If you’re killing yourself to lose weight in the gym and dieting, you’re killing your metabolism

too.

Obese people can maintain stable weight loss

• Study shows that if an overweight person is able to maintain an initial weight loss – in this case for a year – the body will eventually accept the new weight

• Brain hormones adjust to a new set point

European Journal of endocrinology 2016

Always Hungry?

• Obesity patterns remain at historic highs

• Despite 40-year focus on low-calorie, low-fat diets

• Counting calories rarely produces lasting weight loss:

• Usually causes suffering and shame

• Implies no self-control

Always Hungry? By David Ludwig, MD, PhD

Always Hungry? (cont’d)

• Breakthrough – the process of becoming fat makes us overeat

• Tame “hunger fat”

• Fat cells are sucking up and storing too many calories, leaving too few for the rest of the body

Always Hungry? By David Ludwig, MD, PhD

Always Hungry? (cont’d)

• Brain perceives low-energy resources and releases starvation response (eat more, slow metabolism)

Always Hungry? By David Ludwig, MD, PhD

Always Hungry? (cont’d)

• Insulin – the ultimate fat-cell fertilizer

Always Hungry? By David Ludwig, MD, PhD

Always Hungry? (cont’d)

• Stress, sleep deprivation, sedentary causes fat storage

• Processed carbs overstimulate fat cells

Change what we eat, not how much

Always Hungry? By David Ludwig, MD, PhD

Resistant starch

• Improves metabolism

• Increase insulin sensitivity

• Improves blood sugar

• Increases fat burning

• Reduces fat storage in your cells

• Optimize your gut flora

• Digested only by the good bacteria in your gut (prebiotic)

• “Resists” digestion and doesn’t spike blood sugar or insulin

Resistant starch for a healthy gut

• Resistant starch:• Beans, whole grains, rice, potatoes – high in amylase

• Passes through stomach and small intestine

• Doesn’t enter bloodstream

• Food your microbes – prebiotics

• Build up butyrate:• Short-chain fatty acid

• Primary energy source for cells of large intestines (cell membrane)

• Inhibits cytokines

• Makes colon inhospitable place for cancer

Genetically engineered salmon approved for consumption

Federal regulators approved genetically engineered salmon as fit for consumption, making it the first genetically altered animal to be

cleared for American supermarkets and dinner tables

NYTimes, Nov 19, 2015

A genetically engineered salmon from AquaBountyTechnologies, rear, with a conventionally raised sibling roughly the same age.Credit Paul Darrow for The New York Times

New study finds organic diet for one week drops pesticide levels by 90 percent in adults

• RMIT University study published in Environmental Research: organic diet for just one week significantly reduced pesticide exposure in adults

• Study found – urinary dialkylphosphates (DAPs) measurements 89% lower when they ate an organic diet for seven days compared to conventional diet for the same amount of time

New study finds organic diet for one week drops pesticide levels by 90 percent in adults (cont’d)

“A lot of these agents were initially developed as nerve gases for chemical warfare, so we do know that they have toxic effects on the nervous system at high doses. Conventional food production commonly uses organophosphate pesticides, which are neurotoxins that act on the nervous system of humans by blocking an important enzyme. Recent studies have raised concerns for health effects of these chemicals even at relatively low levels. This study is an important first step in expanding our understanding about the impact of an organic diet.” – Dr. Liza Oates

New Nutrition Label

New label by July 26, 2018

• Serving sizes – reflects what people currently eat, not what the company deems reasonable

• Calories – total calories now highlighted in huge letters

• Added sugars – measured in both grams and as a percent daily value

• Multi servicing products – two columns to indicate per serving and per package calorie and nutrition information

• Odd-sized packages – all considered one serving

• Sodium and dietary fiber – based on 2015-2020 dietary guidelines

• Vitamin D & K – percent daily values and gram amount

• Vitamin A & C – no longer required on labels

• Fat – total fat, saturated and trans fat

• Percent daily value – more streamlined

Are we at a crossroad?Not so effective….

Dysbiosis + Obesity“We don’t think the bacteria

are directly making the mice

eat more, but the

bacteria are causing

low-grade

inflammation, which

causes insulin

resistance.”

The environment within: how gut microbiota may influence metabolism and body composition

Diabetologia Vol. 53 Issue 4

Dysbiosis +

Poor Diet

=

Insulin Resistance

The environment within: how gut microbiota may influence metabolism and body composition

Diabetologia Vol. 53 Issue 4

“Seeking an inflammatory factor causative of the onset of insulin resistance, obesity, and diabetes, we have identified bacterial lipopolysaccharide (LPS) as a triggering factor.”

Metabolic endotoxemiainitiates obesity and insulin resistance

Diabetes. 2007 Jul;56(7):1761-72. Epub 2007 Apr 24

The gut immune system and Type-1 diabetes

• Intestinal walls of people with type-1 diabetes found to be more permeable than those without type-1 diabetes

• Those with type-1 diabetes – intestinal immune system seems to be more active due to inflammation

Vaarala O. Ann N.Y. Acad Sci. 2002 Apr;958:39-46

Human Intestinal Microbiota and Type-1 diabetes

• Gut inflammation and permeability also likely accompanied by changes in gut microbiota

• Alterations in gut microbiota may explain the increased gut permeability, inflammation and immune dysfunction in type-1 diabetes

Vaarala O. Curr Diab Rep. 2013 Oct;13(5):601-7

Antibiotics Raise Diabetes Risk via Gut Microbiota• U.S. researchers: People who take multiple courses of antibiotics face

increased risk of developing both type-1 and type-2 diabetes through alterations in gut microbiota

• Risk was increased by 37%

European Journal of Endocrinology online, March 24, 2015

Antibiotic use tied to diabetes risk

• Those who filled two to four prescriptions had 23 percent higher risk for diabetes

• Those who filled five or more had 53 percent higher risk

• Scientists suggest that antibiotics may disrupt gut biota, causing changes in insulin sensitivity and glucose tolerance, which can lead to diabetes

Journal of Clinical Endocrinology & Metabolism, Sept 2015

Artificial sweeteners disrupt body blood sugar controls

• Sweeteners alter microbiome

• The different mix of microbiomes changes the metabolism of glucose causing levels to rise higher after eating and to decline more slowly than otherwise

• Big 3:• Saccaharine

• Sucralose

• Aspartame

Journal Nature, Sept. 2014

Artificial sweeteners induce glucose intolerance by altering the gut microbiota• Recent study of mice and people suggest that saccharin interferes

with gut’s microbial community, initiating metabolic changes associated with obesity and diabetes

• Saccharin-fed mice on a high-fat diet – resulted in impaired glucose metabolism in five weeks

• Mice fed glucose-laced water – normal metabolism

• Researchers compared 40 people who ate artificial sweeteners and 236 who did not – those consumed artificial sweeteners more likely to have impaired glucose metabolism

J. Suez et al. Nature. Published online Sept. 17, 2014

Metabolic effects of non-nutritive sweeteners (NNSs)• Consumption of NNSs increased risk to develop:

• Obesity

• Metabolic syndrome

• Type-2 diabetes

Pepino MY. Physiol Behav 2015

Metabolic effects of non-nutritive sweeteners (NNSs) (cont’d)• NNSs interfere with learned responses that contribute to control

glucose and energy homeostasis

• NNSs interfere with gut microbiota and induce glucose intolerance

• NNSs interact with sweet-taste receptors expressed throughout the digestive system that play a role in glucose absorption and trigger insulin secretion

Pepino MY. Physiol Behav 2015

Artificial Sweeteners

• Sugar substitutes may cut calories but no health benefits for individuals with obesity

• Study suggests that bacteria in the gut may be able to break down artificial sweeteners, resulting in negative health effects (glucose management)

Applied Physiology, Nutrition, and Metabolism. 2016

Eat Food

Cells Resist Insulin

Make Insulin

Sugar Stores As Fat

Feel Tired & Hungry Insulin

Resistance

Targeting Insulin Resistance

Visceral Fat

Inflammation

Glucose Toxicity

Lipotoxicity

Testosterone

Growth Hormone

Low Carbohydrates

SGLT2-I

Exercise

Non-surgical Weight Reduction

Bariatric Surgery

Very Low Calorie Diet

Metformin

TZDs

Insulin

InsulinSensitivity

High Dose Salicylates

Hamdy O. Joslin Diabetes Center, 2014

21st Century Health Problems:Carbohydrate Intolerance & Glucose Toxicity

• Over consumption of sugars and low quality carbohydrates.

• Leading to the development of glucose toxicity and chronic illness well before Diabetes.

• Nearly 60% of the population is predisposed to carbohydrate intolerance.

• Without a solution, this national epidemic will continue to grow.

Glycemic Dysregulation If you eat too much or eat too many sweets your blood sugar will shoot up quickly and then drop down precipitously. On the way down your adrenal glands make cortisol to keep your blood sugar stable

Glucose requirements

Blood sugar spikes INSULIN rushes

to store excess

Hunger begins

Insulin continues unopposed

ADRENALS must “catch”

Fat

Cortisol

This is where many of our patients live

Blood Sugar Level

Healthy blood sugar range

Remaining blood sugar from previous meal

Sugar is rapidly absorbed into your bloodstream, causing blood sugar spike

Pancreas pumps insulin into the blood in an attempt to bring blood sugar back to proper range

Due to high amount of sugar, pancreas overestimates how much insulin to pump into the blood. Result: too much sugar is removed from the blood, causing blood sugar crash

You eat a sugary meal

30-60 mins. later

Time

Diabetes

ReleaseBlood glucose

IL-1

Multiple times

Monocytes transform into macrophages (in pancreas)

Ultimately

Beta cells

Atherosclerosis

Endothelial cells

Glucose

ATP + superoxide free radical

NF-κB

Atherosclerosis

Cutting sugar rapidly improves heart health markers

• Obese children who cut sugar from their diets saw improvements in markers of heart disease after just 9 days

Study – same number of calories per group:• Lowered dietary sugar from 28 to 10 percent

• Fructose from 12 to 4 percent

• After 9 days:• 33 percent drop in triglycerides

• 49 percent reduction in APOC-III

Atherosclerosis, July, 2016

Dietary glycemic index linked to lung cancer risk in select populationsStudy identifies most significant associations in those who had never smoked

• Consuming a diet with high glycemic-index, a classification of how rapidly carbohydrates elevate blood sugar levels, was independently associated with increased risk of developing lung cancer in non-Hispanic whites – new epidemiologic study

University of Texas M.D. Anderson Cancer Center, Mar 4, 2016

Mediterranean diet cools down the inflammatory milieu in type-2 diabetes

At 1 year: CPR decreased by 37%, adiponectin rose by 43%

Endocrine, Feb. 9, 2016

Mediterranean Diet for Diabetes

• Adhering to Mediterranean-style diet may help reduce risk for type-2 diabetes, even when people don’t lose weight or increase exercise levels

NYTimes.com

ModifiedMediterranean Diethas been shown to be an effective foodplan for those withmetabolic syndrome

B. Schiltz, et al. Metabolic Syndrome and Related Disorders, Vol. 7, Num 3, 187-192

Lifestyle Changes Staves Off Diabetes, Death

• 6-year lifestyle intervention decreased incidence of diabetes, cardiovascular mortality, and all-cause mortality in adults with impaired glucose tolerance

The Lancet Diabetes & Endocrinology online

• During 23 years of follow-up, individuals in the intervention group had a 45% lower risk of developing diabetes

• Had a 41% decrease in cardiovascular mortality

Blood sugar dysregulation

AGEs – more than just markers of aging since they can exert adverse biological effects on tissues and cells including the activation of intracellular signal transduction pathways, leading to the up-regulation of cytokine and free radical production (oxidative stress)

Alzheimer’s Disease – Synergistic Effects of Glucose Deficit, Oxidative Stress and Advanced Glycosylation End Product. Munch. G., et al. Journal of Neural Transmission. 105(4-5):439-61, July 1998

Advanced glycation end products associated with diabetes and insulin resistance promote

brain neural cell degeneration

Strict control of blood glucose throughout the lifetime would seem to be logical. At one time, the ADA recommended keeping average

blood glucose below 140 mg/dL.

This recommendation has evolved to a current push to recommend that at NO time should blood glucose be elevated above normal

parameters.

Should we all be on a diabetic diet?

Components of Metabolic SyndromeAHA/NHLBI Scientific Statement

Measure Categorical Cut Points

Elevated Waist Circumference

40 inches in men

35 inches in women

Elevated TG 150 mg/dL (or drug tx for elevated TG)

Reduced HDL-C < 40 mg/dL in men

< 50 mg/dL in women

Elevated BP 130 mm Hg systolic BP or 85 mm Hg diastolic BP or drug tx for HTN

Elevated fasting glucose 100 mg/dL or drug tx for elevated glucose

Grundy SM et al. AHA/National Heart, Lung, and Blood Inst. Oct. 25, 2005:112(17), p.2735-52

(3 of 5 Criteria needed for Diagnosis of Metabolic Syndrome)

2-Hour Post-Prandial

80 – 120 Optimal

120 – 140 Caution

140 – 200 Impaired glucose tolerance

200 Diabetes mellitus

Note: Lab values based on clinical experience and manual of laboratory and diagnostic tests by Frances Fischbach

Fasting Glucose and 2-Hour Post-Prandial Glucose

Fasting

65 – 99 Optimal

100 – 125 Impaired fasting glucose (pre-diabetes)

> 126 Diabetes

Source: www.MayoClinic.com

Fasting and 2-hour Post-Prandial Insulin

• Can be done in conjunction with a GTT or fasting blood glucose test

Fasting 2-Hour post-prandial

< 17 miu/ml (normal) < 55 miu/ml (normal)

> 17 miu/ml (resistant) > 55 miu/ml (resistant)

Note: Lab values based on clinical experience and manual of laboratory and diagnostic tests by Frances Fischbach

Fructosamine Test

• Used whenever the practitioner wants to monitor a patient’s average glucose over the past 2 – 3 weeks

• Used to monitor short-term dietary change

• Reference range: 190 – 260 umol/L

HgA1c

• Hemoglobin A1C is the component of hemoglobin that most strongly combines with glucose

• The percent of HgA1C that is “glycosylated” is a strong indicator of the amount of glucose available in the blood stream over the past 100-120 days (the life span of the RBC)

• Normal values: • 2%-4.9% non-diabetic adult

• 2.5%-5.9% good diabetic control

• >6% diabetes

• Dr. Rob’s reference range: non-diabetics (< 5.5%)

In Control Out-of-control

5%

9%

8%

10%

11%

6%

7%

A1c(%)

Blo

od G

lucose (

mg/d

l

90120

150180

210240

270300

12%

A Simple Test for Insulin Resistancea key component of Metabolic Syndrome

TG/HDL Ratio

≤ 3.0 normal

≈ 5.0 suggestive of insulin resistance

≥ 8.0 diagnostic of insulin resistance

Ann Int. Med. Nov. 18, 2003. 139(10), p.802-9

What is Normal Glucose Response & Control?

Adapted from Nauck MA et al. Diabetologia 1996;39:1546-53 and Drucker DJ Diabetes1998;47:159-69

Promotes satiety and reduces appetite

b-cells:Enhances glucose-dependent insulin

secretion

Liver: controls hepatic glucose output

Gut: Helps regulate gastric emptying

b-cell response

Major Sites of Glucose Control:Gut, Liver, Muscle, Adipose, Pancreas

Okay…let’s see what supplements might help…

Trigger

DNA

IKb-a

NF-kb

IKK

SYK

GSK3

MSK

PI3k

Kinase

Kinase

Kinase

Kinase

Kinase

I

Glucose ConversionTo Glycogen

II

GG

XG

X

XX

Impaired Insulin FunctionThe Role of Kinases in Insulin Resistance

Response to Messages of Poor Health:

1. Trigger (message) is translated to keep GSK activated

2. Without modulation, GSK leads to insulin resistance

3 GSK also triggers NF-kappaB, initiating the inflammatory cascade

Trigger

DNA

IKb-a

NF-kb

IKK

SYK

GSK3

MSK

PI3k

Kinase

Kinase

Kinase

Kinase

Kinase*Selective Kinase Response Modulators

Glucose Conversionto Glycogen

II

IG G

G

Healthy Insulin FunctionThe Role of HOPS in Insulin Sensitivity

*HOPS modulate selective kinase

responses associated with Insulin Resistance

HOPS influence intra-cellular communication resulting in improved insulin sensitivity.

8 Week Double-Blind, Placebo-Controlled Trial Examining the Effects of HOPS Supplementation on Insulin Homeostasis

Robert H. Lerman, MD, PhD, Matthew L. Tripp, PhD, and Jeffrey S. Bland, PhD.Functional Medical Research Center, the clinical arm of Metagenics, Inc., Gig Harbor, WA.