Relation Between Plasma Vitamin K2 and Glycemic Control and Metabolic Parameters in Type 2 Diabetic Patients.
Condition: Vitamin k2 in Type 2 DM
Study type: Observational [Patient Registry]

Summary: 
      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: 
      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 :

        1. Relation between plasma vitamin K2 and glycemic control in Type 2 diabetic patients.

        2. Relation between plasma vitamin K2 and metabolic parameters in Type 2 diabetic patients.

      Secondary outcome parameters :

        1. Relation between plasma vitamin K2 and disease duration in Type 2 diabetic patients.

        2. Relation between plasma vitamin K2 and forum of antidiabetic treatment in Type 2
           diabetic patients.
    

Intervention name(s): blood sampling
Intervention type(s): Diagnostic Test
Intervention description(s): blood sampling from peripheral vein
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        - 90 subjects, 60 subjects with type 2 diabetes divided into 30 with uncontrolled type 2 DM
        patients (group I) and 30 controlled type 2 DM patients (group II) and 30 healthy subjects
        as a control group (group III).
      
Biospecimen description: 
      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.).
    
Keywords: vitamin k2; type 2 DM; glycemic control