Insulin Resistance in Smokers Undergoing Smoking Cessation

This study is a prospective, open cohort study of smokers who undergo a smoking cessation
program, and who subsequently may or may not resume smoking spontaneously. Eligible
subjects will be characterized at baseline with respect to their metabolic and CVD risk
profiles, body fat composition and distribution. Subjects will then undergo an intensive
8-week smoking cessation program using bupropion plus cognitive behavioral counseling.
Those who successfully abstain will be reassessed. Since most individuals who quit smoking
will naturally resume smoking again over time, subjects will be assessed again after an
additional 4 months of follow-up when a subset of subjects will be expected to have
naturally resumed smoking.

Inclusion Criteria:

- Age 25 to 70 inclusive; any ethnicity

- Cigarette smoking for at least 3 years, at a rate of at least 1 but not more than 2
packs per day

- BMI 19 kg/m2 or greater and 40 kg/m2 or less

- Willing to enter, and be able to comply with the instructions and scheduled follow-up
of a smoking cessation program

Exclusion Criteria:

- Any physical disabilities that prevent the subject from participating in the study,
as determined by the investigators

- History of CVD (ventricular arrhythmias, atrial arrhythmias with a history of
hemodynamic instability, unstable angina, myocardial infarction, invasive coronary
revascularization, or any hospitalization for CVD within the last 3 years, NYHA Class
III or IV CHF)

- Current abuse of illicit drugs or heavy ethanol use

- History or baseline laboratory evidence of diabetes mellitus

- History of chronic obstructive pulmonary disease (COPD)

- BMI < 19 or > 40 kg/m2

- Subjects not following a regular diet and lifestyle pattern (e.g, homeless)

- Uncontrolled hypertension (BP 170 mmHg or greater systolic or 110 mmHg or greater
diastolic)

- Fasting triglycerides 700 mg/dL or greater, or LDL-cholesterol 200 mg/dL or greater

- History of chronic renal or liver disease (hepatic transaminase elevations > 3 times
the upper limit of the normal range; creatinine > 1.5 mg/L), malignancies not
currently in remission, gastrointestinal disorders that interfere with nutrition;
history of malnutrition, chronic infections (including HIV), or recent (within 30
days) surgeries or hospitalizations

- Concurrent use of medications that may alter metabolic parameters (including
metformin, sulfonylurea agents, thiazolidinediones, weight loss agents, androgens or
systemic glucocorticoids); lipid-lowering agents and oral contraceptives will be
permitted as long as formulations, dosages and adherence remain unchanged throughout
the course of the study. Oral contraceptives that are started during the course of
the study will require the subject to be withdrawn from the study

- Perimenopausal women experiencing irregular menses, because of changing metabolic
status during the perimenopause; these patients may be included if menses have ceased
for at least 6 months

- Women who are pregnant, seeking to become pregnant in the next 6 months, or who are
breastfeeding

- Any history of depression, suicidality, or any contraindications to bupropion
(history of seizures, anorexia or bulimia)

- Current use of nicotine replacement products (gum or patch)

- Any other factors that, in the opinion of the investigators, may interfere with the
safe conduct, successful completion, or data integrity of the study