ADIPONECTINE AND DIABETES
~JClinical Endocrinol Metab.2008 27,(Epub ahead of print.)
ABSTRACT
Adiponectine is protein produced by and secreted exclusively by adipocytes. It regulates the metabolism of lipids and glucose. It influences the body response to insulin. It has antiflammatory action on the cells lining the walls of the blood vessels. Increase in Adiponectine decreases risks of heart attacks. The article looks t\at the tests and the conclusion drawn by various researching bodies.
INTRODUCTION
Decreased, Adiponectine levels particularly the heavy molecular weight (HMW) is not only an early indicator of gestation diabetes(GDM) with a potential to progressive diabetes mellitus. higher levels of Adiponectine particularly HMW is associated with type1 diabetes mellitus(T1DM) , and type 2 diabetes mellitus(T2DM) though relation was found between severity of retinopathy and nephropathy but not neuropathy.
Diabetes mellitus:
Diabetes Mellitus (DM) Better known just as "diabetes" -- a chronic disease associated with abnormally high levels of the sugar glucose in the blood. Diabetes is due to one of two mechanisms:(1) Inadequate production of insulin (which is made by the pancreas and lowers blood glucose) or(2) Inadequate sensitivity of cells to the action of insulin.The two main types of diabetes correspond to these two mechanisms and are called insulin dependent (type 1) and non-insulin dependent (type 2) diabetes.. Gestation diabetes mellitus(GDM) is a condition seen in women during pregnancy where there is frank hyperglycemia and glycosuria.
Adiponectine:
Orthologs

Human
Mouse
Entrez
9370
11450
Ensembl
ENSG00000181092
ENSMUSG00000022878
Uniprot
Q15848
Q6GTX4
Refseq
NM_004797 (mRNA)NP_004788 (protein)
NM_009605 (mRNA)NP_033735 (protein)
Location
Chr 3: 188.04 - 188.06 Mb
Chr 16: 23.06 - 23.07 Mb
Symbols--ADIPOQ,ACDC,ACrP30,APM-1 APM1,GBP28,
History -- Adiponectine first characterized in mice as a transcript the human analogue was found in adipose and was found to decrease obesity despite of being created by the adipose cell. The cell was localized to chromosome 3p27 region affecting susceptibility to T2DM and obesity.
Function:
It regulates the metabolism of lipids and glucose.
It influences the body response to insulin
It has antiflammatory action on the cells lining the walls of the blood vessel
Increase Adiponectine decrease risks of heart attacks.
Association of diabetes mellitus and Adiponectine
T1DM is associated with higher levels than healthy subjects. Increase is associated with HMW sub form and is unaffected by gender and diabetic kidney disease.—
T2DM shows higher HMW Adiponectine this is also associated with renal insufficiency
A correlation to HMW Adiponectine was found between severity of retinopathy and nephropathy but not with neuropathy in T2DM
HMW Adiponectine was an independent risk factor for progressive T2DM particularly the HMW isoform
HMW Adiponectine is decreased in GDM deficiency of HMW may indicate an early event in natural T2DM.
RESEARCH
Adiponectine and T1DM
In type 1 diabetes there is no insulin or not enough of it.
T1DM is per se associated with higher Adiponectine level as compared to healthy individuals—a study conducted by Tarnow I,Rosssing P, Parving HH, Flybjerg A. at the medical research laboratories Clinical Institute,Aaarlus university hospital, steno diabetes center Gentofle, department. Of endocrinology, Righshospital University of Copenhagen
Aim: to investigate the distribution of the three molecular subforms of Adiponectine in well characterized group of T1DM with varying degrees of nephropathy and healthy control patients.
The presentation of Adiponectine was seen in 3 isoform.
High molecular weight(HMW) which was a primary active form
Medium molecular weight (MMW) a subforms
Low molecular weight(LMW) an unresolved molecular form
Study-207 patients were studied. The patient distribution was thus.
58 with normal albuminuria
46 with micro albuminuria
46 with macro albuminuria
57 matched control.
A fast protein liquid chromatography was done and results measured with immunoflorometric assay. the results observed where:
The relative concentration of total Adiponectine and all subforms were higher in T1DM that healthy controls.
Relative fractions when up regulated where.
P<0.001 in HMW subforms
P<0.001 in MMW subforms
P<0.05 in LMW subforms.
Levels of total and HMW were unaffected by nephropathy status defined by albumin excretion rate
Unaffected by gender
Unaffected by kidney; disease.
ADIPONECTIN AND T2DM

In type 2 diabetes, there is generally enough insulin but the cells upon it should act are not normally sensitive to its action
The serum HMW Adiponectin concentrations are higher in T2DM with nephropathy and lese levels are also associated with renal insufficiency---is the conclusion drawn by a study conducted by Komba H, Igaki N, Goto S, Yokota K, Doi H, Take moto T, Kohmo , Hirosue Y at the department of internal medicine Takasago Municipal hospital, Japan(hkomba@med.kobe-u.ac.jp )
Aim: was to study if the HMW complex of Adiponectin is associated with renal insufficiency in T2DM
Method: a total of 179 T2DM patients were selected from the outpatient. These patients where then divided to 4 groups depending on the albumin: creatine ratio (n).
Normal albuminuria n=86
Micro albuminuria n=44
Macro albuminuria n= 23
Hemodialysis n=26
This was then specifically assayed for HMW Adiponectin with a commercially available enzyme-linked immunosorbent assay kit.
Results:
Patient condition
Adiponectin level microgms/ml
hemodialysis
17.1+/-8.2
Macroalbuminuria
14.3+/-8.7
Microalbuminuria
10.8+/-7.0
Glomerular filtration rate related negatively with Adiponectin concentrations (r=0.42,p<0’001) in normalalbuminuria, microalbuminuria, and macroalbuminuria when univariate linear regression analysis was done.
pioglitazone therapy, gender differences and systolic blood pressure were independently associated with associated with HMW Adiponectin levels when multiple stepwise regression analysis was disclosed.
With reference to retinopathy and nephropathy in T2DM total Adiponectin and HMW Adiponectin are positively correlated, but not with neuropathy.
~are the results of the study conducted by Kato K, Osawa H, Ochi M, Kusunoki Y, Ebisui O, Ohno K, Ohashi J, ShimizuI, Fuiji Y, Tanimoto M, Makino H of Ehime Prefectural Hospital, Ehime Japan on serum total and high molecular weight Adiponectin levels and correlation with severity of diabetic retinopathy and nephropathy.
Aim: was to determine the relation between serum total or HMW Adiponectin and diabetic microangiopathy.
As Adiponectin is secreted by adipocytes and it improves insulin sensitivity its high molecular weight isoform should be more effective.
Design
Number of patients analyzed 198
Criteria – T2DM patients whose fasting serum samples were available
ELISA(enzyme-linked immunosorbent assay) was used to measure serum total and HMW Adiponectin.
Results:
Increased total serum Adiponectin was seen both in retinopathy and nephropathy.
Serum Adiponectin level in Retinopathy
Mg/l
P<0.004
Serum Adiponectin level in nephropathy
Mg/l
P<0.001
Mean+/-none
Stage I- 7,0+/-0.3
6.9+/- simple
stageII ,7.7+/-0.5
8.3+/-1.0 preproliferate
stageIII 9.5+/-0.9
8.4+/-0.8 proliferative
Stage IV 16+/-4.5
12+/-1.1


Increased HMW Adiponectin was seen both in retinopathy and nephropathy.
Serum HMW Level in retinopathy
Mg/l
P=0.005
Serum HMW level in nephropathy
Mg/l
P=0.007
4.6+/ 0.5
3.7+/0.2
4.6+/0.6
4.3+/0.4
8.4+/0.8
5.3+/0.7

7.9+/2.2

Neuropathy was correlated to neither total Adiponectin nor HMW Adiponectin.
HMW ; total Adiponectin ratio did not correlate to microangiopathy
In retinopathy and nephropathy stage total Adiponectin and HMW Adiponectin were independent factor.
Retinopathy
P=
Nephropathy
P=
0.0055
0.0003
0.0027
0.0018

Other factors that effect independently are age, gender, body mass index, duration of T2DM .these are even more important when serum creatinine, and hypertension are added.
Thiazolidinediones do not affect.

Decreased total Adiponectin is an independent risk factor for the progression to T2DM and HMW is more closely associated
~is the conclusion drawn by Nakashima R,Kamei N, Yamane K, Nakanishi S, Nakashima A, Kohno N.—dept of molecular and internal medicine, graduate school of biomedical sciences, Hiroshima University, 1-2-3 Kauum I Minami_ku, hishoshima city 734-8552 Japan.
Aim: of the study was to assess whether decreased total and HMW Adiponectine are independent risk factors for the development of T2DM
Design.
Japanese-American patients of Hawaii- Los Angels -Hiroshima were enrolled between 1992-2002.
Average follow up was 5.4yrs.
Study demo graph 321 men 445 women
Observation:
112 developed into T2DM had decreased total Adiponectin and HMW Adiponectin level(P<0.001)
In a Cox proportional hazards model, both decreased Adiponectin and HMW Adiponectin were independent factors for progressive diabetic risk after tabulation of waist hip ratio, age, gender, BMI homeostasis and glucose tolerance tests/
Hazards ration
Total 0.600 P=0.018
HMW 0.614 P=0.001
Lowest vs. highest dividing teritiles of Adiponectin and hazard ration were
Total 1,787 (95% confidence interval,1.006-3.173)
HMW 2.493(95% confidence interval, 1.342 – 4.632)
Gestation diabetes mellitus(GDM)
Deficiency of serum HMW Adiponectin may be an early event in the natural history of T2DM--This is the conclusion drawn by Retnakumar R, Connelly PW, Maguire G, Sermer M, Zinman B, Hanner A,- of the division of Endocrinology university of Toronto Canada rretnakumar@mtsinai.on.ca after their study high molecular weight Adiponectin in gestational diabetes. and implication for the patho-physiology of T2DM.
AIM: to determine if low serum levels of HMW was a feature of GDM
Antidiabetic activity of Adiponectin has been conclusive by various recent studies.
Circulatory levels of the HMW were found low in T2DM patients so it could be mediating the antidiabetic action.
GDM identifies a population of women who are at high risk in the future for T2DM.
The study focused to correlate them.
Method:
A total of 121 women were studied at Oral Glucose Tolerance Test (OGTT)
Based on the OGTT 40 women with GDM and 80 women were studied.
The serum was then immunoassayed and measured for HMW isoforms.
Results:
Median HMW was lower in women with GDM (3.5mircogm/ml) as compared to women without (5.5 microgm/ml)(p<0.0001)
After adjusting the covariates the HMW Adiponectin was still lower in GDM women 3.6 vs. 5.3 microgm/l, p<0.001
Insulin sensitivity IS(OGTT) was directly proportional to HMW Adiponectin in the blood r=0.38, p<0.0001
Pancreatic B-cells function is directly proportional to the serum HMW Adiponectin. The insulin sensitivity index shows r = 0.33,p<0.0002
Blood glucose levels including area- under the glucose curve during OGTT was inversely proportional r=0.31,p=0.0007
Multiple linear analysis shows HMW Adiponectin is an independent determinant of AUC (glucose),IS(OGTT) ISSI respectively.



CONCLUSION

Adiponectine is protein produced by and secreted exclusively by adipocytes. It regulates the metabolism of lipids and glucose. It influences the body response to insulin. It has antiflammatory action on the cells lining the walls of the blood vessels. Increase in Adiponectine decreases risks of heart attacks.
REFERENCES
Medicine Net.com
Wikipedia