Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type 2 Diabetes

Background. Cathepsin D has been recently implicated in insulin resistance and cardiovascular disease. This study was designed to investigate the relationship between cathepsin D and newly diagnosed type 2 diabetes. Methods. Circulating cathepsin D levels and metabolic variables were measured in 98 cases and 98 controls. Myocardial performance index “Tei index” that reflects both left ventricular systolic and diastolic function was measured with Doppler echocardiography in cases. Results. Newly diagnosed type 2 diabetes demonstrated significantly higher circulating cathepsin D concentrations than controls (median level: 227 ng/ml versus 174 ng/ml, P<0.01). In newly diagnosed type 2 diabetes, a significant correlation was found between cathepsin D levels and HOMA-IR (homeostatic model assessment of insulin resistance) (r=0.25, P=0.01). In contrast, no significant correlation was found between cathepsin D levels and clinical parameters in the control group (all P>0.05). Interestingly, correlation analysis revealed a positive association between cathepsin D levels and Tei index in type 2 diabetes (r=0.22, P=0.03). Conclusions. Increased levels of circulating cathepsin D are closely linked with the presence of type 2 diabetes, and cathepsin D might serve as a novel biomarker for cardiac dysfunction in newly diagnosed type 2 diabetes.

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Increased circulating levels of musclin in newly diagnosed type 2 diabetic patients

Diabetes and Vascular Disease Research ◽

10.1177/1479164116675493 ◽

2017 ◽

Vol 14 (2) ◽

pp. 116-121 ◽

Cited By ~ 8

Author(s):

Wen-Jia Chen ◽

Yue Liu ◽

Yu-Bin Sui ◽

Bo Zhang ◽

Xiao-Hui Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Plasma Levels ◽

Control Group ◽

Diabetic Patients ◽

Model Assessment ◽

Newly Diagnosed

Background: Musclin is a newly identified skeletal muscle–derived secretory factor, which has been recently characterized as a stimulator that induces insulin resistance in mice. However, the pathophysiological role of musclin in humans remains poorly understood. The aim of this study was to explore the potential correlations between musclin plasma levels and various metabolic parameters in patients with type 2 diabetes mellitus. Materials and methods: In this hospital-based study, plasma samples were collected from the enrolled individuals, including 38 newly diagnosed, treatment-naive type 2 diabetes mellitus patients and 41 age- and gender-matched control subjects. Plasma musclin levels were examined by radioimmunoassay. Results: Compared with the control group, musclin plasma levels were significantly higher in untreated type 2 diabetes mellitus patients. Musclin levels in the plasma of newly diagnosed type 2 diabetes mellitus patients were positively correlated with fasting plasma glucose, haemoglobin A1c, serum insulin, triglycerides and homeostasis model assessment of insulin resistance. Furthermore, multivariate logistic regression analysis showed that the level of musclin was associated with the presence of type 2 diabetes mellitus. Receiver operating characteristic curve analysis yielded an area under the curve for musclin of 0.718 in type 2 diabetes mellitus. Conclusion: The circulating concentration of musclin was significantly increased in type 2 diabetes mellitus patients. Our results suggest that musclin has a strong relationship with insulin resistance in type 2 diabetes mellitus.

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Correlation between Blood Activin Levels and Clinical Parameters of Type 2 Diabetes

Experimental Diabetes Research ◽

10.1155/2012/410579 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Hui Wu ◽

Michael Wu ◽

Yi Chen ◽

Carolyn A. Allan ◽

David J. Phillips ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Glucose Tolerance ◽

Fasting Glucose ◽

Serum Levels ◽

Activin A ◽

Oral Glucose ◽

Clinical Parameters ◽

Model Assessment

Aims. Activins A and B, and their binding protein, follistatin, regulate glucose metabolism and inflammation. Consequently, their role in type 2 diabetes (T2D) was examined.Methods. Blood was taken from fasted participants (34 males; 58 females; 50–75 years) with diabetes or during an oral glucose tolerance test (OGTT). Clinical parameters were assessed, and blood assayed for activins, follistatin, and C-reactive protein.Results. Serum levels of activin A (93.3 ± 27.0 pg/mL, mean ± SD), B (81.8 ± 30.8 pg/mL), or follistatin (6.52 ± 3.15 ng/mL) were not different (P>0.05) between subjects with normal OGTT (n=39), impaired glucose tolerance and/or fasting glucose (n=17), or T2D (n=36). However, activin A and/or activin B were positively correlated with parameters of insulin resistance and T2D, including fasting glucose (P<0.001), fasting insulin (P=0.02), glycated hemoglobin (P=0.003), and homeostasis model assessment of insulin resistance (HOMA-IR;P<0.001). Follistatin was positively correlated with HOMA-IR alone (P=0.01).Conclusions. These data indicate that serum measurements of activin A, B, or follistatin cannot discriminate risk for T2D in individual patients, but the activins display a positive relationship with clinical parameters of the disease.

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Aberrant Expression of Long Non-Coding RNAs in Newly Diagnosed Type 2 Diabetes Indicates Potential Roles in Chronic Inflammation and Insulin Resistance

Cellular Physiology and Biochemistry ◽

10.1159/000484388 ◽

2017 ◽

Vol 43 (6) ◽

pp. 2367-2378 ◽

Cited By ~ 17

Author(s):

Xiaoli Wang ◽

Xiangyun Chang ◽

Peipei Zhang ◽

Ling Fan ◽

Ting Zhou ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Target Genes ◽

Chinese Patients ◽

Control Group ◽

Newly Diagnosed ◽

Aberrant Expression ◽

Healthy Control ◽

Non Coding Rnas

Background/Aims: Long non-coding RNAs (lncRNAs) have emerged as key players in several biological processes and complex diseases. The risk of type 2 diabetes (T2D) is determined by a combination of environmental factors and genetic susceptibility. The purpose of this study was to identify aberrant lncRNAs involved in T2D pathogenesis. Methods: Microarray analysis was performed using whole blood samples from patients newly diagnosed with T2D and healthy controls. Pathway and Gene Ontology (GO) analyses were utilized to annotate the target genes. Coding non-coding co-expression (CNC) analysis was performed to construct a co-expression network. Results: We found 55 lncRNAs and 202 mRNAs were differentially expressed in the T2D group compared to the healthy control group. Pathway and GO analyses demonstrated that dysregulated mRNAs were mainly associated with immune regulation, inflammation, and insulin resistance, whereas CNC analysis identified 10 pairs of co-expressed lncRNA-mRNAs in our patient cohort (R > 0.99). Furthermore, expression of the top three upregulated lncRNAs in the T2D group was correlated with measures of glycometabolism (P < 0.05). Conclusion: This study identified aberrantly expressed lncRNAs and mRNAs in Han Chinese patients with T2D, and demonstrated that dysregulated lncRNAs may have roles in T2D pathogenesis through regulation of inflammation and insulin resistance.

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Serum concentrations of asprosin in new-onset type 2 diabetes

10.21203/rs.3.rs-15208/v1 ◽

2020 ◽

Author(s):

Shakiba Naiemian ◽

Mohsen naeemipour ◽

Mehdi Zarei ◽

Ali Gohari ◽

Mohammad Reza Behroozikhah ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Model Assessment ◽

Serum Concentrations ◽

Atherosclerotic Risk Factor

Abstract Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status . Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants . Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group . Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion : Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.

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Value of simple clinical parameters to predict insulin resistance among newly diagnosed patients with type 2 diabetes in limited resource settings

PLoS ONE ◽

10.1371/journal.pone.0248469 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0248469

Author(s):

Keddagoda Gamage Piyumi Wasana ◽

Anoja Priyadarshani Attanayake ◽

Thilak Priyantha Weerarathna ◽

Kamani Ayoma Perera Wijewardana Jayatilaka

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Sri Lanka ◽

Lipid Profile ◽

Limited Resource ◽

Small Sample ◽

Clinical Parameters ◽

Fasting Insulin ◽

Newly Diagnosed

Background Insulin resistance (IR) has been considered as a therapeutic target in the management of type 2 diabetes mellitus (T2DM). Readily available, simple and low cost measures to identify individuals with IR is of utmost importance for clinicians to plan optimal management strategies. Research on the associations between surrogate markers of IR and routine clinical and lipid parameters have not been carried out in Sri Lanka, a developing country with rising burden of T2DM with inadequate resources. Therefore, we aimed to study the utility of readily available clinical parameters such as age, body mass index (BMI), waist circumference (WC) and triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C) in the fasting lipid profile in predicting IR in a cohort of patients with newly diagnosed T2DM in Sri Lanka. Methods and findings We conducted a community based cross sectional study involving of 147 patients (age 30–60 years) with newly diagnosed T2DM in a suburban locality in Galle district, Sri Lanka. Data on age, BMI, WC, fasting plasma glucose (FPG) concentration, fasting insulin concentration and serum lipid profile were collected from each subject. The indirect IR indices namely homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI) and McAuley index (MCA) were estimated. Both clinical and biochemical parameters across the lowest and the highest fasting insulin quartiles were compared using independent sample t-test. Linear correlation analysis was performed to assess the correlation between selected clinical parameters and indirect IR indices. The area under the receiver operating characteristic (ROC) curve was obtained to calculate optimal cut-off values for the clinical markers to differentiate IR. BMI (p<0.001) and WC (p = 0.01) were significantly increased whereas age (p = 0.06) was decreased and TG/HDL-C (p = 0.28) was increased across the insulin quartiles. BMI and WC were significantly correlated (p<0.05) with HOMA, QUICKI and MCA. Out of the clinical parameters, age showed a borderline significant correlation with QUICKI and TG/HDL-C showed a significant correlation only with MCA. The area under ROC of BMI was 0.728 (95% CI 0.648–0.809; p<0.001) and for WC, it was 0.646 (95% CI 0.559–0.734; p = 0.003). The optimized cut-off value for BMI and WC were 24.91 kg/m2 and 81.5 cm respectively to differentiate the patients with IR or ID. Study limitations include small sample size due to recruitment of patients only from a limited geographical locality of the country and not totally excluding of the possibility of inclusion of some patients with slowly progressive type 1 DM or Latent onset diabetes of adulthood from the study population. Conclusions The results revealed that there was a significant positive correlation between BMI, WC and HOMA while a significant negative correlation with QUICKI and MCA among the cohort of patients with newly diagnosed T2DM. The cut-off values of BMI and WC as 24.91 kg/m2 and 81.5 cm respectively could be used as simple clinical parameters to identify IR in newly diagnosed patients with T2DM. Our results could be beneficial in rational decision making in the management of newly diagnosed patients with T2DM in limited resource settings.

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THE EFFECT OF PUGUNTANO (CURANGA FEL-TERRAE [LOUR.]) EXTRACT ON ADIPONECTIN RECEPTOR (ADIPOR) IN RATS WITH TYPE 2 DIABETES MELLITUS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i2.30456 ◽

2019 ◽

pp. 551-553

Author(s):

DHARMA LINDARTO ◽

YETTY MACHRINA ◽

SANTI SYAFRIL ◽

AWALUDDIN SARAGIH

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

Treatment Group ◽

Control Group ◽

Model Assessment ◽

Anti Inflammatory

Objective: This study aimed to determine whether the antidiabetic effects of puguntano (Curanga fel-terrae [Lour.]) extract involve anti-inflammatory effects mediated through adiponectin receptors (AdipoRs). Methods: Type 2 diabetes mellitus (T2DM) Wistar rats were induced by a combination of high-fat diet for 5 weeks and injection small dose streptozotocin 30 mg/kg bw/rat. This study was conducted in 48 T2DM rats, which were randomly assigned into two weight-matched groups (n=24, each). Only the treatment group received 0.2 mg/g bw of puguntano extract suspension through oral for 10 days. The clinical characteristics of T2DM and AdipoR were assessed before and after the treatment period. Results: The treatment group demonstrated significantly lower body weight, fasting blood glucose, and homeostasis model assessment-insulin resistance (HOMA-IR) but higher AdipoR than the control group (all, p<0.001). Furthermore, there were also negative correlations between AdipoR to body weight and HOMA-IR (all, p<0.05). Conclusion: Our data suggest that puguntano could improve glucose metabolism and ameliorate insulin resistance and have anti-inflammatory effects mediated through AdipoR in T2DM.

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Study on Association of Serum Uric Acid and Calcium with Insulin and its Resistance in Newly Diagnosed Type 2 Diabetes Mellitus Patients

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/49062.15472 ◽

2021 ◽

Author(s):

Saffalya Nayak ◽

Roma Rattan ◽

Manmath Kumar Mandal ◽

Debjyoti Mohapatra

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Serum Uric Acid ◽

Serum Insulin ◽

Model Assessment ◽

Newly Diagnosed

Introduction: Type 2 Diabetes Mellitus (T2DM) is a multifactorial pathological condition associated with insulin resistance and insulin deficiency. Uric acid and calcium have shown inconsistent association with occurrence of diabetes. Aim: To evaluate the role of uric acid and calcium in development of T2DM. Materials and Methods: This was a case-control study conducted in Department of Biochemistry from March to November 2019 in Sriram Chandra Bhanja, Medical College and Hospital, Cuttack, Odisha, India. A 180 subjects undertaken with the objective of finding any association of serum uric acid and calcium with insulin and its resistance in newly diagnosed T2DM cases. Newly diagnosed T2DM patients were taken as cases. Age and sex matched healthy individuals were taken as controls. Fasting Plasma Glucose (FPG), serum insulin, serum uric acid and ionised calcium were measured in autoanalyser and insulin resistance was calculated using Homeostasis Model Assessment for Insulin Resistance (HOMA- IR). Other confounding risk factors for T2DM like Body Mass Index (BMI), family history was taken into account. Results: A significant positive correlation of serum uric acid with serum insulin (p=0.029) and its resistance (p=0.032) in cases. Serum calcium was negatively associated with insulin and its resistance in both cases and controls. Regression models showed serum uric acid as a strong independent risk factor for levels of insulin and its resistance. Conclusion: The findings of the study showed that regular evaluation of serum uric acid and calcium should be done in those who are at risk of developing T2DM. Larger prospective studies will be required for definite assessment.

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Association between Adiponectin and Insulin Resistance among Sudanese Males with Type 2 Diabetes Mellitus

10.21203/rs.3.rs-582913/v1 ◽

2021 ◽

Author(s):

Eman Ahamed Almakey ◽

Ahmed Mohamed Makeen ◽

Osman Khalafalla Saeed ◽

Khalid Abdelsamea Mohamedahmed

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Serum Adiponectin ◽

Control Group ◽

P Value ◽

Model Assessment ◽

Positive Effects

Abstract Background Adiponectin is associated with improved systemic insulin sensitivity and profound positive effects in adipose tissue, such as increasing mitochondrial density in adipocytes, reducing adipocyte size, and effective esterification of free fatty acids on lipid storage The factor performs forward transcriptional regulation. Diabetes and its complications are considered to be one of the main causes of morbidity and mortality worldwide. Objectives The aim of this study was to correlate serum levels of adiponectin with insulin resistance in Sudanese males' type 2 diabetes mellitus. Methodology: A case-control community-based study carried out among 126 patients with T2DM as cases group (mean ages 45.2 ± 5.4 years); and 126 normal healthy individuals as controls group (mean ages 44.7 ± 5.4 years as) in Aldaraga Diabetic Center, Wad Medani, Gezira State, Sudan. About Five mL of fasting venous blood was obtained from all participants. HbA1c, FPG, FPI, serum Adiponectin, and (HOMA)-IR were analyzed. SPSS (v 20.0) was used for data analysis. Results The mean of serum adiponectin in the cases group (3.03 ± 0.90µg/ml) was lower than the control group (6.02 ± 4.24µg/ml) giving highly significant differences -between them (P = value ≤ 0.000). HbA1c and Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR) differed significantly between the two groups (P-value ≤ 0.000). Serum adiponectin concentrations correlated significantly negative with HOMA IR (r = -0.149, P-value = 0.002). Conclusion We concluded that low plasma adiponectin level was predictive of future development of Insulin resistance in Sudanese males.

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Serum concentration of asprosin in new-onset type 2 diabetes

10.21203/rs.3.rs-15208/v3 ◽

2020 ◽

Author(s):

Shakiba Naiemian ◽

Mohsen naeemipour ◽

Mehdi Zarei ◽

Moslem Lari Najafi ◽

Ali Gohari ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Model Assessment ◽

Serum Concentrations ◽

Atherosclerotic Risk Factor

Abstract Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status. Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants. Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group. Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion: Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.

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CD26/DPP4 Levels in Peripheral Blood and T Cells in Patients With Type 2 Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-4288 ◽

2013 ◽

Vol 98 (6) ◽

pp. 2553-2561 ◽

Cited By ~ 76

Author(s):

Sang Ah Lee ◽

Young Ree Kim ◽

Eun Jin Yang ◽

Eun-Jeong Kwon ◽

Sun Hyung Kim ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

T Cells ◽

Cd8 T Cells ◽

Hemoglobin A1c ◽

Control Group ◽

Model Assessment ◽

Homeostasis Model Assessment

Context: Dipeptidyl peptidase 4 (CD26/DPP4) is expressed on blood T cells and also circulates in a soluble form (sCD26/DPP4). Objective: We aimed to evaluate blood T cell and circulating CD26/DPP4 and its association with metabolic parameters in patients with type 2 diabetes mellitus (T2DM). Designs: We measured CD26/DPP4 expression (percentage of CD26+ cells using flow cytometry) on CD4+ and CD8+ T cells, serum CD26/DPP4 level and activity, and various metabolic parameters in T2DM patients not on DPP4 inhibitor therapy (n = 148). Nondiabetic subjects (n = 50) were included as a control group. Results: Compared with the healthy controls, CD26/DPP4 expression on CD4+ T cells and CD8+ T cells was higher in T2DM patients. Serum CD26/DPP4 levels and enzymatic activities were also higher in patients with T2DM than in the control group only when metformin and/or thiazolidinedione-treated T2DM patients were excluded; metformin and/or thiazolidinedione-treated T2DM patients had lower values compared with other T2DM patients. Various parameters in T2DM patients were related to CD26/DPP4 expression on the T cells (hemoglobin A1c), serum sCD26/DPP4 (hemoglobin A1c and insulin resistance assessed by updated homeostasis model assessment), and serum CD26/DPP4 activity (insulin resistance assessed by updated homeostasis model assessment, γ-glutamyl transferase, and alanine aminotransferase) by multivariate analyses. After active glucose control for 12 weeks in drug-naive T2DM patients (n = 50), CD26/DPP4 expression on blood T cells was significantly decreased. Conclusions: Our results suggest that the CD26/DPP4 level on blood T cells was associated with glucose control status in patients with T2DM.

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