DIAGNOSIS AND REVERSAL

Transcription

1 DIAGNOSIS AND REVERSAL OF TYPE 2 DIABETES BEFORE IT EVER HAPPENS Jonathan V. Wright, M.D. 1

2 INSULIN RESISTANCE/ METABOLIC SYNDROME: CLINICAL EVALUATION Jonathan V. Wright, MD 2

3 SYMPTOMS: Past or Present Sugar and/or carb craving Shaky without food, better after eating Night time awakening, especially at cortisol nadir Anxiety and/or depression accompanying symptoms above Jonathan V. Wright, MD 3

4 Clinical Signs Obesity, especially abdominal Skin tags 80% risk type 2 diabetes, 3 studies Osteoarthritis, particularly at younger ages Jonathan V. Wright, MD 4

5 Osteoarthritis and Insulin Resistance Metabolic Syndrome was detected in 82.3% examinees with OA. Korochina IE, Bagirova GG. [Metabolic syndrome and a course of osteoarthrosis]. Ter Arkh. 2007;79(10): [Article in Russian] HyperC peptidemia was found in 84.36% of patients with OA, hyperinsulinemia in 82.12%. Korochina IE. [Determination of C peptide, serum insulin, and characteristics of tissue insulin resistance in patients with osteoarthrosis]. Klin Lab Diagn Jul;(7): [Article in Russian] 5

6 Osteoarthritis and Insulin Resistance Metabolic syndrome was more prevalent in [those] with OA regardless of sex or race. The association between OA and MetS was greater in younger subjects and diminished with increasing age. Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med Nov;121(6):9 20. Jonathan V. Wright, MD 6

7 Osteoarthritis and Insulin Resistance OA has been linked not only to obesity but also to other cardiovascular risk factors, namely, diabetes, dyslipidemia, hypertension, and insulin resistance. Velasquez MT, Katz JD. Osteoarthritis: another component of metabolic syndrome? Metab Syndr Relat Disord Aug;8(4): Jonathan V. Wright, MD 7

8 Osteoarthritis and Niacinamide Kaufman W. The Common Form of Joint Dysfunction: It s Incidence and Treatment E. L. Hildreth & Company Brattleboro, Vermont 1949 Jonathan V. Wright, MD 8

9 In your presenter s experience since 1976, niacinamide, 1000 millligrams TID, completely controls the symptoms of osteoarthritis in the very large majority of individuals. Jonathan V. Wright, MD 9

10 Another Niacinamide Diabetes Connection? Vaca P et al. Nicotinamide induces both proliferation and differentiation of embryonic stem cells into insulin producing cells. Transplant Proc Aug;35(5): Vaca P et al. Nicotinamide induces differentiation of embryonic stem cells into insulin secreting cells. Exp Cell Res Mar 10;314(5): Jonathan V. Wright, MD 10

11 Clinical Correlations Peyronie s disease Du Puytren s contracture Lens opacity at early age Susceptibility to yeast & fungal infection (also evaluate thyroid) Jonathan V. Wright, MD 11

12 Laboratory Correlations Hyperlipidemia (Also evaluate thyroid) Hypertension (Also evaluate toxic metals, Na/K balance, Vitamin D, misalignment C1, C2 ) Hemoglobin A1C borderline Hair minerals: simultaneously high calcium, magnesium, and zinc Jonathan V. Wright, MD 12

13 Positive family history is another very important factor, but many with insulin resistance have no positive family history. Jonathan V. Wright, MD 13

14 Lab Testing Jonathan V. Wright, MD 14

15 Kraft, Joseph Detection of diabetes mellitus in situ (occult diabetes) Lab Med 1975;6(2): Jonathan V. Wright, MD 15

16 Lab Testing Of 3650 individuals referred specifically for evaluation of possible type 2 diabetes: 1937 were positive for diabetes based on glucose measurements 1713 judged negative, based on glucose measurements alone Jonathan V. Wright, MD 16

17 Lab Testing Of the 1713 negative : 568 (33%) were not pre diabetic based on interpretation of insulin measurements 862 (50%) were pre diabetic (diabetes mellitus in situ ) 240 (14%) were borderline 43 (2.5%) had a low insulin response pattern (islet cell exhaustion ) Jonathan V. Wright, MD 17

18 3 HR GLUCOSE TOLERANCE INSULIN RESISTANCE TEST KRAFT S CRITERIA FOR INTERPRETATION Jonathan V. Wright, MD 18

19 Lab Testing, Examples Jonathan V. Wright, MD 19

20 CASE 1: 58 Year old Male, High Cholesterol & High Blood Pressure Jonathan V. Wright, MD 20

21 CASE 2: Normal Glucose with Insulin Resistance Jonathan V. Wright, MD 21

22 CASE 3: Symptomatic Hypoglycemia, Very Early Insulin Resistance (theoreticlly, weak cortisol) Jonathan V. Wright, MD 22

23 CASE 3 GITT Results Ref. range for fasting glucose: mg/dl Normal Glucose Tolerance: <140 mg/dl Impaired Glucose Tolerance: 1 Hr Glu mg/dl Diabetes Mellitus: 2 Hr Glu >199 mg/dl Jonathan V. Wright, MD 23

24 CASE 4: Diabetes 2 Insulin Resistance Jonathan V. Wright, MD 24

25 DON T MISS THESE CASES! Men over 40 with family history of type 2 diabetes (one in three men) have a high probability of gradually worsening hyper aromatization directly induced by excess insulin signal. Jonathan V. Wright, MD 25

26 CASE 5: Diabetes 2 Insulin resistance. Early islet cell weakness? Jonathan V. Wright, MD 26

27 CASE 5 GITT Results Ref. range for fasting glucose: mg/dl Normal Glucose Tolerance: <140 mg/dl Impaired Glucose Tolerance: 1 Hr Glu mg/dl Diabetes Mellitus: 2 Hr Glu >199 mg/dl Jonathan V. Wright, MD 27

28 Case 6: 57 Year Old Man, Suspected Gluten/Gliaden Sensitivity July 2010 hair mineral results showed poor essential mineral status with 80% significantly low. Possible long term absorptive difficulties. Patient asked to complete stool gluten sensitivity testing. Results 9/2010: Fecal Antigliadin IgA: 17 (Normal Range < 10 Units). Patient advised to adopt a gluten/gliaden free diet. Jonathan V. Wright, MD 28

29 Case 6: 57 Year Old Man, September 2010 follow up Family history of Type II Diabetes. Symptoms of blood sugar and insulin problems, previous low free testosterone. Modest improvement in free testosterone results after adjusting application site and carrier base, see next slide with comparative results. Excess estrogens had also been suspected serum estradiol tested also in September. Estrogens elevated, per results on following slide. Jonathan V. Wright, MD 29

30 Case 6: 57 Year old Man Testosterone & Estradiol Serum Results 8/09 & 9/10 Serum Results 9/10 Serum Results Jonathan V. Wright, MD 30

31 Case 6: 57 Year Old Man, Hyperaromatizing, Gluten Sensitive, Suspect Diabetes 2 or 1? Insulin Tolerance Test completed Oct Ref. Range for Fasting Glucose: mg/dl Criteria for Diagnosis: Normal Glucose Tolerance: <140 mg/dl Impaired Glucose Tolerance: 1 Hr Glu mg/dl Diabetes Mellitus: 2 Hr Glu >199 mg/dl Jonathan V. Wright, MD 31

32 Insulinopenic response to this test can indicate either islet cell near exhaustion or gluten sensitivity or both; gluten sensitivity more likely in younger individuals. Test with stool specimen for siga anti gliadin antibody. (This individual already known to have elevated siga anti gliadin antibodies.) Jonathan V. Wright, MD 32

33 Case 6: 57 Year old Man, Insulin Tolerance Test Results Indicate Type 1 Diabetes Potential Patient s insulin level extremely low, with blood sugars charting an irregular curve rather than the usual peak and decline. From Kraft s criteria: Pattern V Insulinopenic Pattern Low Insulin Response: All Values < 30 If glucose values are elevated: Considered to be the juvenile pattern of Diabetes. In effect insulin deficiency, probably because of dead or near dead islet cells. If normal or borderline glucose tolerance; may be due to a low carbohydrate diet. Kraft JR. Detection of diabetes mellitus in situ (occult diabetes).laboratory Medicine 1975;6:

34 Case 6: 57 Year Old Man Treatment Recommendations #1 from November 2010 Follow up Visit: 1. Niacinamide, 1500 mg time release capsule, one capsule twice daily. Vaca P et al. Nicotinamide induces both proliferation and differentiation of embryonic stem cells into insulin producing cells. Transplant Proc Aug;35(5): Vaca P et al. Nicotinamide induces differentiation of embryonic stem cells into insulin secreting cells. Exp Cell Res Mar 10;314(5): Jonathan V. Wright, MD 34

35 Case 6: 57 Year Old Man Treatment Recommendations #2, November 2010 follow up visit 2. Gymnema sylvestre (Medi Herb used in this example), two capsules twice daily. Shanmugsundaram E et al. Possible Regeneration of the Islets of Langerhans in Streptozotocin Diabetic Rats Given Gymnema Sylvestre Leaf Extracts. J Ethno pharm 1990;30: Jonathan V. Wright, MD 35

36 Case 6: Repeated 2 Hour Insulin Tolerance, Improved Insulin Resistance August 2011 with October 2010 prior results Ref. Range for Fasting Glucose: mg/dl Criteria for Diagnosis: Normal Glucose Tolerance: <140 mg/dl Impaired Glucose Tolerance: 1 Hr Glu mg/dl Diabetes Mellitus: 2 Hr Glu >199 mg/dl Jonathan V. Wright, MD 36

37 Case 6: Summary Despite family history of Diabetes 2 and hyperaromatization with excess estrogen usually a sign of pre Diabetes 2 glucose tolerance insulin resistance test proved islet cell near exhaustion and pre Diabetes 1. Pancreatic islet cell functionality improved with niacinamide and gymnema. Recommendation: Continue supplements and gluten/gliaden free diet. Jonathan V. Wright, MD 37

38 CASE 7: Strong Insulin Resistance 09/04 Minimal Insulin Resistance 5/05 Initial Test: 9/04 Follow Up: 5/05 Jonathan V. Wright, MD 38

39 TREATMENT Diet Jonathan V. Wright, MD 39

40 Jonathan V. Wright, MD 40

41 BASIC BOOKS: The Paleo Diet Loren Cordain, Ph.D. (for everyone) Victory Over Diabetes William Philpott, M.D. (for those with significant food allergy) Jonathan V. Wright, MD 41

42 CARBOHYDRATE CONTROL!!! Degree dependent on severity of insulin resistance and psychology of the individual. For difficult carb and sugar control, Chromium liquid: 3,000 6,000 micrograms daily Jonathan V. Wright, MD 42

43 Compared with placebo, individuals who took chromium 600 micrograms daily had significantly less carbohydrate craving, appetite, over eating, and mood variability. Docherty JP et al. A double blind, placebo controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate craving. J Psychiatr Pract Sep;11(5): Jonathan V. Wright, MD 43

44 EXERCISE: High Intensity! Jonathan V. Wright, MD 44

45 Tjonna AE et al. Aerobic interval training versus continuous moderate intensity exercise as a treatment for the metabolic syndrome: a pilot study. Circulation 2008;118(4): Jonathan V. Wright, MD 45

46 32 Metabolic Syndrome Patients Randomly Assigned to 3 Groups: Aerobic interval training (AIT) Continuous moderate exercise (CME) Control Jonathan V. Wright, MD 46

47 Jonathan V. Wright, MD 47

48 Both groups demonstrated significant exercise induced increases in testosterone, younger men more than older men. Kraemer WJ et al. Effects of heavy resistance training on hormonal responses in older vs. younger men. J Appl Physiol 1999;87(3): Jonathan V. Wright, MD 48

49 Godfrey RJ, Whyte GP, Buckley J, Quinlivan R. The role of lactate in the exercise induced human growth hormone response: evidence from McArdle disease. Br J Sports Med Jul;43(7):521 5 Jonathan V. Wright, MD 49

50 McArdle s disease patients produce no lactate in response to exercise. Increased blood lactate concentration has been suggested as a primary stimulus of exercise induced improvement in HGH levels. 9 of 11 McArdle s patients had no improvement in HGH with moderately intense exercise. Jonathan V. Wright, MD 50

51 Hormones and a Vitamin/Hormone Testosterone, DHEA, thyroid, estradiol replacement if needed all help to lessen insulin resistance. Measure, monitor Vitamin D (1,25 di hydroxy & 25 hydroxy vitamin D) 5,000 IU daily or more to reach optimal levels. Jonathan V. Wright, MD 51

52 BERBERINE FOR DIABETES TYPE 2 (AND PROBABLY INSULIN RESISTANCE WITHOUT HYPERGLYCEMIA) Jonathan V. Wright, MD 52

53 Yin, J., H. Xing, et al. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism, 2008:57(5): (2 separate studies reported in one paper). Jonathan V. Wright, MD 53

54 Study #1 Newly diagnosed diabetes, Type 2 36 adults, randomized Metformin 500 milligrams TID Or Berberine 500 milligrams TID Jonathan V. Wright, MD 54

55 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). Jonathan V. Wright, MD 55

56 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). Jonathan V. Wright, MD 56

57 Study #2 48 adults, poorly controlled diabetes 2. Already on Metformin, other patent medication, and insulin. Berberine 500 milligrams TID added. No other changes for 90 days. Jonathan V. Wright, MD 57

58 Results Jonathan V. Wright, MD 58

59 Adverse Effects Study #1: No severe gastro intestinal side effects Study #2: Adverse gastro intestinal events 34.5% : Diarrhea 10% Constipation 7% Gas 19% Abdominal Pain 3.4% Berberine dose milligrams TID until all side effects gone. Jonathan V. Wright, MD 59

60 Zhang, Y., X. Li, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab. 2008;93(7): Jonathan V. Wright, MD 60

61 116 Adults, Diabetes Type 2 Randomized Double blind 90 days Berberine 500 milligrams BID Placebo Jonathan V. Wright, MD 61

62 Berberine: Average Result Jonathan V. Wright, MD 62

63 Average Result Berberine Group Placebo Group Jonathan V. Wright, MD 63

64 Berberine: Adverse Effects Mild to moderate constipation Berberine 5, Placebo 1 2 in berberine cleared after berberine milligrams Jonathan V. Wright, MD 64

65 Berberine: Mechanisms of Action 1 Activates AMPK, which upregulates: Cellular uptake of glucose Synthesis of GLUT4 (glucose transporter) Oxidation of fatty acids Increases number/activity of insulin receptors Inhibits protein tyrosine phosphatase 1B (PTP1B) PTP1B inhibits insulin receptors Jonathan V. Wright, MD 65

66 Berberine: Mechanisms of Action 2 Increases glucagon like peptide 1 (GLP1) Increases insulin release Lowers glucagon release Inhibits dipeptidyl peptidase 4 DDP4) DdP4 breaks down GLP 1, other incretins Jonathan V. Wright, MD 66

67 Berberine and Insulin Resistance Considering these mechanisms of action, berberine should also be effective in reversing insulin resistance, perhaps with lower doses. However, there is presently no published research directly addressing this relationship. Jonathan V. Wright, MD 67

68 Supplemental Items: from YALE! Chromium picolinate/biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism. (Biotin 2 mg., Chromium picolinate 600 mcg) Jonathan V. Wright, MD 68

69 Supplemental Items from YALE! Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo controlled, double blinded, randomized trial. Diabetes Technol Ther Dec;8(6): Jonathan V. Wright, MD 69

70 NUTRIENTS & BOTANICALS DECREASING INSULIN RESISTANCE Dozens of supplemental items help re regulate blood sugar! Those listed next have been found to act specifically by lowering insulin resistance. Jonathan V. Wright, MD 70

71 Nutrients & Botanicals Decreasing Insulin Resistance Alpha lipoic acid: milligrams Chromium: 1,000 5,000 micrograms Biotin: 2 5 milligrams D, L carnitine: 1000 milligrams Vanadium (as bis glycinato oxo vanadium): 1 3 milligrams Omega 3 fatty acids: 1 2 table spoonsfull Magnesium: milligrams daily Jonathan V. Wright, MD 71

72 Nutrients & Botanicals Decreasing Insulin Resistance Cinnamon Green Tea polyphenols Galega officinalis (Metformin is a patentable take off of Galega) Jonathan V. Wright, MD 72

73 Supplemental items improving blood sugar regulation and variably often lipid levels and blood pressure Jonathan V. Wright, MD 73

74 Mechanisms of Action Include (but are not limited to): Increasing pancreatic beta cell insulin production. Insulinomimetic activity. Treating deficiencies common in blood sugar dysregulation. And the ever popular unknown. Jonathan V. Wright, MD 74

75 Silymarin Lagerstroemia speciosa (banaba) Maitake (grifola frondosa) S X fraction Gymnema sylvestre Mormordica charantia N acetylcysteine Niacinimide Sambucus nigra (elderberry) Jonathan V. Wright, MD 75

76 Jonathan V. Wright, MD 76

77 The End Jonathan V. Wright, MD 77