Paul Clayton Sundevollen 20/5/07 - Weight Management - cardiovascular disease & diabetes.

Paul ClaytonSundevollen 20/5/07

- Weight Management

- cardiovascular disease & diabetes

18971897

19191919

Korea 1951

Fife 1953Fife 1953

California 1955

Ob / ob/ob normal

1885: first automobile (Karl Benz)1885: first automobile (Karl Benz)

1912: first traffic jams1912: first traffic jams

1929: first parking problems

Reduced energy expenditureReduced energy expenditure

1600

1800

2000

2200

2400

2600

2800

60 65 70 75 80 85 90 95Year

kcal per day

DoH ’98, USDA ’02, NIH ’03, NCHS ‘04

1940 50 60 70 80

Positive energy balancePositive energy balance

1600

1800

2000

2200

2400

2600

2800

60 65 70 75 80 85 90 95Year

kcal per day

DoH ’98, USDA ’02, NIH ’03, NCHS ‘04

1940 50 60 70 80

Obesogenic culture (AHA ’03)

Avge US adult sedentary 8 hours / day, < 2,000 steps / day (NYS Public Health Assocn ‘05)

Amish 16,000 steps /day: obesity 9% women, 0% men (Bassett et al ’04)


1600

1800

2000

2200

2400

2600

2800

60 65 70 75 80 85 90 95Year

kcal per day

DoH ’98, USDA ’02, NIH ’03, NCHS ‘04

1940 50 60 70 80 90 2000

AHA 2002: ‘obesogenic culture’AHA 2002: ‘obesogenic culture’

Fewer bus-stops, remote parking

Exercise to be mandatory at all levels of educational system

No ‘junk foods’ to be sold / served in schools

‘baby bells’: constructive inconvenience

Why is weight gain so easy?Why is weight gain so easy?

Multiple satiation mechanisms Protein: amino acids (fish > whey > casein)Protein: amino acids (fish > whey > casein)Fats: fatty acids (distal jejeunum)Fats: fatty acids (distal jejeunum)Carbs: glucose (Hoodia)Carbs: glucose (Hoodia)Fermentable carbs: SCFA (propionic)Fermentable carbs: SCFA (propionic)Insufficient calorific throughputInsufficient calorific throughputHigh calorific densityHigh calorific densityInstant gratificationInstant gratification


1600

1800

2000

2200

2400

2600

2800

60 65 70 75 80 85 90 95Year

kcal per day

DoH ’98, USDA ’02, NIH ’03, NCHS ‘04

1940 50 60 70 80

Overweight but starvingOverweight but starving

W.H.O. ‘02: ‘Globally, overweight more of a health problem than underweight.’

U.N.O. ’06: ‘Overweight but malnourished’ (=Type B malnutrition)40-60% hospital admissions malnourished (US/UK)

And in the community (USDA and other surveys)

MICRONUTRIENTSMICRONUTRIENTS CALORIESCALORIESMALNUTRITIONMALNUTRITION

TYPE A

MICRONUTRIENTSMICRONUTRIENTS CALORIESCALORIESMALNUTRITIONMALNUTRITION

TYPE A

TYPE B

Percentage of Population DepletedPercentage of Population DepletedIn Vitamins (USDA 1997)In Vitamins (USDA 1997)

C E A B1 B2 C E A B1 B2 NiacinNiacin Folate Folate B6 B12 B6 B12------------------------------------------------------------------------------------------------------------------------------------------37 68 55 32 31 27 34 54 1737 68 55 32 31 27 34 54 17

Vitamins

%

* Gregory et al 2000. National Diet and Nutrition Surveys, HMSO

Iron from all sources (including supplements)% of children of all ages with intakes below RNI and LRNI

84

57

14

28

39

59 60

96

43

93

16

40 1 1 3 3

44

2

48

0

10

20

30

40

50

60

70

80

90

100

<4 >4 Boys Girls Boys Girls Boys Girls Boys Girls

1.5 - 4.5 Age 4-6 Age 7-10 Age 11-14 Age 15-18

% < RNI

% < LRNI

* Gregory et al 2000. National Diet and Nutrition Surveys, HMSO

Vitamin A from food% of children of all ages with intakes below RNI and LRNI

0

10

20

30

40

50

60

70

80

<4 >4 Boys Girls Boys Girls Boys Girls Boys Girls

1.5 - 2.5 Age 4-6 Age 7-10 Age 11-14 Age 15-18

% < RNI

% < LRNI

DIETARY SHIFTDIETARY SHIFT

Flavonoids 75%Vit C 50-60%Omega-3 50% Methyl groups 95%Carotenoids 40%Phospholipids 50% since 1900Selenium 50% ” 1960 (UK)Prebiotic fiber 50% ” 1960 (Fr)Sterols 66% ” 1960 (SA)

since Stone Age

WHO Technical Report Series 916WHO Technical Report Series 916

‘Diet, Nutrition and the Prevention of Chronic Diseases’

Report of Joint FAO / WHO Expert Consultation

Geneva May 2003

RSM 2005: Pathogenic culture?RSM 2005: Pathogenic culture?

Type 2 diabetes

Osteoporosis ARMD Neurodegenerative disease Lymphoma, leukaemia, melanoma, germ cell

tumours in teens & young adults ADD / ADHD / dysphasia / dyspraxia Allergy, asthma

heart disease, stroke, cancers, kidney disease, blindness, Alzheimer’s

Type B Malnutrition worsens Type B Malnutrition worsens with agewith age

Reduced activity / calorie requirements

Institutional diet

Financial hardship

Poor dentition

Swallowing problems (xerostomia)

Loss of sense of taste


Progressive depletion of anabolic factors

(vits C, B’s, D; Zn, Cu, Se, Fe, Ca, Mg; amino acids etc)

Progressive depletion of anti-catabolic factors

(vit E; Zn, Cu, Mn, Se; sterols, flavonoids, carotenoids etc)


Progressive depletion of anabolic factors

decreased tissue repair, damage clearance etc

Progressive depletion of anti-catabolic factors

increased free radical activity, hexosylation, nitrosation, inflammation

= CATABOLIC DOMINANCE= CATABOLIC DOMINANCE

Multiple agent interventionMultiple agent intervention

CDD’s have multiple patho-aetiology

CAD risk factors: hypertension, smoking, inactivity, obesity

LDL / HDL, LDL-ox.lag, HbA1c, hyperHc, ICAM-1, VCAM-1, VWF etc

Reduced risk: lycopene, quercitin, omega 3, methyl groups, alcohol, lutein, vitamin E, soy etc

CVD: HOW DRUGS WORKCVD: HOW DRUGS WORK

LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE


LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE

Statins - - - - - -


LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE

Statins - - - - - -Ace

inhibitors - - - - - -


LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE



Beta

blockers - - - - - - -

CVD: HOW SUPPLEMENTS WORKCVD: HOW SUPPLEMENTS WORK

LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE



Beta

blockers - - - - - - -

Nutrients

E,C, bC

How PharmacoNutrition WorksHow PharmacoNutrition Works

LDL HDL LDL ox. Hc

V/CAM

I/CAM PLATELETS ACE



eta

blockers - - - - - - -

Nutrients

RS Pl’s

E,C, bClycopene

B4, 6, 12, ’10’

flavonoids

Omega 3

flavonoids

flvd’s

Prevention of (secondary) CADPrevention of (secondary) CAD

Lyon Heart Study (3 years, n=600)

Statins reduced risk of secondary infarct 18 – 23%

Dietary modification reduced risk 50-70% Dietary modification reduced risk 50-70%

de Lorgeril M et al Circulation ‘99:779-785

NIDDM: Therapeutic StrategiesNIDDM: Therapeutic Strategies

The Pharmaceutical model

Expensive, adverse effects: palliative

NIDDM: Therapeutic StrategiesNIDDM: Therapeutic Strategies

The Pharmaceutical model

Expensive, adverse effects: palliative

The Life-style model

Cheaper, other benefits: curative

NIDDM: Life-Style ModelNIDDM: Life-Style Model

Weight loss

Exercise

Nutritional change

Pharmaco-nutritional programs

NIDDM: the Tricameral modelNIDDM: the Tricameral model

1. Glycemic Load (whole diet)

2. Glucose sink(s)

3. Insulin – glucose uptake system

1. Glycemic Load1. Glycemic Load

Log increase since Neanderthal period

Cooked root vegetables

Fine milling (17th C)

The potato (17th C)

Refined sugar (UK 30kg chocolate/year)

2. Glucose sink(s)2. Glucose sink(s)

Skeletal muscle – physiological functionality and volume compromised

BAT – non-induced, therefore compromised

Affects glucose tolerance & plasma lipids

3. Insulin–glucose uptake system3. Insulin–glucose uptake system

Dependent on:

Cr: Cr-oligopeptide insulin receptor kinase (via SH2 domain)

Inositol: phosphoglycans = insulin ‘second messengers’: activate GLUT-4

Mn: phosphoglycan co-factor

Functional Insulin DepletionFunctional Insulin Depletion

Excessive glycation reactionsGlycated insulin and insulin receptors

Effective hypo-insulinaemia

Excessive GL dietDietary anti-glycosylants

(University of Coleraine in Ulster ’01-07)

The Tricameral ModelThe Tricameral Model

Historically high GL diet

Sub-optimal glucose sinks

Impaired glucose handling

Testing the Tricameral ModelTesting the Tricameral Model

Reduced GL foods

Structured exercise and/or cold exposure programme

Cr, D-chiro-inositol, Mn, anti-glycosylants

Prevention of NIDDMPrevention of NIDDM

Diabetes Prevention Program (Mass Gen Hosp, IGT)

10 yr prospective trial: 7% weight loss + 150 mins exercise / week risk of progression to diabetes reduced by 60%

= 2x more effective than prophylactic = 2x more effective than prophylactic metforminmetformin

Knowler WC et al: N.Engl.J.Med 2002: 346:393-403

Reversal of Metabolic SyndromeReversal of Metabolic Syndrome

180 patients ’Prudent’ or Mediterranean diet for 2 yearsM group: reduced weight, hs-CRP, IL-7, IL-18, insulin resistance; improved endothelial functionAt 2 years, 12% P had no features of metabolic syndromeM group: 55% had no featuresM group: 55% had no features

Esposito K et al JAMA 2004:292(12):1440-6

Diabetic complicationsDiabetic complications

Cardiovascular: CAD, stroke, peripheral

Renal damage / failure

Visual impairment

Peripheral neuropathy

Dementia: Alzheimer’s disease, MI

Cancers

Vascular Patho-aetiologyVascular Patho-aetiology

Atherogenic plasma lipid: pp TG, VLDLDirect insulin effects: ie vit CC uptake block, slowed tissue healingAntioxidant defences impairedGlycosylation / denaturation / AGEEndarterial inflammationEndarterial inflammationEssential hypertension Essential hypertension Platelet hyper-activityPlatelet hyper-activityCapillary fragilityCapillary fragility

Renal Patho-aetiologyRenal Patho-aetiology

Depressed immune function + glycosylation of urinary tract epithelial cells + impaired bladder emptying due to nerve damage increased UTI

Glycosylation of glomerular capsular proteins & glycoproteins

Capillary fragility

Neuronal Patho-aetiologyNeuronal Patho-aetiology

Oxidative stress

AGE stress (via RAGE): direct neurotoxicity

Capillary fragility

Pharmaco-Nutritional ManagementPharmaco-Nutritional Management

Weight loss, exercise, reduced GL dietInsulin co-factors (Cr, Mn, D-chiro-inositol)

Phenolics: Vasotrophic, anti-inflammatory, vasodilator, anti-platelet, antioxidant, anti-glycosylant, anti-nitrosylationAntioxidants (C, E, ALA, Cu, Zn, others)Mixed phospholipids HDL, neuronal membrane

DIET: Low sugar or low carbs?DIET: Low sugar or low carbs?

3 categories of carbs

Digestible (simple sugars, starches)

Fermentable (inulin, resistant starches)

Speciality (structural, metabolic poisons, intense sweeteners)

Low GI / GL

The importance of low GLThe importance of low GL

Raised HbA1C increases risk of CAD, stroke etc

.

Brand et al (1991) Diabetes Care 14:95-101



15% reduced GL diet 12 weeks 2% reduced HbA1C (Type 2 diabetics) = 40% reduced risk of CAD, stroke etc

.





Benefit most noticeable in patients with raised HbA1C





Benefit most noticeable in patients with raised HbA1C

Many people have raised HbA1C without knowing itMany people have raised HbA1C without knowing it


Projected benefits of reducing CHO by 30gProjected benefits of reducing CHO by 30g

1.2 % fall in 1.2 % fall in HbAHbA1c1c

1. De Vegt et al 1999; Khaw et al, 2001

≅ 30% 30% reduction in reduction in CHDCHD

1




2. Diabetes Control and Complications Trial, 1996



≅ 25% 25% reduction in reduction in retinopathyretinopathy

1

2




2. Diabetes Control and Complications Trial, 1996

3. Salmeron et al 1997ab; Meyer et al, 2000



≅≅ 25% 25%

reduction in reduction in retinopathyretinopathy

1

2

3>30% reduction >30% reduction in type-2 DMin type-2 DM


<30g/d fall <30g/d fall in glycaemic in glycaemic

loadload

Atkins and other low-GL dietsAtkins and other low-GL diets

Efficacy? (6 vs 12 months; 1 +ve vs 3 –ve)

High fat / protein, low fruit / veg diet increases risk of bowel & other cancer

Therapeutic index!1 in 3 adults have renal impairment; worsened by high protein diet Knight et al ’03

low phytate diet Curran et al ‘04

Who has renal impairment? Overweight, IGT

Paul ClaytonSundevollen 20/5/07

- Weight Management

- cardiovascular disease & diabetes

Paul Clayton Sundevollen 20/5/07 - Weight Management - cardiovascular disease & diabetes.

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Transcript of Paul Clayton Sundevollen 20/5/07 - Weight Management - cardiovascular disease & diabetes.