Comprehensive
Cardiometabolic
Risk-Reduction
Program
Phase 2
2009
Sponsored by National Lipid Association
Case Study
Special Considerations for the
Overweight/Obese Patient
Case Study
Overview
• A 46-year-old male lawyer is referred by his physician for
persistent weight gain and high cardiomyopathy risk
• Patient has hyperlipidemia and hypertension;
comorbidities include asthma, attentiondeficit/hyperactivity disorder (ADHD), chronic fatigue,
and depression
• Family history of obesity, type 1 and 2 diabetes
• Current weight of 305.7 pounds is his highest
– Admits poor nutritional habits and a low activity level
• Reports waking up “snorting” from snoring at night
– Experiences morning headaches and daytime somnolence
The Regulation of Food Intake Is a
Complex Process
Brain
Central Signals
Stimulate
NPY
AGRP
Galanin
Orexin-A
Dynorphin
Peripheral Signals
Glucose
–
CCK, GLP-1,
Apo A-IV
Vagal afferents
+
Insulin
Ghrelin
–
+
Inhibit
a-MSH
CRH/UCN
GLP-I
CART
NE
5-HT
External Factors
Emotions
Food characteristics
Lifestyle behaviors
Environmental cues
Peripheral Organs
Gastrointestinal
tract
Food
Intake
Adipose
tissue
Leptin
Cortisol
Adrenal glands
Zhang Y, et al. Nature. 1994;372:425-432; Schwartz MW, et al. Nature. 2000;404:661-671.
NPY=neuropeptide Y, AGRP=agouti-related
protein, α-MSH=alpha-melanocyte-stimulating
hormone, CRH/UCN=corticotropin-releasing
hormone/urocortin, GLP-1=glucagon-like
peptide-1, CART=cocaine- and amphetamineregulated transcript, NE=norepinephrine, 5-HT=
seratonin, CCK=cholecystokinin, Apo A-IV=
apolipoprotein A-IV.
Case Study
Overview
• Medications
–
–
–
–
–
–
Metoprolol 100-mg BID
Atorvastatin 10-mg QD
Niacin 1500-mg BID
Paroxetine 40-mg QD
Lithium 900-mg QD
Amphetamine/
dextroamphetamine 40-mg QD
Starting Your Investigation
• Look for
–
–
–
–
Obstructive sleep apnea (OSA)
Medications causing weight-gain
Depression
Metabolic syndrome, prediabetes
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.
October 2000. NIH Publication No. 00-4084.
Clinical Pearl
A Vicious Cycle
Weight Gain
Depression
Sleep Apnea
Drug-Associated Weight-Change Reference
Remember to keep this list in your office!
© 2007 Cardiometabolic Support Network
Case Study
Medications That May Be Contributing to This Patient’s
Excess Body Weight
MAOIs=monoamine oxidase inhibitors, TCAs=tricyclic
antidepressants, ACE=angiotensin-converting enzyme
Case Study
Laboratory Results
• Glucose: 106 mg/dL
• hs-CRP: 8.2 mg/L=high risk
• TC: 184 mg/dL
• A1c: 5.9%
• HDL-C: 33 mg/dL
• Creatinine: 1.2 mg/dL
• LDL-C: 103 mg/dL
• AST: 27 U/L
• TG: 240 mg/dL
• ALT: 43 U/L
• eGFR: >60 mL/min
• Non–HDL-C: 151 mg/dL
• EKG: sinus bradycardia,
rate 56
TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein
cholesterol, TG=triglycerides, AST=aspartate aminotransferase, ALT=alanine aminotranferase, hsCRP=high-sensitivity C-reactive protein
Case Study
Initial Registered-Dietitian Appointment
• Weight: 305.1 pounds, height: 72 inches, BMI: 41.4 kg/m2, waist: 48 inches
• Former athlete with low activity level
• Volume eater with little sense of satiety “when he gets started”
• Daytime fatigue noted, being treated for ADHD
• Diet
–
Little fast food/red meat
–
Eats before bed and sometimes wakes up in the middle of the night to eat
–
Breakfast: nothing, lunch: salad, snack: fruit, dinner: Greek salad with chicken or stirfry, snack: “bad”
• Plan
–
Keep food records
–
Begin to eat breakfast
–
Eat higher lean-protein lunches and dinners and begin to reduce refined
carbohydrates
–
Goal of 30 minutes of walking/day
ADHD=attention-deficit/hyperactivity disorder, BMI=body mass index
Clinical Pearl
High-frequency telephone- and
web-based nutritional counseling
can be effective ways
to help patients lose weight
Clinical Pearl
Breakfast and Nighttime Eating
• Skipping breakfast can drive nighttime
eating
–
–
–
–
Breakfast=none
Lunch=breakfast
Dinner=lunch
Nighttime snack=dinner
• Nighttime eating drives skipping breakfast
• The cycle continues…
ARS Question
Which may be the best diet for someone
with a lack of satiety?
A. Low protein
B. Low fat
C. Low glycemic
Glycemic Index (GI)
• Although data vary, a low-GI meal may
reduce subsequent energy intake1
• Cochrane systematic review indicates that
decreasing the GI* of a diet may be an
effective way to promote weight-loss and
improve lipid profiles2
*GI=area under the curve (AUC) of the 2-hour blood
glucose response curve divided by the AUC of an equal
amount of glucose, multiplied by 100
Low GI food/meal = 55 or less
1. Flint A, et al. Am J Clin Nutr. 2006;84:1365-73.
2. Thomas DE, et al. Cochrane Database Syst Rev. 2009;(1):CD005105.pub2.
Clinical Pearl
Diet: What Is Most Important?
Calorie restriction, with high
macronutrient quality*
*High quality indicates more than 5 servings of fruits and
vegetables/day, lean protein sources including some vegetarian
sources, nuts, healthy oils, nonfat dairy products, whole grains,
low in sweets and refined carbohydrates, low in fat
Favorable Option for This Patient
• Low refined-carbohydrate diet with increased
fiber intake
–
–
–
–
Patient has prediabetes
Rapid weight-loss is desirable
Patient’s snacks tend to be refined carbohydrates
Lower refined-carbohydrates reduce hunger in some
patients
– Higher fiber associated with satiety
• Higher protein intake
– Protein increases satiety
– Lean protein has little fat and saturated fat, making it a
healthy option for weight loss
Practical Tips:
Increasing Fiber and Lean Protein
• Fiber
– Fiber One® bran cereal
• Sprinkle it on low-fat yogurt as a bedtime snack
– Whole grains, fruits, and vegetables
• Lean protein
– Ham, turkey, and roast beef are the leanest sandwich
meats
• Have 1/2 sandwich, but double the thickness
– Carnation® Instant Breakfast® No Sugar Added with skim
milk=inexpensive, low-GI meal replacement
– Modified pastas that are no longer “refined carbohydrates”
• Barilla® PLUS® (2-cups cooked)=17-g protein, 7-g fiber, 360mg omega-3 fatty acid
Case Study
Initial MD Appointment
• Weight: 305.7 lbs, height: 72 inches, BMI: 41.5
kg/m2, blood pressure: 138/90, heart rate: 68
bpm, waist: 48 inches
• Patient is at his highest weight
– Several prior weight-loss attempts: no significant progress,
has been steadily gaining weight
– Admits poor nutritional habits and a low activity level
• Reports waking up “snorting” from snoring at
night
– Has morning headaches and daytime somnolence
• Food records show nighttime eating pattern, with
large quantities consumed after 6:00 PM
Case Study
• Medications
–
–
–
–
–
–
Metoprolol 100-mg BID
Atorvastatin 10-mg QD
Niacin 1500-mg BID
Paroxetine 40-mg QD
Lithium 900-mg QD
Amphetamine/dextroamphetamine 40-mg QD
• Action plan
–
–
–
–
Reinforce importance of continued dietitian visits
Sleep study to evaluate for obstructive sleep apnea
Stop metoprolol; initiate ramipril, titrate ↑ to 5-mg BID
Begin metformin ER 500-mg QD, with goal to increase
Clinical Pearl
What if β-Blockers Are Necessary?
If a β-blocker is necessary as part of a
multi-agent antihypertensive regimen, an
agent that does not aggravate insulin
resistance (eg, carvedilol) may be a
favorable choice
ARS Question
According to the 2007 ADA Consensus Statement on
impaired fasting glucose (IFG) and impaired glucose
tolerance (IGT), which of the following is not true?
Metformin is appropriate for use in patients with IFG, IGT, and
A.
A1c ≥5.0%
B.
Hypertension
C.
BMI ≥35 kg/m2
D.
Family history of diabetes in first-degree relative
ADA=American Diabetes Association, BMI=body mass index
Pharmacological Intervention in the
Progression to Diabetes: Recent Statements
• ADA 2007 Consensus Statement
– Metformin as an adjunct/alternative to lifestyle in
patients with IFG and IGT, and any of the
following
• <60 years of age, BMI >35 kg/m2, family history of
type 2 diabetes in first-degree relative,
↑ triglycerides, ↓ HDL-C, hypertension, A1C >6.0%
• ACE 2008 Consensus Statement
– Metformin or acarbose as an adjunct to lifestyle in
patients with prediabetes at particularly high risk
ADA=American Diabetes Association, IFG=impaired fasting glucose, IGT=impaired glucose tolerance, BMI=body mass
index, HDL-C=high-density lipoprotein cholesterol, ACE=American College of Endocrinology
Nathan DM, et al. Diabetes Care. 2007;30:753-759.
American College of Endocrinology Task Force on Pre-Diabetes. Available at:
www.aace.com/meetings/consensus/hyperglycemia/hyperglycemia.pdf. Accessed November 1, 2008.
Diabetes Prevention Program
Don’t Forget:
Lifestyle Is More Effective Than Metformin
Weight Decrease
loss
in risk*
Cumulative Incidence
of Diabetes (%)
40
Placebo
0.1 kg
30
Metformin
20
Lifestyle
10
0
0
1
2
Years
3
4
P<0.001 for each comparison.
*Decrease in risk of developing diabetes compared to placebo group.
Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.
2.1 kg
31%
5.6 kg
58%
Case Study
Month 2—MD Visit 2
• Weight: 294.5 lbs, blood pressure: 140/90, heart
rate: 64 bpm, waist: 47 inches
• Followed diet very strictly for first few weeks
– Now on diet ≈70% of the time
– Still skips breakfast
• Patient rescheduled sleep study, reminded of
importance by MD
– Reports being very fatigued and realizes he eats to stay
awake
• Action plan
– Increase metformin 500-mg to BID, eat protein breakfast
instead of skipping the meal
Case Study
Sleep-Study Results
• Apnea-hypopnea index (AHI) of 57.8
– Diagnosis: severe obstructive sleep apneahypopnea syndrome
• Action plan
– Began continuous positive airway pressure
(CPAP) treatment with 12 cm H20
• Follow-up AHI of 5.0
Clinical Pearl
Many patients won’t tolerate CPAP…
Risk of erectile dysfunction can be a
strong motivator
Case Study
Month 3—Registered-Dietitian Visit 2
• Weight: 290.6 lbs
• Not eating breakfast
– “No time, no interest, not hungry”
• Eating less at night
• Patient hurt his back and is going to physical therapy,
but little aerobic activity secondary to fatigue
• Seeing new psychiatrist who will evaluate medical
regimen
• Plan
– Meal replacements for breakfast
– Continue low-glycemic index diet (increase vegetables,
steak only 1x/week)
Meal Replacements
• Important for patients
who have
– Little time for food
shopping and
preparation
– Hit a weight plateau
– Persistent difficulty
managing food and
social cues related to
overeating
• Advantages
– Provide adequate and
consistent nutrition as a
low-fat, calorie-controlled
replacement for 1 or 2
meals per day
– Eliminate food choices
and temptations
– Simplify food shopping
and preparation
– Convenient to carry and
store
Meal Replacements Promote
Short- and Long-Term Weight Loss
Phase 1*
Phase 2
CF
MR-1
Weight Loss (%)
0
5
MR-2
10
15
0
2
4
6
8
10 12 18
Time (mo)
24
*1200–1500 kcal/d diet prescription
CF=conventional foods; MR-2=replacements for 2 meals, 2 snacks daily;
MR-1=replacements for 1 meal, 1 snack daily
Fletchner-Mors, et al. Obes Res. 2000;8:399.
30
36
45
51
Case Study
Month 5—MD Visit 3
• Weight: 277.7 lbs (-28 lbs), BMI: 37.7 kg/m2;
blood pressure: 130/80, heart rate: 64 bpm,
waist: 44 inches
• Now on CPAP at 12 cm H20
– Notes that he feels much better, with more energy
and focus
• Since sleep study and CPAP use, psychiatrist
decreased lithium to 600-mg QD, paroxetine to
20-mg QD, and amphetamine/
dextroamphetamine to 20-mg QD
DHA/EPA=docosahexaenoic acid/eicosapentaenoic acid
Case Study
Month 5—MD Visit 3
Lab Results
•
•
•
•
•
•
Glucose: 92 mg/dL
TC: 176 mg/dL
HDL-C: 30 mg/dL
LDL-C: 106 mg/dL
TG: 200 mg/dL
Non–HDL-C: 146 mg/dL
•
•
•
•
•
hs-CRP: 3.1 mg/L
A1c: 5.6%
Creatinine: 1.2 mg/dL
AST: 25 U/L
ALT: 40 U/L
TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, hsCRP=high-sensitivity C-reactive protein, AST=aspartate aminotransferase, ALT=alanine aminotranferase
ARS Question
Which of the following would you be most
likely to consider as part of the action plan for
this visit?
A. Increase statin dosage
B. Switch to a different statin
C. Add a fibrate
D. Discontinue niacin and add omega-3 FAs
Case Study
Month 5—MD Visit 3
Action plan
• Discontinue niacin
• Start omega-3 (DHA/EPA) fatty acids (FA) 2000-mg QD,  to BID
• Increase metformin to 850-mg BID
Clinical Pearl
Due to the negative effect of niacin on glucose control
and insulin resistance1,2, omega-3 fatty acids may be a
preferred alternative in patients at risk for diabetes*
*Reflects opinion of program Steering Committee.
TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein cholesterol, TG=triglycerides, hsCRP=high-sensitivity C-reactive protein, AST=aspartate aminotransferase, ALT=alanine aminotranferase
1. Vittone F, et al. J Clin Lipidol. 2007;1:203-210. 2. Goldberg RB, et al. Mayo Clin Proc. 2008; 83:470-8.
Case Study
Month 6—Registered-Dietitian Visit 3
• Weight: 274.6 lbs
• Patient has been doing well with breakfast
meal replacements, but is bored with diet
and feels he has hit a weight plateau
• Plan
– Congratulate him on losing 30 lbs!
– Continue low-glycemic index diet, but brainstorm
alternative breakfast and snack options
– Food records 3 days/week, self-monitor weight
every day for next 2 weeks
– Reinforce need for physical activity
Case Study
Month 8—MD Visit 4
• Weight: 270.7 lbs (-35 lbs [-11%]), blood pressure:
124/82, heart rate: 68 bpm, waist: 43 inches
• Current meds: atorvastatin 10-mg QD, metformin 850mg BID, omega-3 fatty acids (DHA/EPA) 2000-mg BID,
ramipril 5-mg BID, amphetamine/dextroamphetamine
20-mg QD, paroxetine 20-mg QD, lithium 600-mg QD
• Using CPAP regularly and has good energy level
• Fair compliance to diet secondary to stress/family
– Has some night eating, but generally minimizing sugar and
carbohydrates
• He now feels active enough to exercise and is
walking 20 min/day 4x/week
Case Study
Month 8—MD Visit 4, Laboratory Results
• Glucose: 90 mg/dL
• TC: 157 mg/dL
• HDL-C: 42 mg/dL
• LDL-C: 91 mg/dL
• TG: 120 mg/dL
• Non–HDL-c: 115 mg/dL
• A1c: 5.2%
• hs-CRP: 1.2 mg/L
TC=total cholesterol, HDL-C=high-density lipoprotein cholesterol, LDL-C=low-density lipoprotein
cholesterol, TG=triglycerides, hs-CRP=high-sensitivity C-reactive protein
Case Study
Month 8—MD Visit 4, Action Plan
• Psychiatrist stopped lithium, reduced
paroxetine to 10-mg QD and reduced
amphetamine/dextroamphetamine to 10mg QD
• Continue metformin 850-mg BID and use
of CPAP
• Prescribe exercise regimen
Clinical Pearl
• In addition to
lifestyle factors,
biology favors
weight regain
Eckel RH. N Engl J Med. 2008;358:1941-1950.
ARS Question
According to the US Department of Health and
Human Services 2008 guidelines, how many minutes
per week of moderate-intensity exercise do many
people need to maintain their weight after a
significant amount of weight loss?
A.
B.
60
120
C. 180
D. >300
US Department of Health and Human Services. Available at:
http://www.health.gov/paguidelines/guidelines/default.aspx. Accessed February 6, 2009.
Clinical Pearl
Although caloric restriction is the key
to weight loss, regular physical
activity is crucial to maintaining a
lower body weight
National Weight Control Registry: Cardinal
Behaviors of Successful Long-Term Weight
Management
• Self-monitoring
– Diet: record food intake daily, limit certain foods or food
quantity
– Weight: check body weight >1x/week
• Low-calorie, low-fat diet
– Total energy intake: 1300–1400 kcal/day
– Energy intake from fat: 20%–25%
• Eat breakfast daily
• Regular physical activity: 2500–3000 kcal/week
(eg, walk 4 miles/day)
Klem, et al. Am J Clin Nutr. 1997;66:239.
McGuire, et al. Int J Obes Relat Metab Disord.1998;22:572.
Key Learnings: Medical
• Look for sleep apnea and treat it
• Get your patients off drugs that cause
obesity (when possible)
• Consider insulin sensitizers
• Assess medications for aggravation of
comorbidities
• Ask patients how well they are sticking to
their intended lifestyle changes
Key Learnings: Behavioral
• Adapt the diet to your patient
• Inform patients that breakfast is
associated with weight loss/lower bodyweight
• Encourage self-monitoring
– Food records
– Regular “weigh-ins”
• Reinforce that exercise is critical for the
maintenance of weight loss
At the initial clinical presentation, would this patient
have been a candidate for bariatric surgery?
• Weight: 305.7 lbs, BMI: 41.5 kg/m2, waist: 48 inches,
blood pressure: 138/90, heart rate: 68 bpm
• Patient at his highest weight and gaining
– Several weight-loss attempts without significant progress
• Hyperlipidemia, hypertension, asthma, attentiondeficit/hyperactivity disorder, fatigue, depression,
obstructive sleep apnea
• Family history of obesity, type 1 and 2 diabetes
Laboratory Test Results
• TC:
184 mg/dL
• HDL-C:
33 mg/dL
• LDL-C:
103 mg/dL
• TG:
240 mg/dL
BMI=body mass index
•
•
•
•
Non–HDL-C:
Glucose:
A1c:
hs-CRP:
151 mg/dL
106 mg/dL
5.9%
8.2 mg/L
Bariatric Surgery
• Indications
– BMI >40 kg/m2 or BMI 35–39.9 kg/m2 and lifethreatening cardiopulmonary disease, severe
diabetes, or lifestyle impairment
– Failure to achieve adequate weight-loss with
nonsurgical treatment
• Contraindications
– History of noncompliance with medical care
– Certain psychiatric illnesses: personality disorder,
uncontrolled depression, suicidal ideation,
substance abuse
– Unlikely to survive surgery
Adapted from www.obesityonline.org.
NIH Consensus Development Panel. Ann Intern Med. 1991;115:956.
Clinical Pearl
Surgeon experience is the single best
predictor of success
To locate an ASMBS Center of Excellence
http://www.surgicalreview.org/
ASMBS=American Society of Metabolic and Bariatric Surgery.
ARS Question
Which of the following is true about the
effects of bariatric surgery?
A. It has not yet been associated with a
significant improvement in overall mortality
B. At 10-years postprocedure, it is associated
with a decrease in the incidence of
hypertension
C. At 10-years postprocedure, over 1/3 of
patients with diabetes at baseline no longer
had the disease
Swedish Obese Subjects Study
Bariatric Surgery: Long-Term Effects on
Weight and Cardiovascular Risk Factors
• Prospective, controlled intervention trial of 4047 obese subjects (age=48
years, BMI=41 kg/m2); gastric surgery* vs conventional treatment
• At 10 years
– Weight change—surgery: 16.1%
– Weight change—control: 1.6% (P<0.001)
– Lower incidence of diabetes, hypertriglyceridemia, and hyperuricemia
(P<0.05 for each)
Rate of Recovery
(% of Subjects)
100
†
73
80
†
60
40
Control
53
†
46
†
Surgery
48
36
‡
24
27
19
13
11
20
0
Hypertriglyceridemia
Low HDL
Cholesterol
Sjostrom L, et al. N Engl J Med. 2004;351:2683-2693.
Diabetes
Hypertension
Hyperuricemia
*Banding, vertical-banded gastroplasty, gastric bypass
†P≤0.001
‡P=0.02
Swedish Obese Subjects Study
Bariatric Surgery: Long-Term Weight
Loss and Decreased Mortality
• Up to 16 years follow-up
• Overall mortality
– Hazard ratio*=0.76 (95% CI: 0.59–0.99), P=0.04
14
Cumulative Mortality (%)
Change in Weight (%)
0
Control
10
Banding
-20
Vertical-Banded Gastroplasty
Gastric Bypass
-30
12
Control
10
8
6
Surgery
4
P=0.04
2
0
0 1 2 3 4
6
8
10
Years
*Surgical group vs control group at 16 years
Sjostrom L, et al. N Engl J Med. 2007;357:741-752.
15
0
2
4
6
8
Years
10
12
14
16
Key Learnings: Bariatric Surgery
• Advantages
– “Forced” lifestyle changes
– Improved cardiometabolic risk-factors
– Decrease in diabetes
• Both recovery and  incidence
– Decrease in mortality
• Pitfalls
– Surgical complications
– “Forced” lifestyle changes
– Patients can “get around” the surgery