They Shoulda Told Me

James W. Wright, MD

September 2015

Company Confidential ©2015 Genworth Financial, Inc. All rights reserved.

CIMTCarotid Intima Media Thickness

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What is it?• B-mode ultrasound (cross-

section)• Distal 1 cm of the common

carotid artery far wall• Thickness of the intima and

media combined

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Atherosclerosis Progression

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Rationale for CIMT

CAD is leading cause of death in US (25% of all deaths)

Increased CIMT correlates with atherosclerosis progression in coronary and cerebral vessels

Detects disease at early (presymptomatic) stage

Assess early intervention strategies

Improves risk prediction beyond use of traditional risk factors

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How Results Are Reported

Mean thickness in mm, right and left

Percentile for age and sex

Percentiles >75th indicate increased risk

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Clinical Use

Most useful in middle age

Most useful for those at intermediate risk–Family history of premature CAD in 1st-degree relative

–Persons <60 with severe abnormality of a single risk factor

–Women <60 with at least 2 CAD risk factors

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Use in Life Insurance and LTC

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Traditional CVD Risk AssessmentFramingham Risk Score – 10-year risk

Age and Sex Women get CAD at older ages; risk may be underestimated

Race

Total Cholesterol With extreme levels of a single risk factor, FRS may underestimate risk

HDL Cholesterol With extreme levels of a single risk factor, FRS may underestimate risk

Systolic BP

BP Meds (Y/N) But risk is actually graded, not just present or absent

Diabetes (Y/N) But risk is actually graded, not just present or absent

Smoker (Y/N) But risk is actually graded, not just present or absent

Other factors (Meh!)CRP

Hyperhomocysteinemia

Lipoprotein a

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How to Use the CIMTin Insurance Underwriting

Underwriting Heuristic – create a rule that

modifies the current risk assessment

Replace chronological age with vascular age– Example 1: 45 yo man with low FRS (5% risk) and 50th percentile CIMT =

no adjustment

– Example 2: 45 yo man with low FRS (5% risk) but CIMT similar to 55 yo

man. Using 55 in the FRS calculation instead of 45 yields a 16% risk.

Thanks to Dr. Robert Pokorski

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“Chronic Lymes Disease”

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Dr. Irv SalitProfessor of MedicineUniversity of Toronto

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Thanks to:

The Basics

Caused by the bacterium Borrelia burgdorferi

Transmitted to humans by infected ticks

Acute disease symptoms: rash (erythema migrans), fever,

headache, fatigue (days to weeks)

Early disseminated disease: cranial nerve palsies, radiculopathy,

peripheral neuropathy, lymphocytic meningitis (weeks to months)

Untreated disease late manifestations (months to years)

– Intermittent arthritis in a few large joints

– Subtle cognitive problems

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Reported Cases of Lyme Disease - United States, 2013

Source: CDC

Diagnosis

Usually based on symptoms, characteristic rash, history of tick exposure

Blood tests (serologies) have problems– Negative is early stage of disease

– Often positive in endemic areas without evidence of active disease

– European forms of the disease require different tests

– Some labs use unreliable tests with high false-positive rate

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Treatment

Most cases are treated successfully with

a two-week course of an antibiotic.

Those with late, untreated disease may

require intravenous antibiotics.

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Outcomes

Close to 100% are cured with a 2-week course of an antibiotic

10–20% have lingering symptoms (PTLDS)– Fatigue, joint and muscle aches

– Persistent symptoms for 6 months or more

– Mechanism unknown

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“Chronic Lyme Disease”

Lyme Group – Persisting symptoms after treatment for Lyme disease, called “post-treatment Lyme disease syndrome” (PTLDS)

CFS Group – Never had Lyme disease but have symptoms similar to PTLDS. In their search for the cause, found serologic evidence of Lyme disease.

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CFS — Lyme Connection

Chronic fatigue syndrome (CFS) symptoms are common

Positive Lyme serology tests are common– Positive predictive value in patients with only nonspecific

symptoms is poor.– Some labs use non-validated tests

Leads to misdiagnosis based on a false-positive serologic test

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Misattribution Leads to Inappropriate Treatment

Some doctors believe CFS symptoms are caused by persistent B. burgdorferi infection

Treat with prolonged courses of antibiotics

Patients who receive prolonged courses of antibiotics fare no better than those treated with placebo.

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Treatment of PTLDS

Treat like fibromyalgia or CFS

Encourage patients to stay active

Rest, healthy diet

Cognitive behavioral therapy

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Chronic Lyme Subculture

Similar to CFS, chronic candidiasis,

chronic EBV infection, etc.

Pseudoscience

Internet-based:– support groups– meetings– literature– activist groups

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Bottom Line

10–20% of Lyme patients have post-treatment

symptoms that may last months

This does not mean persistent infection

No proof that chronic Lyme disease exists

Chronic antibiotic therapy is not needed

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“Newer” Diabetes Medicines

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Type 2 Diabetes

Insulin Resistance

o Muscle

o Liver

Impaired insulin secretion

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Noninsulin Antidiabetes Medications

Insulin secretagogues

Sulfonylureas

Meglitinides

Insulin sensitizers

Biguanides

Thiazolidinediones

Glucosidase inhibitors

Peptide analogs

Glucagon-like peptide-1 analogs

Dipeptidyl peptidase-4

inhibitors

Amylin analogs

Glucosurics (SGLT-2

inhibitors)

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Insulin secretagogues

Sulfonylureas• Glyburide

(Glucotrol)• Glipipzide

(Diabeta)• Glimepiride

(Amaryl)

Meglitinides• Repaglinide

(Prandin)• Nateglinide

(Starlix)

Insulin sensitizers

Biguanides• Metformin

(Glucophage)

Thiazolidinediones• Rosiglitazone

(Avandia)• Pioglitazone

(Actos)

∝-Glucosidase inhibitors

Miglitol (Glyset)

Acarbose (Precose)

Peptide analogs

Glucagon-like peptide-1 analogs•Exenatide (Byetta)•Liraglutide (Victoza)•Albiglutide (Tanzeum)•Dulaglutide (Trulicity)

Dipeptidyl peptidase-4 inhibitors•Sitagliptin (Januvia)•Vildagliptin (Galvus)•Saxagliptin (Onglyza)•Linagliptin (Tradjenta)•Alogliptin (Nesina, Vipidia)

Amylin analogs•Pramlintide (Symlin)

Glucosurics (SGLT-2 inhibitors)

Canagliflozin (Invokana)

Empagliflozin (Jardiance)

Dapagliflozin (Farxiga)

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Peptide Analogues

GLP-1 Analogues

DPP-4 Inhibitors

Amylin Analogues

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Exenatide (Byetta) – “lizard spit” GLP-1 Analogue Isolated from gila monster saliva Approved 2005 Injection only Now available in one weekly dosing (Bydureon) Others in this class: liraglutide (Victoza), albiglutide (Tanzeum),

dulaglutide (Trulicity)

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Peptide Analogues

GLP-1 Analogues

DPP-4 Inhibitors

Amylin Analogues

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Sitagliptin (Januvia)

Inhibits DPP-4, thereby increasing levels of GLP-1

Approved 2006 Taken orally Others in this class

– Saxagliptin (Onglyza)– Linagliptin (Tradjenta)– Alogliptin (Takeda)– Vildagliptin (Galvus) - pending

Others in other countries and others in development

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Peptide Analogues

GLP-1 Analogues

DPP-4 Inhibitors

Amylin Analogues

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Pramlintide (Symlin)

Amylin is secreted from the beta cell with

insulin Actions:

– Delays gastric emptying

– Promotes satiety

Synthetic analogue pramlintide approved 2005 Must be injected

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Glucosurics (SGLT-2 Inhibitors)

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SGLT-2 Inhibitors

canagliflozin (Invokana) – 2013

empagliflozin (Jardiance) – 2014

dapagliflozin (Farxiga) – 2014

All are taken orally.

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Combination Meds - 1

Metformin+ glipizide = Metaglip+ glyburide = Glucovance+ pioglitazone = Actoplus Met+ rosiglitazone = Avandamet+ repaglinide = Prandimet+ saxagliptin = Kombiglyze+ sitagliptin = Janumet+ linagliptin = Jentadueto+ alogliptin = Kazano+ dapagliflozin = Xigduo

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Combination Meds - 2

Glimepiride (Amaryl)+ rosiglitazone = Avandaryl+ pioglitazone = Duetact

Pioglitazone (Actos)+ alogliptin = Oseni

Sitagliptin (Januvia)+ simvastatin = Juvisync

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