Framingham and the Muddy Waters Jeffry N Gerber

Framingham and the Muddy Waters Jeffry N. Gerber, MD Denver’s Diet Doctor

“Those with cardiovascular disease not identified with diabetes… are simply undiagnosed” - Dr. Joseph R. Kraft

Dr. Joseph R. Kraft - diabetesepidemic. com

Standard Methods Inferior • FBG>100 mg/dl (5. 5 mmol/l) screening • 2 hr OGTT>140 mg/dl (7. 8 mmol/l) • Hb. A 1 c

Dr. Kraft 5 hr Insulin Assay • Gold standard based on RIA insulin • • (u. IU/ml) 14, 384 subjects, 5 hr glucose plus insulin Defined 5 distinct patterns 3 patterns of hyperinsulinemia – Diabetes In-Situ Redefining diabetes at its earliest stage

Pattern 1 - Euinsulinemia Image curtesy Ivor Cummins BE(Chem) CEng MIEI

Patterns 2, 3, 4 - Hyperinsulinemia Image curtesy Ivor Cummins BE(Chem) CEng MIEI

Patterns 5 - Insulinopenic Image curtesy Ivor Cummins BE(Chem) CEng MIEI

Hyperinsulinemia before Hyperglycemia Catherine Crofts M. Phil, B. Pharm, NZReg. Pharm, Ph. D Candidate Public Health. Images curtesy Ivor Cummins

Glucose vs. Insulin Hyperinsulinemia Positive Hyperglycemi a Test Negativ e Totals Disease No Disease True Positives 6180 False Positives 186 False Negatives 5764 11944 Totals 6366 PPV 97% True Negatives 2254 8018 NPV 28% 2440 14384 Sensitivity Specificity 52% Data recompiled 92% from Kraft J. R. Diabetes Epidemic & You. 2011

Euglycem NFG & NGT ia Negative Predictive Value 28% Normal - Kraft Pass True Negatives 72% 'Normal' - Kraft Fail False Negatives

Hyperglycemi IFG or IGT or DMGTa Sensitivity 52% Abnormal - Kraft Fail True Postives 48% 'Normal' - Kraft Fail False Negatives

Predicting population risk • NHANES prevalence 2015: 49%-52% in the US now pre-diabetic or diabetic • UCLA 2016: 55% of Californians are prediabetic or diabetic • Kraft would predict that many more have hyperinsulinemia Menke A, et al. JAMA. 2015; 314(10): 1021 -1029. doi: 10. 1001/jama. 2015. 10029. healthpolicy. ucla. edu/publications/search/pages/detail. aspx? Pub. ID=147

Diabetes Paradox? • Despite more diabetes & obesity there’s less heart disease • Morbidity & mortally not to be confused with incidence and prevalence Diabetes Care March 2003 vol. 26 no. 3 905 -910 doi: 10. 2337/diacare. 26. 3. 905

Dr. Kraft on CV risk • Atherosclerosis is a metabolic disease • Missing pre-diabetes and diabetes also misses cardiovascular disease

Gerald M. Reaven, MD Diabetes December 1988 vol. 37 no. 12 1595 -1607 doi: 10. 2337/diab. 37. 12. 1595. Slide curtesy lipidsonline. org

Framingham Distraction • • Lipids, Smoking, HTN, Diabetes Guidelines, risk calculators Lowering cholesterol Diabetes risk buried

Lipid Lowering Therapy • Hyperlipidemia requires remedy • Mechanisms remains elusive • Diet-heart hypothesis unproven • Statins provide small benefit

Debunking the Lipid Hypothesis • Get with the Guidelines 2009 • Towards a Paradigm Shift in Cholesterol Treatment 2015

Hyperinsulinemia and blood vessel damage Mark A. Creager et al. Circulation. 2003; 108: 15271532

Framingham vs. Diabetes Risk • Framingham risk calculators: CV risk increased 2 -3 fold (middle risk population) • Diabetes alone: CV risk increased 6 -8 fold Circulation. 2002; 105: e 132 -e 137 doi: 10. 1161/01. CIR. 0000013953. 41667. 09

It’s the Insulin Stupid! • • Atherosclerosis is a symptom of diabetes Focus insulin excess, IR, and inflammation Many at risk are missed Diet and lifestyle, not medicine

Diet and Lifestyle ü Low carb best ü Eliminating processed food ü Eating less ü Movement & activity ü Smoking cessation ü Proper sleep & happiness

Clinical assessment • Early level of suspicion • FBG & Hb. A 1 c - are poor screening tools alone • 2 hr OGTT including 1 hr glucose <155 mg/dl (8. 6 mmol/l) • Insulin - fasting, 5 hr assay, 2 hr <30 u. IU/ml • Inflammatory markers, lipid quality, etc… doi: http: //dx. doi. org/10. 1210/jc. 2015 -2573

Cardiovascular imaging • • • Heart catheterization CIMT IVUS CT angiogram Coronary artery calcium score

CAC Score Calcium Score Risk Equivalent 10 -Year Event Rate, % 0 1 -100 101 -400 >1000 Very low Low Intermediate High Very high 1. 1 -1. 7 2. 3 -5. 9 12. 8 -16. 4 22. 5 -28. 6 37 J Am Coll Cardiol Img. 2015; 8(5): 579 -596

CAC Progression Arterioscler Thromb Vasc Biol. 2004; 24: 12721277

Diabetes is a Vascular Disease