long term weight loss following abdominoplasty: neurocrine factors
DESCRIPTION
Long term weight loss was associated with abdominoplasty in a group of 22 patients providing that the BMI was 25 or greater at the time of teh procedure, p< 0.001. Neuropcrine factors are discussed in this pilot study, whish is the first of it's kind.TRANSCRIPT
Permanent Weight Reduction after Abdominoplasty: Neurocrine Factors, A Pilot Study
Rex Moulton-Barrett, MD & Jennifer Fuller, B.A. Plastic & Reconstructive Surgery Alameda and Brentwood, Ca
The Role for Abdominoplasty ?
Just because you can, does not mean you should ?
After Abdominoplasty Some Patients: Lost weight & Lost no weight
•
Questions
• Does abdominoplasty lead to long-term weight loss ?
• Which group of patient’s benefit most ?
• What are the cause(s) of weight loss after surgery ?
Obesity Epidemic
• BMI: Body Mass Index: weight kg/(height m)2
• <1/3 of U.S. Normal BMI 19-25
• 1/3 of U.S. Overweight BMI 25-30
• 1/3 of U.S. Obese BMI 30-40
• The prevalence of obesity has more than doubled since 1980
• 3% of U.S. Morbid-Super Obese BMI> 40
Treatment of Obesity
3 main methods of treatment:
• Life Style Modification – Moderately effective but difficult to monitor and sustain
• Pharmacological Therapy– Few effective treatments exist
• Surgical Treatment– Significant and permanent weight loss
– Insurance criteria morbid obesity (BMI ≥40)
Life Style Modification
• Convert to ‘ negative energy gap ’
• Increased energy expenditure:reduce non-active time: car, chair, sofaincreased exercise time
increased energy lost during exercise
• Diet: high protein low carbohydrate low sugar ‘+ ketogenic diets’ reduce appetite ( Am J of Clin Nutrition, 2008: 87(1), 44-55 )
avoid exercise before meals: 20 minute run = 20oz ie avoid post exercise ‘calorie rewards’
Current Weight Reduction Drugs( 1% of 59 billion dollars spent to loose fat in USA / yr )
% body weight lost % pts lost at least
minus placebo 5% body weight
a.c.t. placebo ‘/x’
• FDA Approved– Meridia: Sibutramine 4.3 55/27– Xenical: Orllstat 2.9 54/33
• New drugs pending approval– Qnexa 9.0 67/19– Contrave 4.6 53/21– Lorcaserin 3.4 47/23
1997:fen-phen (fenfluramine-phentermine) & Redux (dexfenfluramine) removed from market
Mechanism of Action
• Meredia: Monoamine RI (serotonin & noradrenaline)
(Abbott) may BP, HR: not to use if hypertensive
unlike fenfluramine does not elevate serum serotonin
controls binge eating
• Qnexa: Phentermine & Topiramate
(Vivus) 56 week course: 37 lb loss: BP, glucose, cholesterol
may be useful in type 2 DM
Phentermine: hypothalamic norepinephrine release
high dose: potential for dependence
Topiramate: ( Topamax ), anti-epileptic,
anti-migraine,
bipolar/binge eating
Surgical TreatmentGastric Bands
Partial Gastric & Intestinal Bypass
( Roux en Y )
Abdominoplasty ?
Abdominoplasty Work-Up
• Obese versus abdominal laxity or symptomatic pannus ?
• First consultation: attempt weight reduction if >200lbs
• Charge about 25% more if over 200lbs
• ‘3 S plan’: South Beach Diet, Sugarless house, Stationary bike with 45 minute 3x week TV contract after meals
• + Meridia if unsuccessful > 4 weeks & binge eating ?
Abdominoplasty Technique
• Low incision 4 cm above the anterior labial commissure
• Aggressive midline Rectus Abdominus plication
• Jack knife sitting / Trendelenburg position closure
• Closure: interrupted Scarpa’s fascia
running dermal barbed 3.0 V -Lock Suture
skin glue and 1 inch Steri-Strips
• Lateral flank liposuction for contour
• 5 day pain pump & overnight in surgery center
• Rented surgical bed at home for 2-4 weeks
• Prolonged paper taping for 6 months when clothed
• 3 S’s starting 6 weeks post-op
Methods
• Retrospective case review: chart & structured interview
• same surgeon and one post-graduate student
• n= 21 patients post-abdominoplasty
• Follow up to > 1 year: 2007-2009
Methods
Data collected included:
• Age, sex, and height
• Weight prior to abdominoplasty
• Minimum weight and time attained
• Time when weight regained
• Weight at 1 year post-surgery
• Current Weight
• Complications of surgery
• Previous bariatric surgery ?
• Changes in satiety
• Patient’s beliefs about cause of wt loss
• Patient satisfaction with surgical results
• Changes in diet & exercise after surgery
• Weight of pannus resected
Results: Patient Population
Range Mean
Age 21-61 years 45 years
Height 5’0” – 6’0” 5’5”
Pre-op Weight 105-245 lbs 167.5 lbs
Pannus Weight 1.8 – 12.5 lbs 5.74 lbs
5/21 patients previously underwent bariatric surgery
Results: BMI’s
My patients BMI US population
• 21 % Normal 33 %
• 50 % Overweight 33 %
• 29 % Obese 33 %
• None Morbid Obesity 3 %
My patients BMI mean: 27.66, lowest 18, highest 33.5
Results: Patient Weight loss
• 90.5 % reported weight loss
• 47.6% maintained weight loss > 1 yr after surgery
Results: Patient Weight Loss
Percent of Patients
Mean Pre-op Weight(lbs)
Mean Maximum Weight loss (lbs)
Mean Time of Max Weight Loss (months)
Mean Time of Weight Regain (months)
Short term weight loss only (<1 year)n=9
42.9 161.8 8.7 2.3 7.1
Long term weight loss (> 1 year)n=10
47.6 170.4 16.4 3.7 ___
No Weight lossn=2
9.5 175.5 ___ ___ ___
Results: Patient Weight loss Weight loss as a function of Pannus Weight:
Weight of Pannus
No. of Patients
Pre-op Weight
Maximum weight loss
% with long-term weight loss(> 1 year)
≤ 4 lbs 7 144.9 5.3 33 %
> 4 lbs 14 178.7 14.7 54 %
Results: Patient Weight Loss
• The greatest predictor of weight loss: pre-operative weight
Pre-op Weight (lbs)
No. of Patients
Mean Weight of Pannus (lbs)
Mean Maximum Weight Loss (lbs)
Mean Time Max Weight Loss reached (months)
No. Patients with long term weight loss (>1year)
< 140 lbs 4 2.5 1.8 1.4 0
140 ≥ to < 210 14 5.6 15 3.5 9 (64.3%)
≥ 210 3 9.2 8.6 2.2 1 (33.3%)
Pre-operative weight associated with long term weight loss
WEIGHT
(LBS)
LONG TERM
WEIGHT LOSS
( >/= 4lbs & >1 YR )
NO LONG TERM
WEIGHT LOSS
( < 4lbs & > 1 YR )
< 140 & ≥ 210 1 6
≥ 140 to 210 9 5
p<0.0005
Pre-operative BMI associated With long term weight loss
BMI
LONG TERM
WEIGHT LOSS
( >/= 4lbs & >1 YR )
NO LONG TERM
WEIGHT LOSS
( < 4lbs & > 1 YR )
<24.5 & ≥ 33.5 1 8
≥ 24.5 to <33.5 9 3
p<0.0023
Results: Weight Loss & Satiety
No change
in appetite
(%)
Sense of satiety only after eating (%)
Lack of appetite at
all times (%)
Unpleasant abdominal sensation
Short-term weight loss only (<1year) n=9
2 (22.2) 4 (44.4) 3 (33.3) 2 (22.2)
Long-term weight loss (>1 year) n=10
1 (10) 4 (40) 5 (50) 1 (10)
No weight lossn=2
2 (100) 0 (0) 0 (0) 0 (0)
All Patientsn=21
5 (23.8) 8 (38.1) 8 (38.1) 3 (14.3)
Reason(s) for Weight Loss
• Most frequent reason sited for weight loss: increased sense of satiety
• 84.2 % experienced an increase in satiety– 1/2 report satiety throughout the day, 1/2 report satiety only after eating
• 90% of long-term weight loss patients: reported increased satiety
• Mean duration of sense of satiety 7.3 months
Conclusions
• The greatest predictor of long-term weight
loss was pre-operative weight then BMI
• 64.3% of patients weighing between 140
and 210 lbs had long term weight loss
• Only 14.3 % of patients outside this range
had long-term weight loss
Conclusions
• The key factor in patient weight loss is
an increase in satiety
• Short-term weight loss patients began
to regain their weight at 7.1 months,
about the same time when their
satiety dissipated
CNS Regulation of CNS Regulation of Appetite / SatietyAppetite / Satiety
2 Areas :2 Areas :
The HypothalamusThe Hypothalamus
• One of the Hypothalamic Nuclei is called One of the Hypothalamic Nuclei is called the the Arcuate Nucleus (ARC)Arcuate Nucleus (ARC)
• ARC incomplete blood-brain barrier ARC incomplete blood-brain barrier
• Allows CNS entry of peripheral peptidesAllows CNS entry of peripheral peptides
and proteinsand proteins
The ARCThe ARC• ARC contains two major populations of ARC contains two major populations of
neurotransmitter releasng neurons :neurotransmitter releasng neurons :
• stimulatestimulate feeding: feeding:– agouti-related peptide (agouti-related peptide (AgRPAgRP) & neuropeptide Y () & neuropeptide Y (NPYNPY))
• inhibit inhibit feeding:feeding:– Cocaine & amphetamine regulated transcript (Cocaine & amphetamine regulated transcript (CARTCART) & ) &
proopiomelanocortin (proopiomelanocortin (POMCPOMC), ),
– POMCPOMC cleaves into cleaves into -MSH-MSH. . Feeding
Feeding
ARC
Hypothalamus
2nd order neurons
Neural/ endocrine signals
-MSH
The ARCThe ARC
-MSH-MSH acts as a ligand at the melanocortin - 4 acts as a ligand at the melanocortin - 4 receptor ( receptor ( MC4 MC4 ))
• Defects of this receptor: implicated in up to 4-6% Defects of this receptor: implicated in up to 4-6% of all of all
monogenetic childhood onset obesity in humansmonogenetic childhood onset obesity in humans
-MSH-MSH inhibits the receptor to inhibits the receptor to AgRPAgRP: inhibiting : inhibiting appeptiteappeptite
• AgRPAgRP inhibits the inhibits the MC4MC4 receptor: stimulating receptor: stimulating appetiteappetite
The BrainstemThe Brainstem
Appetite signals: Appetite signals:
A.A. from circulating hormones via the area from circulating hormones via the area postremapostrema: incomplete blood-brain barrier: incomplete blood-brain barrier
B.B. neural signals from the vagus nerve neural signals from the vagus nerve
C.C. Bidirectional connections with Bidirectional connections with hypothalamushypothalamus
The Vagus NerveThe Vagus Nerve
• Afferent signalsAfferent signals: mechanical & chemical: mechanical & chemical
• Cell bodies of afferent neurons in the Cell bodies of afferent neurons in the Nodose GangliaNodose Ganglia
• Projects into brainstem to interface with hypothalamusProjects into brainstem to interface with hypothalamus
The Vagus Nerve ContinuedThe Vagus Nerve Continued
• The stretch receptor stimulation The stretch receptor stimulation
dependent on gastric volumedependent on gastric volume
• May suppress meal size independent of contentMay suppress meal size independent of content
• Effect is abolished by subdiaphragmatic vagotomyEffect is abolished by subdiaphragmatic vagotomy
• Gastric distension Gastric distension is insufficient to account for all is insufficient to account for all
aspects of satietyaspects of satiety
The Vagus NerveThe Vagus Nerve
• Contains receptors for a number of gut Contains receptors for a number of gut hormoneshormones
• Vagotomy abolishes appetite-modifying Vagotomy abolishes appetite-modifying action ofaction of
many gut hormones: many gut hormones: CCK, PYY, GLP-1
• Vagus nerve is thought to be a major Vagus nerve is thought to be a major sight of gut hormone signalingsight of gut hormone signaling
A Very Quick Overview of Appetite Regulating Hormones
Appetite-regulating hormones:
• Ghrelin, released from the stomach, is the only known appetite stimulant, acting via hypothalamic expression of NPY and AgRP.
– Ghrelin levels rise preprandially in humans
– Administration of exogenous ghrelin leads to increased food intake and weight gain
Appetite-regulating Hormones:
• In contrast, a growing number of peptide hormones have been found to produce satiety and decrease food intake.
Adiponectin
Insulin
Amylin
Cholecystokinin (CCK)
Apolipoprotein A-IV (apo A-IV)
Peptide YY (PYY)Pancreatic
Polypeptide (PP)Leptin
Oxyntomodulin (OXM)
Vasoactive Intestinal Polypeptide (VIP)
Glucagon-like peptide-1 (GLP-1)
Vagus
Nerve
Bombesin
Intestines
Vagus
Summary: Gut HormonesSummary: Gut Hormones
Ghrelin
OXM
CCK
GLP-1
PYY
VIP
Apo A-IV
PP
PP
Bombesin
Pancreas
Stomach
Energy Regulatio
n
+
-
-
-
-
Another Important Satiety Another Important Satiety Regulator: LeptinRegulator: Leptin
• Leptin, is released from adipose tissue, Leptin, is released from adipose tissue, mammary glands, ovarian follicles, placenta, mammary glands, ovarian follicles, placenta, skeletal muscle, and the P cell and chief cells of skeletal muscle, and the P cell and chief cells of the stomachthe stomach
• 25% of circulating leptin is derived from the 25% of circulating leptin is derived from the stomachstomach
• Leptin levels positively correlate with body fat: Leptin levels positively correlate with body fat: higher circulating leptins with greater BMI higher circulating leptins with greater BMI
• Leptin mediates central regulation of energy Leptin mediates central regulation of energy homeostasis via receptors in the ARC and homeostasis via receptors in the ARC and peripherally via the vagus nerveperipherally via the vagus nerve
Leptin StudiesLeptin Studies• after binding in the hypothalamus receptor:
• leptin inhibits NPY and AgRP and
stimulates POMC and CART
• decreasing appetite & increasing energy expenditure (Cowley M, et al; Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. 2001)
• mice with mutation of the Leptin receptor are profoundly obese. (Farooqi I, et al; Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. 2007)
Ob /Ob mouse
Appetite-regulating hormones:
• Starvation: : ghrelin, : PYY-3-36, insulin, leptin
• Post-prandial satiety: : ghrelin, : PYY-3-36, insulin, leptin
• Receptor mutations: CCK, OXM, insulin, PYY, leptin & bombesin : food intake and obesity
• Receptor antagonist or antisera for CCK, OXM, apo A-IV, PYY, and GLP-1 : food intake
• Jejuno-ileal bypass surgery or vertical-banded gastroplasty : GLP-1, PYY & PP levels
• Roux-en-Y : : 77% reduction in serum ghrelin
• 2 clinical studies from U London: a. s/cut injections CCK: Med students ate 25% less curry b. s/cut Modulin: 17 % less food intake & 26 % increased energy expenditure : 1 pound / wk. weight loss
Future Study
• Patients are tested before abdominoplasty and incrementally after for levels of specific gut hormones
• Is there an association between hormone expression levels, reported satiety, and patient weight loss?
Methods
• 15 patients to participate in our study
• Prior to surgery: age, weight, height, gynecological history, previous bariatric surgeries, and exercise regimens
• Fasting blood draw: Prior to & 1, 3, 6, and 12 months after surgery • At surgery weight of the pannus will be recorded
Methods
• Blood plasma specimens will be shipped to Inter Science Institute on dry ice then assayed for PYY, GLP-1, PP, CCK, leptin, bombesin, and ghrelin
• At 0, 1, 3, 6, and 12 months post-abdominoplasty, document:
– Ranking on a 0-3 scale of:
» Appetite at rest
» Postprandial satiety
» Unpleasant abdominal feeling associated with poor appetite
» Amount of food consumed during a meal
Budget