1. Polyol Pathway
2. Advanced Glycosylated End Products
3. Protein Kinase C Activation
4. Hexosamine Pathway

1. Endothelial Dysfunction
2. Increased oxidative stress
3. Pro-inflammatory Effects
4. Protein Glycosylation
5. Altered coagulation --> increased thrombosis

1. Uncontrolled blood glucose
2. Uncontrolled blood pressure
3. Uncontrolled cholesterol
4. Pregnancy
5. Hispanic or African-American heritage

1. Early NPDR (mild)
2. Middle NPDR (moderate-severe-very severe)
3. Advanced PDR (detachment of retina can occur)

1. Control blood glucose
2. Control blood pressure
3. Control lipid panel
4. Eye Exams

initial eye exam -- within 5 years of diagnosis

follow up -- annually

initial eye exam -- ASAP post diagnosis

follow up -- annually

initial eye exam -- 1st trimester

follow up -- regular basis for first year postpartum

Dialysis

Renal transplant

1. Uncontrolled blood glucose
2. Uncontrolled high blood pressure and cholesterol
3. Smoking
4. DM1 before age 20
5. African Americans, Hispanic, or Native American origin

Early stages --> typically no symptoms

Later stages --> symptoms start to appear

1. headache
2. fatigue
3. N/V
4. poor appetite
5. swelling
6. weight gain

1. Control blood glucose
2. Control blood pressure
3. Control lipid panel
4. ACE/ARB
5. Possibly protein restriction?
6. Regular "checks"

initial -- within 5 years of DM1 diagnosis

follow up -- annaully

creatinine -- annually

initial -- ASAP post diagnosis

follow up -- annually

creatinine -- annually

normal < 30

microalbuminuria 30-299

macroalbuminuria >299

Kidney Failure

<15 or dialysis

Lower Extremities (feet)

Neuropathic foot ulcers

Neuropathic arthropathy

1. Small fiber damage - can't detect temp, pins and needles, numbness or loss of feelings
2. Large fiber damage - abnormal or unusual sensations, loss of balance, unable to sense position of toes and feet
3. Motor nerve damage - loss of muscle tone in hands and feet
4. Foot deformities

1. Glycemic regulation/control
2. BP regulation/control
3. Achieve lipid goals
4. Smoking cessation
5. Regular nerve "checks"

initial -- at diagnosis

follow up -- annually

initial -- at diagnosis

follow up -- annually

initial -- within 5 years of diagnosis

follow up -- annually

initial -- at diagnosis

follow up -- annually

1. Symptom relief/decrease
2. Tricyclic Antidepressants
3. SSRI's

1. Duloxetine
2. Pregabalin

1. GIT
2. Cardiovascular System
3. Genitourinary
4. Sudomotor
5. Hypoglycemic Autonomic Failure

1. Gastroparesis
2. Esophageal enteropathy
3. Constipation
4. Diarrhea
5. Fecal Incontinence

1. Resting Tachycardia
2. Exercise Intolerance
3. Orthostatic hypotension

1. Sexual Dysfunction - Men, erectile dysfunction, retrograde ejaculation; Women, anorgasmia, decreased lubrication
2. Bladder Dysfunction - recurrent UTI, recurrent pyelonephritis, incontinence

1. Dry skin
2. Loss of sweating (anhidrosis)
3. Heat intolerance

1. Uncontrolled blood glucose
2. Duration of disease
3. Uncontrolled high blood pressure and cholesterol (compromised vasculature can lead to PVD)
4. Smoking

1. Infection
2. Gangrene
3. Ulcers
4. Loss of limbs

Increased risk of silent MI

Conduct mortality HRV testing at diagnosis of DM2/5 years DM1

Neuropathy

1. Amitriptyline (tertiary amine)
2. Imipramine (tertiary amine)
3. Clomipramine ((tertiary amine)
4. Desipramine (secondary amine)
5. Nortriptyline (secondary amine)

1. Drowsiness, nausea
2. Anticholinergic effects
3. CV (arrhythmias, sinus tachycardia, conduction time prolongation, orthostatic hypotension)
4. Weight gain
5. Impaired sexual function

FDA Approved for Distal Symmetric Polyneuropathy

Cymbalta

SSRI

Insomnia, nausea, constipation, black box warning

Do not use in hepatic impairment, substantial alcohol use, or renal impairment (CrCl < 30ml/min)

FDA Approved for Distal Symmetric Polyneuropathy

Lyrica

Renal Dosing is needed

peripheral edema, dizziness, somnolence, blurred vision, substantial confusion or memory impairment

1. Uncontrolled blood glucose
2. Uncontrolled high blood pressure
3. Uncontrolled cholesterol
4. Smoking
5. Obesity
6. Waist circumference

TC: < 200

LDL: < 100, < 70 for overt risk

HDL: Men > 40, Women > 50

TG: < 150

1. elevated levels of plasminogen activator inhibitor-1
2. platelet aggregation
3. impaired fibrinolysis

1. Glycemic regulation/control
2. BP regulation/control
3. Achieve lipid goals
4. ASA Therapy
5. Weight control
6. Smoking Cessation
7. Preventative Self Care (daily foot checks, vaccinations, etc)

TCA

Amitriptyline

tertiary amine

TCA

Imipramine

tertiary amine

TCA

Clomipramine

tertiary amine

TCA

Desipramine

secondary amine

TCA

Nortriptyline

secondary amine