According to the CDC in 2007

Transcription

1 How to effectively understand, reveal, and treat people with insulin resistance using blood tests, calipers, diet & exercise. Richard Maurer, ND 2011 Part of the FatBackDiet According to the CDC in 2007 About 8% of Americans have Diabetes Of which 20% Don t know they have it About 25% of Americans have Pre-Diabetes Currently referred to as Metabolic Syndrome Past was referred to as Syndrome X: Dysmetabolic syndrome, cardiometabolic syndrome Most of these people don t know they have it 1

2 How does insulin resistance look? At 65-years old your lifetime risk of developing DM2 is 3% if your baseline BMI below normal 10% if your baseline BMI low normal 15% if your baseline BMI high normal 27% if your baseline BMI slightly above normal 34% if your baseline BMI obese Based upon data from : Diabetes Care June 2007 vol. 30 no How does insulin resistance look? At 45 years old your lifetime risk of developing DM2 is 8% if your baseline BMI below normal 14% if your baseline BMI low normal** 25% if your baseline BMI high normal** 45% if your baseline BMI slightly above normal 59% if your baseline BMI obese **1 in 3 with normal BMI will develop DM in life Based upon data from : Diabetes Care June 2007 vol. 30 no How does insulin resistance look? At 18-years old the lifetime risk of developing DM2 is 8% if your baseline BMI below normal 16% if your baseline BMI low normal* 28% if your baseline BMI high normal* 50% if your baseline BMI slightly above normal 68% if your baseline BMI obese *44% of Normal BMI teenagers are at risk of DM in life Based upon data from : Diabetes Care June 2007 vol. 30 no

3 THE Definition of Metabolic Syndrome This is a multi foundation international definition of metabolic syndrome [Alberti, Eckert, Grundy, Zimmet, et al. Circulation 120:;1640, 2009] Elevated Abdominal Circumference Triglycerides >150 mg/dl HDL cholesterol Men <40 Women <50 Blood Pressure >130/85 Glycemia >100 mg/dl Perhaps an alternative definition The tendency toward Type II Diabetes is a brilliant evolutionary survival tool that is no longer in balance with someone s diet, environment and physical effort. -Maurer, 2012 What is the Thrifty metabolism Glucose and Insulin: The person who saves a lot. Hypothyroid, the person who spends less The thrifty Gene fun term but inaccurate 3

4 What causes Insulin Resistance (IR) Genes Take a good history! Different prevalence of diabetes in ethnic groups Type 2 diabetes in the direct family Adiposity Lifestyle Fitness Measurement of blood tests & body fat is critical Discussion of exercise habits Assess weight fluctuations throughout life Variation in Insulin Resistance When a regulated amount of glucose and insulin is administered IV: Steady State Plasma Glucose can be measured This experiment relates specifically to tissue resistance or sensitivity to insulin Glucose sensitivity varies 6-8 fold in a large population. This is a HUGE variation! Genetic locations for IR [OMIM.org] Cytogenetic locations of T2DM/ IR 7p13 7q32.1 8q q25.2-q p p p q q q34 15q p q12 17q p q q12-q q q

5 So is it genetic? Yes, but what is it? We should cringe when we see the headline in the sensational media stream, New Gene Found that Causes Type 2 Diabetes. It is not some genetic defect that requires correction with medication. It is a planned and advantageous trait that is more common in people than having blue eyes IT is the diet and lifestyle that we have adopted, with excess calories, excess carbohydrates, no period of starvation and minimal activity What conditions result from IR Weight Gain or Loss Cardiovascular Disease Type 2 Diabetes Essential Hypertension Polycystic Ovarian Syndrome Non-alcoholic Fatty Liver Disease Mental/Emotional/Mood conditions Some Cancers Associated Conditions Heads-up MIGRAINES Psoriasis Gout RLS/Muscle Cramps Erectile Dysfunction Depression Baldness Sleep Apnea Androgenic alopecia (baldness) Dementia Fluid-like joint pains no better NSAIDS 5

6 Tests for Metabolic Syndrome Liver Enzymes: AST/ALT should be <40 Fasting Blood Glucose: is optimal Lipid Panel: Optimal TG:HDL is close to 1 HgbA1C: Optimal is </= 5.5 Fasting Serum Insulin: 3-8 is Optimal [HOMA_IR] Uric Acid: If >5.5, assume some insulin resistance CRP: Assesses generalized inflammatory burden Lipid Panel Triglyceride : HDL ratio A ratio of greater than 3 indicates metabolic syndrome. A ratio of less than 2 is normal A ratio of less than one implies insulin sensitivity A ratio of greater than 3 or 4 implies elevated insulin. Either fasting or post-prandial Tg:HDL with known CVD risk factors Smokers measured with TG:HDL-C Ratios Smokers with higher IR markers had significantly higher risk CVD risk What is interesting is that those (lucky) smokers with the most insulin sensitive findings had minimal increased risks of CVD Jeppesen et al, Arch Intern Med. 2001;161:

7 Tg:HDL with known CVD risk factors Hypertension measuring TG:HDL Normal blood pressure with higher IR markers had significantly higher risk CVD risk People with hypertension but with the most insulin sensitive findings had minimal increased risks of CVD Obviously those with hypertension and IR findings had the highest risk Jeppesen et al, Arch Intern Med. 2001;161: Tg:HDL with known CVD risk factors Physical activity measuring TG:HDL High activity people with low IR markers had the lowest CVD risk no surprise People with lowest activity but with the most insulin sensitive findings had no significant increased risk of CVD Lucky folks, eh? Obviously those with inactivity and IR findings had the highest risk Jeppesen et al, Arch Intern Med. 2001;161: Tg:HDL with known CVD risk factors LDL Cholesterol compared with TG:HDL-C People with the Highest LDL cholesterol with low IR markers had minimal increased CVD risk. People with the lowest LDL but with the insulin resistant findings had significantly increased risk of CVD IR trumps LDL cholesterol Jeppesen et al, Arch Intern Med. 2001;161:

8 Hgb-A1C Look at the patient and lifestyle and diet then assess the A1C. Does it match what is expected? is normal. <5.5 is optimal indicates prediabetes >6.5 indicates diabetes Can help assess one with the amplified sawn phenomenon Insulin Fasting Insulin: Should be between 3 and 8 If Elevated: Early Type 2 Diabetics are often >10. The body is trying to put the glucose away There will usually be excess torso/abdominal bodyfat storage Less than 3 implies a potential for a n easy catabolic state. Seen in under-eating/anorexia/ overexercise/ or inappropriate Low carb dieting Kids during Growth Years are often >10 but <20. This is a normal response to promote growth. Glucose and Insulin HOMA-IR: Insulin Resistance value used in research settings. [Homeostatic Model Assessment of Insulin Resistance] Insulin x Glucose divided by 405 Reference range: Those greater than 2.8 are deemed insulin resistant. Practical values the closer to one the better Essentially as Glucose goes up the body s ability to respond to insulin is going down. Thus, resistance. 8

9 Uric Acid Second Nurse s Health Study [Archives of Internal Medicine Arch Intern Med/Vol 169 (No.2), Jan 26, 2009] moderate (but normal) elevations of uric acid were robustly & substantially linked to increased risk of HBP As a screening test for every adult, routinely measuring this simple and inexpensive biomarker on blood tests should help identify those at risk of cardiovascular disease. Uric acid induces the renin-angiotensin system in the kidney and cause injury to the renal blood vessels as of 2009, 12 of 14 previously published studies found significant association with elevated uric acid and hypertension. Note: uric acid levels are not proven to be causative to HBP. CRP Goal <1 on chronic CRP levels Is associated with IR and should correlate with overall A1C improvement This test is valuable partly due to the ubiquitous acceptance of CRP as a CVD risk marker. 9

10 What happens when Glucose raises Compensation Equilibrium Counteraction HOMEOSTASIS Insulin and High Blood Pressure Insulin induces sodium retention at the Kidney Excess fluid retention follows Insulin has a role in storing magnesium Insulin Resistance results in Impaired Magnesium uptake into the cells. Low tissue magnesium causes tighter arteries - Increase in blood pressure When Insulin compensates upward Dyslipidemia TG elevations or Elevated TG:HDL ratios HDL-C LDL particle diameter: becoming small & dense They are then more vulnerable to oxidation Some degree of glucose intolerance abnormal fasting glucose abnormal post-meal glucose (GTT) 10

11 When Insulin compensates upward More Clotting Fibrinogen Plasminogen activator-1 More Inflammation in the Blood Vessels Elevation of cellular adhesion molecules Elevations of asymmetric dimethylarginine Mononuclear cell adhesion Blood Markers of Cellular inflammation: CRP Fibrinogen WBC When Insulin compensates upward Elevation of Uric Acid Patients who have had an MI have higher uric acid Insulin prevents the removal of uric acid at the kidney Insulin affects the ovaries in women elevating testosterone Triggers infertility/physical changes/pcos Insulin alters sodium regulation at the kidney Indirectly increases blood pressure Drugs for this? Oral Hypoglycemics Biguanides Metformin = Glucophage Sulfonylureas Generic = glyburide, aka Diabeta, Glynase, Micronase / glipizide = Glucotrol / glimepiride = Amaryl DPP-4 Inhibitors Januvia, Onglyza Thiazolidinediones essentially off the market Actos, Avandia 11

12 Pharmacokinetics: biguanides Biguanides Like Metformin. Primarily decreases liver production of glucose Liver produces glucose from fat and recently stored glucose. Liver produces glucose during Dawn phenomenon Stress response/hypoglycemia, through glucagon Dietary intake of protein (which stimulates both insulin AND glucagon Lifestyle versus Metformin Compare 3 plans for metabolic syndrome, after 3-years: Placebo 61% still had met syndrome Metformin: 850 bid 55% still had met syndrome 31% reduction in development to DM2 comp to placebo Exercise: 30 5x/week 43% still had met syndrome 58% reduction in development to DM2 comp to placebo A fourth arm of the study with the drug troglitazone (Rezulin) was discontinued due to liver toxicity Lifestyle versus Metformin Take home message To prevent one case of diabetes in a population of people with metabolic syndrome during a period of three years, about 7 people would have to exercise 150 per week, and 14 would have to receive metformin. 12

13 Make a drug to increase Insulin? Sulfonylureas like Glyburide or Micronase Hypoglycemia with related dizziness/ nausea Beta cell burnout Weight gain Adverse reaction with alcohol Antabuse-like reaction Worsening of Met-syndrome findings related to elevated-tg and BHS May Increase Death from CVD Compared to Metformin Alone Increased all cause mortality Increased development of CHF Researchers state: Our findings suggest a relatively unfavorable risk profile of sulphonylureas compared with metformin for all outcomes Ioanna Tzoulaki, Ioanna; Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database BMJ 2009; 339:b4731 Sulfonylurea Assess insulin 1 st Test basal and post challenge insulin without the drug half-life is 5-10 hours 3 days off may be adequate to assess insulin, wait as long as possible and practical If patient is taking insulin, do not order insulin levels Instead order C Peptide. C-Peptide has 30 half-life compared to insulin 5 Elevated level indicate elevated endogenous insulin secretion 13

14 Assess Insulin-Glucose Balance Goals in health, weight management, prevention of illness require an assessment for insulin responsiveness or resistance. Blood tests Past medical history Family history Body fat distribution "What gets measured gets managed Use of Body Fat Calipers 14

15 Reason to use calipers Compares locations of body fat: Abdominal vs leg/arm Helps allocate importance of diet and exercise in order of importance Tracks compliance of diet separate from exercise Takes the emphasis off of the cursed scale Triceps skinfold is greater Means Overall Metabolism is Slow/Efficient First, assure thyroid is well evaluated TSH & FT4 Anti-TPO Assess exercise log on a regular basis Assure very regular exercise with aerobic & anaerobic components Build a lifestyle of activity 10,000 steps perhaps Caliper measurement of Triceps 15

16 To Correct Triceps Get Metabolism Moving 6 days per week Aerobic to 75% of maximum HR minutes duration Last 5-10 minutes of workout should be with an anaerobic push Weights, increased resistance of any kind OR Try lactic load workouts Go until you can t Rest until you can. EXERCISE Why the anaerobic push?? In a 2006 study in Norway, found oxygen uptake doubled with higher intensity exercise for the same duration. The American Heart Association now states for those with Metabolic Syndrome Short bursts of high-intensity exercise, rather than longer spells of moderate-intensity, exercise may improve the health of people with metabolic syndrome. Study on Exercise and Insulin People with elevated fasting blood G: Mild - moderate - intense weight routines Blood glucose improved in all groups. But significantly greater insulin sensitivity was found in the highest intensity exercisers who did four sets of eight upper and lower body strength exercises at high intensity, the participants did less than 10 repetitions of each exercise. Journal of Strength and Conditioning Research, 2010; 24 (4):

17 Caliper measurement of Hip Skinfold (mm) is Greater in the Hip Assume excess Insulin Check Diet History carefully Ask about diabetes family history Assure a good run of blood tests to assess placement continuum of Insulin Resistance TG:HDL, Liver Enzymes, FBG, A1C, Fasting Insulin If Abdominal bodyfat is excess Emphasize dietary intervention first Low Glycemic Load Diet Low carbohydrate Note this does NOT mean whole grain White bread* 75±2 Whole wheat/whole meal bread 74±2 Moderate Protein High Fats Reduce alcohol intake Avoid artificially sweetened beverages 17

18 Sleep effects on adiposity and IR Sleep Pattern irregular feast famine sleep patterns exacerbated IR findings and was assoc w/adiposity This study was on kids <10-yo C-reactive protein Insulin Lipids [Sleep Duration, Sleep Regularity, Body Weight, and Metabolic Homeostasis in School-aged Children, Spruyt, Karen, et.al. Pediatrics, February 2011] Carbohydrate Intake The world is not a fair place The greater the insulin response to carbohydrate The greater the fatty weight gain The greater the insulin response to carbohydrate How do we then eat these necessary foods and not trigger insulin excess Four Insulin triggers in the diet 1. Carbohydrate intake 2. Protein (amino acid) intake Things that taste sweet 4. Stretching the stomach 18

19 Carbohydrate Intake Sugars and Starch Simple carbs: Monosaccharides Glucose, fructose, galactose, xylose, ribose Disaccharide Sucrose, lactose, maltose, cellobiose, trehalose Complex carbs: Starch based foods Amylopectin and amylose Plant starch is glycogen s 1 st cousin Sugars and Starch How much? NIDDM 6 breakfast/ lunch/ dinner Significant insulin resistance Break/ lunch and dinner Minor insulin resistance 20 Breakfast/ lunch and dinner Non-insulin resistance Breakfast/ lunch and dinner 19

20 Sugars and Starch For reference: Potato medium, sweet or white): 25 grams Rice, cooked 1 cup: 40 grams Legumes, ½ cup cooked: 25grams Chard, ¼ pound: 5 grams Fruits fructose content: 2 medjool dates 15 grams 1 medium pear 11 grams A medium apple 10 grams 1 cup of diced watermelon 5 grams 1 banana 5 grams 10 grapes 4 grams Protein Intake Protein Intake As amino acids increase in the bloodstream: Insulin and Glucagon are secreted. Insulin lowers blood sugar and enhances the muscle uptake of amino acids Glucagon raises blood sugar in a presumed attempt to allow proteins to make tissue, while allowing the elevated glucose to be burned as energy post-meal In studies: just 25g of pure protein was enough for significant release of insulin 20

21 Protein Intake Diets that are greater than 50% protein are considered significantly high protein Diets that are about 25% - 35% protein are considered normal protein diets The world health organization considers about 15% as a basis requirement Maine Metabolism Rule: Ingest gram per pound of lean body mass Diabetic equivalents A Type 1 Diabetic uses: Per 8 grams of Carbohydrate: 1 unit of Regular Insulin Per 1.5 Ounces of Protein: 1 unit of Regular Insulin There is no immediate dosing of insulin to accommodate fat calories at a meal. Fat will be broken down AS NEEDED for an efficient energy burn Overeating GASTRIC NEURO-HORMONAL RESPONSE The stomach has stretch receptors that signal hormone and digestive secretions and motility. One of the hormone secretions: Glucose-Dependent- Insulinotrophic Pepetide: GIP stimulates insulin secretion. 21

22 Things that taste sweet It is not accidental that all phenomena of human life are dominated by the search for daily bread.... Precise knowledge of what happens to food entering the organism must be the subject of ideal physiology, the physiology of the future. Ivan Pavlov, Nobel Lecture, 12 December 1904 Things that taste sweet Over 100 years after Pavlov Eating artificially sweetened foods has been shown to cause increase total caloric intake Drinking artificially sweetened beverages is associated with obesity even when controlling for caloric differences It is postulated that Non-caloric sweet tasting foods and beverages cause a Pavlov-style cephalic insulin response What s Left? If carbohydrates are best limited and protein is only about 35% of the dietary calories WHAT IS LEFT? FATS 22

23 Fats in the Diet? From WebMD Heartwire March 29 th, 2010 Dr Dariush Mozaffarian (Harvard University, Boston, MA) told heartwire... a recent meta-analysis of prospective epidemiologic studies showing that there was no significant evidence that dietary saturated fat is associated with an increased risk of coronary heart disease or cardiovascular disease [2]. Dietary caloric percentages If 2400 calories is the maintenance goal Carbs- for example someone has to limit carb grams to 20/40/40[B,L,D]. Thus a total daily carb intake of 100 grams calories 17% of calories Proteins say the daily goal is about 150 grams of protein. This adds up to 600 calories 25% of the dietary calories The other 1400 calories have to come from somewhere...fats. 58% of dietary calories Dietary fats have minimal to no significant effect on insulin, so visceral fat and circulating triglycerides do not increase in response to dietary fats. Glycemic Index or Why the glycemic index of individual foods is moot The glycemic index of individual vs. mealbound foods 23

24 F:1 Glycemic index of single and mixed meal foods among common Japanese foods Conclusions about mixed meals on GI Among mixed meal foods, the combination of carbohydrate foods with vinegar, dairy products, and bean products significantly decreased the GI value of white rice of 20-40%. Sugiyama M, Tang AC, Wakaki Y, Koyama W. Eur J Clin Nutr Jun;57(6): F:1 Barley Bread Containing Lactic Acid Improves Glucose Tolerance at a Later Meal in Healthy Individuals Conclusions about Lactic Acid: when the barley bread with lactic acid was given as a breakfast. At 45 min after the lunch meal, the insulin level was significantly lower (-21%, P = 0.045) after the lactic acid bread breakfast, Ostman EM, Liljeberg Elmstahl HG, Bjorck IM. J Nutr Jun;132(6): F:2 The glycemic index: importance of dietary fiber and non-glucose parts of a food Conclusions about Fiber Content: the higher dietary fiber content with low-gi foods add to the metabolic merits of a low-gi diet. An LGI barley (GI 53) meal rich in fiber improved gluc. tolerance from evening to breakfast, whereas an evening meal of pasta (GI 54) had no effect Bjorck I, Elmstahl HL. Proc Nutr Soc Feb;62(1):201-6 [Proceedings of the Nutrition Society] Note: This study indicates it is the SOLUBLE FIBER 24

25 F:3 Glycemic Index and Dietary Fat Stimulates the hormone cholecystokinin (CKK). CKK inhibits gastric activity, thereby allowing time for nutrients in the duodenum to be digested and absorbed without excessive stomach activity. Enhances pancreatic enzyme secretion and activity. Dietary Fat via CCK: Lower the glycemic index of the meal due to a slower pace of gastric emptying. Three F - Conclusions Fat- All foods should have their original fat content intact. Fiber meals should contain a fiber-rich food, preferably a concentrated (cooked) dark green vegetable Fermentation lactofermented food such as yoghurt and sauerkraut Metabolic syndrome: pre-diet 25

26 Blood tests related to Met Syn Test Date 1/4/2008 9/18/08 11/22/08 Cholesterol Triglyceride HDL TG:HDL Fasting glucose Fasting insulin hr glucose hr insulin 99.7 Body Fat Calipers for Mr. S. DATE Triceps Biceps Back Hip MM Total % BF 2/19/ % 3/5/ % 4/29/ % 7/17/ % 9/23/ % Metabolic syndrome: post-diet 26

27 Nutrients Chromium Dose anywhere mcg. CoQ10 If HBP, If High lipids Alpha Lipoic Acid 600/day. Think with neuropathy Mg If HBP, If Constipation, If Leg cramps Fibers Beta-glucan: Oat Bran / Barley Grain Fats and Oils Dose for vitamin D, EFA def. Botanical Ginseng Taken before each meal resulted in lower post prandial blood sugars Gymnema Limited scientific evidence. Shown to lower glucose levels in Type I Diabetics over a 20 month trial. Soluble Fiber Perhaps a supplemental fiber, psyllium, if dietary sources remain inadequate Core Nutrient Plan Multiple Vitamin Omega-3 as CLO or Fish oil Lipoic Acid and/or CoQ10 Magnesium with other mineral support A blood sugar control combination product Adequate Vitamin D 27

28 USDA Then USDA Now Ligurian Bacon 28

29 A world supermarket The bread is a <10% of the calories Note the oily broth 29

30 Thank You FatBackDiet.com --- MaineMetabolism.com 30