edwin lee, m.d., f.a.c.e 2011 - revive...
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The following potential conflict of interest relationships are germane to my presentation.
Equipment: N/ASpeakers Bureau: Amylin PharmaceuticalStock Shareholder: N/AGrant/Research Support N/AConsultant: N/A
Status of FDA devices used for the material being presented: N/AStatus of off label use of devices, drugs or other materials that constitute the subject of this presentation: Exantide, Liraglutide and Pramlintide.
2/3 of every American is overweight‐ Approximately 190 million Americans are overweight
Childhood obesity has tripled in the last 30 years
Approximately 60 million Americans have pre diabetes
www.diabetes.org/diabetes‐basics/prevention/pre‐diabetes
Most of them have insulin resistance or Metabolic Syndrome
Family history of type 2 diabetes is common
Look for the Belly fat
What is the root problem (hormone) with Pre Diabetes? Also what is involved with increasing the risk of losing memory, developing Hypertension, Heart disease, Stroke, Impotence, Infertility, AutoImmune disease and cancer?
Increases the risk of Developing Alzheimer’s DiseaseMatsuzaki T et al. Neurology. 2010 Aug 31;75(9):764‐70
Causes Endothethial DysfuctionLeads to Hypertension and Male Impotence
International Journal of Impotence Research (2008) 20, 460–465
Increases the risk for heart diseaseCardiol Rev. 2011 Jan‐Feb;19(1):5‐11
Increases the risk for strokes
Increases the risk of developing Polycystic Ovary SyndromeDis Markers. 2009;26(4):163‐70. Metabolism. 2009 Jul;58(7):954‐62
Increases the risk of developing AutoImmune disease
Increases the risk of developing CancerJ Natl Cancer Inst (2003) 95 (1): 67‐71 Diabetologia. 2009 Sep;52(9):1745‐54
Precursor of Diabetes
Elevated Insulin levels
The Fat, Muscle and Liver become resistant to insulin
The pancreas thus produces more insulin since the demand is higher.
Diagnosis with 3 or more
Elevated waist circumferenceMen > 40 inchesWomen > 35 inches
Elevated Triglycerides > 150HDL Men < 40 and Women < 50High Blood pressure > 130/85High Fasting Blood sugar > 100
Endocr Pract. 2003 Sep‐Oct;9 Suppl 2:22‐112.
2 types of Belly Fat
1) Subcutaneous fat (external)
2) Visceral fat (internal)Can’t be removed with LiposuctionVisceral fat drains in the Portal VeinInvolved with Insulin Resistance
Am J Physiol Endocrinol Metab vol 280 pages E745‐E751 (2001)
Visceral Fat
1) Endocrine Gland – secretes Adiponectin (decreases with becoming diabetic) – Adiponectin helps with glucose and fat metabolism.
Also secretes cytokines (TNF, IL‐6, plasminogenactivator inhibitor 1), and the hormones leptin and resistin
Visceral Fat and Chronic Inflammation
25 extremely obese patients undergoing gastric bypass surgery
IL‐6 (Interleukin 6) was 50% higher in the Portal vein compared to Radial vein
The high IL‐6 directly correlates to the elevated CRP
1) Poor quality diet (high in refined sugars, low in fiber)2) High Levels of Insulin2) Visceral Fat3) High secretion of cytokines – leading to chronic
inflammation4) Endothelial dysfunction 5) High levels of Free Fatty acids – decreases insulin effect and
unable to decrease glycogen synthesis in the liver
Treatment
Life style modificationLower Insulin levelsEating healthierIncrease physical activity Optimize Nutritional support
Other conditions associated with Metabolic SyndromeVitamin D Deficiency Hypogonadism Steroid useCushing’s diseasePolycystic Ovary Syndrome Atypical antipschotics (Zyprexa, Risperadol, Clozaril)
Alcohol use
Diabetes Prevention Program
Major multicenter research studyover 3000 patients with pre diabetes3 groups
1) Lifestyle modification2) Metformin 850 mg twice a day3) Placebo
N Engl J Med. 2002 Feb 7;346(6):393‐403.
Diabetes Prevention Program
The lifestyle Modification group had a intensive training healthier and fewer calories and exercised 150 minutes a week. Goal was to lose 7% of body weight and to maintain it off
Lifestyle modification reduced the risk of diabetes by 71% Better than Metformin (31%) or placebo group (11%).
N Engl J Med. 2002 Feb 7;346(6):393‐403.
Other treatmentsEPA:DHACurcuminFlavanoidsAlpha Lipoic AcidCoQ‐10MagnesiumChromiumVitamin DGarlicGinsengGreen TeaCinnamon
Curcumin dates back to 2000 BC
n the 90th Annual Meeting of the Endo Society a study was presented that rats that were genetically prone to weight gain. One group of rats received curcumin and the other not. The group that received curcumin has a lower rate of developing diabetes.
Endocrinology. 2008 Jul;149(7):3549‐58.
One study showed a lowering of insulin use in humans with curcumin
Indian J Med Sci. 1972 Apr;26(4):269‐70
Anti carcinogenic properties on curcumin on cancer
Also curcumin has been shown to decrease inflammation with decreasing TNF and Nuclear Factor kappa Beta
World J Gastrointest Oncol. 2010 Apr 15;2(4):169‐76.
No Clearly established dosage, but dosage of 1000 mg to 2000 mg day appears to be ffective
Flavonoids are a class of water soluble plant pigments. i.e. citrus
Resveratrol is a polyphenols and belongs to the subclass of flavonoids
Resveratrol has been shown to lower SIRT 1 levels (increase nsulin resistance). Also shown to improve on survival in mice and other species. Limited human data.Nature. 2006 Nov 16;444(7117):337‐42 Cell Metab. 2007 Oct;6(4):307‐19.
0,000 plus patient study in Finland over a year showed that higher intake of Flavonoids lower the risk of developing diabetes
Am J Clin Nutr. 2002 Sep;76(3):560‐8.
owa Women’s Health Study there were over 34,000 women that were free of heart disease and followed for 16 years. It was noted hat foods rich in flavonoids (apples, pears, grapefruit, trawberries and red wine) were associated with less heart disease, stroke and also early death
Am J Clin Nutr. 2007 Mar;85(3):895‐909. Dosage of 1000 mg a day
Alpha lipoic acid (ALA) has been shown as a powerful antioxidant and has been shown to help against pancreatic cancer and hepatitis C
ALA has been shown to improve on insulin resistance
4 Clinical trials showed that Intravenous ALA has helped with neuropathyDiabet Med. 2004 Feb;21(2):114‐21.
ALA has been shown to increase the GLUT 4 receptors (helps brings glucose into the cells)
Diabetes. 2001 Jun;50(6):1464‐71.
ALA has been shown to decrease inflammation with decreasing IL‐6 and PAI‐1 and improving on Endothelial dysfunction
Circulation. 2005 Jan 25;111(3):343‐8.
Dosing of 300 mg to 1200 mg a day
CoQ‐10 otherwise known as ubiquinoneOver 50 years of studies‐ first discovered in a cows heart
CoQ‐10 is involved in energy productionCoQ‐10 has been shown to help patients with congestive heart failureJ Am Coll Cardiol. 2008 Oct 28;52(18):1435‐41.
CoQ‐10 is lowered with the use of a Statin drugJ Am Coll Cardiol. 2007 Jun 12;49(23):2231‐7.
200 mg of CoQ‐10 has helped lower Blood glucose and HbgA1c in type 2 diabetics
Diabetes Care. 2009 May;32(5):810‐2.
CoQ‐10 has been shown to improve on insulin resistanceJ Hum Hypertens. 1999 Mar;13(3):203‐8.
CoQ‐10 has been shown to lower inflammation TNFBiofactors. 2007;31(1):35‐41.
Dosage of 100 mg to 300 mg a day of ubiquinone
Magnesium is crucial mineral and is found in green leafy vegetables
Less than 1 % of Magnesium is in out blood most is intracellular
Important to measure magnesium by RBC magnesium. There is a poor correlation b/w RBC magnesium and serum magnesium
Arch Intern Med. 1988 Nov;148(11):2415‐20.
Magnesium has been shown to improve on insulin resistance. Doses of 365 mg a day
Diabetes Obes Metab. 2010 Nov 18. doi: 10.1111/j.1463‐1326.2010.01332.x. [Epub ahead of print]
Women’s Heart Study of 39,345 women 6 year follow up reported a significant relationship of low dietary magnesium intake and a higher risk of developing diabetes. Diabetes Care. 2004 Sep;27(9):2108‐15
Randomized double blind study (gold standard) showed in diabetics that a dose of 1000 mg of magnesium oxide improved glucose control. Diabetes Care. 1998 May;21(5):682‐6. Dosage of 300 mg to 1000 mg a day
Another important mineral
Randomized double blind placebo control trial showed in type 2 diabetics chromium picolinate 1000 mcg a day help with weight loss and also improved on insulin sensitivity and glucose control Diabetes Care. 2006 Aug;29(8):1826‐32
chromium picolinate in type 2 diabetics and showed that patients with more insulin resistance had better response to chromium.Metabolism. 2010 May;59(5):755‐62
Chromium has been shown to decrease inflammation markers ike TNF, CRP and IL‐6. ree Radic Biol Med. 2007 Oct 15;43(8):1124‐31
Chromium has been shown to increase GLUT‐4 receptors allowing more glucose enter into the cells. Biol Trace Elem Res. 2009 Nov;131(2):133‐42
Dosage 200 mcg to 1000 mcg a day
Vitamin D is considered a hormone (fat soluble)
Shown to reduce cancer and heart disease
26 healthy Californians showed that level of Vitamin D is associated with insulin sensitivity. If one had a vitamin D levels ess than 20 ng/ml then one had a higher risk of insulin esistance and metabolic syndrome.
Am J Clin Nutr. 2004 May;79(5):820‐5.
Over 1700 people with out heart disease for over 5 years noted hat if one had a very low vitamin D level of less than 15 ng/ml had a 62% increase first incidence of a heart attack
Circulation. 2008 Jan 29;117(4):503‐11
n a recent 2011 study showed that pre diabetics and also pre hypertension adults are associated with low Vitamin D of less than 30 ng/ml
GLP‐1 hormoneLowers blood sugarsLowers glucagon levelsSlows down the glucose absorptionHelps with weight loss
Minor Side effect is mild nausea and rarely vomiting.
Don’t use it with patients with gastroparesis, renal failure, history of pancreatitis and during pregnancy
With proper lifestyle modification I have seen significant weight oss and the reversing of pre diabetes and type 2 diabetes
Dosage start at 5 mg before the largest meal and if necessary itrate to 10 mcg BID
FDA approval of Jan 2010
Longer acting GLP‐1
Avoid use with a history of Medullary thyroid cancer
Dosage from 0.6 mg to 1.8 mg a day
Hormone is called Amylin
Amylin is co secreted with Insulin
Helps with lowering glucagon levels
Slows down gastric emptying
Helps with weight loss
Most important is to improve on Nutrition and physical activityFocus with 2 to 3 serving of vegetables per mealLimit alcohol intakeSelf Monitoring of blood sugarsLimit to 15 to 20 grams of carbs per mealPhysical activity should involve balance, core, cardio with nterval workouts and also with weightsNutraceuticals, Minerals and BotanicalsConsider Byetta, Symlin or VictozaThe key is to prevent diabetes not treat it
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