Type 2 Diabetes – Etiology and Reversibility

The twin cycle hypothesis of type 2 diabetes Taylor R Dia Care 2013;36: Copyright © 2011 American Diabetes Association, Inc.

Two Phases of Diabetes Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009; 373: 2215–2221.

On 120 units Insulin/ day and 2 g metformin Diabetes for 27 years HbA1c went from 7.0% to 6.6% Lost 64 pounds and 7 inches

The Big Myths 1.Diabetes is a chronic progressive disease 2.Lowering blood sugars is the primary goal of therapy The Truth 1.Diabetes is a curable dietary disease 2.Diabetes is a disease of high insulin resistance Treatment is directed to lowering resistance

Bariatric Surgery Long standing diabetic – morbidly obese – 500 units insulin/day – Bariatric surgery Diabetes cured

Surgery cures diabetes Bariatric Surgery versus Intensive Medical Therapy in Obese Patients with Diabetes N Engl J Med 2012;366: Schauer PR

A: Fasting plasma glucose and weight change 2 years after randomization either to gastric banding or to intensive medical therapy for weight loss and glucose control. Adjustable gastric banding and conventional therapy for type 2 diabetes JAMA 2008;299: Taylor R Dia Care 2013;36: Gastric Banding cures Diabetes

Fasting Diabetes for 10 years – Loses 50 pounds on diet including fasting – Diabetes cured

Treatment of Diabetes Mellitus 1916 ”That temporary periods of under-nutrition are helpful in the treatment of diabetes will probably be acknowledged by all after these two years of experience with fasting” p676 ”the practice, observed by many clinicians of the old school, who advantageously fasted their diabetics one day a week have given the cue to intermittent fasting” p679 Can Med Assoc J. Aug 1916; 6(8): 673–684. Elliot P Joslin

Food Rationing decreases Diabetes

Fasting vs. Bariatric Surgery Rapid Improvement of Diabetes After Gastric Bypass Surgery: Is It the Diet or Surgery? Diabetes Care Mar 25, Lingvay I

Low Carb Diets 27 year old graduate student in physiology – Recent diagnosis of diabetes HgBA1C 10.4% – Started on 3 medications – Very low carb diet (ketogenic) – Weight loss 20 pounds HgBA1c 5.5% off all meds Diabetes cured

Cases you don’t hear Diabetes – Started on high doses of insulin – Now completely better and off all medications Diabetes – Started on sulphonyurea – Now much better and off all medications Diabetes NOT CURED

Type 2 Diabetes CureNo Cure Bariatric SurgeryInsulin Drugs Low Fat Diets Fasting Very Low Carb Diets Current Treatment Protocol Current Research Current Goal – normalized blood sugars

Learned Helplessness Fact: For most people, type 2 diabetes is a progressive disease. eventually oral medications may not be enough to keep blood glucose levels normal. Using insulin to get blood glucose levels to a healthy level is a good thing, not a bad one. Actually – this is a lie WTF?

Learned Helplessness Over time most people with type 2 diabetes will also need tablets and many will also need insulin. It is important to note that this is just the natural progression of the disease Diabetes/What-is-Diabetes/Type-2-Diabetes/

Big Lie #2 Lowering blood sugars is the goal of treatment

Complications of Diabetes Type 1 and 2 Diabetes High Blood Sugars (Oxidative Stress) (Advance Glycation End Products) Complications of Diabetes

The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358: ACCORD Hazard Ratio 1.22

Cumulative Incidences of Events, According to Glucose-Control Strategy The ADVANCE Collaborative Group. N Engl J Med 2008;358: ADVANCE

Low A1C is NOT good for you 27,965 patients intensified from oral monotherapy to combination therapy Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study Lancet 2010; 375:481-89, Currie CJ Oral Combination Insulin Adjusted Hazard Ratios by A1c

Type 2 Diabetes DiseaseCauseTreatment SymptomSymptomatic Treatment Diabetes Insulin Resistance ?????????High Blood Sugars Insulin OHA InfectionBacteriaAntibioticFeverAcetominophen Does not alter disease process

Diabetes is getting worse! Disease – Insulin Resistance Current target – Blood Sugar Metformin Glyburide Insulin More Insulin More Insulin Time

Towards a Cure for Diabetes ??????? Insulin Resistance Type 2 Diabetes High Blood Sugars What causes type 2 Diabetes? Start by studying the cure that we know

Type 2 Diabetes CureNo Cure Bariatric SurgeryInsulin Drugs Low Fat Diets Fasting Very Low Carb Diets Current Treatment Protocol Current Research Current Educational Goals

Type 2 Diabetes CureNo Cure Bariatric SurgeryInsulin Drugs How does Bariatrics work? 1.GI effects 2.Loss of Subcutaneous Fat Mass 3.Acute profound caloric reduction Current treatment Fasting

COUNTERPOINT Study Hypothesis: Twin defects of beta cell failure and insulin resistance can be reversed by acute negative energy balance alone Early change in hepatic insulin sensitivity and slower change in beta cell function Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol Diabetologia 2011;54:

Taylor R Dia Care 2013;36: Counterpoint Study BG 9.6 mmol/L to 5.9 in 7 days!

Taylor R Dia Care 2013;36: Copyright © 2011 American Diabetes Association, Inc. Decreased Liver Fat Mean 30% decrease in liver fat Mean weight loss 15kg

Taylor R Dia Care 2013;36: Copyright © 2011 American Diabetes Association, Inc. Decrease in Pancreatic Fat

Taylor R Dia Care 2013;36: Copyright © 2011 American Diabetes Association, Inc. Restoration of Beta Cell Function

Steatosis Insulin Resistance Does Fatty Liver cause Insulin Resistance?

Steatohepatitis precedes Diabetes Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor. Diabetes 2007; 56: 984– months prior to diagnosis of DM Long silent scream from the liver Diabetes No Diabetes

Hepatic Fat Preoperative weight loss with a very-low-energy diet Am J Cli Nutr 2006;84: Mean loss of liver volume 28.7% 80% by first 2 weeks

Hepatic Fat Preoperative weight loss with a very-low-energy diet Am J Cli Nutr 2006;84:

Improved Hepatic Insulin Sensitivity Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes

Fatty Liver How do you get fatty liver? 1.High Insulin Levels 2.Carbohydrate Excess

Eat Food Store Sugar in Liver Produce Fat in Liver Increase Insulin No Food “Fasting” Burn Stored Sugar in Liver Burn Fat in Liver Decrease Insulin Normal Insulin Action 1.Inhibits Glycogenolysis 2.Inhibits Gluconeogenesis 3.Stimulates De Novo Lipogenesis

De Novo Lipogenesis Oxidized for Energy Exported as VLDL Stored in Liver What happens to excess carbs?

How to get Fatty Liver Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans Am J Clin Nutr 2012;96:727– 34 2% increase weight 27% increase liver fat 27% increase DNL

How to Get Fatty Liver 1.High Insulin Levels 2.Excess carbohydrates

Correlation of Hepatic Fat and Insulin Dose Hepatic Fat Content and Insulin Action on Free Fatty Acids and Glucose Metabolism Rather Than Insulin Absorption Are Associated With Insulin Requirements During Insulin Therapy in Type 2 Diabetic Patients Diabetes 49:749–758, 2000

Type 1 Diabetes Reduced intrahepatic fat content is associated with increased whole- body lipid oxidation in patients with type 1 diabetes Diabetologia (2005) 48: 2615–2621 DM1Control

Liver Cells Stored Sugar Glycogen Stored Fat De Novo Lipogenesis High Insulin Low Insulin

Insulin Resistance! Stored Sugar Stored Fat High Insulin Low Insulin

Twin Cycles – starting to connect the dots Insulin Fatty Liver Hepatic Insulin Resistance Excess Carbs

Twin Cycles Insulin Hepatic Steatosis Hepatic Insulin Resistance Fatty Pancreas Beta Cell Dysfunction High Sugars

Insulin causes type 2 Diabetes

Towards a Cure for Diabetes Inciting factors High insulin levels Excess carbohydrates Cure for diabetes Decrease insulin Decrease carbohydrates – Preferential release of fat from liver – Decrease insulin resistance – Removal of fat from pancreas – Reversal of beta cell dysfunction Reversing the Twin Cycles!

Type 2 Diabetes CureWorsening Diabetes Bariatric SurgeryInsulin Drugs Low Fat Diets Fasting Very Low Carb Diets Increase insulin! Decrease Insulin! Type 2 Diabetes is a disease of too much insulin StupidSmart

Can We Cure Type 2 Diabetes? No Diabetes – no diabetic nephropathy, no diabetic foot ulcers, diabetic retinopathy, reduced stroke, MI, cancers No Drugs, No Surgery, No Cost It only requires knowledge and the courage to challenge conventional thought

The Cure for Diabetic Nephropathy Diabetes Diabetic Nephropathy ACEI ARB DRI

Time to get started… Diabetes (type 2) is CURABLE in 90% of cases

DM for 11 years prior to IDM Taking 56 IU of insulin Lost 67 pounds and 16 inches

DM for 7 years 210 IU of insulin HbA1c went from 7.2% to 6.7% Lost 30 pounds and 4 inches

DM for 13 years Was taking Diamicron, Onglyza, and Metformin HbA1c went from 8.6% to 5.7% Lost 4 pounds and 5 inches

DM for 43 years Was taking 75 IU of insulin HbA1c went from 7.0% to 6.1% Lost 37 pounds and 9 inches

DM for 30 years Was taking 70 IU of insulin HbA1c went from 6.1% to 5.5% Lost 7 pounds and 5 inches

DM for 18 years Reduced from 4 medications to 1 HgbA1c 7.0% to 6.6% 53 kg weight loss 117 pounds

Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. Dual Add-On Therapy in Poorly Controlled Type 2 Diabetes on Metformin: Randomized Double-Blind Trial of Saxagliptin+Dapagliflozin vs Saxagliptin and Dapagliflozin Alone. 127-LB, American Diabetes Association,