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 - diabetes-epidemic.com

• FBG>100 mg/dl (5.5 mmol/l)

screening

• 2hr OGTT>140 mg/dl (7.8 mmol/l)

• HbA1c

Standard Methods Inferior

• Gold standard based on RIA insulin (uIU/ml)

• 14,384 subjects, 5hr glucose plus insulin

• Defined 5 distinct patterns

• 3 patterns of hyperinsulinemia – Diabetes

In-Situ

• Redefining diabetes at its earliest stage

Dr. Kraft 5hr Insulin Assay

Image curtesy Ivor Cummins BE(Chem) CEng MIEI

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

Hyperinsulinemia before Hyperglycemia

Catherine Crofts M.Phil, B.Pharm, NZRegPharm, PhD Candidate Public Health. Images curtesy Ivor Cummins BE(Chem) CEng MIEI

Hyperinsulinemia

Disease No Disease Totals

Hyperglycemia

Test

Positive True Positives

6180

False Positives

186

6366

PPV

97%

Negative False Negatives

5764

True Negatives

2254

8018

NPV

28%

Totals 11944 2440 14384

Sensitivity

52%

Specificity

92%

Glucose vs. Insulin

Data recompiled from Kraft J. R. Diabetes Epidemic & You. 2011

Euglycemia

NFG & NGT

Negative Predictive Value

28% Normal - Kraft Pass

True Negatives

72% 'Normal' - Kraft Fail

False Negatives

Hyperglycemia IFG or IGT or DMGT

Sensitivity

52% Abnormal - Kraft Fail

True Postives

48% 'Normal' - Kraft Fail

False Negatives

• NHANES prevalence 2015: 49%-52% in the US

now pre-diabetic or diabetic

• UCLA 2016: 55% of Californians are pre-

diabetic or diabetic

• Kraft would predict that many more have

hyperinsulinemia

Predicting population risk

Menke A, et al. JAMA. 2015;314(10):1021-1029. doi:10.1001/jama.2015.10029.

healthpolicy.ucla.edu/publications/search/pages/detail.aspx?PubID=1472

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

• Atherosclerosis is a metabolic disease

• Missing pre-diabetes and diabetes also

misses cardiovascular disease

Dr. Kraft on

CV risk

Gerald M. Reaven, MD

Diabetes December 1988 vol. 37 no. 12 1595-1607 doi:10.2337/diab.37.12.1595. Slide curtesy lipidsonline.org

• Lipids, Smoking, HTN, Diabetes

• Guidelines, risk calculators

• Lowering cholesterol

• Diabetes risk buried

Framingham Distraction

• Hyperlipidemia requires remedy

• Mechanisms remains elusive

• Diet-heart hypothesis unproven

• Statins provide small benefit

Lipid Lowering Therapy

• Get with the Guidelines 2009

• Towards a Paradigm Shift in Cholesterol

Treatment 2015

Debunking the Lipid Hypothesis

Mark A. Creager et al. Circulation. 2003;108:1527-1532

Hyperinsulinemia and blood vessel damage

• Framingham risk calculators: CV risk increased

2-3 fold (middle risk population)

• Diabetes alone: CV risk increased 6-8 fold

Framingham vs. Diabetes Risk

Circulation. 2002; 105: e132-e137 doi: 10.1161/01.CIR.0000013953.41667.09

• Atherosclerosis is a symptom of diabetes

• Focus insulin excess, IR, and inflammation

• Many at risk are missed

• Diet and lifestyle, not medicine

It’s the Insulin Stupid!

Low carb best

Eliminating processed food

Eating less

Movement & activity

Smoking cessation

Proper sleep & happiness

Diet and Lifestyle

• Early level of suspicion

• FBG & HbA1c - are poor screening tools alone

• 2 hr OGTT including 1hr glucose <155 mg/dl (8.6

mmol/l)

• Insulin - fasting, 5hr assay, 2hr <30 uIU/ml

• Inflammatory markers, lipid quality, etc…

Clinical assessment

doi: http://dx.doi.org/10.1210/jc.2015-2573

• Heart catheterization

• CIMT

• IVUS

• CT angiogram

• Coronary artery calcium score

Cardiovascular imaging

CAC Score

Calcium Score

Risk Equivalent

10-Year Event Rate, %

0 Very low 1.1-1.7

1-100 Low 2.3-5.9

101-400 Intermediate 12.8-16.4

>400 High 22.5-28.6

>1000 Very high 37

J Am Coll Cardiol Img. 2015;8(5):579-596

CAC Progression

Arterioscler Thromb Vasc Biol. 2004;24:1272-1277

Diabetes is a Vascular Disease