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

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Xuemin Peng ◽  
Jiaojiao Huang ◽  
Huajie Zou ◽  
Bei Peng ◽  
Sanshan Xia ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Statistical Significance ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Enzyme Linked Immunosorbent Assay ◽  
Insulin Resistant ◽  
Age Related ◽  
Plasma Leptin

Abstract Background A 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). Methods The 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. Results The 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. Conclusions Leptin 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.

scholarly journals Associations between homocysteine, inflammatory cytokines and sarcopenia in Chinese older adults with type 2 diabetes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhi-Jing Mu ◽  
Jun-Ling Fu ◽  
Li-Na Sun ◽  
Piu Chan ◽  
Shuang-Ling Xiu
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Pathological Process ◽  
Clinical Indicators ◽  
Chinese Older Adults ◽  
Age Related ◽  
Hs Crp

Abstract Background Sarcopenia, an age-related disease, has been implicated as both a cause and consequence of type 2 diabetes mellitus (T2DM) and a symbol of poor prognosis in older adults with T2DM. Therefore, early detection and effective treatment of sarcopenia are particularly important in older adults with T2DM. We aimed to investigate the prevalence of sarcopenia in Chinese older T2DM patients and explore whether homocysteine and inflammatory indexes could serve as biomarkers and participate in the development process of sarcopenia. Methods T2DM patients aged over 60 years were consecutively recruited from the ward of department of Endocrinology, Xuanwu Hospital between April 2017 and April 2019. Sarcopenia was defined based on the standard of the Asian Working Group of Sarcopenia, including muscle mass, grip strength and gait speed. Logistic regression was used to explore the association between biochemical indicators and sarcopenia. Receiver operating characteristic (ROC) curves were applied to determine the diagnostic effect of these clinical indicators. Results Totally 582 older adults with T2DM were characterized and analyzed in the study. Approximately 8.9% of the older T2DM patients had sarcopenia. After adjusting for age, sex, body mass index (BMI) and hemoglobin A1c (HbA1c), increased concentrations of homocysteine [odds ratio (OR): 2.829; 95% confidence interval (CI), 1.064–7.525] and high-sensitive C-reactive protein (hs-CRP) (OR: 1.021; 95% CI, 1.001–1.042) were independent predictors of sarcopenia; but not interleukin-6. The combination of age, sex, BMI and HbA1c provided a discriminatory effect of sarcopenia with an area under the curve (AUC) of 0.856, when homocysteine was added to the model, the value of the ROC curve was further improved, with an AUC of 0.861. Conclusion In the current study, we demonstrated a positive correlation of homocysteine, hs-CRP with sarcopenia in older adults with T2DM and the relationship remained significant even after adjustment for HbA1c. These biomarkers (homocysteine and hs-CRP) may play important roles in the pathological process of sarcopenia.

scholarly journals The Effect ofTinospora crispaon Serum Glucose and Insulin Levels in Patients with Type 2 Diabetes Mellitus

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Theerawut Klangjareonchai ◽  
Chulaporn Roongpisuthipong
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Healthy Subjects ◽  
Statistical Significance ◽  
Area Under The Curve ◽  
Serum Glucose ◽  
Dry Powder ◽  
Insulin Levels

Objective. To determine the effects ofTinospora crispaon serum glucose and insulin levels in healthy subjects and patients with type 2 diabetes mellitus.Method. Serum from 10 healthy subjects and 10 diabetic participants, who had fasted overnight, were obtained every 30–60 minutes during the 3 hours of continued fasting and during the 3 hours after ingestion of 75 g of glucose with or without ingestion of 125 or 250 g ofTinospora crispadry powder capsule. Glucose and Insulin levels were analyzed and the areas under the curve for mean serum glucose and insulin levels were calculated.Result. The areas under the curve of mean serum glucose and insulin levels in both healthy and diabetic participants were not significantly different between with or withoutTinospora crispadry powder capsule. In diabetic participants the area under the curve of glucose was slightly lesser when 250 mg ofTinospora crispawas ingested, but not reaching statistical significance (478 and 444 mg min/ml, resp.,P=0.57).Conclusion. The results suggest thatTinospora crispaingestion cannot affect serum glucose and insulin levels in healthy subjects or patients with type 2 diabetes mellitus.

scholarly journals Genetic Relationship Between Interleukın-6 rs1800796 Variants,  Interleukın-6 Plasma Levels and Susceptibility to Type 2 Diabetes Mellitus and Diabetic Nephropathy

2021 ◽  
Author(s):  
Nezaket COBAN ◽  
Aysegul Bayramoglu ◽  
Zeynep TEMIZ
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Inflammatory Cytokines ◽  
Interleukin 6 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference

Abstract Type 2 diabetes mellitus (T2DM) is very common worldwide and genetically heterogeneous. One of the microvascular complications is diabetic nephropathy (DN). In recent years, T2DM has been described as a disease caused by chronic inflammation. The imbalance between pro- and anti-inflammatory cytokines causes inflammation. One of the candidate genes associated with T2DM and DN is the Interleukin-6 (IL-6) gene, one of the pro-inflammatory cytokines. This study was conducted to determine the polymorphism frequencies of the IL-6 gene rs1800796 and investigate the role of this polymorphism in the development of T2DM and DN. Genomic DNA that was obtained from 261 people was used in the study. IL-6 gene rs1800796 polymorphism was determined using the PCR, restriction fragment length polymorphism (RFLP) and electrophoresis. IL-6 gene PCR products were discontinued by treatment with restriction enzyme BsrBI and were analyzed in 2% agarose gel electrophoresis. IL-6 (Bioassay technology laboratory, Shangai, China) level was examined by enzyme-linked immunosorbent assay (ELISA) using a commercial kit. The results were statistically analyzed. The frequencies of rs1800796 genotypes were found to be GG 70.7%, GC 28.5%, CC 0.8% in the control group and GG 87.8%, GC 9.9 %, CC 2.3% in T2DM patients. Although there was a statistically significant difference between the control group and the T2DM patient group in genotype and allele frequencies, there was no significant difference in DN. The G allele frequency was also significantly higher in the T2DM group (p=0.000). IL-6 levels were determinated increased in patients with Type-2 diabetes compared to the control group. However; there was no significant statistically. We can say that IL-6 rs1800796 polymorphism is related to T2DM and G allele can be used as a useful genetic marker; this polymorphism is not related to DN, though.

scholarly journals The Clinical Value of Serum Adropin Level in Early Detection of Diabetic Nephropathy

2021 ◽  
pp. 1-7
Author(s):  
Ali Es-haghi ◽  
Tuqa Al-Abyadh ◽  
Hassan Mehrad-Majd
Keyword(s):  
Type 2 Diabetes ◽  
Logistic Regression ◽  
Diabetic Nephropathy ◽  
Early Detection ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Peripheral Tissues

<b><i>Background/Aims:</i></b> Adropin is a metabolic hormone secreted by the liver, brain, and many peripheral tissues and is involved in energy homeostasis and insulin sensitivity. Some reports have indicated a significant decrease in serum adropin levels in type 2 diabetic patients. However, the significance of a decline in adropin level in early detection of diabetic nephropathy (DN) remains to be clarified. The purpose of this study was to evaluate the serum levels of adropin in patients with type 2 diabetes with and without nephropathy. <b><i>Methods:</i></b> A total of 135 unrelated subjects (including 45 diabetic patients with nephropathy, 45 without nephropathy, and 45 healthy controls) were enrolled in this study. Fasting venous blood samples were collected from all patients. Serum adropin levels of all cases were analyzed by an enzyme-linked immunosorbent assay method. The correlations of serum adropin levels with anthropometric and biochemistry variables were determined. Logistic regression was performed to assess the association of adropin with odds of nephropathy. A receiver operating characteristic (ROC) curve was obtained to explore the optimum serum adropin concentration in distinguishing diabetic patients with and without nephropathy. <b><i>Results:</i></b> Diabetic patients with nephropathy showed lower serum adropin levels than those in patients without nephropathy and healthy controls (<i>p</i> &#x3c; 0.001). Pearson correlation analysis indicated that serum adropin was negatively correlated with BMI, FBS, HbA1c, blood urea, creatinine, LDL, and ACR and positively correlated with HDL and albumin. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing diabetic nephropathy. Moreover, in ROC analysis, at cutoff value 3.20 (mg/dL) with an AUC = 0.830, adropin had 80% sensitivity and 60% specificity for distinguishing the diabetic nephropathy. <b><i>Conclusions:</i></b> This study demonstrates that decreased level of adropin is associated with renal dysfunction in patients with type 2 diabetes mellitus. Serum adropin concentrations may be used as a biomarker for early detection of diabetic nephropathy.

Abstract MP09: Sex Differences And Development Of Advanced Diabetic Nephropathy In Type 2 Diabetic Nephropathy Rats

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Denisha Spires ◽  
Oleg Palygin ◽  
Vladislav Levchenko ◽  
Sherif Khedr ◽  
Oksana Nikolaienko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Function ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Glucose Levels ◽  
Age Related ◽  
Increased Risk ◽  
Type 2 Diabetic

Diabetic kidney disease (DKD) is a severe complication of diabetes, which causes an increased risk of cardiovascular diseases and end-stage renal failure. Recent clinical data have demonstrated distinct sexual dimorphisms in the pathogenesis of DKD in humans, which impacts both severity- and age-related risk factors. A type 2 diabetic nephropathy (T2DN) rat model characterized by spontaneous development of an advanced form of diabetic nephropathy (DN) was used here to study sexual dimorphisms in the development of type 2 diabetes with DN. Male and female T2DN rats at late stages of the disease were used to evaluate hyperglycemia, renal injury, and kidney function. During late stage DKD (>46 weeks), glucose tolerance tests (GTT) revealed higher glucose levels in males (378 ± 19 vs. 183 ± 48 mg/dL) compared to females. This was accompanied by pathological changes in kidney function including urinary nephrin shedding, albuminuria (11.8 ± 5.7 vs. 0.98 ± 0.64 Alb/Cre ratio), and glomerular damage. To test the role of the endocrine environment in the pathophysiology of type 2 diabetes with DKD, we performed gonadectomies on male and female T2DN rats at 9 to 10 weeks of age, and animals were monitored until the full development of DKD (>46 weeks). All T2DN rats (intact and gonadectomized) maintained their diabetic phenotype, which was verified by higher end point blood glucose levels following a GTT (intact vs gonadectomized, male and female, respectively; 404 ± 21 vs 466 ± 32 and 264 ± 20 vs 291 ± 25 mg/dL). Based on kidneys to body weight ratios, gonadectomized male T2DN rats had a significant reduction in kidney hypertrophy (intact vs gonadectomized; males and females, respectively: 9.9 ± 0.2 vs 7.4 ± 0.2 and 7.7 ± 0.2 vs 7.0 ± 0.2 ratio). Moreover, FITC-inulin based GFR measurements revealed gonadectomized males had improved GFRs, whereas the GFRs of gonadectomized females rats were worsened (7.5 ± 1.5 vs. 4.1 ± 0.7 for male and 4.1 ± 0.2 vs. 7.3 ± 1.3 for female μg/mL/min; gonadectomy vs intact, correspondingly). In conclusion, male T2DN rats develop more severe DKD compared to age-matched females, and this phenotype is partially attenuated by the absence of sex hormones in males and exacerbated by the absence of hormones in females.

scholarly journals Dietary Restriction Ameliorates Diabetic Nephropathy through Anti-Inflammatory Effects and Regulation of the Autophagy via Restoration of Sirt1 in Diabetic Wistar Fatty (fa/fa) Rats: A Model of Type 2 Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Munehiro Kitada ◽  
Ai Takeda ◽  
Takako Nagai ◽  
Hiroki Ito ◽  
Keizo Kanasaki ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Dietary Restriction ◽  
Electron Microscopic Observation ◽  
Mitochondrial Morphology ◽  
Electron Microscopic ◽  
Beneficial Effects ◽  
Age Related ◽  
Anti Inflammatory

Aim. Despite the beneficial effects of dietary restriction (DR) on lifespan, age-related diseases, including diabetes and cardiovascular diseases, its effects on type 2 diabetic nephropathy remain unknown. This study examined the renoprotective effects of DR in Wistar fatty (fa/fa) rats (WFRs).Methods. WFRs were treated with DR (40% restriction) for 24 weeks. Urinary albumin excretion, creatinine clearance, renal histologies, acetylated-NF-κB (p65), Sirt1 protein expression, and p62/Sqstm 1 accumulation in the renal cortex, as well as electron microscopic observation of mitochondrial morphology and autophagosomes in proximal tubular cells were estimated.Results. DR ameliorated renal abnormalities including inflammation in WFRs. The decrease in Sirt1 levels, increase in acetylated-NF-κB, and impaired autophagy in WFRs were improved by DR.Conclusions. DR exerted anti-inflammatory effects and improved the dysregulation of autophagy through the restoration of Sirt1 in the kidneys of WFRs, which resulted in the amelioration of renal injuries in type 2 diabetes.

scholarly journals Assessing reproducibility and utility of clustering of patients with type 2 diabetes and established CV disease (SAVOR -TIMI 53 trial)

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259372
Author(s):  
Yasunori Aoki ◽  
Bengt Hamrén ◽  
Lindsay E. Clegg ◽  
Christina Stahre ◽  
Deepak L. Bhatt ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Disease Progression ◽  
Risk Scores ◽  
Predictive Utility ◽  
Insulin Resistant ◽  
Age Related ◽  
Cardiovascular Outcome Trial ◽  
Cv Disease

Objective To assess the reproducibility and clinical utility of clustering-based subtyping of patients with type 2 diabetes (T2D) and established cardiovascular (CV) disease. Methods The cardiovascular outcome trial SAVOR-TIMI 53 (n = 16,492) was used. Analyses focused on T2D patients with established CV disease. Unsupervised machine learning technique called “k-means clustering” was used to divide patients into subtypes. K-means clustering including HbA1c, age of diagnosis, BMI, HOMA2-IR and HOMA2-B was used to assign clusters to the following diabetes subtypes: severe insulin deficient diabetes (SIDD); severe insulin-resistant diabetes (SIRD); mild obesity-related diabetes (MOD); mild age-related diabetes (MARD). We refer these subtypes as “clustering-based diabetes subtypes”. A simulation study using randomly generated data was conducted to understand how correlations between the above variables influence the formation of the cluster-based diabetes subtypes. The predictive utility of clustering-based diabetes subtypes for CV events (3-point MACE), renal function reduction (eGFR decrease >30%) and diabetic disease progression (introduction of additional anti-diabetic medication) were compared with conventional risk scores. Hazard ratios (HR) were estimated by Cox-proportional hazard models. Results In the SAVOR-TIMI 53 trial based dataset, the percentage of the clustering-based T2D subtypes were; SIDD (18%), SIRD (17%), MOD (29%), MARD (37%). Using the simulated dataset, the diabetes subtypes could be largely reproduced from a log-normal distribution when including known correlations between variables. The predictive utility of clustering-based diabetic subtypes on CV events, renal function reduction, and diabetic disease progression did not show an advantage compared to conventional risk scores. Conclusions The consistent reproduction of four clustering-based T2D subtypes can be explained by the correlations between the variables used for clustering. Subtypes of T2D based on clustering had limited advantage compared to conventional risk scores to predict clinical outcome in patients with T2D and established CV disease.

scholarly journals Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus patients

2017 ◽  
Vol 15 (4) ◽  
pp. 441-444
Author(s):  
Marcelo Rodrigues Bacci ◽  
Beatriz da Costa Aguiar Alves ◽  
Marina Romera Cavallari ◽  
Ligia Ajaime Azzalis ◽  
Ross Martin de Rozier-Alves ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Protein Gene ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diabetic Patients ◽  
Glucose Levels

ABSTRACT Objective: To evaluate the gene expression of beta-trace protein in urine of diabetic patients, with no reduction in glomerular filtration rate, which was defined as below 60mL/min/1.73m2. Methods: Type 2 diabetes mellitus patients were recruited, and a group of non-diabetic individuals served as control. Beta-trace protein gene expression was analyzed by quantitative PCR. Blood samples were collected to establish glucose levels and baseline kidney function. Accuracy was analyzed using ROC curves. Results: Ninety type 2 diabetes mellitus patients and 20 non-diabetic individuals were recruited. The area under the curve was 0.601, sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18% showed an expression above the cutoff point. Conclusion: These results of accuracy of beta-trace protein gene expression in urine of diabetic patients are promising, although they did not achieve a higher area under the curve level.

scholarly journals Insulin Resistance as a Predictor of Age-Related Diseases

2001 ◽  
Vol 86 (8) ◽  
pp. 3574-3578 ◽  
Author(s):  
Francesco S. Facchini ◽  
Nancy Hua ◽  
Fahim Abbasi ◽  
Gerald M. Reaven
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Proportional Hazards ◽  
Clinical Event ◽  
Insulin Resistant ◽  
Clinical Events ◽  
Age Related

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988–1995 in 208 apparently healthy, nonobese (body mass index &lt; 30 kg/m2) individuals, who were then evaluated 4–11 yr later (mean ± sem = 6.3 ± 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox’s proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.

scholarly journals Thyroid Function in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy: A Single Center Study

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Zhao ◽  
Xinyu Li ◽  
Xuhan Liu ◽  
Lu Lu ◽  
Zhengnan Gao
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Thyroid Function ◽  
Pearson Correlation ◽  
Statistical Significance ◽  
Glycosylated Hemoglobin ◽  
Diabetic Patients

Background. Diabetes mellitus is a common metabolic disease and the prevalence is increasing rapidly. Thyroid disorders including subclinical hypothyroidism (SCH) and low triiodothyronine (T3) syndrome are frequently observed in diabetic patients. We conducted a study to explore thyroid function in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. We included 103 healthy volunteers, 100 T2DM patients without DN, and 139 with DN. Physical examinations including body mass index and blood pressure and laboratory measurements including renal function, thyroid function, and glycosylated hemoglobin were conducted. Results. Patients with DN had higher thyroid stimulating hormone (TSH) levels and lower free T3 (FT3) levels than those without DN (p < 0.01). The prevalence of SCH and low FT3 syndrome in patients with DN was 10.8% and 20.9%, respectively, higher than that of controls and patients without DN (p < 0.05). Through Pearson correlation or Spearman rank correlation analysis, in patients with DN, there were positive correlations in TSH with serum creatinine (r = 0.363, p = 0.013) and urinary albumin-to-creatinine ratio (r = 0.337, p = 0.004), and in FT3 with estimated glomerular filtration rate (eGFR) with statistical significance (r = 0.560, p < 0.001). Conclusions. High level of TSH and low level of FT3 were observed in T2DM patients with DN. Routine monitoring of thyroid function in patients with DN is necessary, and management of thyroid dysfunction may be a potential therapeutic strategy of DN.

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