Relation Between Plasma Vitamin K2 and Glycemic Control and Metabolic Parameters in Type 2 Diabetic Patients.

Study Overview
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Brief Summary
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Background and Rationale: The agents inducing type 2 diabetes are yet to be clarified. Current studies show that several genetic and environmental parameters are associated with type 2 diabetes . Vitamin K is emerging as an important micronutrient for its beneficial role in improving insulin sensitivity and glucose metabolism and reducing the risk of type 2 diabetes (T2 D) . Studies demonstrated the lowest prevalence of Metabolic syndrome and its five components among individuals with the highest phylloquinone intake. Objectives : The aim of our study was to evaluate the relation between plasma vitamin K2 and uncontrolled Type 2 diabetic patients.

Detailed Description
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The frequency of diabetes mellitus is increasing globally and it is expected that this latent disorder will affect 300 million by 2025. Type 2 diabetes mellitus (T2DM) is a metabolic and chronic disease characterized by hyperglycemia representing the major cause of various micro and macrovascular complications The agents inducing type 2 diabetes are yet to be clarified; however, it has been suggested that diabetes is an immune-dependent disease . Current studies show that several genetic and environmental parameters are associated with type 2 diabetes . Vitamin K is a fat soluble vitamin . Two vitamin K- dependent-proteins, osteocalcin and matrix gamma carboxy glutamate (Gla ) protein, present in skeletal and vascular system , vitamin K exists mainly in two biologically active forms: vitamin K1 (also known as phylloquinone) and vitamin K2 (also known as menaquinone) . According to current studies, vitamin K2 has a wider range of effects besides coagulation and functioning as a cofactor for γ--glutamate carboxylase (GGCX ) . The effect on bone is to prevent and treat osteoporosis and the effect on the cardiovascular system is to prevent and treat vascular calcification. study by Sogabe N et al ., reported an important role of vitamin K in the regulation of dyslipidemia and vitamin K2 treatment delayed the progression of atherosclerotic plaque formation, intima-thickening, and pulmonary atherosclerosis. study by Dam V et al ., demonstrated the lowest prevalence of Metabolic syndrome and its five components among individuals with the highest phylloquinone intake. Among the five components of Metabolic syndrome , an increase in dietary phylloquinone intake was significantly associated with a decrease in the prevalence of elevated blood pressure and reduced HDL cholesterol . Vitamin K is emerging as an important micronutrient for its beneficial role in improving insulin sensitivity and glucose metabolism and reducing the risk of type 2 diabetes (T2 D) . The effect of vitamin K supplementation on insulin sensitivity and glycemic status has been reviewed by study by Manna et al . They integrated currently available evidences and proposed that both vitamin K1 and vitamin K2 supplementation were beneficial to the reduced risk of T2DM. This also suggests a beneficial role of vitamin K2 on insulin sensitivity and glucose metabolism. studies by (Yan Li et al ., 2018 - Prasenjit Manna And Jatin Kalita , 2016 ) provided an overview of the currently available studies to assess the effect of vitamin K2 supplementation on insulin sensitivity, glycaemic control and reviewed the underlying mechanisms. Overall, carboxylation of vitamin K-dependent protein osteocalcin, anti-inflammatory property, regulation of adipokine levels and lipid-lowering effect were three mechanisms underlying vitamin K2 reduced risk of T2DM and vitamin K2 had a better effect than vitamin K1 on T2DM. The interpretation of this review will increase comprehension of the development of a therapeutic strategy to prevent and treat T2DM. Objectives: The aim of our study was to evaluate the relation between plasma vitamin K2 and uncontrolled Type 2 diabetic patients. Patients and methods: A case control study including 90 subjects aged 20 to 65 years, 30 healthy subjects as a control group and 60 patients with type 2 DM .Patients will be collected from the endocrinology outpatient clinic, Kasr El Ainy, Cairo university. Patients will be divided into 3 groups, (group I) 30 patients with uncontrolled type 2 DM, (group II) 30 controlled type 2 DM and (group III) 30 non DM as control group. All subjects will be consented and then subjected to full history taking emphasizing on the age , duration of diabetes mellitus and its treatment and full clinical examination including blood pressure measurement, weight, height, BMI (kg/m2) and waist circumference . Laboratory investigations : in the form of fasting blood glucose (FBG), 2 hr postprandial blood glucose (2 hr -PPG), fasting lipids {total cholesterol (TC), triglycerides (TAG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C)}, glycosylated hemoglobin (Hb A1c) and Vitamin K 2 levels will be assessed . laboratory methodology: Two milliliters of peripheral venous blood were collected after 8 hour fasting from each participant. The measurement of Vit K2 was achieved by commercial ELISA kit based on its protocol (Glory science Co., Ltd: U.S.A.). -Study outcomes: Primary outcomes : Relation between plasma vitamin K2 and glycemic control in Type 2 diabetic patients. Relation between plasma vitamin K2 and metabolic parameters in Type 2 diabetic patients. Secondary outcome parameters : Relation between plasma vitamin K2 and disease duration in Type 2 diabetic patients. Relation between plasma vitamin K2 and forum of antidiabetic treatment in Type 2 diabetic patients.

Official Title
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Relation Between Plasma Vitamin K2 and Glycemic Control and Metabolic Parameters in Type 2 Diabetic Patients.

Conditions
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Vitamin k2 in Type 2 DM

Intervention / Treatment
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* Diagnostic Test: blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 20 to 65 years old with controlled and uncontrolled DM . Exclusion Criteria: • Subjects with hepatic , gastrointestinal or cardiovascular disease Subjects with osteoporosis. Subjects using vitamin supplements containing vitamin K. Subjects using oral anticoagulants.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| I<br>30 with uncontrolled type 2 DM patients | Diagnostic Test: blood sampling<br>* blood sampling from peripheral vein<br>|
| II<br>30 controlled type 2 DM patients | Diagnostic Test: blood sampling<br>* blood sampling from peripheral vein<br>|
| III<br>30 healthy subjects as a control group | Diagnostic Test: blood sampling<br>* blood sampling from peripheral vein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma vitamin k2 level | Plasma vitamin K2 level as ng/ml in type 2 diabetes patients | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin k2, type 2 DM, glycemic control