대한당뇨병학회35차추계학술대회대한당뇨병학회식품에 함유된 최종당화산물 대한당뇨병학회

35차추계학술대회식품에 함유된 최종당화산물

(AGEs)과 당뇨병

한림대의료원강동성심병원강동성심병원

김 두 만

대한당뇨병학회35차추계학술대회

Source of AGEs in the Body

• Endogenous formation of AGEs

• Exogenous sources of AGEs• Exogenous sources of AGEs- foods; Maillard or browning reaction- smoking

대한당뇨병학회35차추계학술대회대한당뇨병학회

35차추계학술대회

대한당뇨병학회35차추계학술대회

Types of Browning

• Enzymatic• Caramelization• Maillard• Lipid• Lipid

Polymers lead to color and small molec les to fla ormolecules to flavor.

C li ti대한당뇨병학회

35차추계학술대회

Caramelization• Heat to 200°C

– 35 min heating, 4% moisture lossg,• Sucrose dehydrated (isosacchrosan)

– 55 min heating, total 9% moisture lossg, %• Sucrose dimerization and dehydration caramelan

– 55 min heating, total 14% moisture loss55 min heating, total 14% moisture loss• Sucrose trimerization and dehydration caramelen

• More heating darker larger polymersMore heating darker, larger polymers insolubilization

Flavor• Flavor

Maillard Browning대한당뇨병학회

35차추계학술대회Maillard Browning

“ the sequence of events that begins with

reaction of the amino group of amino acids

with a glycosidic hydroxyl group of sugars;with a glycosidic hydroxyl group of sugars;

the sequence terminates with the formationthe sequence terminates with the formation

of brown nitrogenous polymers org p y

melanoidins” - John deMan

대한당뇨병학회35차추계학술대회

Maillard Browning

1. Formation of an N-glucosamine; esp. lysine

2 Amadori rearrangement2. Amadori rearrangement3. (Formation of diketosamine)4. Degradation of Amadori product; mild

sweed flavorsweed flavor5. Condensation and polymerization; color

Maillard Browning in Cooked Chicken대한당뇨병학회

35차추계학술대회Maillard Browning in Cooked Chicken

대한당뇨병학회35차추계학술대회

Exogenous Sources of AGE: DietExogenous Sources of AGE: DietHeating of food can create reactive AGE products by accelerating glycationp y g g y

- ribose > fructose > glucose

- broiling, grilling, frying and roasting > boiling

Food manufacturers enhance natural flavoursFood manufacturers enhance natural flavours by incorporating synthetic AGE’s into foods

- Foods with significant browning, caramelization

대한당뇨병학회35차추계학술대회AGEs in the BodyAGEs in the BodyAGEs in the BodyAGEs in the Body

Undergo renal clearance at a very slow rateUndergo renal clearance at a very slow rate

Affect nearly every type of cell and molecule in the body

Direct damage to myelin sheath fibrinogen- Direct damage to myelin sheath, fibrinogen,

collagen or endothelial cells

- Indirectly affect body function through side-

d t f d i th ti l di t AGEproducts formed in the reaction leading to AGEs

대한당뇨병학회35차추계학술대회Examples of AGEsExamples of AGEspp

Basta, G., Schmidt, A. M., De Caterina, R. (2004). Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovascular Research, 63, 582-592.

AGE t t f l t d f d it (1)대한당뇨병학회

35차추계학술대회

AGE content of selected food items: (1)

Fats AGE content (kU/g)

Almonds, roasted 66.5

Oil olive 120Oil, olive 120

Butter 265

Mayonnaise 94

AGE content: CML-like immunoreactivity, assessed by ELISA.

Goldberg TW et al. J Am Diet Assoc

AGE content of selected food items: (2)대한당뇨병학회

35차추계학술대회AGE content of selected food items: (2)

Proteins AGE content (kU/g)Chicken, broiled (15 min) 58 Chicken, fried (15 min) 61Beef, boiled (60 min) 22Beef, broiled (15 min) 60T t d (40 i ) 6Tuna, roasted (40 min) 6Tuna, broiled (10 min) 51Cheese American 87Cheese, American 87Cheese, brie 56Tofu raw 8Tofu, raw 8Tofu, broiled 41

Goldberg TW et al. J Am Diet AssocAGE content: CML-like immunoreactivity, assessed by ELISA.

AGE content of selected food items: (3)대한당뇨병학회

35차추계학술대회

AGE content of selected food items: (3)

C b h d t AGE t t (kU/ )Carbohydrates AGE content (kU/g)

Bread, whole wheat 0.5

Pancakes, homemade 10

Apple 0.13

Bananas 0.01Bananas 0.01Carrots 0.1Green beans 0 2Green beans 0.2

AGE content: CML-like immunoreactivity, assessed by ELISA.

Goldberg TW et al. J Am Diet Assoc

y, y

대한당뇨병학회35차추계학술대회

Quizs:

1. highest AGE content in food;

2 Highest AGE content in beverage;2. Highest AGE content in beverage;

AGE content of selected food items: (4)대한당뇨병학회

35차추계학술대회

AGE content of selected food items: (4)

• Foods high in protein and lipid> CHO• Foods high in protein and lipid> CHO- 12- and 30-fold higher AGE level, respectively

M t d t d i d d t d• Meat and meat-derived products processed by high, dry heat such as broiling, grilling, frying and roasting

• Reactivity of sugar in Maillard reaction;Reactivity of sugar in Maillard reaction; ribose > fructose > glucose

Uribarri J et al. Ann NY Acad Sci, 2005

I i l Ab i f AGE

대한당뇨병학회35차추계학술대회

Intestinal Absorption of AGEs• Negligible GI absorption; bioavailability 10%• Significant increase in plasma AGE levels within g p

two hours following a single AGE-rich meal• In animal studies; a correspondence betweenIn animal studies; a correspondence between

dietary AGE content and serum and tissue AGE levelslevels

• In diabetics and renal failure patients; a significant association between dietary and circulating AGEassociation between dietary and circulating AGE levels

Uribarri J et al. Ann NY Acad Sci, 2005

대한당뇨병학회35차추계학술대회

A i ti b t di t AGE d AGEAssociation between dietary AGEs and serum AGE levels in healthy subjects. Uribarri J et al. Am J Kidney D, 2003

대한당뇨병학회35차추계학술대회

Uribarri J et al. J Am Soc Nephrol, 2003

Biological Effects of Food-derived AGEs

• Induce protein cross-linking and intracellular oxidant stress similar to endogenous AGEsg

• High AGE diet; LDL added to cultured human endothelial cellshuman endothelial cells- increase in MAPK phosphorylation, NF-kB activity and VCAM secretion

대한당뇨병학회35차추계학술대회

1. Fasting glucose (A), serum insulin levels (B), body weights (C), and individual daily food intake (D) of db/db mice on LAD and HAD andindividual daily food intake (D) of db/db mice on LAD and HAD and control mice on LAD and HAD. Hofmann SM et al. Diabetes, 2002

대한당뇨병학회35차추계학술대회

Vlassara H et al. J Intern Med, 2002

대한당뇨병학회35차추계학술대회

Vlassara H et al. J Intern Med, 2002

대한당뇨병학회35차추계학술대회

Lin R-Y et al. Atherosclerosis, 2003

대한당뇨병학회35차추계학술대회

Vlassara H et al. PNAS, 2002

Interventions to Reduce AGE AccumulationInterventions to Reduce AGE Accumulation

• Inhibition of AGE formation- aminoguanidine, pyridoxamineg py- metformine, cerivastatin, ACEI, ARB

drugs reduce oxidative stress- drugs reduce oxidative stress• AGE breaking; alagebrium• AGE-RAGE interaction blocker; s-RAGE• Reduction of exogenous AGEsg

- stop smoking- low AGE diet- low AGE diet

대한당뇨병학회35차추계학술대회

Stirban A et al. Diabetes Care, 2006

대한당뇨병학회35차추계학술대회

Change in serum AGEs and dicarbonyls following HAG and HAG+BT in type 2 diabetes mellitus.

Stirban A et al. Diabetes Care, 2006

대한당뇨병학회35차추계학술대회

Change in FMD and reactive hyperemia following HAG and HAG+BT in type 2 diabetes mellitus.

Stirban A et al. Diabetes Care, 2006

대한당뇨병학회35차추계학술대회

Change in E-selectin and TBARS following HAG and HAG+BT in type 2 diabetes mellitus.

Stirban A et al. Diabetes Care, 2006

대한당뇨병학회35차추계학술대회

Uribarri J et al. Ann NY Acad Sci, 2005

대한당뇨병학회35차추계학술대회Thanks for your attention!Thanks for your attention!

감사합니다.