ISSUES AND CONTROVERSIES IN WOMEN’S HEALTH
Educational Objectives
| The goal of this program is to improve management of patients who are obese and overweight and improve
management of patients with type 2 diabetes. After hearing and assimilating this program, the clinician will be
better able to:
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 | 1. Recognize patients at risk for health consequences related to body mass index (BMI).
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| 2. Counsel patients about weight loss diets and the role of exercise in weight loss and maintenance.
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| 3. Counsel patients about the use of weight loss medication or bariatric surgery for the treatment of obesity.
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| 4. Explain the cause of deteriorating glucose control in type 2 diabetes and discuss the rationale for intensifying
therapy.
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| 5. Define clinical inertia and discuss how to avoid it in the management of patients with type 2 diabetes.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes
quality in health care and not a proprietary business or commercial interest. For this program, the faculty and planning
committee reported nothing to disclose.
Acknowledgements
Dr. Baron was recorded at Controversies in Women’s Health, sponsored by the University of California, San Francisco,
School of Medicine, held on December 6-7, 2007, in San Francisco. Dr. Cook was recorded at Women’s Health Update
2008, sponsored by Mayo Clinic College of Medicine, held on April 17-19, 2008 in Scottsdale, AZ. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
| CURRENT ISSUES IN OBESITY: DIET, EXERCISE, DRUGS, AND SURGERY —Robert B. Baron, MD, MS, Professor
of Medicine; Associate Dean for Graduate and Continuing Medical Education; Vice Chief, Division of General
Internal Medicine, University of California, San Francisco, School of Medicine
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| Body mass index (BMI): normal BMI 18.5 to 25; overweight 25 to 30; 3 categories of obesity; extreme obesity
(class III) BMI >40 (surgeons refer to as morbid obesity); morbidity can occur at any BMI; National Health and Nutrition
Examination Survey (NHANES)—showed no excess mortality associated with excess body weight in people
with BMI of 25 to 30; raises possibility that consequences of being overweight overdefined; broader ranges of
weight associated with best health outcome; healthiest weights extend to BMI of 30 in blacks (blacks have more
subcutaneous (SC) than intra-abdominal fat); frailty (especially in elderly) and obesity associated with poor health
outcomes; studies show health consequences associated with obesity decreasing; risk for health consequences important
consideration when considering bariatric surgery
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| Metabolic syndrome: abdominal obesity worse than lower-body obesity; determine patient’s waist-to-hip ratio or
waist circumference; distinguish benign obesity from metabolically active obesity that accounts for clinical problems
associated with obesity (eg, dyslipidemia, hypertension, diabetes) and leads to heart disease
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| Criteria for diagnosis: 3 of 5 establish diagnosis; 1) increased waist circumference; 2) low high-density lipoprotein
(HDL); 3) high triglycerides; 4) elevated blood pressure; 5) elevated fasting glucose; ≈60% of patients with obesity
meet criteria for metabolic syndrome; consider secondary causes of obesity (eg, endocrinopathies, mood disorders,
eating disorders; uncommon in stable obesity) and determine whether health consequences of obesity
present; criteria useful if patient overweight, somewhat useful in patients of normal weight, and begin to lose
utility in very obese because most of these patients do poorly anyway
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| Cardiovascular disease (CVD) mortality and metabolic syndrome: data show metabolic syndrome alone doubles
risk for mortality, even in patients of normal weight (may explain minimal health problems in some overweight
patients); measuring fasting glucose and lipid levels in overweight patients helpful in categorizing patient’s
health risk
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| Diet: transtheorectic model (developed for smoking cessation) effective for management of weight loss and for exercise
prescriptions; determine patient’s level of readiness to begin weight loss program
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| Meal replacement (low-calorie diets and very low-calorie diets): shakes, bars, prepackaged food; effective for
quick weight loss; removes patient from food environment (eg, food shopping, cooking, restaurants); low calorie
diet—typically 1200 to 1400 calories/day; very low-calorie diet—800 calories/day; leads to twice as much weight
loss in first year, but weight loss becomes comparable as duration increases; data show Gaussian distribution of
results (ie, some patients lose significant amount of weight while others do not); expected weight loss—close to
10% of weight in first year, 20% with very low-calorie diet, 40% with surgery; very low-calorie diet option for
patient with severe type 2 diabetes or who needs to lose significant weight before operation can be performed
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| Atkins, Ornish, Weight Watchers, and Zone: comparison showed study “completers” (stayed on diet for 1 yr) did
twice as well as “noncompleters”; weight loss modest; no statistical difference in outcomes among diets compared;
weight loss associated with adherence, not type of diet; each diet improved lipids; low-carbohydrate approach
to weight loss shown safe, effective, and more readily accepted than in past; in new diet pyramid,
macronutrient ranges wider and more liberal than in past
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| Exercise: in short term, not associated with weight loss; exercise combined with diet resulted in greater weight reduction
than diet alone; exercise effective in improving risk factors associated with obesity (eg, hypertension,
HDL), and small dose effect present; fitness and mortality—observational study showed cardiovascular mortality
higher in men who were normal weight, but not physically fit, than in overweight or obese men who were physically
fit, data also showed fewer health effects from metabolic syndrome in overweight and obese participants who
were physically fit, compared to normal-weight participants
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| Maintenance of weight loss: fewer calories needed to maintain weight as patient loses weight; resting metabolic
expenditure less; less muscle mass causes fewer calories to be expended when exercising; also, independent of
muscle mass, metabolic down-regulation after weight loss causes reduction in energy expenditure
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| Strategies used by successful weight loss maintainers: 1381 calories consumed per day on average; low-fat diet (total
calories more important than macronutrients); several small meals throughout day (generates thermogenic effect
of food); avoid fast food; engage in high levels of physical activity (≈1 hr/day of moderate intensity
exercise) 7 days/wk; regularly self-monitor weight (at least daily or weekly); maintain same eating pattern on
weekends as on weekdays
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| Goals for weight management: be as fit as possible at current weight; prevent further weight gain; if successful at
first 2 goals, begin weight loss program
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| Key elements of behavior therapy: goal setting, self-monitoring, and cognitive skills; cognitive behavioral therapy
(CBT) shown effective in management of weight loss; team approach recommended
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| Medication: ≈5% weight loss from baseline; weight regained when medication stopped; never prescribe at first office
visit; prescribe only after patient has demonstrated behavior changes (ie, diet and exercise); prescribe only
one month’s supply (results at 1 mo correlate well with results at 12 mo)
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| Off-label medications: selective serotonin reuptake inhibitors (SSRIs); modest weight loss associated with bupropion
(eg, Wellbutrin; speaker’s first choice for overweight and obese patients who are depressed); metformin
(drug of first choice for type 2 diabetes; associated with weight loss and improved outcomes in type 2 diabetes);
exenatide (Byetta; given SC; aids in controlling blood glucose; associated with weight loss rather than weight
gain typically seen with insulin); off-label medications should be considered only if patient has coexisting condition
(ie, depression, prediabetes, type 2 diabetes, polycystic ovary syndrome [PCOS])
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| Rimonabant: available in Europe; cannabinoid receptor blocker; associated with depression; never on US market
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| Weight loss surgery: Roux-en-Y gastric bypass—risk for death 30 days postoperatively, 1 in 50; accounts for 80%
of bariatric surgery; restrictive with malabsorptive component; lap band—less invasive; slower initial weight loss
than Roux-en-Y gastric bypass; adjustment of band requires regular follow-up; possibility of erosion of band and
conversion to gastric bypass; vitamin and mineral deficiencies; weight loss from bariatric surgery ≈30% of baseline;
improvement in comorbidities; mortality rate after bariatric surgery—1 in 200 for low-risk patients having surgery
at best centers (statistic applies to white women from suburban communities who have private insurance); 1 in
50 for older patients; data show 24% reduction in all-cause mortality in surgery group (mainly Roux-en-Y gastric
bypass) compared to controls; counsel patient small mortality benefit with bariatric surgery (after 11 yr, one additional
patient alive for every 77 patients who have surgery)
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| UPDATE ON THERAPEUTIC STRATEGIES IN TYPE 2 DIABETES —Curtiss B. Cook, MD, Professor of Medicine,
Mayo Clinic College of Medicine, Scottsdale, AZ
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| Initial therapeutic approach in newly diagnosed type 2 diabetes: fasting blood glucose <200 mg/dL and random
blood glucose <250 mg/dL—attempt lifestyle changes; hyperglycemic crisis (fasting blood glucose >300 mg/dL,
random blood glucose >350 mg/dL, excessive thirst and urination)—start insulin therapy; fasting blood glucose 200 to
399 mg/dL, random blood glucose 250 to 350 mg/dL—start oral agent, possibly exenatide
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| Case: woman, 42 yr of age; random glucose 257 mg/dL, hemoglobin A1c (HbA1c ) 8.5%; confirmed diabetes;
management—start oral hypoglycemic agent; start blood glucose self-monitoring; assess for CVD risk factors; focus
on lowering lipids and controlling blood pressure; consider prescribing daily aspirin
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| Oral hypoglycemic agents: meta-analysis showed all monotherapies decreased Hb A1c by 1%; metformin had
greatest benefit on weight and LDL lowering; sulfonylureas associated with greater risk for hypoglycemia; A Diabetes
Outcome Progression Trial (ADOPT)—5-yr follow-up study; looked at proportion of people who failed monotherapy;
glyburide failed in 34% of people; metformin in ≈21%, rosiglitazone (Avandia) in ≈15%; maintenance of
β-cell function worst with glyburide and best with rosiglitazone; adverse effects of medication increase starting at
≈50% of recommended dosage; consider adding second hypoglycemic agent before maximizing dosage of single
agent
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| Deteriorating glycemic control: United Kingdom Prospective Diabetes Study (UKPDS) showed that blood glucose
control deteriorates over time, due to loss of β cells, and more therapies required to maintain control; currently
no therapy to preserve β-cell function; ongoing debate whether insulin should be used earlier in management of
type 2 diabetes
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| Insulin: improves glucose disposal and suppresses hepatic glucose output (increased hepatic glucose accounts for
fasting hyperglycemia); improves survival of β-cell function; reasons for not using include weight gain, risk for hypoglycemia,
and patient’s reluctance; insulin often presented as threat to patient, rather than as benefit in management
of type 2 diabetes; UKPDS—showed insulin added to glyburide early in management more effective in
controlling blood glucose than insulin alone; Treat-to-Target Trial—showed comparable reductions in fasting glucose
and Hb A1c with both human NPH and glargine at bedtime; glargine associated with fewer hypoglycemic episodes
(human NPH acceptable choice when cost factor)
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| Clinical inertia: ≈38% of patients compliant with diet and exercise regimen for controlling diabetes; clinical inertia
defined as not intensifying therapy when therapy should be intensified; avoid clinical inertia by making significant
changes often enough
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| Management approaches: traditional staged approach to management—lifestyle modification; monotherapy;
combination (noninsulin) therapy; insulin (multiple daily injections); insulin pump; modified staged approach—
lifestyle modification plus metformin; add second agent; insulin (multiple daily injections); insulin pump; determinants
of therapy—patient’s desire; contraindications to medication; severity of patient’s hyperglycemia; proximity
to glucose goal; duration of diabetes; cost of therapy
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| Summary: hyperglycemia progressive; each phase of glucose tolerance defined based on glucose level; type 2 diabetes
can be prevented, delayed, and effectively managed; consider early use of combination therapy and early use
of insulin; expect to intensify treatment and intensify often; avoid clinical inertia
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Suggested Reading
Bolen S et al: Systematic review: comparative effectiveness and safety of oral medications for type 2 diabetes mellitus.
Ann Intern Med 147:386, 2007; Dansinger ML et al: Comparison of the Atkins, Ornish, Weight Watchers,
and Zone diets for weight loss and heart disease risk reduction: a randomized trial. JAMA 293:43, 2005; Flum DR et
al: Toward the rational and equitable use of bariatric surgery. JAMA 298:1442, 2007; Katzmarzyk PT et al: Metabolic
syndrome, obesity, and mortality: impact of cardiorespiratory fitness. Diabetes Care 28:391, 2005; Riddle
MC et al: The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2
diabetic patients; Shaw K et al: Exercise for overweight or obesity. Cochrane Database Syst Rev 28:CD0003817,
2006; Turner RC: The U.K. Prospective Diabetes Study. A review. Diabetes Care 21 Suppl 3:C35, 1998; Viberti
G et al: A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in
North America and Europe. Diabet Med 23:1289, 2006; Wing RR, Phelan S: Long-term weight loss maintenance.
Am J Clin Nutr 82(1 Suppl):222s, 2005.
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