SOCIETASOCIETA’’ ITALIANA DI NUTRIZIONE UMANAITALIANA DI NUTRIZIONE UMANAMilano 29Milano 29--30 novembre 200730 novembre 2007

Geltrude Geltrude MingroneMingrone

Istituto di Clinica MedicaIstituto di Clinica MedicaUniversitUniversitàà Cattolica S. CuoreCattolica S. Cuore

RomaRoma

Treatment Goals for Type IITreatment Goals for Type II

Achieve normal or nearAchieve normal or near--normal blood normal blood glucose levels.glucose levels.Provide adequate calories for reasonable Provide adequate calories for reasonable body weight.body weight.Prevent, delay or treat nutrition related Prevent, delay or treat nutrition related complications.complications.Improve health through optimal Improve health through optimal nutrition.nutrition.

Finnish studyFinnish study

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Study Year

CONTROLCONTROL

INTERVENTIONINTERVENTION Tuomilehto, NEJM 2001

Self-Reported Change in Dietary and Exercise Habits during the First Year of the Intervention, According to Treatment Group

Tuomilehto J et al. N Engl J Med 2001;344:1343-1350

Diabetes Prevention Program Diabetes Prevention Program -- studystudy

Placebo Metformin Life style

Incidence 11% 7.8% 4.4%

Relative risk reduction

31% 58%

Number Needed to Treat

13.9

6.9

Diabetes GuidelinesDiabetes GuidelinesOutcome Measures Outcome Measures

Clinical GuidelineClinical Guideline Description of Study MeasureDescription of Study Measure

BP controlBP control Last BP < 130/80Last BP < 130/80

Triglyceride controlTriglyceride control Last triglyceride < 150 mg/dlLast triglyceride < 150 mg/dl

LDLLDL--cholesterol controlcholesterol control Last LDLLast LDL--C < 100 mg/dlC < 100 mg/dl

HDLHDL--C controlC control Last HDLLast HDL--C >45 mg/dlC >45 mg/dl

Glycosylated hemoglobin control Glycosylated hemoglobin control Last glycosylated hemoglobin <7%Last glycosylated hemoglobin <7%

JAMA. 2006;295:1688-1697

Plasma Glucose Response to Plasma Glucose Response to Different Carbohydrate SourcesDifferent Carbohydrate Sources

6080

100120140160180200220

0 15 30 45 90 120 150 180

Minutes

Blo

od g

luco

se (m

g/dL

)

StandardSimple SugarSoluble Fiber + SugarStarch

GlycemicGlycemic IndexIndex

GI first GI first developeddeveloped in 1981 in 1981 byby Dr. David Dr. David JenkinsJenkins, professor of , professor of nutritionnutrition at University of at University of Toronto, Canada and ACN Toronto, Canada and ACN FellowFellow

GlycemicGlycemic indexindex isis a a numericalnumerical system ofsystem ofmeasuringmeasuring the the degreedegree of rise in of rise in bloodblood sugarsugar ininresponseresponse toto variousvarious carbohydratescarbohydrates

The The higherhigher the the bloodblood glucoseglucose responseresponse, the, thehigherhigher the the glycemicglycemic indexindex

A GI of 70 or more A GI of 70 or more isis high, A GI of 56high, A GI of 56--69 69 isismedium, and GI of 55 or medium, and GI of 55 or lessless isis lowlow asas comparedcomparedtoto glucoseglucose whichwhich hashas a GI of 100a GI of 100

GlycemicGlycemic IndexIndex

●● Describes the incremental increase in Describes the incremental increase in blood glucose from fasting levels over a blood glucose from fasting levels over a defined time interval following ingestion defined time interval following ingestion of CHO (AUC) relative to a standardof CHO (AUC) relative to a standard

●● Property of food sources of digestible Property of food sources of digestible CHO CHO

●● Function of efficiency of digestion and Function of efficiency of digestion and rate of absorptionrate of absorption

GI ASSESSMENTGI ASSESSMENT

1.1. AnAn amountamount of food of food containingcontaining a standard a standard amountamount of of carbohydratecarbohydrate ((usuallyusually 50 50 gramsgrams) ) isis givengiven toto a a volunteervolunteer totoeateat..

2.2. Over the Over the nextnext twotwo hourshours (or (or threethree hourshours ifif the the volunteervolunteer hashasDM), a DM), a samplesample of of theirtheir bloodblood isis takentaken everyevery 15 15 minutesminutesduringduring the first the first hourhour and and thereafterthereafter everyevery 30 30 minutesminutes..

3.3. BloodBlood--glucoseglucose levellevel isis plottedplotted on a on a graphgraph and the area under and the area under the curve the curve isis integratedintegrated

4.4. The The volunteervolunteer’’s s responseresponse toto the the carbohydratecarbohydrate isis comparedcomparedwithwith hishis or or herher bloodblood--glucoseglucose responseresponse toto 50 50 gramsgrams of pure of pure glucoseglucose (the (the referencereference food).food).

5.5. The The referencereference food food isis testedtested on on twotwo or or threethree separate separate occasionsoccasions and and anan averageaverage valuevalue isis calculatedcalculated..

6.6. The The averageaverage GI GI valuevalue foundfound in 8 in 8 toto 10 people 10 people isis the GI the GI valuevalueof of thatthat food.food.

How GI is measured in the lab

Pure Pure glucoseglucose producesproduces the the greatestgreatest rise inrise inbloodblood glucoseglucose levelslevels

Pure Pure glucoseglucose isis set at 100 and set at 100 and everyevery otherotherfood food isis rankedranked on a scale on a scale fromfrom 0 0 toto 100100

GlycemicGlycemic Indexes of FoodsIndexes of Foods

Food AUC mg/L at 3 hours

÷Standard x 100

White bread 866 100 Whole wheat bread 811 94 Rice 652 75 Cornflakes 954 110 Oatmeal (coarse) 424 49 Spaghetti 583 67 Potatoes (boiled) 638 74 Lentils 263 30 Chickpeas 263 30 Kidney beans 258 30

Problems with the Problems with the GlycemicGlycemic IndexIndex

If high GI food is eaten in combination with lowIf high GI food is eaten in combination with low GI food, GI food, the GI response is moderatethe GI response is moderate

Insulin response to a given food is not linear andInsulin response to a given food is not linear and is not is not consistently related to either the CHOconsistently related to either the CHO content or content or glycemicglycemiceffect of the food (varieseffect of the food (varies within the person depending on within the person depending on the time, and,the time, and, from person to person)from person to person)

Not always the best indicator of healthy foodNot always the best indicator of healthy food choices choices (Snickers candy bar (Snickers candy bar vsvs watermelon)watermelon)

Some studies did not always take into accountSome studies did not always take into account the the amountamount of of carbohdyratecarbohdyrate

GlycemicGlycemic Index CRITICISMIndex CRITICISM

(ADA (ADA DiabetesDiabetes Care 2004)Care 2004)

The The specificspecific typetype of CHO in a of CHO in a particularparticular foodfooddoesdoes notnot alwaysalways predictpredict itsits effecteffect

on on bloodblood glucoseglucoseHigh High variabilityvariability eithereither withinwithin individualsindividuals

and and betweenbetween individualsindividuals (23(23--54%) 54%) –– howeverhowever normalizednormalized valuesvalues givegive

10% 10% variabilityvariability --

GlycemicGlycemic Load = Load = GI x g CHO in a servingGI x g CHO in a serving((SalmeronSalmeron etet al.al. DiabetesDiabetes Care 1997)Care 1997)

Primary Determinants Primary Determinants of of GlycemicGlycemic IndexIndex

●● Amount of CarbohydrateAmount of Carbohydrate–– Portion sizePortion size–– Energy densityEnergy density

●● Availability of CarbohydrateAvailability of Carbohydrate–– SolubilitySolubility–– DigestibilityDigestibility–– Extent of processingExtent of processing–– Type of processingType of processing

POSTPOST--ABSORPTIVE BLOOD GLUCOSE CONCENTRATIONABSORPTIVE BLOOD GLUCOSE CONCENTRATION

Rate of Rate of appearanceappearance ((absorptionabsorption))

LiverLiver first passfirst pass

TISSUESTISSUES

INSULININSULIN

INSULIN INSULIN SENSITIVITYSENSITIVITY

INSULIN INSULIN SECRETIONSECRETION

NaNa++--dependent dependent glucoseglucosetransportertransporter SGLT1 SGLT1

facilitatedfacilitated fructosefructosetransportertransporter GLUT5GLUT5

51 %51 %

35 %35 %

14 %14 %

Castello et al. Biochem J 1995

GLUT5GLUT5

GLUT5GLUT5

GLUT5GLUT5

SGLT1SGLT1

SGLT1SGLT1

SGLT1SGLT1

15 %15 %

30%30%

55 %55 %

FRUCTOSE

GLUCOSE

GALACTOSE

GLUT 5GLUT 5SGLT1SGLT1

GLUT 2GLUT 2

MW < 10 MW < 10 kDakDa

OXYNTOMODULIN OXYNTOMODULIN 37 amino acid peptide that contains the 29 amino acid sequence o37 amino acid peptide that contains the 29 amino acid sequence of f glucagonglucagon

GlucagonGlucagon--like peptidelike peptide--11

GlucagonGlucagon--like peptidelike peptide--22

Gastric Inhibitory PolypeptideGastric Inhibitory Polypeptide

Gastric Inhibitory Polypeptide ReceptorGastric Inhibitory Polypeptide Receptor

GIPGIPGLP1GLP1

00 439439

VASOSTATINEVASOSTATINEßß--GRANINEGRANINE

CHROMOCHROMOSTATINESTATINE

PANCREAPANCREASTATINESTATINE

PARASTATINEPARASTATINE

PROCHROMACINEPROCHROMACINE

Structure and expression of rodent preproStructure and expression of rodent prepro--glucoseglucose--dependent dependent insulinotropicinsulinotropic polypeptide (preproGIP)polypeptide (preproGIP)

Ugleholdt, R. et al. J. Biol. Chem. 2006;281:11050-11057

Mean plasma glucose (Mean plasma glucose (toptop), insulin (), insulin (middlemiddle), ), and Cand C--peptide (peptide (bottombottom) concentrations in 10 ) concentrations in 10

subjects during oral glucose tolerance test (OGTT) subjects during oral glucose tolerance test (OGTT) and and isoglycemicisoglycemic intravenous glucose infusion (Iintravenous glucose infusion (I--IVG) IVG)

Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

Insulin secretion (Insulin secretion (toptop) and its dynamic () and its dynamic (SRdSRd; ; middlemiddle) ) and static (and static (SRsSRs; ; bottombottom) components during OGTT ) components during OGTT

and Iand I--IVG. Shaded areas indicate regions where IVG. Shaded areas indicate regions where OGTT and IOGTT and I--IVG values are significantly different IVG values are significantly different

((PP < 0.05, < 0.05, Wilcoxon'sWilcoxon's signedsigned--rank test, rank test, test performed at sampling times) test performed at sampling times)

Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

IncretinIncretin potentiationpotentiation on insulin secretion (on insulin secretion (toptop) ) and its 2 contributions from and its 2 contributions from SRdSRd ((middlemiddle) and ) and

SRsSRs ((bottombottom) components. Shaded areas indicate ) components. Shaded areas indicate regions where OGTT and Iregions where OGTT and I--IVG values are IVG values are significantly different (significantly different (PP < 0.05, < 0.05, Wilcoxon'sWilcoxon's

signedsigned--rank test, test performed at sampling times). rank test, test performed at sampling times).

Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

CALORIMETRIC CHAMBERCALORIMETRIC CHAMBER

TYPE 2 DIABETIC WOMAN (50 yrs)

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TYPE 2 DIABETIC WOMAN (50 yrs)

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Bertuzzi A, Salinari S, Mingrone G. AJP 2007 293(1):E396-409

Bertuzzi A, Salinari S, Mingrone G. AJP 2007 293(1):E396-409

Bertuzzi A, Salinari S, Mingrone G. AJP 2007 293(1):E396-409

Modified by Roduit R. et al.Diabetes 2004

GLUCOSEGLUCOSE

PyruvatePyruvate

CitrateCitrate

PCPC

PDHPDHAcetylAcetyl--CoACoA

AcetylAcetyl--CoACoA

MalonylMalonyl--CoACoA

ACCACC MDCMDC

LCLC--CoACoA

TCA CycleTCA Cycle

AcylAcyl--CoACoA

CPT

2CPT

1C

AR

N ßß--oxidationoxidation

PyruvatePyruvate

CLCL

KK++ ATPATP

CaCa2+2+

ATP/ADPATP/ADP

++

--

++

--

DAGDAG

PKCPKC

++

++

++

At this time, there is insufficient informationto determine whether there is a relationship

between glycemic index or glycemic loadof diets and the development of diabetes.However, GI can provide an additional

benefit over that observed when total CHO is considered alone.

Dr. M. Dr. M. MancoMancoDr. D. Dr. D. GniuliGniuli

Dr. C. Dr. C. GuidoneGuidoneDr. A. Dr. A. IaconelliIaconelliDr. L. Dr. L. LeccesiLeccesi

Mrs. A. Mrs. A. Caprodossi

Prof. M. Prof. M. CastagnetoCastagnetoProf. G. Prof. G. NanniNanniDr. F. Dr. F. RubinoRubino

Caprodossi