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2.10.07 nutrition.ppt 1

DISORDERS OF NUTRITION, OBESITY AND ITS CONSEQUENCES

LECTURES FROM GENERAL

PATHOLOGICAL PHYSIOLOGY

OLIVER RÁCZ, FRANTIŠEK NIŠTIAR,

IWAR KLIMEŠ, ANNA ŠOFRANKOVÁ

DANIELA KUZMOVÁ, ANDREJ JANCO


GLOBALISATION

❚ Undernutrition, malnutrition - 1/3 of world

❚ Obesity - 1/3 of world (Globesity?)

❚ Obesity combined with malnutrition (micronutrient deficiency, McDonaldisation, Coca-colonisation)

❙ ARE WE LOSING THE BATTLE?

❙ Economical growth and cultural changes in developing regions (South Africa, Japanese in USA, etc.


Undernutrition, malnutrition

❚ Absolute starvation - with water 2 months❙ glycogenolysis, gluconeogenesis, lipolysis, ketosis

❙ curtailed physiological processes, impaired immunity

❙ weight loss 40-50 % threatens life (protein catabolism)

❙ Blood glucose remains around the lower margin of the normal range!

❚ Kwashiorkor - protein malnutrition❙ manifestation after lactation

❙ weakness, growth retardation, hypalbuniemia, ascites, intercurrent infections, apatia...

EATING DISODERS (ANOREXIA, BULIMIA) PSYCHIATRIC DISEASES?



Undernutrition in rich

countries??!

Hospitals, hospices, chronic diseases

❚ Decreased oral intake❙ anorexia, nausea, dysphagia, pain, dentition

❙ poverty, old age (tea & toast diet), social isolation, alcohol or drug abuse, depression

❚ Increased losses❙ Diarrhea, malabsorption, bleeding, nephrotic sy….

❚ Increased requirements❙ fever, infection, burns, neoplasma, thyreotoxicosis...


OBESITYAre we fighting a losing battle ?

BMI = kg/(m)2

norm 19 - 25 (0)

overweight 25 - 30@ (I)

obesity 30 - 40 (II)

extreme ob. > 40** (III)

M W

Fat 10-20% 20-30%

WHR* < 1,0 < 0,8

Waist < 94 cm < 80 cm

+ weight % + mortality %

5 8

10 18

15 28

20 45

25 56

30 67

35 81

45 116

But: in an obese type 2 diabetic

100→90 kg adds 7 years of life

*Waist to hip ratio @27! or 22??! **120 kg for 1,72 m


The obesity pandemic

❚ COUNTRY M/W > BMI 30❚ SLOVAKIA 19/14❚ USA 20/25❚ JAPAN 8/3❚ RUSSIA 11/28❚ SOUTH AFRICA 8/44❚ KUWAIT 32/44❚ GREECE 27/18

❚ BUT!

❚ SIMPLE OVERWEIGHT IS ≈ ≈ ≈ ≈ 30/50 %❚ ALARMING INCREASE IN THE PAST 20 YEARS

❚ ALARMING INCREASE IN CHILDREN




OBESITY - external factors

❚ PHYSICS❙ no obesity without excess calories (+ 1 % = 10kg in 10 years)

❙ excess calories - not always obesity (substrate cycles, UCP)

❚ Once a day, without breakfast

❚ Infant formulas

❚ Fast food, quick eating

❚ Nibbling (TV)

❚ Stress

❚ Night eating

❚ Binge eating

❚ Alcohol (beer)

◆ Eating disorders - anorexia mentalis & bulimia


OBESITY - genes & forms

❚ Bodystat (glucostat, lipostat), appetite

❚ Basal output of energy = 75 %; ion transport!

❚ Postprandial output

❚ Spontaneous physical activity

❚ Lipid metabolism (lipases)

❚ Insulin sensitivity

◆ Rare hereditary and/or endocrine diseases formy -hypothalamus, Prader-Willi sy, etc. (connected with hyperphagia)

◆ Gynoid (Renoir) and android [lower & upper body obesity; pear & apple]

◆ sugar & fat eaters ?


Different types of obesity

❚ Gynoid and android

❙ (female, male, lower and upper body, gluteal and abdominal, Renoir and Rubens)

❚ Mild gynoid – fertility

❚ Mild android – health risk

❚ And visceral – high risk

❚ Diagnosis – waist circumference


OBEZITA



OBESITY - which genes?

❚ Ob gene coding leptin (167 AA)

◗ leptin is excreted from fat

◗ binds to its receptor in hypothalamus

◗ through increased activity of SNS (?!) decreases food intake and increases energy output

◗ ob/ob mice are obese, leptin applications helps

◗ obese men are not mice* (receptor mutation?)

*John Steinbeck: About Mice and Men


Many accelerators, few brakes,

and a lot of other things

❚ Leptin

❚ Resistin

❚ Adiponectin

❚ Adipsin

❚ Agouti related p.

❚ Acylation stimulating p.

❚ ...

❚ TNF αααα❚ Interleukin 6

❚ Complement factors

❚ Apo E

❚ Angiotensinogen

❚ Prostaglandins

❚ ...


What is obesity ?

❚ Deviation from the normal range of weight?

❚ Pathological condition ?❙ Of metabolism, caused by ???

❙ Of brain ???

❚ Disease(s) - nosological unit(s)❙ If it is a pandemic, it is a disease

❚ Risk factor of many (other) diseases

❚ A phenotype (manifesting if conditions are favourable)


Genotyp and environment

“The thrifty genotype”

Very thriftygenes

Less thriftygenes

Food shortage

Less thriftygenes

Very thriftygenes

Surplus of food

4 combinations2 fatal

☺ � ☺ �


Genotype versus environment

It was not so simple:Homo sapiens 1 500 000 yearsEuropean ancestors 50 000 years tall and healthy hunter/gatherersFarming, villages 10 000 years

Increased morbidity (famine, infections) decrease in height. Thrifty metabolism, strong immunity – t2dm and allergy

Very thriftygenes

Less thriftygenes

Food shortage

Less thriftygenes

Very thriftygenes

Surplus of food

4 combinations2 fatal


Genes (polymorphisms of genes) are responsible for diet induced obesity is about 67 %

They are permissive

Most of them (600 !) are involved in appetite regulation

Appetite is not the same as hunger

There is a broad field for intervention

Healthy life style – everybody

Pharmacology – small portion

Surgery - exceptionally


OBESITY - consequences

❚ METABOLIC (Insulin resistance, Diabetes mellitus,...)

❚ ENDOCRINE (sex hormones. growth h., glucocorticoids)

❚ CACRDIOVASCULAR (Hypertension*, Coronary artery disease, stroke, varices)

❚ GIT (gallbladder – also in gynoid obesity)

❚ RESPIRATION (Pickwick sy., snoring, sleep apnoea)

❚ ORTOPEDIC

❚ SKIN

❚ PSYCHOSOCIAL

❚ ONCOLOGICAL

*at BMI 30 the risk of hypertension is increased 5 – 13 times


Risk of diseases at BMI > 27

0,8Fracture of femur2,5Gout

1,2Breast Ca3,1Stroke

1,3Colorectal Ca1,9Myocardial infarction

1,8Arthrosis2,9Diabetes Type 2

2,0Cholecystopatia2,9Hypertension

RRDiseaseRRDisease


INSULIN RESISTANCE

1. Causes

❚ PRIMARY FORMS (HEREDITARY)

❙ abnormal insulin molecule, insulin receptor gene mutations, mutations of genes of glucose metabolism

❚ SECONDARY

❙ puberty, gravidity, high age

❙ unhealthy life style (lipids, fructose), obesity

❙ nonesterified fatty acids

❙ stress, starvation, hyperglycemia

❙ uremia, cirrhosis, ketoacidosis

❙ glucocorticoids, growth hormone, katecholamines, glucagon

❙ amylin (B cells of Langerhans islets)

Repeat the mechanism of insulin action!


INSULIN RESISTANCE

2. Consequences - glucose metabolism

GENETIC BACKGROUND + SECONDARY FACTORS

1. HYPERINSULINEMIA, NORMOGLYCEMIA

X-SYNDROME

2. IMPAIRED GLUCOSE TOLERANCE

GLUCOSE TOXICITY, VITIOUS CYCLE

3. TYPE 2 DIABETES MELLITUS

EXHAUSTION OF B CELLS


INSULIN RESISTANCE

(HYPERINSULINEMIA)

3. Consequences for the whole body

DYSLIPOPROTEINEMIA

TAG, small dense LDL, HDL-CH, postprandial hyperlipidemia

HYPERTENSION

Sodium & water resorption, ion transport, activity of SNS (?!)

HEMOCOAGULATION DISORDER

fibrinogen, fibrinolysis, hemorrheologic abnormalities

HYPERURICEMIA

HYPERANDROGENISM IN WOMEN

ENDOTHELIAL DYSFUNCTION(INSULIN IS A GROWTH FACTOR)ATHEROSCLEROSIS


INSULIN RESISTANCE

(HYPERINSULINEMIA, METABOLIC SY)

Unanswered questions

❚ Name ? Reaven? Metabolic? X? Z? syndrome

❚ Syndrome or atherogenic constellation of RF ?

❚ Causal interactions ?

❚ The beginning - the thrifty genotype ?

❚ Or is it in the opposite way? - impaired sympathetic regulation?

❚ Or subclinical inflammation ?

❚ Practical implications ? Prevention, education, therapy?

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