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16/12/2011

DIABESITY
( )

TON 21o
: . MD, PhD, MRCGP
/ .

-

Diabesity
(is a registered trademark of
Shape Up America!)
Available at:
http://www.shapeup.org/prof/diabesity.
Accessed April 28, 2006.

From Medscape General Medicine

Diabesity -- The Biggest


Epidemic in Human History
Paul Zimmet, AO, MD, PhD, FRACP, FRCP
Authors and Disclosures
Posted: 08/20/2007

A Letter from the President


Shape Up America!
November 18, 2011

Yesterday I learned the U.S. Congress has blocked the U.S. Department of
Agriculture's efforts to improve school meals. Thanks to lobbying by the food
industry, pizza and French fries will remain the centerpiece of many school
lunches for millions of children in America. I have nothing against such foods
on an occasional basis. But not as every day fare as they are in thousands of
U.S. schools with fast food franchises.
We now know that more than 12 million U.S. children are obese (this is defined
as the 95th percentile or higher on the pediatric BMI growth curves) and
of those children, an estimated 2 million are SEVERELY obese. Here is the
picture of severe obesity painted by a leading pediatrician in Boston:
Dr. David Ludwig, New England Journal of Medicine, Dec. 6, 2007: Fixing
school meals will not solve childhood obesity, but it is one step in the right
direction. The powerful food industry has been lobbying against any legislative
efforts that will hamper their ability to market directly to kids. To them, kids are
fair game.
Now kids are getting ill with obesity-related problems such as diabetes (type 2
diabetes which is far and away the most common type of diabetes and is the
type related to obesity), high cholesterol and sleep apnea. These diseases were
unheard of in children 25 years ago. Think about it. Put a stop to marketing to
children. People will look back on this period in our history and say, What
were they thinking?
Barbara J. Moore, PhD

Time, September 4,
2000

Newsweek, September 4,
2000

, - 2007

No Data

<10%

10%14%

15%19%

20%24%

25%29%

30%

CDC, BRFSS, 2007


,.
80%

75%

70%
60%
50%

66%

65%
56%
46%

41%

40%
23%

20%
10%

34%

31%

30%

15%

14%

15%

0%
1976 - 1980

1988 - 1994

overweight (BMI >25)

1999 - 2000

current

obese (BMI > 30)

2015 Est.
HP 2010 Goal

Sources: Flegal et al. JAMA 2002; Wang et al, Epidemiologic Reviews 2007

&

20
:
9,3%
95% : 6,2
6,2--11,4%

.
702 , 20 65

( WHR> 0.90
0,85 ) :
63 %

95% : 59,459,4-66,6 %
.
. 9 2005;
..

95%

95%

K ( /)

1.019

1.001--1.03
1.001

1.018

1.001--1.04
1.001

NS

1.66

1.16--2.38
1.16

4.96

2.56--9.53
2.56

<0.001

3.77

2.68--5.27
2.68

2.19

1.80--2.66
1.80

<0.05

2.04

1.25--3.35
1.25

2.18

1.02--4.69
1.02

NS

. N
N

5.11

3.77--7.01
3.77

3.14

2.68--3.67
2.68

<0.05

(per
(per 1 kg/m2)
kg/m2)

1.002

0.98--1.01
0.98

1.001

0.92--1.02
0.92

NS

0.91

0.80--0.98
0.80

0.84

0.61--1.14
0.61

NS

score

0.86

0.80--.92
0.80

0.81

0.75--0.84
0.75

<0.05

(12 gr )

1.23

1.10--1.37
1.10

1.03

0.78--1.46
0.78

NS

0.87

0.79--0.97
0.79

0.53

0.46--0.60
0.46

<0.001

( -)

0.86

0.65--1.13
0.65

0.86

0.48--1.54
0.48

NS

(CES
(CES--D>15
D>15--CES
CES--D<15
D<15))

1.58

1.25--1.99
1.25

1.93

1.85--2.01
1.85

<0.07

Cardio 2000

(Kcal )

(gr)

(gr)

(gr)

187
877
7 596

70+
70
+23

193+
193
+98

67+
67
+36

16%

16,31%

36,17%

.
. 9 2005;
..

...

:
, :

Premature death
Type 2 diabetes
Heart disease
High blood cholesterol
Stroke
Hypertension
Gallbladder disease
Osteoarthritis
(degeneration of cartilage
and bone in joints)
Sleep apnea
Asthma
Breathing problems
Increased surgical risk

Cancer (endometrial, colon,


kidney, gallbladder, and
post-menopausal breast
cancer)
Complications of pregnancy
Menstrual irregularities
Hirsutism (presence of
excess body and facial hair)
Stress incontinence (urine
leakage caused by weak
pelvic-floor muscles)
Psychological disorders
such as depression
Psychological difficulties
due to social stigmatization

(Adapted from http://win.niddk.nih.gov/statistics/index.htm)

- :
.1 30
(2004)

Source: CDC

Source: Am. J Health Prom. 20(1): 45-51 (2005)


Estimated $200 billion / year U.S. alone
Over 10% of all health care costs (20% by
2020)
Up to 60% of the cost of diabetes
27% of health insurance increase (1987
2001)
CDC < 400,000 deaths per year in U.S.

-
25




,

( >200i.u insulin /
).

, , ,


.

Genetics
&

Acquired

Researchers at Massachusetts General


Hospital and Harvard Medical School
Discovered an association between five amino acids
isoleucine, leucine, valine, tyrosine and
phenylalanine and the development of diabetes. A
combination of three amino acids predicted future
diabetes (with a more than fivefold higher risk for
individuals in top quartile). The results were replicated in
an independent, prospective cohort. These findings
underscore the potential key role of amino acid
metabolism early in the pathogenesis of diabetes
and suggest that amino acid profiles could aid in
diabetes risk assessment.The point is to be able to
identify how an interaction of genes and environment
affect risk for diabetes,
Metabolite profiles and the risk of developing diabetes
Nature Medicine,Volume:17,Pages:448453(2011)

, , -
,
-SNPs
rifampicin, isoniazid, olanzapine, risperidone,
progestogens, corticosteroids, insulin-therapy,
glucocorticoids, low testoterone, low vitamin D3, low
-3 , anti-HIV , bisphenol, heavy metals,
herbicides, pesticides (endocrine disruptors),

-SNPs(~1500, 20 ),.
1.Insulin receptor mutations (Donohue
Syndrome)

/
SNPs
Insulin receptor
Glucose transporter
Signaling proteins

Common Forms
Largely unidentified

Inactivity
Over eating
Aging
Medications
Obesity
Elevated FFAs

32

-: ,
,
, -receptor

insulin receptors.

Hyperinsulinemic, euglycemic clamp (EHC): gold standard:


insulin and glucose infused; steady state when glucose
infusion equals rate of glucose disposal rate (GDR)
Homeostasis Model of Assessment (HOMA): fasting glucose
and insulin measured for calculation of insulin sensitivity:
http://hepcnomads.co.uk/HOMACalc.ht
Asymmetric Dimethylarginine: ADMA, Better indicator of
insulin resistance than any other single marker, a form of
AGEs SCOUT DS (Canadian-CE marked)
Pro-insulin
(low-grade): AA/EPA
McClenaghan, 2005
plasma


(3)


Adipose
Tissue

Liver &
Muscle

Adipokines
B-cells

B-cells

HDL

PAI-1

,
LDL

MacFarlane S et al. J Clin Endocrinol Metab. 2001;86:713-718.


The American Association of Clinical Endocrinologists
(AACE)
:
BMI of 25 kg/m2 or higher
Triglyceride level of 150 mg/dL or higher
HDL-C level of less than 40 mg/dL in men or less than 50 mg/dL
in women
Blood pressure of 130/85 mm Hg or higher
Glucose level of more than 140 mg/dL 2 hours after
administration of 75 g of glucose
Fasting glucose level of 110-126 mg/dL

:
(
.)

...
100-125 mg/dL ,
(http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/#diagnosis. August 15,
2011).

spikes
()?
!!!
Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria.The
DECODE study group.Diabetes epidemiology:Collaborative analysis of diagnostic criteria in Europe.
Lancet, 1999 Aug.21;354(9179):617-21
Nakagami T.Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of
Asian origin.Diabetologia, 2004 Mar;(3):385-94.
Monnier L, Collete C.Glycaemic variability:should we and can we prevent it? Diabetes Care.2008 Feb; 31Suppl
2:S 150-4
Monnier L, Collete C, Owens DR.Glycemic variability: the third component of the dysglycemia in diabetes. It is
important?
How to measure it? J Diabetes Sci Technol.2008 Nov;2(6): 1094-100.
Triggle CR.The early effects of elevated glucose on endothelial function as a target in the treatment of type 2
diabetes.Timely Top Med Cardiovascular Dis.2008;12:E3
Gerstein HC, ..Yusuf S.Relationship of glucose and insulin levels to the risk of myocardial infraction: a casecontrol study. J Am Coll Cardiol.. 1999 Mar; 33(3):612-9
Lin HJ , Lee BC, Ho YL,et al.Postpradial glucose improves the risk prediction of cardiovascular death beyond the
metabolic syndrome in the nondiabetic population. Diabetes Care .2009 Sep;32(9): 1721-6

...

,
58% 21mg/dL .
26%.

.. 95 mg/dL
150 mg/dL.
, , , ,
.(The Oncologist online, Sweden Study, May 17,2010).
O 27% 18mg/dL ,
83 mg/dL.(Batty GD, ET AL.: Post-challenge blood glucose concetration and stroke mortality rates
in non diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study.
Diabetologia.2008 July;51(7):1123-6)

/ 13%
, 8%
.
http://docnews.diabetesjournals.org/content2/8/1.2.full. Accessed August 16, 2011.

...

- -
GLUCOSE-6-PHOSPHATASE,

(
.)
5-lipoxygenase or 5LOX (-) 7
10
, overload

().

SAN DIEGO (June 27, 2011) In the constant battle to lose inches
or at least stay the same, we reach for the diet soda. Two studies
presented Saturday [June 25] at the American Diabetes
Associations Scientific Sessions suggest this might be selfdefeating behavior.
Epidemiologists from the School of Medicine at The University of
Texas Health Science Center San Antonio reported data showing
that
diet soft drink consumption is associated with increased waist
circumference in humans, and a second study that found
aspartame raised fasting glucose (blood sugar) in diabetesprone mice (may damage the brain cells involved in helping us
feel full.)

(1)
(FFA) ,
-
.
(2) , adipocytokines,
, ,

.


- : adipokines
and pro-inflammatory mediators, amongst others, leptin, AGEs,
leukotrienes, adiponectin, resistin , adipsin, omentin, TNF, IL-6 and
PAI-1




low-grade
inflammatory-state

.
(insulin resistance).

Qatanani M , Lazar M A Genes Dev. 2007;21:1443-1455

,
.

Qatanani M , Lazar M A Genes Dev. 2007;21:1443-1455

:
vs

Normal

Tabetes
Courtesy of Wilfred Y. Fujimoto, MD.


: .
,1994 .

Leptin is a 167-amino acid protein


adipocytes-
.


1.
1.
2.
3.
4.
5.
6.
7.
8.

:

()
,

( )
,

.



,
.

.



.
Jak-Stat signal transduction
pathway

Appetite is
suppressed
CNS

Hypothalamus
arcuate nucleus
JAK-STAT
Leptin
receptor

MSH
POMC:
pro-opiomelanocortin
(from peptide-amine hormone
biosynthesis lecture)

Periphery

Metabolic activity
increases to burn fat
Leptin

MSH

+
Adipose
Adipose stores are HIGH

Hypothalamus
Appetite is
enhanced
CNS

JAK-STAT

Leptin
receptor

AGRP from hunger neurons


Block MSH binding
MSH
Periphery
Metabolic activity decreases
limiting fat burning

Leptin

Adipose

Adipose stores are low



-
-
-
-


(ob/ob)
, ,
, .
leptin
.


.
:
- .

Martin, S. S. et al. J Am Coll Cardiol 2008;52:1201-1210

Copyright 2008 American College of Cardiology Foundation. Restrictions may apply.


Adiponectin 247-amino acid
cross-sectional ,
adiponectin
,
waist to hip ratio, ,
,CVD,
.
Adiponectin
TNF- .

adiponectin
risk factor
. .
Adiponectin

.
adiponectin
FFA
fatty acid
.


.


ADIPONECTIN
Adiponectin
,
, -.


.

Resistin adipocyte-secreted
.
tissuespecific signaling molecules,
resistin-like molecules .

Resistin, ,
.
resistin
.
.

resistin

diet-induced
.

OMENTIN
Omentin, adipokine,
,
body mass index (BMI),
, ,

adiponectin (HDL).

-
interface

, .

:
M 6kg
-
.
. 80% - .


.
Viardot A, Lord RV, Samaras K. The Effects of Weight Loss and Gastric Banding
on the Innate and Adaptive Immune System in Type 2 Diabetes and
Prediabetes.
J Clin Endocrinol Metab. 2010 Apr 7 View Abstract

TNF-
TNF- is a pro-inflammatory cytokine

.
TNF-


.

TNF 1. FFA

2. adiponectin
3. insulin signaling

.
: IL-6, hs-CRP
:

, glucose
homeostasis, hypertriglyceridemia,
HIV .
-.
,
( adipocyte) ,
,
. :
.(
-.)
TG
....


.
leptin
.

leptin
TG .
-


TG .



adipocytokines
.


. ,

cytokines:,
.

!!
Reversal of type 2 diabetes: normalisation of beta
cell function in association with decreased
pancreas and liver triacylglycerol,
E. L. Lim & K. G. Hollingsworth & B. S. Aribisala & M. J. Chen & J. C.
Mathers & R. Taylor. Diabetologia., 24th June 2011, Newcastle University

I no longer needed my diabetes tablets


At the end of the trial, I was told my insulin
levels were normal and after six years, I no longer
needed my diabetes tablets. Still today, 18
months on, I dont take them. Its astonishing
really that a diet hard as it was could change
my health so drastically. After six years of having
diabetes I can tell the difference - I feel better,
even walking round the golf course is easier.



,
( MIND-BODY),

(,: ... ,
),
...
...
..