electronic database of the Diabetes Clinic of the Imam Khomeini Hospital Complex (IKHC) in Iran. Recursive feature elimination using the cross-validation (RFECV) technique was then used with the three classification algorithms to select the important risk factors. Next, five ML algorithms were used to construct a predictive model for DN in T2DM patients. Finally, the results of the algorithms were evaluated according to the AUC criteria and the one with the best performance in terms of prediction and classification was selected. The 18 DN risk factors selected by RFECV were age, diabetes duration, BMI, SBP, hypertension, retinopathy, ALT, CVD, 2HPP, uric acid, HbA1c, waist-to-hip ratio, cholesterol, LDL, HDL, FBS, triglyceride, and serum insulin. Based on a 10-fold cross-validation, the best performance among the five classification algorithms was that of the random forest with 85% AUC. This investigation validates the known risk factors for DN and emphasizes the importance of controlling the blood pressure, weight, cholesterol, and blood sugar of T2DM patients. In addition, as an example of the application of ML approaches in medical predictions, the findings of this study demonstrate the advantages of using these techniques.

Relationship between diabetic complications and the nutritional index in untreated diabetes.

This study aimed to determine the association between diabetic complications and the nutritional index at the first hospital visit in untreated patients with diabetes. Two hundred and four patients with untreated type 2 diabetes were enrolled in the present study. Nutrition-related risks were assessed using the Geriatric Nutritional Risk Index (GNRI). The patients were divided into the following three subgroups: major/moderate risk, low risk, and no risk. Intergroup comparisons of clinical characteristics were carried out. The risk of complications related to diabetes was associated with the GNRI. The major/moderate-risk group (GNRI < 92) had a high risk for diabetic retinopathy, diabetic nephropathy, and diabetic foot, while the low-risk group (GNRI of 92 to ≤ 98) had a high risk for diabetic nephropathy only. The odds ratio of diabetic retinopathy for a major/moderate risk was 17.6. The odds ratio of diabetic nephropathy for a major/moderate risk was 16.7. Nutritional assessment at the first hospital visit using the GNRI could be a simple and useful tool for predicting the risk of diabetic complications in untreated patients with diabetes.

Association Between Globulin and Diabetic Nephropathy in Type2 Diabetes Mellitus Patients: A Cross-Sectional Study.

BackgroundWith the development of economy, the living standard of people all over the world has been greatly improved, and the incidence of diabetes is also increasing. Many people with diabetes also develop other complications that reduce their quality of life. Diabetic nephropathy is a common complication of type2 diabetes. Understanding the related factors of diabetic nephropathy is greatly significant to control the occurrence of diabetic nephropathy and improve patient’s life quality.Data and MethodsData were collected from 2009 to 2018 in NHANES. Curve fitting graph was performed to investigate the association between globulin (GLB) and diabetic nephropathy(DN). Four logistic regression models were conducted to control the potential confounding factors. Subgroup analysis was carried out to assess the stability of results.ResultsGLB was positively correlated with the occurrence of DN after controlling for potential confounders. Higher GLB was associated with an increased risk of diabetic nephropathy [odds ratio(OR), 1.10; 95% confidence interval (CI), 1.07-1.13, P < 0.001].ConclusionsIn this cross-sectional study, GLB was significant positively correlated with the occurrence of DN in patients with type2 diabetes mellitus.

Association of the Transcription Factor 7-Like 2 (TCF7L2) rs7903146 Polymorphism with the Risk of Diabetic Nephropathy: A Meta-Analysis.

Transcription factor 7-like 2 (TCF7L2) polymorphism plays an essential role in the occurrence and development of patients living with diabetes, but the current conclusions are inconsistent on the relationship between TCF7L2 polymorphism and the risk of diabetic nephropathy. This meta-analysis aims to explore the exact association between TCF7L2 rs7903146 locus polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were searched for studies on the relationship between single nucleotide polymorphism at TCF7L2 rs7903146 locus and susceptibility to diabetic nephropathy until January 10, 2022. The data were analyzed by Stata 15.0 software. A total of 7 articles were included, covering 1443 patients with diabetic nephropathy and 2129 diabetic non-nephropathy patients. The results showed that allele C at TCF7L2 rs7903146 locus, compared to allele T, the pooled odds ratio (OR)=0.69 (95% CI: 0.56-0.85, p≤0.05). In the dominant gene inheritance model, recessive gene inheritance model, homozygous genetic model, and heterozygous genetic model, the pooled OR was 0.47 (95% CI: 0.36-0.61), 0.63 (95% CI: 0.54-0.73), 0.39 (95% CI: 0.29-0.51), and 0.59 (95% CI: 0.45-0.78), respectively, and the differences were statistically significant. In conclusion, TCF7L2 rs7903146 polymorphism is associated with susceptibility to diabetic nephropathy. Allele T and genotype TT can increase the risk of diabetic nephropathy.

The Causal Effect of Systolic Blood Pressure Lowering on Vascular Outcomes in Diabetes: A Mendelian Randomization Study.

The effect of lowering systolic blood pressure (SBP) on clinical outcomes in diabetic patients is controversial. We used 2-sample mendelian randomization (MR) to study the causal effect of decreasing SBP on the risk of macrovascular and microvascular outcomes in diabetic patients. We used 362 SBP-related genetic variants from a large genome-wide association study (n = 299 024) and UK Biobank (n = 375 256) as exposure. We evaluated 5 macrovascular and microvascular complications up to 60 742 cases as outcomes in diabetes, including coronary artery disease (CAD), peripheral artery disease (PAD), nephropathy, retinopathy, and composite complications. All cases were diagnosed together with diabetes. We performed follow-up analyses by conducting 7 sensitivity analyses and comparing the present MR with results in general population, and clinical trials. Genetic predisposition of each 10-mm Hg SBP decrease was significantly associated with a 28% decreased risk of CAD (odds ratio [OR]: 0.72; 95% CI, 0.59-0.89; P = .002), a 34% decreased risk of nephropathy (OR: 0.66; 95% CI, 0.54-0.81; P < .001), and a 34% decreased risk of the composite complications (OR: 0.66; 95% CI, 0.58-0.76; P < .001), and was nominally associated with a decreased risk of PAD (OR: 0.69; 95% CI, 0.48-0.99) and retinopathy (OR: 0.90; 95% CI, 0.81-0.99). The MR results in diabetes were similar with that in the general population and clinical trials. SBP lowering was causally associated with an attenuated risk of diabetic CAD and nephropathy. It provides genetic evidence for the beneficial effect of lifelong SBP control in preventing diabetes-related vascular outcomes.

Association of prediabetes with death and diabetic complications in older adults: the pros and cons of active screening for prediabetes.

active screening can improve health outcomes for people with prediabetes. However, its efficacy in older adults remains uncertain. the study aimed to analyse the progression from prediabetes to diabetes in older adults, including associated complications and mortality rates, to determine the benefits of active screening. retrospective cohort study. Korean National Health Insurance Service claims database. a total of 36,946 adults aged ≥65years who underwent national health examinations from 2006 to 2008. follow-up was until 31 December 2015. Cox's proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for death and diabetic complications. over a median follow-up of 8.2years, 19.3% of older adults with prediabetes progressed to diabetes. Compared with normoglycaemic adults, the multivariable-adjusted HRs (95% CI) for major adverse cardiovascular events were 1.01 (0.95-1.07), 1.08 (0.95-1.23), 1.14 (1.05-1.23) and 1.50 (1.35-1.68) in adults with prediabetes, newly diagnosed diabetes, diabetes not on insulin and diabetes on insulin, respectively. The corresponding HRs (95% CI) for diabetic retinopathy risk were 1.28 (1.15-1.43), 3.16 (2.71-3.69), 6.58 (6.02-7.19) and 9.17 (8.21-10.24). Diabetic nephropathy risk also significantly increased. progression from prediabetes to diabetes is an important concern among older adults. Prediabetes is associated with the risk of microvascular complications, but not cardiovascular complications and mortality. Therefore, active regular screening for prediabetes is necessary to prevent microvascular complications.

Sarcopenia Is an Independent Risk Factor for Severe Diabetic Nephropathy in Type 2 Diabetes: A Long-Term Follow-Up Propensity Score-Matched Diabetes Cohort Study.

Simple SummaryDiabetic nephropathy is a common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide and results in tremendous wastage of medical resources. Determining the indicators of diabetic nephropathy, such as sarcopenia, and implementing early interventions to prevent disease progression is crucial. The effect of sarcopenia on the risk of severe diabetic nephropathy in patients with type 2 diabetes (T2DM) remains unclear. This study, to date, has the largest sample size and the longest follow-up period among studies investigating this effect by comparing patients with T2DM with and without sarcopenia. This propensity score–matched, population-based cohort study demonstrated that patients with T2DM and sarcopenia may be at a higher risk of severe diabetic nephropathy than are those without sarcopenia. The patients with T2DM and sarcopenia were at a higher risk of severe diabetic nephropathy than were those without sarcopenia irrespective of age, sex, and diabetes severity. Our results may serve as a valuable reference for relevant government authorities in establishing health policies promoting early detection of sarcopenia and exercise to help patients with T2DM overcome sarcopenia.Background: Diabetic nephropathy is a common cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide and results in tremendous wastage of medical resources. Determining the indicators of diabetic nephropathy, such as sarcopenia, and implementing early interventions to prevent disease progression is crucial. Purpose: The effect of sarcopenia on the risk of severe diabetic nephropathy in patients with type 2 diabetes (T2DM) remains unclear. Patients and Methods: We recruited patients with T2DM and categorized them into two groups, propensity score–matched at a ratio of 1:1, according to whether they had sarcopenia. We subsequently compared the groups’ risk of severe diabetic nephropathy. Results: The matching process yielded a final cohort of 105,166 patients with T2DM (52,583 and 52,583 in the sarcopenia and nonsarcopenia groups, respectively) who were eligible for inclusion in subsequent analyses. According to both the univariate and multivariate Cox regression analyses, the adjusted hazard ratio (aHR) (95% confidence interval) of severe diabetic nephropathy for the sarcopenia diabetes group compared with the control group was 1.10 (1.08–1.13; p < 0.001). Conclusion: The patients with T2DM and sarcopenia were at a higher risk of severe diabetic nephropathy than were those without sarcopenia. Our results may serve as a valuable reference for relevant government authorities in establishing health policies to promote early detection of sarcopenia and exercise to help patients with T2DM overcome sarcopenia.

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN). Methods The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA). Results Significant differences were detected in the distribution of IL-1β (−511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489–5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1β level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1β level was significantly different between IL-1β (−511C/T) locus variants (P < 0.05). Conclusion The IL-1β (−511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

Association of Dietary Fish and n-3 Unsaturated Fatty Acid Consumption with Diabetic Nephropathy from a District Hospital in Northern Taiwan.

Nephropathy caused by diabetes mellitus (DM) is the main cause of end-stage renal disease (ESRD). To understand the association of dietary intake with renal function indicators among patients with diabetic nephropathy (DN), this cross-sectional study was conducted at the dietetic consultation clinic of the Taoyuan Armed Forces General Hospital in Taiwan. In total, 317 participants were recruited for this study. Patients with diabetes who had a urinary albumin–creatinine ratio (UACR) of ≥30 mg/g were defined as having DN. The anthropometric characteristics, blood biochemistry, and renal function of the participants were assessed. Furthermore, a semiquantitative food frequency questionnaire (SQFFQ) was administered to investigate the dietary intake of the participants in the DM and DN groups. The result showed that participants in the DN group were older, had longer diabetes duration and poorer glycemic control and renal function than those in the DM group. Logistic regression models revealed that intake of high-fat marine fishes had the lowest odds ratio (OR) for DN risk compared with other fishes (OR: 0.868; 95% CI: 0.781–0.965, p = 0.009). Shellfish, soybean products, and skim milk also provided better protective effects to decrease the risk of DN. A further analysis of polyunsaturated fatty acids revealed that Σn-3 PUFAs significantly reduced DN risk, while Σn-6 PUFAs did not, especially EPA (OR: 0.821; 95% CI: 0.688–0.979, p = 0.029) and DHA (OR: 0.903; 95% CI: 0.823–0.992, p = 0.033) regardless of whether the variables were adjusted, including diabetes duration, age, and HbA1c. Our findings suggest that a diet that incorporates high-fat fish, shellfish, soybean products, and a lower Σn-6/Σn-3 ratio can mitigate DN risk.

Diabetic nephropathy ameliorated in patients with normal home blood pressure compared to those with isolated high home systolic blood pressure: A 5-year prospective cohort study among patients with type 2 diabetes mellitus.

Background:Using normal home blood pressure (home BP) as a reference, isolated high home systolic blood pressure (IH-home SBP) increases the risk of diabetic nephropathy. However, whether diabetic nephropathy would improve among diabetic patients without IH-home SBP has not been previously assessed.Methods:This prospective 5-year cohort study of 264 patients with moderate or severe albuminuria investigated the effect of IH-home SBP or normal home BP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Improvement of diabetic nephropathy was defined as remission or regression from moderate or severe albuminuria to normal or mildly increased albuminuria.Results:Improvement of diabetic nephropathy was shown in 59 out of 264 patients during 5 years. The adjusted odds ratio (95% confidence interval) of normal home BP for improving diabetic nephropathy was 2.52 (1.01–5.99, p = 0.05).Conclusion:Normal home BP had relation to an improvement in diabetic nephropathy among type 2 diabetic patients with moderate and severe increased albuminuria in the observation period of 5 years. Good home BP control might be valuable to ameliorate diabetic nephropathy.

Mitochondrial‐derived ROS Contribute to the Development of Hypertensive‐Diabetic Kidney Injury

Hypertension (HTN) is common in diabetes mellitus (DM) and substantially increases the risk for diabetic nephropathy. Current therapies only slow the progression to end‐stage renal disease (ESRD) in hypertensive‐diabetic patients rather than halt it. Thus, new insights into the mechanisms of this disease are needed.To investigate the mechanisms by which HTN and DM interact to promote renal injury, we developed a model combining streptozotocin (STZ)‐induced type 1 DM and inter‐renal aorta constriction (AC)‐induced HTN in male Wistar rats. In this model (Wistar‐DM+AC), both kidneys are exposed to the same levels of hyperglycemia, circulating hormones, and neural influences, but the left kidney below the AC has normal to slightly reduced blood pressure (BP), while the right kidney above the AC is exposed to elevated BP. To assess the roles of mitochondrial‐derived reactive oxygen species (ROS) and mitochondrial dysfunction in causing kidney injury, Wistar‐DM+AC rats were also treated with saline vehicle or mito‐TEMPO, a mitochondrial‐targeted antioxidant, for 6 weeks starting 2 weeks after AC surgery (0.4mg/kg/day, osmotic mini‐pump). Eight weeks after AC or sham surgery, glomerular filtration rate (GFR) and urinary albumin excretion (UAE) in left and right kidneys were measured separately by collecting urine from each kidney to evaluate the change of renal function. Mitochondrial oxygen consumption rate and superoxide generation from the cortex of left and right kidneys were measured simultaneously by Oroboros high‐resolution respirometry.Kidneys exposed to DM or HTN alone had only mild glomerular injury and slightly increased UAE. In contrast, right kidneys from Wistar‐DM+AC rats which had been exposed to DM plus HTN for 8 weeks had much greater increases in UAE (3.4±0.7 vs1.9±1.3 μg/min), significantly reduced GFR (0.5±0.1 vs 0.7±0.1 ml/min/g of kidney weight) as well as reduced mitochondrial oxygen consumption rate and increased mitochondrial ROS generation compared to left kidneys of Wistar‐DM+AC rats. In Wistar‐DM+AC rats that received mitoTEMPO treatment, the right kidneys exposed to the same levels of elevated BP and blood glucose had lower albumin excretion (1.7±0.3 μg/min), higher GFR (1.3±0.2 ml/min/g of kidney weight), and preserved mitochondrial oxygen consumption with reduced mitochondrial‐derived ROS compared to the right kidneys of vehicle‐treated Wistar‐DM+AC rats.These results suggest that mitochondrial‐derived ROS may contribute to kidney injury when HTN is superimposed on DM. Pharmacological inhibition of mitochondrial ROS generation attenuates kidney injury and may be a potential therapeutic strategy for diabetic nephropathy.

Development and Validation of a Model That Predicts the Risk of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study.

PurposeTo develop a nomogram model that predicts the risk of diabetic nephropathy (DN) incidence in type 2 diabetes mellitus (T2DM) patients.MethodsWe collect information from electronic medical record systems. The data were split into a training set (n=521) containing 73.8% of patients and a validation set (n=185) holding the remaining 26.2% of patients based on the date of data collection. Stepwise and multivariable logistic regression analyses were used to screen out DN risk factors. A predictive model including selected risk factors was developed by logistic regression analysis. The results of binary logistic regression are presented through forest plots and nomogram. Lastly, the c-index, calibration plots, and receiver operating characteristic (ROC) curves were used to assess the accuracy of the nomogram in internal and external validation. The clinical benefit of the model was evaluated by decision curve analysis.ResultsPredictors included serum creatinine (Scr), hypertension, glycosylated hemoglobin A1c (HbA1c), blood urea nitrogen (BUN), body mass index (BMI), triglycerides (TG), and Diabetic peripheral neuropathy (DPN). Harrell’s C-indexes were 0.773 (95% CI:0.726–0.821) and 0.758 (95% CI:0.679–0.837) in the training and validation sets, respectively. Decision curve analysis (DCA) demonstrated that the novel nomogram was clinically valuable.ConclusionOur simple nomogram with seven factors may help clinicians predict the risk of DN incidence in patients with T2DM.

A Novel Study of Protein Kinase C Beta Gene Polymorphism (rs3760106) and Protein Kinase C Activity Levels as a Predictor of Nephropathy Complications in Iraqi Diabetic Patients

Objective: This study aimed to investigate the relation between the risk of (PRKCB-1504 C/T) gene polymorphisms and diabetic nephropathy pathogenesis and its association with its levels and some other biomarkers in serum of Iraqi diabetic nephropathy patients.&#x0D; Methods: A cross-sectional study was performed on 130 samples obtained from Al-Hussein Teaching Hospital / Kerbala – Iraq during Feb., 2020 to March. 2021. Seventy three patients of them with type 2 diabetes mellitus (T2D) and the remaining patients with type 2 diabetes mellitus with nephropathy complications (DN). Phenotypic analysis included determination of protein kinase C (PKC) activity levels, HbA1c%, serum insulin levels and renal function tests. Five ml of whole blood was obtained from each patients, 4.0 ml was centrifuged for serum separation used for biomarkers determinations and the remaining 1.0 ml was used for genomic DNA extraction for molecular analysis and polymorphism of PRKCB (rs3760106) by allele specific-amplification refractory mutational system-polymerase chain reaction (allele specific ARMS-PCR), followed by electrophoresis on 1% agarose gel. Various statistical analyses were applied to analyze the obtained data.&#x0D; Results: The amplification of the PRKCB gene gives one genotypes as indicated by (200 bp) bands for those with homozygous wild type (CC), homozygous mutant (TT) genotypes and two genotypes bands (200 bp) for those with heterozygous (CT). Genotype frequencies of rs3760106 polymorphism were found to be consistent with Hardy–Weinberg equilibrium. Allele frequencies (23.3 %, 26.7 %, 50 %) of CC, CT, TT in cases of DN group. While the frequencies in the non-DN group were (30 %, 45%, 25%) and for healthy control group were (50%, 33.4%, 16.6%) for wild, heterozygous, and homozygous in an order. In healthy control group, the risk of diabetic nephropathy was significantly higher among carriers of T allele under codominant TT (OR=6.42, 95%CI=(1.66-24.85), P=0.007), dominant CT+TT (OR=3.2, 95%CI = (1.08-9.95),P=0.03) and recessive model (OR=5, 95%CI = (1.51-16.56), P=0.008) while in T2DM without nephropathy the risk of diabetic nephropathy was significantly higher among carrier of T allele under recessive model (0R=3, 95%CI = (1.09-28.25), P= 0.003). Serum level of PKC-B1 activity was significantly higher among DN group than T2DM and control groups (43.35 ± 18.69, 30.35 ± 11.96, 27.42 ± 10.31, P=0.001), also PKC-B1 activity in DN group was significantly correlated with fasting blood glucose, HOMA-IR and renal function tests such as GFR, urea and creatinine.&#x0D; Conclusion: This study indicates that the PRKCB (C/T-1504) rs3760106 single nucleotide polymorphism was significantly associated with increased diabetic nephropathy susceptibility of Iraqi patients with T2DM and serum level of PKCB activity was associated with increase the risk of diabetic nephropathy complications.

Short chain fatty acids for the risk of diabetic nephropathy in type 2 diabetes patients

This study aimed to explore relationships short chain fatty acids with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients. We extracted the clinical and omics data of 100 T2D patients and 100 DN patients from April 2018 to April 2019 from a tertiary hospital. Restricted cubic splines were used to examine full-range associations of short chain fatty acids with DN in T2D.Query Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). Acetate, butyrate and isovalerate were negatively correlated with DN. Isobutyrate was positively correlated with DN. Propionate ≥ 4.4μg/mL and isobutyrate ≥ 1.4μg/mL had threshold effects and their increasing levels above the cutoff points were associated with rapid rises in the risk of DN. The additive interaction between high propionate and high isobutyrate in serum significantly increased the risk of DN (OR34.35; 95%CI 7.11 to 166.08). Presence of hypertension further increased the OR of high propionate for DN to 8.27(95%CI 1.82 to 37.57) with a significant additive interaction. The additive interaction of the high isobutyrate and hypertension was not significant. Acetate, butyrate and isovalerate were negatively associated with DN. Isobutyrate was positively associated with DN. Serum high propionate and high isobutyrate worked independently and synergistically to increase the risk of DN in T2D. Presence of hypertension further amplified the effect of copresence of high propionate on DN risk.

Establishment and Validation of a Nomogram Model for Prediction of Diabetic Nephropathy in Type 2 Diabetic Patients with Proteinuria.

PurposeTo establish and validate the nomogram model for predicting diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) patients with proteinuria.MethodsA total of 102 patients with T2DM and proteinuria who underwent renal biopsy were included in this study. According to pathological classification of the kidney, the patients were divided into two groups, namely, a DN group (52 cases) and a non-diabetic renal disease (NDRD) group (50 cases). The clinical data were collected, and the factors associated with diabetic nephropathy (DN) were analyzed with multivariate logistic regression. A nomogram model for predicting DN risk was constructed by using R4.1 software. Receiver operator characteristic (ROC) curves were generated, and the K-fold cross-validation method was used for validation. A consistency test was performed by generating the correction curve.ResultsSystolic blood pressure (SBP), diabetic retinopathy (DR), hemoglobin (Hb), fasting plasma glucose (FPG) and triglyceride/cystatin C (TG/Cys-C) ratio were independent factors for DN in T2DM patients with proteinuria (P<0.05). The nomogram model had good prediction efficiency. If the total score of the nomogram exceeds 200, the probability of DN is as high as 95%. The area under the ROC curve was 0.9412 (95% confidence interval (CI) = 0.8981–0.9842). The 10-fold cross-validation showed that the prediction accuracy of the model was 0.8427. The Hosmer-Lemeshow (H-L) test showed that there was no significant difference between the predicted value and the actual observed value (X2 = 6.725, P = 0.567). The calibration curve showed that the fitting degree of the DN nomogram prediction model was good.ConclusionThe nomogram model constructed in the present study improves the diagnostic efficiency of DN in T2DM patients with proteinuria, and it has a high clinical value.

Body Mass Index and Risk of Diabetic Nephropathy: A Mendelian Randomization Study.

The associations of obesity and diabetic nephropathy (DN) in type 2 diabetes are inconsistent in observational studies, and causality remains unclear. To explore the causal effect of body mass index (BMI) on DN, estimated glomerular filtration rate (eGFR), and proteinuria in type 2 diabetes by a 2-sample Mendelian randomization (MR) analysis. A total of 56 genetic variants were selected as instrumental variables for BMI in 158 284 participants from BioBank Japan, and their effects on DN risk, eGFR, and proteinuria were estimated in 3972 individuals with type 2 diabetes. Then, sex-stratified MR analysis was performed between BMI and DN. We selected generalized summary MR analysis as the primary method and 6 other robust methods to test MR assumptions. One SD increase in BMI was causally associated with higher DN risk [odds ratio (OR) 3.76, 95% CI 1.88-7.53, P < 0.001] and lower eGFR level (OR 0.71, 95% CI 0.59-0.86, P < 0.001). However, BMI was not causally associated with proteinuria (P = 0.22). Sex-stratified analyses indicated the causal effect of BMI on DN was stronger in women (OR 14.81, 95% CI 2.67-82.05, P = 0.002) than in men (OR 3.48, 95% CI 1.18-10.27, P = 0.02). Sensitivity analyses did not show evidence for violation of the MR assumptions. Genetic evidence showed that higher BMI levels were causally associated with increased risk of DN and decreased eGFR levels. Moreover, the increase in BMI level had a greater impact on DN risk in women.

Data-driven subgroups of type 2 diabetes, metabolic response, and renal risk profile after bariatric surgery: a retrospective cohort study

A novel data-driven classification of type 2 diabetes has been proposed to personalise anti-diabetic treatment according to phenotype. One subgroup, severe insulin-resistant diabetes (SIRD), is characterised by mild hyperglycaemia but marked hyperinsulinaemia, and presents an increased risk of diabetic nephropathy. We hypothesised that patients with SIRD could particularly benefit from metabolic surgery. We retrospectively related the newly defined clusters with the response to metabolic surgery in participants with type 2 diabetes from independent cohorts in France (the Atlas Biologique de l'Obésite Sévère [ABOS] cohort, n=368; participants underwent Roux-en-Y gastric bypass or sleeve gastrectomy between Jan 1, 2006, and Dec 12, 2017) and Brazil (the metabolic surgery cohort of the German Hospital of San Paulo, n=121; participants underwent Roux-en-Y gastric bypass between April 1, 2008, and March 20, 2016). The study outcomes were type 2 diabetes remission and improvement of estimated glomerular filtration rate (eGFR). At baseline, 34 (9%) of 368 patients, 314 (85%) of 368 patients, and 17 (5%) of 368 patients were classified as having SIRD, mild obesity-related diabetes (MOD), and severe insulin deficient diabetes (SIDD) in the ABOS cohort, respectively, and in the São Paulo cohort, ten (8%) of 121 patients, 83 (69%) of 121 patients, and 25 (21%) of 121 patients were classified as having SIRD, MOD, and SIDD, respectively. At 1 year, type 2 diabetes remission was reported in 26 (81%) of 32 and nine (90%) of ten patients with SIRD, 167 (55%) of 306 and 42 (51%) of 83 patients with MOD, and two (13%) of 16 and nine (36%) of 25 patients with SIDD, in the ABOS and São Paulo cohorts, respectively. The mean eGFR was lower in patients with SIRD at baseline and increased postoperatively in these patients in both cohorts. In multivariable analysis, SIRD was associated with more frequent type 2 diabetes remission (odds ratio 4·3, 95% CI 1·8-11·2; p=0·0015), and an increase in eGFR (mean effect size 13·1 ml/min per 1·73 m2, 95% CI 3·6-22·7; p=0·0070). Patients in the SIRD subgroup had better outcomes after metabolic surgery, both in terms of type 2 diabetes remission and renal function, with no additional surgical risk. Data-driven classification might help to refine the indications for metabolic surgery. Agence Nationale de la Recherche, Investissement d'Avenir, Innovative Medecines Initiative, Fondation Cœur et Artères, and Fondation Francophone pour la Recherche sur le Diabète.

POS-343 BODY MASS INDEX AND DIABETIC NEPHROPATHY: A MENDELIAN RANDOMIZATION STUDY

The association between obesity and diabetic nephropathy (DN) has been studied but the results of these epidemiological studies are not entirely consistent. The causal effect of body mass index (BMI) on DN and kidney traits in type 2 diabetes was evaluated by a two-sample Mendelian randomization (MR) analysis. A total of 59 independent genetic variants were selected as instrumental variables for BMI in 158,284 participants from Biobank Japan, and their effects on DN risk, eGFR and proteinuria were estimated in 3972 Chinese individuals with type 2 diabetes. Then, subgroup analysis was performed with different BMI levels or sex. In addition, the sensitivity analyses were performed including MR-Egger regression for detecting genetic directional pleiotropic effects, and power calculation for evaluating the reliability of the study. The generalized summary-data-based MR (GSMR) method showed that a one standard deviation increase in BMI was causally associated with a 3-fold increase in the risk of DN (odds ratio [OR], 4.05; 95% confidence interval [95% CI], 2.10 to 7.82; P<0.001), and a 35% decrease of eGFR level (OR, 0.65; 95% CI, 0.54 to 0.78; P<0.001). However, BMI was not associated with the level of proteinuria (OR, 1.26; 95% CI, 0.89 to 1.79; P=0.19). In addition, subgroup analysis showed a positive association between BMI and the risk of DN in individuals with different BMI levels (BMI≥25 vs BMI<25 kg/m2) or sex. Analyses stratified by sex indicated the casual effect of BMI on DN was stronger in women (OR, 9.82; 95% CI, 1.83 to 52.67; P=0.008) than in men (OR, 3.39; 95% CI, 1.23 to 9.34; P=0.02). In sensitivity analyses, the MR-Egger regression intercepts indicated that the results were less likely to be affected by pleiotropy. Based on 1,314 DN cases and 2,658 controls, our study had ≥80% power to detect the causal effect of BMI on DN risk if the genuine OR≥1.69 per standard deviation increase of BMI. Genetic evidence showed that higher BMI levels was causally associated with increased risk of DN and decreased eGFR level, but not with proteinuria. The DN risk for women was more susceptible to BMI levels than men.

Roles of plasma leptin and resistin in novel subgroups of type 2 diabetes driven by cluster analysis

BackgroundA novel classification has been introduced to promote precision medicine in diabetes. The current study aimed to investigate the relationship between leptin and resistin levels with novel refined subgroups in patients with type 2 diabetes mellitus (T2DM).MethodsThe k-means analysis was conducted to cluster 541 T2DM patients into the following four subgroups: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild age-related diabetes (MARD). Individuals meeting the exclusion criteria were eliminated, the data for 285 patients were analyzed. Characteristics were determined using various clinical parameters. Both the leptin and resistin levels were determined using enzyme-linked immunosorbent assay.ResultsThe highest levels of plasma leptin were in the MOD group with relatively lower levels in the SIDD and SIRD groups (P < 0.001). The SIRD group had a higher resistin concentration than the MARD group (P = 0.024) while no statistical significance in resistin levels was found between the SIDD and MOD groups. Logistic regression demonstrated that plasma resistin was associated with a higher risk of diabetic nephropathy (odds ratios (OR) = 2.255, P = 0.001). According to receiver operating characteristic (ROC) curves, the area under the curve (AUC) of resistin (0.748, 95% CI 0.610–0.887) was significantly greater than that of HOMA2-IR (0.447, 95% CI 0.280–0.614) (P < 0.05) for diabetic nephropathy in the SIRD group.ConclusionsLeptin levels were different in four subgroups of T2DM and were highest in the MOD group. Resistin was elevated in the SIRD group and was closely related to diabetic nephropathy.