SOCIETA ITALIANA DI NUTRIZIONE UMANA Milano novembre Geltrude Mingrone. Istituto di Clinica Medica Università Cattolica S.

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1 SOCIETA ITALIANA DI NUTRIZIONE UMANA Milano novembre 2007 Geltrude Mingrone Istituto di Clinica Medica Università Cattolica S. Cuore Roma

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

3 Finnish study Cumulative Probability of Remaining Free of Diabetes 1 0,9 0,8 0,7 0,6 0,5 0, Study Year CONTROL INTERVENTION Tuomilehto, NEJM 2001

4 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:

5 Diabetes Prevention Program - study Placebo Metformin Life style Incidence 11% 7.8% 4.4% Relative risk reduction Number Needed to Treat 31% 58%

6 Diabetes Guidelines Outcome Measures Clinical Guideline Description of Study Measure Glycosylated hemoglobin control Last glycosylated hemoglobin <7% BP control Last BP < 130/80 LDL-cholesterol control Last LDL-C C < 100 mg/dl HDL-C C control Last HDL-C C >45 mg/dl Triglyceride control Last triglyceride < 150 mg/dl JAMA. 2006;295:

7 Plasma Glucose Response to Different Carbohydrate Sources Blood glucose (mg/dl) Minutes Standard Simple Sugar Soluble Fiber + Sugar Starch

8 Glycemic Index GI first developed in 1981 by Dr. David Jenkins,, professor of nutrition at University of Toronto, Canada and ACN Fellow Glycemic index is a numerical system of measuring the degree of rise in blood sugar in response to various carbohydrates The higher the blood glucose response,, the higher the glycemic index A GI of 70 or more is high, A GI of is medium, and GI of 55 or less is low as compared to glucose which has a GI of 100

9 Glycemic Index Describes the incremental increase in blood glucose from fasting levels over a defined time interval following ingestion of CHO (AUC) relative to a standard Property of food sources of digestible CHO Function of efficiency of digestion and rate of absorption

10 GI ASSESSMENT 1. An amount of food containing a standard amount of carbohydrate (usually 50 grams) is given to a volunteer to eat. 2. Over the next two hours (or three hours if the volunteer has DM), a sample of their blood is taken every 15 minutes during the first hour and thereafter every 30 minutes. 3. Blood-glucose level is plotted on a graph and the area under the curve is integrated 4. The volunteer s response to the carbohydrate is compared with his or her blood-glucose response to 50 grams of pure glucose (the reference food). 5. The reference food is tested on two or three separate occasions and an average value is calculated. 6. The average GI value found in 8 to 10 people is the GI value of that food.

11 How GI is measured in the lab Pure glucose produces the greatest rise in blood glucose levels Pure glucose is set at 100 and every other food is ranked on a scale from 0 to 100

12 Glycemic Indexes of Foods Food AUC mg/l at Standard 3 hours x 100 White bread Whole wheat bread Rice Cornflakes Oatmeal (coarse) Spaghetti Potatoes (boiled) Lentils Chickpeas Kidney beans

13 Problems with the Glycemic Index If high GI food is eaten in combination with low GI food, the GI response is moderate Insulin response to a given food is not linear and is not consistently related to either the CHO content or glycemic effect of the food (varies within the person depending on the time, and, from person to person) Not always the best indicator of healthy food choices (Snickers candy bar vs watermelon) Some studies did not always take into account the amount of carbohdyrate

14 Glycemic Index CRITICISM The specific type of CHO in a particular food does not always predict its effect on blood glucose High variability either within individuals and between individuals (23-54%) however normalized values give 10% variability - (ADA Diabetes Care 2004) Glycemic Load = GI x g CHO in a serving (Salmeron et al. Diabetes Care 1997)

15 Primary Determinants of Glycemic Index Amount of Carbohydrate Portion size Energy density Availability of Carbohydrate Solubility Digestibility Extent of processing Type of processing

16 TISSUES POST-ABSORPTIVE BLOOD GLUCOSE CONCENTRATION Rate of appearance (absorption) Liver first pass INSULIN

17 INSULIN SECRETION INSULIN SENSITIVITY

18 Castello et al. Biochem J 1995 FRUCTOSE GLUCOSE GALACTOSE SGLT1 15 % GLUT5 51 % SGLT1 30% GLUT5 35 % Na + -dependent glucose transporter SGLT1 SGLT1 55 % facilitated fructose transporter GLUT5 GLUT5 14 %

19 SGLT1 GLUT 5 GLUT 2

20 MW < 10 kda OXYNTOMODULIN 37 amino acid peptide that contains the 29 amino acid sequence of o glucagon Glucagon-like like peptide-1 Glucagon-like like peptide-2 Gastric Inhibitory Polypeptide

21 Gastric Inhibitory Polypeptide Receptor GIP GLP1

22 PROCHROMACINE VASOSTATINE ß-GRANINE CHROMO STATINE PANCREA STATINE PARASTATINE

23 Structure and expression of rodent prepro-glucose glucose-dependent insulinotropic polypeptide (preprogip) Ugleholdt, R. et al. J. Biol. Chem. 2006;281:

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25 Mean plasma glucose (top( top), insulin (middle( middle), and C-peptide C (bottom( bottom) ) concentrations in 10 subjects during oral glucose tolerance test (OGTT) and isoglycemic intravenous glucose infusion (I-IVG) IVG) Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

26 Insulin secretion (top( top) ) and its dynamic (SRd( SRd; middle) and static (SRs( SRs; bottom) ) components during OGTT and I-IVG. I IVG. Shaded areas indicate regions where OGTT and I-IVG I IVG values are significantly different (P < 0.05, Wilcoxon's signed-rank test, test performed at sampling times) Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

27 Incretin potentiation on insulin secretion (top( top) and its 2 contributions from SRd (middle)) and SRs (bottom)) components. Shaded areas indicate regions where OGTT and I-IVG I IVG values are significantly different (P( < 0.05, Wilcoxon's signed-rank test, test performed at sampling times). Campioni et al. Am J Physiol Endocrinol Metab 292: E54-E60, 2007

28 CALORIMETRIC CHAMBER

29 TYPE 2 DIABETIC WOMAN (50 yrs) Plasma GIP (pm) Before BPD After BPD Time (hours)

30 TYPE 2 DIABETIC WOMAN (50 yrs) Before BPD After BPD GLP1 (pm) Time (hours)

31 Bertuzzi A, Salinari S, Mingrone G. AJP (1):E

32 Bertuzzi A, Salinari S, Mingrone G. AJP (1):E

33 Bertuzzi A, Salinari S, Mingrone G. AJP (1):E

34 DAG + - LC-CoA CoA GLUCOSE Pyruvate - CPT1 CARN CPT2 Acyl-CoA Pyruvate PDH ß-oxidation Acetyl-CoA PC K + ATP + ATP/ADP PKC + + Ca 2+ Citrate CL Acetyl-CoA TCA Cycle + ACC MDC Malonyl-CoA Modified by Roduit R. et al. Diabetes 2004

35 At this time, there is insufficient information to determine whether there is a relationship between glycemic index or glycemic load of diets and the development of diabetes. However, GI can provide an additional benefit over that observed when total CHO is considered alone.

36 Prof. M. Castagneto Prof. G. Nanni Dr. F. Rubino Dr. M. Manco Dr. D. Gniuli Dr. C. Guidone Dr. A. Iaconelli Dr. L. Leccesi Mrs. A. Caprodossi