Metabolic Syndrome & Insulin Resistance

Metabolic Syndrome &Insulin Resistance By Elizabeth Large, ND Gordon Medicalassociates 3471 Regional Parkway Santa Rosa, CA 95403 707.575.5180 info@gordonmedical.com www.gordonmedical.com

Metabolic Syndrome Metabolic syndrome is called a syndrome rather than a disease because it refers to a group of risk factors that occur together and increase the risk for coronary artery disease, peripheral artery disease, type 2 diabetes and stroke. It is believed to effect approximately 25% of the population.

Risk Factors Genetics Hypertension Insulin Resistance Hyperlipidemia Obesity especially increased abdominal girth** Sleep Apnea

Metabolic Syndrome Criteria 3 + of the following Central or abdominal obesity (waist): Men - Greater than 40 inches and Women - Greater than 35 inches, Triglycerides greater than or equal to 150 Blood HDL - Men - Less than 40 Women - Less than 50 Blood pressure greater than or equal to 130/85 Fasting glucose greater than or equal to 100

Truncal Obesity

Genetics The Thrifty Gene proposed by geneticist James Neel in 1962. Historically advantageous in times of famine, but then became detrimental in the modern world. Thrifty genes are genes which enable individuals to efficiently collect and process food to deposit fat during periods of food abundance. Those carrying the thrifty gene survived when food was scarce.

Thrifty Gene Research shows that those with this gene have a slowed metabolic rate. The mitochondria produce 70% less ATP than controls. Ethnic Groups commonly effected were stressed populations: African Americans (50%), Pima Indians (nearly 100%), Polynesians, Mexican Americans (50%) Genetic theories are unproven at this point

Insulin and Glucose When food is eaten, carbohydrates are broken down to the end product of glucose. This stimulates the release of Insulin which the body needs to absorb glucose into fat, heart, liver and muscle cells which act as a sponge. Overtime, the cells began to ignore the insulin messenger. When that signal is ignored, the body’s insulin producers—beta cells—have to work harder and harder, overproducing insulin to get the job done causing insulin resistance.

Insulin promotes fat storage Excess glucose can also be converted to fatty acids, which are the immediate precursors of fats (triglycerides) In addition to facilitating the transport of fatty acids into cells that need them as fuel, insulin promotes their conversion to fat for storage in adipocytes (fat cells). if we overeat and don’t exercise enough, the supply of fat will exceed the demand for energy. That can lead to obesity, the main cause of insulin resistance, which can lead to diabetes.

Insulin in Excess Signals the body to store fat causing obesity Inflammation Oxidative stress Increases vagal nerve gastric acid production Alters sex hormone production (PCOS, low testosterone in men, high in women, increased estrogen in men) Virulizationof women and feminization in men Fatty liver disease

Obesity/Inflammation Connection Obesity is a state of chronic low-grade inflammation that is initiated by changes in the adipose tissue. Research suggest that as fat cells increase in size, the composition of their lipid membrane composition changes in a manner that may make these cells more prone to triggering inflammation.

Inflammation/IR Increased plasma levels of pro-inflammatory markers including cytokines and C-reactive protein (CRP) in obese individuals Many of the inflammatory markers found in plasma of obese individuals appear to originate from adipose In chronic inflammation, chemicals released such as TNF and IL6 directly interfere with insulin signaling pathways making cells more insulin resistant.

Vicious Cycle of Obesity "Now we know that fat cells are little hotbeds of inflammation. Therefore excess belly fat is a great source of inflammation. Therefore being obese can cause insulin resistance and insulin resistance can cause obesity.

Cardiovascular Effects Insulin resistance significantly increases the risk of ischemic stroke in nondiabetic adults, independent of traditional vascular risk factors or metabolic syndrome , “October 2010 issue of Archives of Neurology” Individuals in the top quarter of insulin resistance had a 45 percent greater risk of any type of vascular event.

Cardiovascular Effects Insulin stimulates the sympathetic nervous system, increasing nor-epinephrine release contributing to high blood pressure Insulin increases triglycerides and cholesterol. Eat eggs not sugar!

Cardiovascular Effects Insulin damages the endothelium or cells lining our blood vessels. Endothelin dysfunction reduces nitric oxide production needed for healthy blood vessels. It also reduces blood flow by causing vascular smooth muscle contraction and the growth of vascular smooth muscle cells. As a result, the blood vessels are thicker with a smaller lumen; blood flow is slower and there is increased risk of clotting inside the vessels (thrombosis) and stroke.

Stroke Insulin resistance significantly increases the risk of ischemic stroke in non-diabetic adults. October 2010 issue of Archives of Neurology

Hormonal activation Aromatization -Testosterone is chemically converted to estrogen. In people with excess fat and especially abdominal fatwith higher aromatase so greater conversion of testosterone to estrogen. Insulin increases LH blocking testosterone production. Testosterone: lower in men and higher in women.

Hormonal Activation – PCOS Polycystic Ovarian Syndrome Production of multiple small cysts beneath the ovarian capsule. These insulin-damaged ovaries act like testicles; they make excessive androgens, from DHEA to testosterone Increased Luteinizing hormone. Anovulation

PCOS A woman’s body converts these androgens to estrogens as and levels of both testosterone and estrogens can significantly exceed that of progesterone Symptoms: excess facial hair, lack of ovulation, heavy periods, painful periods, irregular or absent periods, acne or oily skin, depression or mood swings

Fatty Liver Fatty liver, also known as fatty liver disease (FLD), is a reversible condition where fat accumulates in liver cells Despite the strong association between insulin resistance and dyslipidemia/fatty liver, the precise mechanism linking these conditions is unclear. Signs: Decreased (HDL) cholesterol and increased (VLDL) and possible elevated liver enzymes. Dx: Ultrasound or a non-contrast CT scan of the abdomen

Cortisol/Adrenaline Those with Metabolic syndrome has been shown to have higher cortisol levels. High sugar causes cortisol to spike. ANew York Times article on a study showing when children eat sugar, their adrenaline levels rise far higher than those of adults – up to 15x higher than baseline.

Another vicious cycle.. Cortisol effects worsen insulin resistance and its consequences include weight gain, especially with increased abdominal fat; elevated blood pressure; higher blood sugar; insomnia and reduced activation of thyroid hormone. Insulin resistance increases cortisol production, which in turn worsens insulin resistance.

Inflammation Chronic inflammation and its cytokine messengers, especially TNFa and IL-6 increase energy demands in an already-challenged system; they worsen insulin resistance, and add to sympathetic nervous system activation. The effect of insulin on oxidative load: depletes our glutathione, vitamin C, vitamin E and other antioxidants

IR and Type 2 Diabetes Diabetes mellitus type 2 – or adult-onset diabetes a metabolic disorder characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.

IR and Type 2 diabetes Pre-diabetes :Elevated insulin and borderline glucose levels precede onset of type 2 diabetes. In time elevated insulin will stress the beta cells, which wear out over time. When most are diagnosed with type 2 diabetes, they have already lost some of their ability to make insulin.

Insulin’s Dermatological effects Acne Skin tags Acne rosacea

Testing Glucose/Insulin Tolerance Test: Insulin resistance - insulin levels rise above 200 Lipids (Cholesterol, HDL, LDL, TRIG) VAP Fasting glucose and hA1c CRP - independent biomarker for the development of CVD which emphasizes the connection between inflammation, obesity, and CVD. Homocysteine, Free and Total Testosterone, Estrogen, Liver Enzyems.

Food as Medicine Dietary Goals – Reduce obesity and improve insulin sensitivity. “Hunter Gatherer”Diet. It reflects what our Paleolithic ancestors (i.e., before agriculture) evolved eating over a million years and, as such, has the highest potential of supporting healing and preventing disease. Examples: The Zone, Paleo Diet, Diet Cure, Schwarzbein Principle, South Beach Diet, Candida Diet.

Food as Medicine Avoid: White Foods with a low glycemic index and fast foods. Complex carbohydrates in moderation. Non-Starch Vegetables –should be the majority of carbohydrates. Protein - Beans, Legumes, Fish, Free Range Animal Protein. Grass fed beef. Protein at each meal preferred. Healthy fats – avocado, organic butter, olive oil, coconut. Avoid hydrogenated oils and fried foods. Nuts in moderation.

Food as Medicine Fruit – moderate consumption. Only in season. · Small amounts of fruit are OK but eat it with protein meals and not alone. Berries are best. No dried fruit. Reduction or elimination of sweeteners (including artificial and stevia) Dairy - whole milk is best. But the best is no milk, as it raises the blood sugar.

Lifestyle Changes Exercise may be the single most important factor for reversing insulin resistance. Exercise improves insulin sensitivity, lowers fasting glucose, lowers fat mass, and improves fat metabolism. Sleep - Sleep deficiency significantly worsens insulin resistance, with a nearly 40% decrease in glucose tolerance

Supplements R-Lipoic Acid: Taking 600 mg orally daily improves insulin-sensitivity in diabetics; stimulates glucose uptake by GLUT-4 receptors Carnosine: Antioxidant. Helps prevent damage caused by too much sugar in the body, “glycosylation,” Antioxidants in general to protective from oxidative stress of high insulin. Cinnamon:decreases blood glucose and improves insulin sensitivity – 1-6 G for 4 months.

Supplements Berberine - 1500 mg per day improves insulin sensitivity Fiber - slows down release of glucose into the blood. Guar gum, glucomannan, oat fiber. Vanadium – Research slows activates GLUT 4 transporters. Chromium improves glucose metabolism. 300-1000 mcg per day

Berberine Study “Compared with metformin, berberine exhibited an identical effect in the regulation of glucose metabolism, such as HbA1c, FBG [fasting blood glucose], PBG [blood sugar after eating], fasting insulin and postprandial insulin [insulin level after eating]. In the regulation of lipid metabolism, berberine activity is better than metformin. By week 13, triglycerides and total cholesterol in the berberine group had decreased and were significantly lower than in the metformin group (P<0.05).” http://tahomaclinicblog.com/berberine-diabetes/

Drug Therapy • Metformin: commonly used for type 2 diabetes and to treat young women with infertility due to PCOS • Improves insulin sensitivity, with “increased peripheral uptake and utilization” • Decreases intestinal absorption of glucose. The reduced absorption of glucose from the gut means less sugar gets into the blood stream to stimulate pancreatic insulin release. • Patients with larger body-mass index (BMI) respond better to metformin treatment than do the more slender

Metformin • Reduced the amount of insulin released in response to drinking sugar (46% less) • Reduced blood levels of LH (67% lower), • Reduced free testosterone (44% less) • SHBG (which rose nearly three times higher than the untreated baseline.) • Reduces Total-cholesterol, LDL-cholesterol and TG

Tests VAP panel (an expanded lipid profile), CRP, hA1c, 2-4 hour Glucose and Insulin Tolerance Test, homocysteine, LH, Free and total testosterone, Estrogen, Liver enzymes and fasting glucose. Adiponectin: A hormone e secreted by fat cells. Improves insulin sensitivity, reduces insulin resistance and may protect pancreatic b cells. High levels are associated with normal insulin sensitivity. Low levels correlate with metabolic syndrom and diabetes.

The road to health Remember metabolic syndrome is an outcome of our sedentary, fast-food oriented modern lifestyle. With commitment to healthy eating, daily exercise and your doctors support, metabolic syndrome can be reversed. Thank you

Contact Dr. Large Elizabeth Large N.D. Gordon Medicalassociates 3471 Regional Parkway Santa Rosa, CA 95403 707.575.5180 info@gordonmedical.com www.gordonmedical.com

Metabolic Syndrome & Insulin Resistance