6/28/2013

Diabetes Mellitus Type 2: The Prototypical Lifestyle Where? Who? Why?

George S. Motto, M.D., CWP, Founder The Metabolism, Weight, & Lifestyle Institute, Ltd. Board Certified in Endocrinology & Metabolism since 1973 www.weightinstitute.com

The Two Types of Diabetes Both Types are Inherited ( genetic) but differently:

 Type 1 (not the “epidemic” or “tsunami” Less Than 10% of People with Diabetes Autoimmunity causes loss of insulin Insulin is Only Treatment Lifestyle disease after diagnosis  Type 2 (gestational is subset) More Than 90% of People with Diabetes Insulin resistance and incomplete insulin production Lifestyle and Oral Agents initial treatment Most patients will eventually need insulin Lifestyle disease before and after diagnosis 85% of patients are overweight or obese Onset and progression can be affected by lifestyle

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Diabetes in the United States

Diagnosed Diabetes: 29 million U.S. Population: 315 million (Diabetes 1 in 8) Undiagnosed (estimate) 1/3 or ~ 10 million

• Incidence: ~ 1.5 million new cases diagnosed yearly; 90%-95% Type 2 • Number of adult patients predicted to grow continually • Increasing numbers of children and pre-teens diagnosed with Type 2 DM USA child born in 2000 has 1 in 3 chance of developing DM in his/her lifetime (1 in 2 for Latino females) Worldwide: 347+ million; By 2030 7th cause of death WHO and CDC and ADA 2013

Medical Complications of Diabetes Microvascular (related to blood sugar):

 Retinopathy (eye)

 Nephropathy (kidney)

 Neuropathy (nerve) Macrovascular (related to blood sugar plus):

 Heart – , heart failure

 Brain – , TIA, carotid artery stenosis

 Extremities (usually feet and legs) - peripheral vascular disease

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Prevalence* of Self-Reported Among U.S. Adults BRFSS, 2011 *Prevalence reflects BRFSS methodological changes in 2011, and these estimates should not be compared to previous years.

15%–<20% 2 20%–<25% 25%–<30% 30%–<35% ≥35% Approximately 65% of Americans are overweight or obese.

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Overweight All Over the World!

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“GENETICS MAY LOAD

THE CANNON, BUT HUMAN

BEHAVIOR PULLS THE

TRIGGER.”

E. Joslin, MD 1924

Natural History Of “Pre”–Type 1

This image cannot currently be displayed. Diabetes Putative trigger -Cell Cellular autoimmunity mass 100% Circulating autoantibodies (ICA, GAD65)

Loss of first-phase insulin response (IVGTT) Clinical Glucose intolerance onset— (OGTT) only 10% of -cells remain Genetic Insulitis “Pre”- predisposition -Cell injury diabetes Diabetes

Time (months)

Eisenbarth GS. N Engl J Med. 1986;314:1360-1368 14

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Interplay of Genes & Lifestyle One Cannot Control One Can Control

Genetic Factors: - Insulin Resistance Overweight, Habits & Behaviors: - Prog. B Cell Failure Obesity, Eat Too Much Food Home & Family Being Physically & Drink Environment Unfit Don’t Do Enough Physical Activity Glucose Intolerance

Cardiovascular (heart; stroke; amputation) Disease Diabetes Eye, Kidney, and Nerve Disease

Alberti KGMM et al. Diabet Med. 1998;15:539-553; Reaven GM. Clinical Diabetes. 1988;37:1596-1607; DeFronzo REA et al. Diabetes Care. 1991;173-194; Bjornthorp P. Ann Med. 1994;24:465-468; Ford ES. JAMA. 2002;287:356-359

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Metabolic Syndrome Type 2 Diabetes and Heart Metabolic Risk The “Perfect Storm”

Causes of Mortality in Patients With Diabetes ( ~ 65% of patients succumb to )

Macrovascular (large blood vessel) Involvement

Pneumonia/ Other Malignant Neoplasms 4% 5% 13%

13% 55% 10%

Diabetes

Cerebrovascular Heart Disease – affects women disproportionately Disease Robs women of “estrogen advantage” 1st MI incidence = 2nd MI incidence after 1st MI (no DM)

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What Causes Macrovascular Complications? Metabolic injury to large vessels

Heart Brain Extremities

Coronary artery disease Cerebrovascular disease Peripheral vascular – Coronary syndrome – TIA disease – MI – CVA – Ulceration – CHF – Cognitive impairment – Gangrene – Amputation

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Risk Factors for Cardiovascular Disease

• Not modifiable – Genetic factors – Family history & environment • Modifiable – Hyperglycemia (high glucose) – (high blood pressure) – Dyslipidemia (cholesterol & triglycerides) – Smoking – Overweight – Physical inactivity

Metabolic Syndrome

Risk Factor Defining Level Abdominal obesity Waist circumference* Men >40 in Women >35 in Triglycerides, mg/dL 150 HDL-C, mg/dL Men <40 Women <50 BP, mm Hg 130/≥85 Fasting glucose, mg/dL 100

*Lower cut points for Asian Americans. Diagnose by presence of 3 or more risk factors

Adapted with permission from Grundy SM, et al. Circulation. 2005;112:2735-2752.

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How to Measure Waist Circumference ● Place a measuring tape, held parallel to the floor, around the patient’s abdomen at the level of the iliac crest ● The tape should fit snugly around the waist without compressing the skin ● Take the measurement at the end of a normal expiration

A waist circumference of ≥40 inches in men or ≥35 inches in women is diagnostic of abdominal obesity and suggests the presence of other cardiometabolic risk factors.

Adapted from Grundy SM, et al. Circulation. 2005;112:2735-2752.

Waist Circumference as Measurement of Visceral Fat Predictor of Risk Independent of BMI Men: > 40 inches Women: > 35 inches

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Intra-abdominal Fat Distribution in Type 2 Diabetes

No Diabetes Type 2 Diabetes

Courtesy of Wilfred Y. Fujimoto, MD.

Atherosclerotic Process in Type 2 Diabetes

1 1. Normal artery 2. Macrophages, 2 monocytes, and 5. Lipid-laden T cells migrate macrophages to the sub- return to endothelium bloodstream, 5 tearing the 3. Macrophages endothelium and 3 become foam causing cells and thrombus 4 combine with formation T cells and 4. Fatty streak smooth muscle evolves into fibrous to form fatty plaque streak Ross R. Annu Rev Physiol. 1995;57:791-804

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Why is this happening And What Can We Do?

Then & NOW

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We’ve Been Adapting & Changing for Millenia Not Always for the Better!

Lifestyle Prev. & Treatment Management Overweight  Increased Physical  Type 2 Diabetes Activity =  High Blood Fats (lipids)  Less calorie (energy) intake = Increased  High Blood Pressure carbohydrates/fiber;  Coronary Artery Disease decreased % total fat;  Sleep Apnea increased “good” fat  Stroke  Smoking Cessation  Decreased  Moderate Intake  Impaired Quality of Life  Stress management  TOO MANY  Adequate sleep MEDICATIONS!

Weight loss ~ 7-10% Is Very Beneficial Subcutaneous adipose tissue

Visceral Physical Activity adipose tissue Medication

Deterioration Improvement Impaired Improved

Blood Glucose Blood Lipids (fats) Blood Pressure

Increased Heart Risk Lowered

Overweight and Obesity After Weight Loss Increased waist circumference Reduced waist circumference AdaptedYou with permissionDon’t from Have Després To JP, etLose al. BMJ. 2001;322:716-720.A Lot of Weight!

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SCIENCE SHOWS LIFESTYLE ACTIVITIES DO WORK TO PREVENT DIABETES (DPPOS)

Placebo: NO TREATMENT Metformin: MEDICATION Lifestyle: 7% WEIGHT LOSS; <25% fat diet 150 MINUTES PHYSICAL ACTIVITY/WEEK DECREASE IN DIABETES! 31% by Metformin 58% by Lifestyle Percent developing diabetes All participants

Lif est yle ( n=1079, p<0. 001 vs. M et , p<0. 001 vs. Plac ) 40 M et f or m in ( n=1073, p<0. 001 vs. Plac) Placebo ( n=1082)

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Theci dence (DPP %) Research Group, NEJM 346:393-403, 2002 n

Prevention Studies Follow Up

 DPPOS (Diabetes Prevention Outcomes Study): 35% reduction in lifestyle group at 10 years

 Da Quing Diabetes Prevention Study: 43% reduction to 14 years

 Finnish Diabetes Prevention Study:43% reduction to 7 years

What Is a “Healthy Lifestyle” Anyway?

Very simply, the components of a “healthy lifestyle” are:

 Healthy eating

 Regular Physical Activity

 Balancing both to maintain or lose weight (if overweight)

 Avoidance of smoking, street drugs, and other “risky” behaviors.

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Our Lifestyle Professional Battle Cry Should Be: “TAKE CHARGE OF YOUR LIFESTYLE, IT DOES WORK TO PREVENT (Type 2) & TREAT DIABETES (Types 1 & 2)!”

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