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Study of serum adiponectin levels in type 2 diabetic individuals & its correlation with BMI and waist hip ratio.

ABBREVIATION: BMI- Body Mass Index, WHR--Waist Hip Ratio.

INTRODUCTION: Adipose tissue is not simply an inert storage depot for lipids but an important endocrine organ that plays a key role in integration of endocrine, metabolic and inflammatory signals for control of energy homeostasis. The Adipocytes secrete many hormones called Adipocytokines which include(1):

1. Leptin.

2. Resistin.

3. Acylation Stimulating Protein.

4. Adiponectin.

Studies have shown that Adiponectin plays an important part in increasing insulin sensitivity and it has anti-atherogenic and anti-inflammatory properties. Low Adiponectin levels are seen in individuals with Type 2 DM who have insulin resistance, obesity, CAD, dyslipidemia indicating that this novel protein may be an important marker of the Metabolic syndrome.(1)

OBJECTIVES:

a) To assess the level of Serum Adiponectin in male and female controls and to correlate with study group (NIDDM individuals)

b) To assess the levels of Serum Adiponectin in Obese individuals.

METHODOLOGY: The study was carried out in seventy seven subjects who included 6 healthy male controls and 6 healthy female controls, 30 diabetic males and 35 diabetic female individuals.

The healthy control both male and female of age around 40 to 50 years (+5 years) was selected with no history of diabetes or hypertension.

The study group was selected of the same age as the control group from the Outpatient Department, diabetology unit of our Medical College.

5 ml of fasting venous blood was drawn and used to measure the parameters like adiponectin, Glucose. 2hrs Postprandial Glucose was also measured.

Individuals Height, Weight and Waist Hip Ratio were measured and BMI was calculated with the formula--Weight in Kg/ Height in [m.sup.2].

Estimation of serum Adiponectin with Human Adiponectin/Acrp 30 Immunoassay by Solidphase ELISA which employed -Quantitative sandwich enzyme immunoassay technique/2) Plasma Glucose by GOD/POD method.

OBSERVATIONS AND RESULT:

The result of the study shows that:

1. Comparison of Serum Adiponectin levels in Type 2 DM subjects and healthy controls show Statistically significant decrease in serum Adiponectin level in Type II DM (P value < 0.05). See Table (1)

a. Male controls 9.6+ 1.46 [micro]g / ml and male diabetics 4.14 + 3.10 [micro]g/ml (P value < 0.05.)

Female controls 10.63 +1.64 [micro]g/ml and female diabetics 5.47+ 2.64 [micro]g /ml (P value < 0.05.)

b. Males have low levels of Adiponectin when compared to females which is not statistically significant (P value > 0.05.).

c. Male control 9.6+ 1.46 [micro]g / ml. Female control 10.63+1.64 [micro]g/ml. This can be explained by the fact that androgens like testosterone inhibit the secretion of adiponectin from 3T3L1 adipocytes. (27,28,29)

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2. In this study comparison between serum Adiponectin levels in male Diabetic individuals and BMI, WHR (Waist Hip Ratio) shows negative correlation. The negative correlation between BMI in males is highly statistically significant. (P -.516, <0.01), WHR correlation value 0.018 (not significant). See Table2.

3. In female diabetics correlation between serum Adiponectin levels and BMI, WHR show a negative correlation between BMI and Adiponectin levels correlation value is -.090(not significant). Studies show there is a negative correlation between WHR and Adiponectin levels in Female diabetics but it is not significant. WHR correlation value is P -.317(not significant)

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DISCUSSION: The adipocytes secrete a variety of bioactive proteins into the circulation called adipocytokines which include:

1. Leptin.

2. TNF--[alpha].

3. Plasminogen Activator Inhibitor Type I.

4. Adipsin.

5. Resistin.

6. Acylation Stimulating Protein.

7. Adiponectin.

Adiponectin was identified in 1995 (3) through human CDNA project targeting on adipose tissue by schrerer et al. (4) It also named as Adipocyte complement related protein of 30 kd (Acrp 30) Adipo Q, Gelatin Binding protein of 28kd (GBP 28). (5) It is a hydrophilic protein 244 amino acids.(6),(7)(8) It is the gene product of adipose tissue, most abundant gene transcript 1 (apM1gene).

It is a collagen like protein with a stretch of 22 collagen (Gly-X-Y) that is exclusively synthesized in White adipose tissue during adipocyte differentiation and circulates at a relatively high ([micro]g/ml) concentration in the serum. (1) The crystal structure of Adiponectin reveals an unexpected homology to TNF family of cytokines. (9) Adiponectin has Trimer, Hexamer and Multimer forms. It has 4 domains.

[ILLUSTRATION OMITTED]

Half-life of Adiponectin is 5-6 hours and kidney seems to play important role in its biodegradation and elimination.

Site of Action: Adiponectin acts on peripheral tissues like liver, skeletal muscle and vascular tissue to exert its effects. (Fig 3.4)

[ILLUSTRATION OMITTED]

MECHANISM OF ACTION:

1. It increases 5' AMP kinase Activity: Which leads to suppression of Gluconeogenesis, promotion of glucose uptake in skeletal muscles, inhibit fatty acid and sterol synthesis, increase fatty acid oxidation and inhibit lipolysis. (11)

2. Enhance insulin stimulated receptor Tyrosine Phosphorylation (11)(12): Increase basal glucose uptake and also increase whole body insulin sensitivity.

3. Peroxisome proliferator activator regulator gamma (PPAR [gamma]) Mediation: It enhances the promoter activity of adiponectin and increase the transcription of adiponectin in adipose tissue. PPAR[gamma] also increase the number of mature adipocytes which respond to enhancing effects of insulin on glucose disposal (13,14,15) and thus increase glucose tolerance and insulin sensitivity

4. Liver receptor homolog-1(LRH-1) Mediated: LRHRE is seen on the adiponectin promoter (16) and functions as a competence factor by enhancing transactivation of PPAR/RXR in Adiponectin promoter.

5. Increase Fatty acid oxidation: Peripheral application of Adiponectin attenuated body weight gain and decreased visceral adipocity by increasing the expression of Uncoupler protein 1, 2, 3.

METABOLIC ROLE OF ADIPONECTIN:

I. Insulin sensitivity / Carbohydrate Metabolism:

1. A strong correlation between Adiponectin and systemic insulin sensitivity has been well established both in vivo and in vitro in humans. (1)

2. The plasma Adiponectin concentration is decreased in insulin resistant states such as obesity and type II DM. (17,18,19,20.21)

3. In Obesity there is an increase in TNF-[alpha] level which leads to insulin resistance. (21) Increased levels of TNF-[alpha] decreased expression of Adiponectin mRNA in adipose tissue by suppressing the promoter region of Adiponectin.(22)

II. Adiponectin and Lipid Metabolism:

1. Decreased Adiponectin levels are associated with increased in small dense LDL, Apo B, TGL.

2. Adiponectin levels correlates positively with HDL Cholesterol. (23,24)

3. Adiponectin decreases the plasma Free Fatty Acid levels and increases [beta] oxidation of fatty acids.

III. Adiponectin as an Anti-inflammatory Agent:

1. Studies have proved that chronic inflammation plays a role in the pathogenesis of Type II DM, Obesity and Insulin Resistance. (25)

2. Adiponectin inhibits the expression of TNF-[alpha], Soluble Intra Cellular Adhesion molecule (SICAM), (26) Soluble Vascular Adhesion Molecule (SVCAM-1) and SE -selectin acting via Nuclear Factor--[sub.k] [beta] signalling pathway which is crucial to inflammatory response. (27)

IV. Adiponectin As an Anti- Atherosclerotic Agent:

1. Experiments have shown that Adiponectin has potential Anti-atherogenic properties. (28,29)

2. Adiponectin inhibits foam cell formation from macrophages, suppress proliferation and migration of vascular smooth muscle cells by decreasing the effect of various growth factors.

V. Obesity, BMI, WHR and Adiponectin:

1. Studies conducted by Masaki et al shows a negative correlation between Adiponectin, WHR and BMI. (30) There is a strong negative relationship between Adiponectin and visceral fat than that of subcutaneous fat because Adiponectin is produced by the visceral fat. This paradoxical decrease in obesity is because less adiponectin is produced by the TGL filled visceral adipocytes which are less insulin sensitive. (31)

DOI:10.14260/jemds/2015/119

REFERENCES:

(1.) Manju Chandran, M.D., Susan A. Phillips, M.D., Theodore Ciaraldi, PHD and Robert R. Henry, M. D., Adiponectin more than just another fat cell Hormone? Diabetes care 26: 2442-2450, 2003.

(2.) Yoshimasa Aso, Ruriko Yamamoto, Sadao Wakabayashi, Toshihiko Uchida et al. Comparison of Serum High-Molecular Weight (HMW) Adiponectin With Total Adiponectin Concentrations in Type 2 Diabetic Patients With Coronary Artery Disease Using a Novel Enzyme-Linked Immunosorbent Assay to Detect HMW Adiponectin. Diabetes July 2006 vol. 55 no. 7 1954-1960.

(3.) The Funagata study Makota Daimon, Toshihide Oizumi, Tamotsu Saitoh et al Decreased serum levels of Adiponectin are a risk factor for the progression to Type 2 Diabetes in Japanese population Diabetes Care 26:2015-2020, 2003.

(4.) Scherer EP, William S, Fogliano M, Badini G: A novel serum protein parallel to ciq, produce exclusively in adipocytes. J.boil chem. 270:26746 -26749, 1995.

(5.) Nakano M, TobeT, Choi-Miura N, MasudaT, Tomita M Isolation and characterization of GBP 28, a novel gelatin binding protein purified from human plasma, J.Biochem (tokyo) 120:803-812, 1996.

(6.) Nagasaka S, Taniguchi, Aiso Y, Yatagai T, Nakamura Efffect of glimipiride on serum adiponectin level in subjects with Type 2 Diabetes Diabetes care 26:215-2216, 2003.

(7.) Katsunori Nonogaki, Hiroaki, Kumano, Yoshihiko Ootsuka, Aye takeuchi Clinical worth of Adiponectin levels in Obesity and Glycemic control of Japanese Type 2 DM patients.

(8.) Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity Alice S. Ryan; Dora M. Berman; Barbara J. Nicklas; Madhur Sinha; Ronald L. Gingerich; Grady S. Meneilly; Josephine M. Egan; Dariush Elahi.

(9.) Utpal Pajvani UB1, Du X, Combs TP, Berg AH, Rajala MW, Schulthess T Engel J, Brownlee M, Scherer PE. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity.

(10.) Bogan JS, Codirh HF., Two Compartments for Insulin-Stimulated Exocytosis in 3t3-L1 Adipocytes Defined by Endogenous Acrp30 and Glut4

(11.) Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease Claudia Menzaghi, Vincenzo Trischitta and Alessandro Doria

(12.) Xiang dong wu, Hiroyuki, Motoshima, Kalyankar Mahodeve, Timomy J. Stalker. Involvement of AMP--activated by the globular domain of Adiponectin in primary rat adipocytes Diabetes 52:1355--1363, 2003.

(13.) Coombs JP, Wagner JA, Berger J, Doebber T, Wang WJ Berg AH, Scherer PE. Induction of Adipocyte complement related protein of 30 KD by PPAR-y agonists. A potential mechanism of insulin sensitization Endocrinology 143:998-1007, 2002.

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(15.) Role of PPAR, transcriptional cofactors, and adiponectin in the regulation of nutrient metabolism, adipogenesis and insulin action: view from the chair J P Berger.

(16.) Interleukin-1 Receptor Antagonist Induction as an Additional Mechanism for Liver Receptor Homolog-1 to Negatively Regulate the Hepatic Acute Phase Response 10.1074/jbc.M608993200 Nicolas Venteclef and Philippe Delerive.

(17.) Peter J. Havel., Update on Adipocyte Hormone, Diabetes 53:S143--S151, 2004.

(18.) Hotta K, Funahashi T, Anta Y, Takahashi M, Matsuda M, Ouchi N, Maeda K Plasma conc of a novel adipose--specific protein, adiponectin in Type 2 DM Artorioscler Thromb Vasc Biol 20:1595 1599, 2000.

(19.) Weyer C, Funahashi T, Tanaka S, Hotta K, Pratlay RE Hypoadiponectinemia in obesity and Type 2 Diabetes: close association with insulin Resistance and hyper insulinemia J Clin Endocrinol Metab 86:1930--1935, 2001.

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(27.) Ouchi N1, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF- kappaB signaling through a cAMPdependent pathway. Circulation. 2000 Sep 12; 102 (11):1296-301.

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Arshiya Begum [1], Chitraa [2], K. Nirmala Devi [3]

AUTHORS:

[1.] Arshiya Begum

[2.] Chitraa

[3.] K. Nirmala Devi

PARTICULARS OF CONTRIBUTORS:

[1.] Associate Professor, Department of Biochemistry, KAPV Government Medical College, Trichy.

[2.] Professor, Department of Biochemistry, Madras Medical College, Chennai.

[3.] Professor, Department of Biochemistry, KAPV Government Medical College, Trichy.

NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:

Dr. Arshiya Begum, 16, Asif Manzil, Khaja Nagar, Trichy-620020.

E-mail: arshiyavasi@gmail.com

Date of Submission: 23/12/2014.

Date of Peer Review: 24/12/2014.

Date of Acceptance: 05/01/2015.

Date of Publishing: 14/01/2015.
Table 1: Shows P value on comparison with Diabetics and
Healthy controls

Variable                Control Male     Diabetic Male     P Value

Number                        6                30
Serum Adiponectin        9.6 + 1.46       4.14 + 3.10       <0.05
  level [micro]g /ml
FPG mg/dl               82.50 + 6.89     150.70 + 48.03     <0.05
PP mg/dl                113.80 + 6.83    199.40 + 38.22     <0.05
BMI                     22.21 + 2.61      24.08 + 4.14      >0.05
WHR                     0.833 + 0.076     0.89 + 0.071      >0.05

Variable                Control Female    Diabetic Female    P Value

Number                        6                 35
Serum Adiponectin        10.63 + 1.64       5.47 + 2.64       <0.05
  level [micro]g /ml
FPG mg/dl                83.33 + 9.30     149.70 + 43.48      <0.05
PP mg/dl                109.83 + 4.02     211.45 + 46.00      <0.05
BMI                      22.10 + 1.95      25.10 + 4.19       >0.05
WHR                      0.89 + 0.071       0.82 + 0.43       >0.05

Table 2: Shows the Correlation value between
Diabetic and healthy controls

Correlation between        Correlation       Significance
Adiponectin levels and        Value

BMI in Male Diabetics       -.516 **      Significant at 0.01
WHR in Male Diabetics         0.018         Not Significant
BMI in Female Diabetics       -.090         Not Significant
WHR in Female Diabetics       -.317         Not Significant
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Title Annotation:ORIGINAL ARTICLE
Author:Begum, Arshiya; Chitraa; Devi, K. Nirmala
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Report
Date:Jan 15, 2015
Words:2526
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