scholarly journals Deep serum proteomics reveal biomarkers and causal candidates for type 2 diabetes

2019 ◽  
Author(s):  
Valborg Gudmundsdottir ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
Marjan Ilkov ◽  
Elias F Gudmundsson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Serum Proteins ◽  
Protein Profile ◽  
Disease Onset ◽  
Serum Levels ◽  
The Body ◽  
Protein Biomarkers ◽  
Clinical Value ◽  
Serum Proteomics

AbstractThe prevalence of type 2 diabetes mellitus (T2DM) is expected to increase rapidly in the next decades, posing a major challenge to societies worldwide. The emerging era of precision medicine calls for the discovery of biomarkers of clinical value for prediction of disease onset, where causal biomarkers can furthermore provide actionable targets. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach measuring serum levels of 4,137 proteins in 5,438 Icelanders to discover novel biomarkers for incident T2DM and describe the serum protein profile of prevalent T2DM. We identified 536 proteins associated with incident or prevalent T2DM. Through LASSO penalized logistic regression analysis combined with bootstrap resampling, a panel of 20 protein biomarkers that accurately predicted incident T2DM was identified with a significant incremental improvement over traditional risk factors. Finally, a Mendelian randomization analysis provided support for a causal role of 48 proteins in the development of T2DM, which could be of particular interest as novel therapeutic targets.

scholarly journals Circulating protein signatures and causal candidates for type 2 diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Valborg Gudmundsdottir ◽  
Shaza B Zaghlool ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Serum Proteins ◽  
Serum Levels ◽  
The Body ◽  
Incident Type ◽  
Complex Processes ◽  
Proteomics Approach ◽  
Independent Case

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.

scholarly journals Circulating protein signatures and causal candidates for type 2 diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Valborg Gudmundsdottir ◽  
Shaza B Zaghlool ◽  
Valur Emilsson ◽  
Thor Aspelund ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Serum Proteins ◽  
Serum Levels ◽  
The Body ◽  
Incident Type ◽  
Complex Processes ◽  
Proteomics Approach ◽  
Independent Case

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.

Vitamin K Insufficiency in an India Population: A Pilot Study (Preprint)

2021 ◽  
Author(s):  
Sidney Stohs ◽  
Ashok DB Vaidya ◽  
Jayesh Sheth ◽  
Shashank Jadhav ◽  
Umakant Mahale ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin K ◽  
Serum Levels ◽  
Vitamin K2 ◽  
The Body ◽  
Coagulation Cascade ◽  
Dietary Intakes ◽  
Fluorescence Detector ◽  
Geographical Regions

BACKGROUND The fat-soluble K vitamins K1 and K2 are well recognized and exert an essential biological role in the blood coagulation cascade. However, vitamin K is less known for its non-essential roles in participating in the growing family of vitamin K-dependent proteins that promote various functions of organs and systems in the body, sustaining health and preventing disease. These less well-known actions depend on the availability of vitamin K for non-essential multi-tasking functions. This fat-soluble vitamin is available predominantly through selective dietary intakes, and its presence is absent or very low in many diets. The lack of vitamin K for non-essential biological functions exemplifies vitamin/nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency. OBJECTIVE The current epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and its content in staple Indian foods. METHODS Serum levels of vitamin K1 and vitamin K2 in the form of MK-7 were assessed by high-performance liquid chromatography (HPLC) coupled with a fluorescence detector in 209 patients with Type 2 diabetes and 50 healthy volunteers and in common, staple foods in India. RESULTS The results indicate that in comparison to populations with high and low serum levels in various geographical regions, the sample of India population of apparently healthy individuals and Type 2 diabetes patients showed low (insufficient) levels of vitamin K2 (menaquinone-7). The staple, commonly consumed Indian foods that were tested in the study showed undetectable content of vitamin K2. CONCLUSIONS The general population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements, with emphasis on patients with diabetes, elevated blood pressure, a harbinger of cardiovascular disease, and compromised immune systems. The results can be extrapolated world-wide. CLINICALTRIAL CTRI 2019/05/014246

IS THERE A CONNECTION BETWEEN PYLORIC HELICOBACTER INFECTION AND METABOLIC DISORDERS?

2019 ◽  
Vol 25 (4) ◽  
pp. 210-214
Author(s):  
Serafima V. German ◽  
A. V Modestova ◽  
I. E Zykova ◽  
I. G Nikitin
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Disorders ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Overweight And Obesity ◽  
The Body ◽  
Lipoprotein Cholesterol ◽  
High Prevalence

Relevance. There are numerous publications of foreign authors about relationship between Pyloric Helicobacter (H. p.) infection with several gastroduodenal diseases, including metabolic disorders. Russia is one of the countries with high prevalence of H. p. infection and metabolic disorders. Determining their relationship is important for both prevention and treatment of metabolic disorders. Purpose - study the possibility of relationship between H. p. infection and type 2 diabetes, dyslipidemia, overweight and obesity. Methods and materials. The study included 1487 working residents of Moscow and the Moscow region, 931 men and 556 women, aged 21 to 77 years (median - 46). H. p. infection was diagnosed by detecting antibodies to IgG bacteria in the blood serum. In 698 infected individuals, the presence of a CagA strain, a marker of virulence of the bacterium, was studied using ELISA. Serum levels of basal glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides were studied, and the body mass index was determined. Results. Infection was discovered in 1348 people (90.6%), CagA positive - 392 (56.2%). Type 2 diabetes was diagnosed in 77 people, 74 - H. p. positive (5.5% ), and 3 - H. p. negative (2.1%). CagA was studied for 31 persons with diabetes. CagA-positive bacterial strain was determined in 22 cases out of 31 (70.1%, p 0,05, by criterion χ²). Among H. p. positive, overweight was registered in 884 cases (65.6%), in H. p. negative - in 74 cases (53.2%) (p

scholarly journals Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Anna M. L. Coenen-Stass ◽  
Graham McClorey ◽  
Raquel Manzano ◽  
Corinne A. Betts ◽  
Alison Blain ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Serum Proteins ◽  
Exon Skipping ◽  
Serum Levels ◽  
Wild Type ◽  
Protein Biomarkers ◽  
Novel Therapy ◽  
Serum Proteomics ◽  
Dystrophin Protein

Abstract There is currently an urgent need for biomarkers that can be used to monitor the efficacy of experimental therapies for Duchenne Muscular Dystrophy (DMD) in clinical trials. Identification of novel protein biomarkers has been limited due to the massive complexity of the serum proteome and the presence of a small number of very highly abundant proteins. Here we have utilised an aptamer-based proteomics approach to profile 1,129 proteins in the serum of wild-type and mdx (dystrophin deficient) mice. The serum levels of 96 proteins were found to be significantly altered (P < 0.001, q < 0.01) in mdx mice. Additionally, systemic treatment with a peptide-antisense oligonucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression caused many of the differentially abundant serum proteins to be restored towards wild-type levels. Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples. Furthermore, ADAMTS5 was found to be significantly elevated in human DMD patient serum. This study has identified multiple novel, therapy-responsive protein biomarkers in the serum of the mdx mouse with potential utility in DMD patients.

Vitamin D Supplementation and Serum Levels of Magne-sium and Selenium in Type 2 Diabetes Mellitus Patients: Gender Dimorphic Changes

2014 ◽  
Vol 84 (1-2) ◽  
pp. 27-34 ◽  
Author(s):  
Nasser M. Al-Daghri ◽  
Khalid M. Alkharfy ◽  
Nasiruddin Khan ◽  
Hanan A. Alfawaz ◽  
Abdulrahman S. Al-Ajlan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Serum Selenium ◽  
Dependent Manner

The aim of our study was to evaluate the effects of vitamin D supplementation on circulating levels of magnesium and selenium in patients with type 2 diabetes mellitus (T2DM). A total of 126 adult Saudi patients (55 men and 71 women, mean age 53.6 ± 10.7 years) with controlled T2DM were randomly recruited for the study. All subjects were given vitamin D3 tablets (2000 IU/day) for six months. Follow-up mean concentrations of serum 25-hydroxyvitamin D [25-(OH) vitamin D] significantly increased in both men (34.1 ± 12.4 to 57.8 ± 17.0 nmol/L) and women (35.7 ± 13.5 to 60.1 ± 18.5 nmol/L, p < 0.001), while levels of parathyroid hormone (PTH) decreased significantly in both men (1.6 ± 0.17 to 0.96 ± 0.10 pmol/L, p = 0.003) and women (1.6 ± 0.17 to 1.0 ± 0.14 pmol/L, p = 0.02). In addition, there was a significant increase in serum levels of selenium and magnesium in men and women (p-values < 0.001 and 0.04, respectively) after follow-up. In women, a significant correlation was observed between delta change (variables at six months-variable at baseline) of serum magnesium versus high-density lipoprotein (HDL)-cholesterol (r = 0.36, p = 0.006) and fasting glucose (r = - 0.33, p = 0.01). In men, there was a significant correlation between serum selenium and triglycerides (r = 0.32, p = 0.04). Vitamin D supplementation improves serum concentrations of magnesium and selenium in a gender-dependent manner, which in turn could affect several cardiometabolic parameters such as glucose and lipids.

Serum Ferritin Status of Patients with Type 2 DM Attending OPD of BIRDEM General Hospital

2020 ◽  
Vol 11 (1) ◽  
pp. 7-10
Author(s):  
Khadiza Begum ◽  
Fahmida Islam ◽  
Farjana Aktar ◽  
Murshida Aziz ◽  
Tohfa E Ayub Tahiya
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Serum Ferritin ◽  
Study Groups ◽  
Acute Phase Reactant ◽  
The Body ◽  
Iron Stores ◽  
Normal Healthy Individual ◽  
Diabetes Patients

Background: In recent times much is talked about of serum ferritin, an acute phase reactant a marker of iron stores in the body and its association with diabetes mellitus. Studies implicate that increased body iron stores and subclinical hemochromatosis has been associated with the development of glucose intolerance, type 2 diabetes and its micro as well as macrovascular complications. Material & Methods: This study was carried out to examine and to observe for any relationship between serum ferritin with Type 2 diabetes mellitus. Our study populations were included 163. Among them 81 type 2 diabetes patients as a case (M=49,F=32, mean 44.68 age in years)and 82 normal healthy individual as a control ( M=35, F=47 , mean 34.71 in years). Results: Majority were healthy outpatients who had come for regular checkup and were matched with controls. Serum ferritin and FBS were estimated and other investigations. Results showed that although Serum ferritin was in the normal range value it was increased in type 2 diabetes patients than in controls and was statistically significant, we did get a positive correlation with duration of diabetes. It can be concluded that there were positive associations between serum ferritin and FBG, age, sex among study groups. Conclusion: In conclusion our study shows that there is significant correlation between increased serum ferritin in diabetes compared to individuals with normal blood sugars in this part and hyper ferritinemia may be one of the causes for development of insulin resistance before overt diabetes. Anwer Khan Modern Medical College Journal Vol. 11, No. 1: Jan 2020, P 7-10

scholarly journals Reduction of estimated fluid volumes following initiation of empagliflozin in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the placebo-controlled, randomized EMBLEM trial

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Michio Shimabukuro ◽  
Hiroki Teragawa ◽  
Yosuke Okada ◽  
Toshinari Takamura ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Repeated Measures ◽  
Medical Information ◽  
Controlled Trial ◽  
Extracellular Volume ◽  
Cardiovascular Outcomes ◽  
Fluid Volume ◽  
The Body

Abstract Backgrounds/Aim Sodium glucose co-transporter 2 inhibitors promote osmotic/natriuretic diuresis and reduce excess fluid volume, and this improves cardiovascular outcomes, including hospitalization for heart failure. We sought to assess the effect of empagliflozin on estimated fluid volumes in patients with type 2 diabetes and cardiovascular disease (CVD). Methods The study was a post-hoc analysis of the EMBLEM trial (UMIN000024502), an investigator-initiated, multi-center, placebo-controlled, double-blinded, randomized-controlled trial designed primarily to evaluate the effect of 24 weeks of empagliflozin treatment on vascular endothelial function in patients with type 2 diabetes and established CVD. The analysis compared serial changes between empagliflozin (10 mg once daily, n = 52) and placebo (n = 53) in estimated plasma volume (ePV), calculated by the Straus formula and estimated the extracellular volume (eEV), determined by the body surface area, measured at baseline and 4, 12, and 24 weeks after initiation of treatment. Correlations were examined between the changes from baseline to week 24 in each estimated fluid volume parameter and several clinical variables of interest, including N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Results In an analysis using mixed-effects models for repeated measures, relative to placebo empagliflozin reduced ePV by − 2.23% (95% CI − 5.72 to 1.25) at week 4, − 8.07% (− 12.76 to − 3.37) at week 12, and − 5.60% (− 9.87 to − 1.32) at week 24; eEV by − 70.3 mL (95% CI − 136.8 to − 3.8) at week 4, − 135.9 mL (− 209.6 to − 62.3) at week 12, and − 144.4 mL (− 226.3 to − 62.4) at week 24. The effect of empagliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in log-transformed NT-proBNP was positively correlated with change in ePV (r = 0.351, p = 0.015), but not with change in eEV. Conclusions Our data demonstrated that initiation of empagliflozin treatment substantially reduced estimated fluid volume parameters in patients with type 2 diabetes and CVD, and that this effect was maintained for 24 weeks. Given the early beneficial effect of empagliflozin on cardiovascular outcomes seen in similar patient populations, our findings provide an important insight into the key mechanisms underlying the clinical benefit of the drug. Trial registration University Medical Information Network Clinical Trial Registry, number 000024502

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