ueda2012 clinical pmi and metabolic disorders-d.leo pruimboom
TRANSCRIPT
Clinical PNI and metabolic disorders When the immune system overrides the selfish
brain Prof. Leo Pruimboom
President of the International Association for Clinical PNI
Associate Professor University of Graz (Austria)
Director European Master in Clinical PNI, University of Graz (Austria)
Februari 2012
"If we could give every individual
the right amount of nourishment
and exercise, not too little and not
too much, we would have found
the safest way to health."
Hippocrates 400 BC
3
“Nothing in biology makes sense without
evolution”
Theodosius Dobzhansky 1973
“Nothing in medicine makes sense without
biology”
Frits Muskiet 2005
The impact of the insulin resistance
syndrome in modern society
Conference Statements and outline
• Adaptive on the short term
• Protective while enough insulin
• Deleterious on the long term
• Based on false triggers
• A psychoneuroendocrinoimmunological
disease
• An evolutionary solution
• The study of origin
Not insulin resistance but
insulin resistance syndrome 1. Pima Indians Higher insulin sensibility >> Obese
2. Low insulin >> Obese
3. High Insulin >> BMR << Obese
4. City Africans >> IR >> Obese
5. Ice-landers << IR
6. Kashmir-Himalayas << IR << Obese
Zargar AH et al. Diab Res Clin Practice 2000, 47:135-146.
Swinburn BA, et al. J Clin Invest 1991, 88:168-173.
Unger RH Nature Medicine 2006, 12(1):56-57
Kahn BB, Flier JS: J Clin Invest 2000, 106(4):473-481.
People eat to much and do not exercise
But they do know that this behavior makes them ill.
So why do they eat too much and don´t engage in
exercise??
Engagement in
minimal estimated
amount of exercise
Medical Hypotheses
77 (2011) 708–713
Offspring of Ad Libidum versus undernourished mothers.
Note; the adult UN offspring is shorter but fatter
Bernhard H. Breier,* Stefan O. Krechowec and Mark H. Vickers. Early life programming of obesity and the lazy phenotype.
Early Life Origins of Health and Disease, edited by E. Marelyn Wintour and Julie A. Owens.
©2006
High Glycemic Load
Insulin and cortisol toxicity
Meal frequency and HGL-Food
Guilherme
et al. Nature
reviews.
2009 (9); 367
– 377
Saltiel 2007)
Obesity and insulin
resistance Syndrome CVD
Diabetes type II
Mental disorders
Depression
Autoimmune diseases
Insulin resistance
Syndrome
Acne
PCOS
Alopecia
Skin tags
Pigmentación
Acanthosis nigricans
Myopia
Cancer
Gout and psuedogout
Secular increase of height
Paradontosis
Apnea
Atherosclerosis Insulin resistance, hypercholesterol and gram-negative bacterial infection; the bodies defense
Specific
Oral Cave
Koren 2010, PNAS
High cholesterol protects against bacterial infection at the account of
atherosclerosis
Ravnskov U. High cholesterol may protect against infections and
atherosclerosis. QJM. 2003 12;96(12):927-34.
Rauchhaus M, Coats AJ, Anker SD. The endotoxin-lipoprotein hypothesis.
Lancet. 2000 09/09;356(9233):930-3.
Kitchens RL, Thompson PA, Munford RS, O'Keefe GE. Acute inflammation
and infection maintain circulating phospholipid levels and enhance
lipopolysaccharide binding to plasma lipoproteins. J Lipid Res. 2003
12;44(12):2339-48.
1. Hunter DJ. Diet, Body size and breast
cancer. Epidem Rev 1993; 15:110-32.
2. Stoll BA. Western diet, early puberty,
and breast cancer risk. Breast Cancer
Res Treat 1998;49:187-93.
3. Hankinson SE et al. Circulating
concentrations of insulin-like growth
factor-1 and risk of breast cancer.
Lancet 1998;351:1393-6
Hypoxie-Stress Reaction, Hypoxie induced
Factor 1 and Insulin Resistance Syndrome
Heel Spur Frey C Foot Ankle Int. 2007 Sep;28(9):996-9.
Epicondylitis lateralis Shiri et al. Am J Epidemiol. 2006 Dec 1;164(11):1065-74.
Epicondylitis madialis Shiri et al. Am J Epidemiol. 2006 Dec 1;164(11):1065-74.
Tendinopathy Gaida et al. Arthritis Rheum. 2009 Jun 15;61(6):840-9.
Achilles Tendinopathy Gaida et al. Med Sci Sports Exerc. 2009 Jun;41(6):1194-7.
Bursopathies Werner et al. J Occup Rehabil. 2005 Mar;15(1):37-46.
Chronic pain Ray et al. Pain. 2011 Jan;152(1):53-9.
Fibrosis Spencer et Am. J. Physiol Endoc. Met. 2010 Dec;299(6):E1016-27.
Divoux et al. Diabetes. 2010 Nov;59(11):2817-25
Keloid buliding Verma. Am J Clin Dermatol. 2010 Dec 1;11(6):433-6
Carpal Tunnel Syndr. Gell et al. J Occup Rehabil. 2005 Mar;15(1):47-55.
Rotator Cuff Tendinitis Wendelboe J Bone Joint Surg Am. 2004 Apr;86-A(4):743-7.
Migraine Takashima Brain Nerve. 2009 Oct;61(10):1143-53.
High IL-1
High IL-6
High TNF alfa High Central Pro-
inflammatory Profile
High NFkappaB
Lower IL-1
Lower IL-6
Lower TNF alfa Low Peripheral Pro-
inflammatory Profile
Lower NFkappaB
Non or hardly immune cell infiltration
The phylogenetical oldest system
= The immune system
JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 306B:496–520
(2006)
Simultaneous appearance
(Big) Brain
High basal metabolic rate
Glucocorticoid Receptor
Complete pancreas (98% exocrine – 2%
endocrine)
Mechanisms of Ageing and
Development 130 (2009) 216–221
Homo sapiens
Comparative
Biochemistry and
Physiology - Part A:
Molecular &
Integrative
Physiology. 2003
9;136(1):5-15.
0
200
400
600
800
Fecal Elastase
Vegetarians
Omivores
0
5
10
15
20
Chymotrypsin
Vegetarians
OmnivoresJournal of Pediatric
Gastroenterology and Nutrition
38:224–226 © February 2004
ug/g stool
p<0.05
U/g stool
p<0.05
Legumes-Fibres
Kunnitz factors
Lipase/protease-
inhibitors
Lectins
Saponins
Bowman-Birk factors
Hypoinsulinemia causes pancreatic atrophy with fat replacement of the
exocrine pancreas in different species. These results indirectly show the
significant role of insulin on pancreatic exocrine function. However,
direct evidence is also available to highlight the key role of insulin. Both
endogenous and exogenous insulin evoke increases in pancreatic
enzyme synthesis and growth. Insulin is not only important in healthy
conditions, but is also involved in the regenerative processes during
pancreatitis. Human studies have also proved the necessity of insulin in
pancreatic exocrine function. In conclusion, insulin has long term effects
on the regulation of the biosynthesis of pancreatic digestive enzymes and short term effects on the stimulation of pancreatic secretion
Vena portaI Intermittent insulin
50% insulin
50% insulin Intact
Gap junction
23% blood
12,2% basic
insulin
25-35% blood
12,5-17,5%
basic insulin
Intrinsic repair of
acinar cells
Vena porta Continuous insulin
90% insulin
10% insulin
Resistance
Absence of
gap junction
23% blood
21% basic
insulin
25-35% blood
22,5-31%basic
insulin
Exogenic insulin
Repair acinar cells
Accumulation of
adipose tissue
Fatty heart
The youngest system Big Brain
The oldest system Immune system
Phylogenesis
Straub. J InternMed2010;267: 543–560
Brascha. Progress in Neuro-Psychopharmacology & Biological Psychiatry 30
(2006) 827–853
Physiology Danger
Energy distribution in Physiology
The immune system = not expensive in rest
L. Pruimboom / Medical Hypotheses 77
(2011) 708–713
- Concepts of health
and disease - Master 45
Muscle Brain
(13 kcal/kilo) (197 kcal/kilo)
Glucose
Fatty acids Heart
Proteins (570 kcal/kilo)
Creatine-P
Liver (216 kcal/kilo)
Kidney (420 kcal/kilo) Immune system
Gut (212 kcal/kilo) (27 kcal/kilo)
Protein turnover (%) during chronic and massive
acute immune activation
Loss of muscles and induction of NPBD
Adapted from Lochmiller,
OIKOS 88: 87–98. Copenhagen 2000
Wound healing and high costs
Immune activation = 380 – 1500 kcal
Deep tissue production = size dependent Hurd TA. Wound Care 2004.
Ord H. Br J Nurs 2007.
Famine (poor countries), IRS, LGI,
Autoinflammatory and Autoimmune diseases
Brain
Stable
-20% Liver - 40%
Kidneys
- 40%
Muscles -20/-40/-60%
AMERICAN
JOURNAL OF
HUMAN BIOLOGY
23:29–34 (2011) Immune
system
Long term inflammation
leads to a non-permissive
brain syndrome with IR and
LR.
L. Pruimboom / Medical Hypotheses 77
(2011) 708–713
The reptile phenotype/loss of thryroid
function/hibernation
• Brain function: depression; poor memory; inability to
concentrate; mood swings; sleep disturbances; anxiety
• Skin/hair quality; dry skinn; puffy eyes; hair loss; coarse or brittle hair
• Reproductive functions; irregular menstruation; heavy
menstruation; infertility; birth defects; erectile dysfunction;
delayed ejeculation
• Circulation/respiratory functions: high cholesterol; high blood
pressure; congestive heart failure; Sleep apnea
• Muscle/joint function: muscle cramps; weakness; pain; deep
voice; horse voice; pins and needles in hands/feet
• Metabolic functions: heat/cold intolerance; weight gain;
constipation; general tiredness
Pruimboom L. Medical Hypotheses 2011
Clinical Psychoneuroimmunology
The science based on the film and not on the photo
Proximate medicine
Present
Loss of husband Sedentary life
Sugar addiction
Insulin Resistance syndrome
Central adiposity Lack of immune migration
Clinical PNI – Metamodel 1
The symptom
Causes
(nutrition, inactivity, lack of
sunshine, tabaco)
Non-complete
systemic
resolution
Non-complete
local resolution
Central appeal
of stress axes Energy allocation
disorders
Clinical PNI – Metamodel 1
The symptom
Causes (nutrition, inactivity, lack of sunshine,
tabaco)
Insulin
resistance
Cortisol
Resistance
LGI
Proximate
medicine
The symptom
Nutrition, inactivity, lack of sunshine, tabaco, shift work, ACE, CLS,
Insulin
resistance
SAM>HPA
Sterile Inflammation
Exocrine
pancreatic
insufficiency
Energy
distribuition
disorder Cortisol resistance
A
C
U
T
E
C
H
R
O
N
I
C Reptile
Phenotype
Symptom
Nutrition, inactivity, lack of sunshine, tabaco, shift work, ACE, CLS,
Cortisol/Insulin
resistance
SAM>>HPA
(Sub)Sterile Low
Grade
Inflammation
Exocrine
pancreatic
insufficiency
Energie
Deficiency NTIS
A
C
U
T
E
C
H
R
O
N
I
C Sedentary
Lifestyle
Increased
Protein turn
over
Causes of low grade inflammation, insulin
resistance syndrome and non
permissive brain disorder
Obesity Reviews. 2011;12(5):339-45
British Journal of
Nutrition (2010), 104,
724–728
Kangaroo meat versus
domesticated meat
The role of food in low
grade inflammation Kangaroo
Hybridised
meat
The study of origin
August 2011
Background: Recovering self-sufficiency in an “original
environment” during a short period of time
should be able to normalize insulin sensibility and
therefore inflammatory and metabolic biomarkers.
Individuals with pathologies based on “modern
lifestyle” should benefit of this intervention
Methodology: 10 persons lived for a period of 10 days in the
pyrenees during the summer of 2011. Searching for
food, water, shelter and day/nighttime biorhythm
were all part of the self-sufficiency study. Immunological and metabolic biomarkers (soft
endpoints) and SF36 questionnaire (hard endpoint)
were used as measurements (6, 3, 1 month
before start, day of study-start, end of study, 4 months after study). Food and water intake was constantly
monitored
Results: Their was a significant improvement of all biomarkers.
hsCRP was raised (as expected) after the study and
normalized 4 months later. Individuals with chronic
fatigue were and are symptom-less (n=2). Two subjects with metabolic syndrome are still in the normal range.
Quality of life was improved in all subjects after
4 months (SF36)
84
85
86
87
88
89
90
91
92
93
Glucose
11/08/11
21/08/11
21/12/11
P < 0,05
*
The study of origin; Pruimboom prep.
Pyrenees 2011
n=10 Glucose
0
1
2
3
4
5
6
Insulin
11/08/11
21/08/11
21/12/11
P < 0,05
*
The study of origin; Pruimboom prep.
Pyrenees 2011
n=10 Insulin
0
10
20
30
40
50
60
70
Triglicerides
11/08/11
21/08/11
21/12/11
P < 0,05
*
The study of origin; Pruimboom prep.
Pyrenees 2011
n=10 Triglicerides
0
0.5
1
1.5
2
2.5
3
3.5
hsCRP
11/08/11
21/08/11
21/12/11
*p < 0,05
**p<0,05
**
*
The study of origin; Pruimboom prep.
Pyrenees 2011
n=10 hsCRP
0
50
100
150
200
250
Cholesterol
11/08/11
21/08/11
21/12/11
P < 0,05
*
The study of origin; Pruimboom prep.
Pyrenees 2011
n=10 Cholesterol