1. Weight Management in Patients With Type 2 Diabetes
JOAN TEMMERMAN, MD, MS, FAAFP, CNS
American Association of Diabetic Educators Annual Meeting, Indianapolis, IN August 3, 2012

2. Objectives Describe the obesity epidemic and its impact on diabetes
Review various options for weight loss and expected results
Review diabetes weight management studies: Look AHEAD & Why WAIT
Distinguish among different bariatric surgical procedures
Summarize the IDF position statement on bariatric surgery in the treatment of obese patients with T2DM
Examine recommendations for pre-operative and post-operative diabetic care

3. The age of obesity: Inactive lifestyle, poor nutrition, calorie imbalance
We live in an obesogenic society: inactive lifestyle, poor nutrition, calorie imbalanceobesity. Physical activity has disappeared; 40% of adults get no activity at all
Threatens steady gains in longevity

4. Obesity Trends* Among U.S. Adults BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
1990
2000
2010
68% of US adults overweight or obese; 32% school-aged children and adolescents
No Data <10% %–14% %–19% %–24% %–29% ≥30%
Source: Behavioral Risk Factor Surveillance System, CDC 4

5. Obesity associated with increased mortality
• 2-3-fold increased risk of death
Serious health effects: obesity major risk for DM, CVD, HTN,stroke, and some cancers
James WPT, J Intern Med 2008:
Nguyen & El-Serag, Gastroenterol Clin North Am. 2010
Disease burden; the global rise of obesity has serious health effects: obesity poses a major risk for DM, CVD, HTN, stroke, and some cancers. Risk of death increased 2-to 3-fold in obese compared with normal weight pts (Nguten & El-Serag, p. 4)
Diabesity: obesity strongly related to the epidemic of type 2 diabetes (T2DM)

6. Strong link between obesity and T2DM
93-fold
increased risk
42-fold
increased risk
strong link between obesity and the risk of developing diabetes. Figure 1 shows Obesity and type 2 diabetes. data combined from two studies, the Nurses Health Study and the U.S. Health Professionals Study. Both are longitudinal studies that look at the effect of lifestyle on chronic illness. In the male health professional study, men with a body mass index (BMI) greater than 35 had an age-adjusted risk of 42.1 times greater than a man with a BMI of less than 23 for developing diabetes. A similar trend was observed in female nurses, with the risk increasing to a staggering 93.2 of developing diabetes with a BMI of greater than 35 kg/m2.
The prevention of type 2 diabetes: an overview
Marrero DG. J Diabetes Sci Technol 2009;3(4):

7. Obesity linked to T2DM
Diabetes primarily caused by obesity: 90% of type 2 diabetes due to excess body weight and lifestyle
Rapid increases in T2DM parallel rise of obesity
26 million Americans have Type 2 diabetes
27% are unaware (7 million people)!
T2DM: 1 in 4 ages ≥ 60 years (27%)
Also occurring at younger ages
Now considered an epidemic: strong and sustained increases in DM since 1990; no signs of slowing down; 7 states have rates >10% (W Virginia, Miss, Tenn, Ala, OK, LA, KY) recent CDC report June 2008
Diabetes is an almost totally avoidable disease.
Anderson JW, Kendall CWC, et al. Importance of weight management in type 2 diabetes: Review with Meta-analysis of clinical studies. J Am Coll Nutr. 2003;22(5):
Ref 1;Cannon C, cardiovascular ds and modifiable cardiometabolic risk factors; clinical cornerstone: cardiometabolic risk and risk management
CDC 2011 National Diabetes Fact Sheet

8. Increased Risk for Diabetes (pre-diabetes)
79 million people in the US with pre-diabetes in (35% of adults)
Up from 57 million 2008
High risk for developing diabetes
Prevention urgent
CDC 2011 National Diabetes Fact Sheet
Many clinicians are not detecting this. Many, many patients unaware. Critical group to identify and intervene. Diabetes & pre-diabetes caused primarily by obesity: 90% of type 2 diabetes due to excess body weight and lifestyle. Recent recommendations from Am College of Endocrinology, and Am Ass of Clinical Endocrinologists to treat pre-diabetes: same cardiovascular goals (blood pressure and lipids) and excess weight; intensive lifestyle management
2011 National Diabetes Fact Sheet uses both fasting glucose and hemoglobin A1c (A1c) levels to derive estimates for undiagnosed diabetes and prediabetes.
Not benign condition, although essentially asymptomatic (Family Practice News 8/15/08)
Recent recommendations from Am College of Endocrinology, and Am Ass of Clinical Endocrinologists to treat pre-diabetes: same cardiovascular goals (blood pressure and lipids) and excess weight; intensive lifestyle management
Ref. 1 Cannon

9. Global projections for the diabetes epidemic: 2010–2030
DIABESITY: We are in the middle of a Type 2 diabetes epidemic and the numbers are continuing to escalate. The epidemic is strongly correlated with increases in obesity and physical inactivity.
In each box, the top and middle values represent the number of people with diabetes mellitus (in millions) in each of seven world regions (depicted with different colors) for 2010 and 2030, respectively; the bottom value is the percentage increase from 2010 to The number of people globally with diabetes mellitus is projected to rise from 285 million in 2010 to 439 million by 2030, a 54% increase. b | The number of people with diabetes mellitus and IGT (in millions) by region among adults aged 20–79 years for the years 2010 and Data courtesy of the International Diabetes Federation Diabetes Atlas.114 Abbreviation: IGT, impaired glucose tolerance.
Chen, L. et al.The worldwide epidemiology of type 2 diabetes mellitus—
present and future perspectives. Nat. Rev. Endocrinol. 2012;( 8):

10. Obesity promotes diabetes; weight loss counteracts it
Weight loss from diet or metabolic surgery correlates with increased insulin sensitivity
Obesity promotes diabetes; weight loss counteracts it
The results (symbols) are means ± SEM in patients undergoing weight loss by diet (ref. 69), RYGB, or BPD (ref. 68). Green arrows connect pretreatment to posttreatment values. The black line and the black dots are the fitting function and 95% CIs of the data in ref. 68 (same as in online appendix Fig. A2, bottom graph). FFM, fat-free mass; T2DM, type 2 diabetes.
ELE FERRANNINI, MD, GELTRUDE MINGRONE, MD2.
Impact of Different Bariatric Surgical Procedures on Insulin Action and β-Cell Function in Type 2 Diabetes. Diabetes Care March 2009 vol. 32 no
Ferrannini E , Mingrone G Dia Care 2009;32:
2011 American Diabetes Association, Inc.

11. Diabetic patients may have more difficulty losing weight
Genetic differences
Metabolic factors inflammation, insulin resistance, adipokines
Medications: insulin, TZDs, sulfonylureas
Increased food to avoid hypoglycemia
Limited physical activity
Diet fatigue (carbohydrate restriction)
Insulin & TZDs promote adipose tissue deposition and fluid retention. Insulin anabolic; inhibits lipolysis in adipose tissue; ketogenesis in liver. Diabetic patients may find it harder to lose weight: Medications: Insulin & TZDs promote adipose tissue deposition and fluid retention.
Anderson JW, Kendall CWC, et al. Importance of weight management in type 2 diabetes: Review with Meta-analysis of clinical studies. J Am Coll Nutr. 2003;22(5):
Anderson JW, Kendall CWC, et al. J Am Coll Nutr. 2003;22(5):

12. T2DM and Lifestyle intervention Look AHEAD Study (Action for Health in Diabetes)
Multicenter randomized 10 year clinical trial examining lifestyle intervention
One of largest diabetes weight management studies using meal replacement (MR) strategy for weight reduction
Weight loss at 1 year directly related to # of MR; addition of MR to lifestyle group increased weight loss to 8.6% (0.7% in usual care/control)
Diabetes Prevention Program (DPP): landmark trial showing efficacy of lifestyle intervention in preventing diabetes
that lifestyle interventions are more cost-effective than medications
Look AHEAD (Action for Health in Diabetes) specifically looks at success factors for weight loss, of which one factor is commercial MR. Look AHEAD one of the largest diabetes weight management studies that used MR strategy for weight reduction; study aim is to follow health outcomes and mortality among diabetic patients who lose and maintain weight loss for up to 10 years. Look AHEAD (Action For Health in Diabetes) is a multicenter randomized clinical trial to examine the effects of a lifestyle intervention designed to achieve and maintain weight loss over the long term through decreased caloric intake and exercise
Look AHEAD is focusing on obesity, type 2 diabetes, and cardiovascular disease. The Look AHEAD trial has completed enrollment of 5,145 obese patients with type 2 diabetes. At study entry, participants were randomly assigned to one of two interventions, IntensiveLifestyle Intervention or Diabetes Support and Education; will be followed for a total period of up to 11.5 years. 1st 6 months 3 group, 1 ind meeting/month; 3 MR + 1 meal (2S, 1B; choice of Slimfast, Optifast, Glucerna, HMR. ) maint: 2 MR, 2 meals
MR also facilitate maintenance of weight loss, Hamdy O, Zwiefelhofer D. Weight management using a meal replacement strategy in type 2 diabetes. Curr Diab Rep. 2010;10: MR central tool; very effective for maint. And long-term weight control as well. Research-based; over a million patients; documented outcomes. Control portions and calories; provide structure, eliminate decision-making and guessing; improve nutrition. 2 long-term studies on the prevention of diabetes and its complications, funded by the NIH. DPP called attention to efficacy of lifestyle change for improving health. Interventions to prevent or delay type 2 diabetes in individuals with prediabetes can be feasible and cost-effective. Research has found that lifestyle interventions are more cost-effective than medications.
Stimulus control: remove from toxic food environment. MR is any prepackaged food product that is portion controlled, calorie controlled, and high nutrition; Typically <300 cal, g protein, g CHO, < 9 g fat. Portion control is one of the biggest factors in successful weight loss. Fabricatore A. The role of structured meal plans and meal replacements in weight management. Medscape Diabetes and Endocrinology; Weight Management Expert Column 3/19/2004. Accessed 1/10/2011 from
Bray GA. Let’s treat obesity seriously. Am Fam Physician 2010;81:
Wadden, West, et al. Obesity 2009;17(4):

13. T2DM and Lifestyle intervention: Why WAIT
Short-term intensive weight loss program effective for 4 yrs
120 patients, weekly group visits for 12 weeks
Lifestyle intervention: 2 MR, 2 snacks, healthy dinner
~50% maintained 10% wt loss (24 #) at 4 years; total group maintained 6.3% at 4 years
Significant metabolic improvements; 50% reduction in diabetic meds & 27% decrease overall health costs
1. Joslin Study Shows Short-Term Intensive Weight Loss Program Works For Four Years. Accessed June 14, 2012 at and
(description of program)
2. Diabetes Weight Management in Clinical Practice: Why WAIT Program. Hamdy O. Accessed June 14, 2012 at
2 Boost MRs; two 100 cal snacks (e.g. Fruit, Nuts) Choice from 15 pre-set dinner menus
cal plan; graded exercise plan, and CBT/behavioral support. Although followed for 4 yrs, were on their own during maintenance. Model cost $2,700. bariatric surgery costs upwards of $20K. Change in A1c -0 .9; 7.36.4%
Components of the Why W AIT?
• Interactive-Intensive Diabetes Treatment
• Structured Modified Dietary Intervention
• Graded-Balanced & Individualized Exercise Plan
• Cognitive Behavioral Support • Group Adult-Educational Sessions
Hamdy O. Diabetes Weight Management in Clinical Practice: Why WAIT Program

14. Why WAIT Program
Results more robust than Look AHEAD 4 year results
Intensive lifestyle modification very valid option to bariatric surgery
At least as effective as common bariatric surgery (gastric banding), much less costly & fewer side effects
Comprehensive lifestyle intervention can produce sustainable clinically significant weight loss
Look AHEAD: 42% maintained 10% wt loss at 4 years
Wadden TA, Neiberg RH, et al, Four-year weight losses in the Look AHEAD Study: Factors associated with long-term success. Obesity (Silver Spring) 2011;19(10):
Hamdy O. Diabetes Weight Management in Clinical Practice: Why WAIT Program

15. Meal Replacements (MRs) highly effective in T2DM
126 overwt/obese adults, T2DM, isocaloric MR vs ADA diet
MR diet: significantly greater weight loss & less regain after 1 year of maintenance than standard, self-selected, food-based diet
Statistically significant improvements in: weight loss, BMI, waist/hip measurements, fasting glucose, insulin and HbA1c level, lipids, & BP
Achieved significantly lower levels of insulin and HbA1c than standard diet group
25% reduced diabetic medications
statistically and clinically significant improvements in the PCD/meal replacement group in a number of important outcomes after the initial weight loss phase. 126 overweight or obese adults with type 2 diabetes; Participants were prescribed either a 25% energy-deficit diet in accordance with standard ADA recommendations (standard diet [SD]) or an equicaloric, portion-controlled diet using Medifast Plus for Diabetics; 34-week weight loss phase and every 4 weeks during the 52-week maintenance phase (After an initial 34-week weight loss period, the SD group continued their diet at a maintenance energy level for 52 weeks. PCD participants were rerandomized for their 52-week maintenance phase to either 26 weeks of PCD followed by 26 weeks of SD (PCD1) or vice versa (PCD2). Cheskin LJ, Mitchell AM, Jhaveri AD, Mitola AH, Davis LM, Lewis RA, Yep MA, Lycan TW. Efficacy of meal replacements versus a standard food-based diet for weight loss in type 2 diabetes: a controlled clinical trial. Diabetes Educ Jan-Feb;34(1):
Cheskin et al; Diabetes Educ 2008;34:

16. Diabetes and MRs
MR are viable and cost-effective for weight loss and maintenance in T2DM
MR diet more effective in reducing metabolic risk factors, insulin & leptin than fat-restricted low-calorie diet
Superior glycemic control with high-protein VLCD compared to traditional low-fat diet
Hamdy O, Zwiefelhofer D. Curr Diab Rep. 2010;10:
Konig D, et al. Ann Nutr Metab 2008;52:74-78
. Weight management using a meal replacement strategy in type 2 diabetes. Curr Diab Rep. 2010;10:
Wing RR, Marcus MD, Salata R, Epstein LH, Miaskiewicz s, Blair EH. Effects of a very-low-calorie diet on long-term glycemic control in obese type-2 diabetic subjects. Arch Intern Med. 1991;151:
MR also facilitate maintenance of weight loss, Hamdy O, Zwiefelhofer D. Weight management using a meal replacement strategy in type 2 diabetes. Curr Diab Rep. 2010;10: MR central tool; very effective for maint. And long-term weight control as well. Research-based; over a million patients; documented outcomes. Control portions and calories; provide structure, eliminate decision-making and guessing; improve nutrition. 2 long-term studies on the prevention of diabetes and its complications, funded by the NIH. DPP called attention to efficacy of lifestyle change for improving health. Interventions to prevent or delay type 2 diabetes in individuals with prediabetes can be feasible and cost-effective. Research has found that lifestyle interventions are more cost-effective than medications.
Stimulus control: remove from toxic food environment. MR is any prepackaged food product that is portion controlled, calorie controlled, and high nutrition; Typically <300 cal, g protein, g CHO, < 9 g fat. Portion control is one of the biggest factors in successful weight loss. Fabricatore A. The role of structured meal plans and meal replacements in weight management. Medscape Diabetes and Endocrinology; Weight Management Expert Column 3/19/2004. Accessed 1/10/2011 from
Bray GA. Let’s treat obesity seriously. Am Fam Physician 2010;81:
Wing, Marcus et al; Arch Intern Med 1991;151:

17. Effects of weight loss with VLEDs on fasting plasma glucose values
for obese persons with type 2 diabetes
I use predominantly VLCDs & intensive nutritional intervention. VLCDs most extensively used weight loss intervention in scientific literature.; one of most effective interventions for significant fat loss. Effects of weight loss with VLEDs on fasting plasma glucose values for obese persons with type 2 diabetes. Values (with SEM bars) are expressed as percentage of baseline values. Baseline fasting plasma glucose values were 14.0 mmol/L (95% CI, 12.0 to 15.9 mmol/L). Mean values from 10 studies (see text) including 152 subjects.
Anderson JW, Kendall CWC, et al. Importance of weight management in type 2 diabetes: Review with Meta-analysis of clinical studies. J Am Coll Nutr. 2003;22(5):
Rapid lowering of plasma glucose (PG) (within days; nadir 1-2 weeks) from calorie/CHO restriction;
Further PG improvement with weight loss as visceral (intra-abdominal) adipose tissue reduced
Rapid weight loss catalyst for lifestyle change.
VLCDs increase insulin sensitivity and reduces the substrate for gluconeogenesis., reducing hepatic glucose output. Thus VLCD treatment may improve glycemic control more than calorie restriction alone. 5-10% weight loss reduces visceral fat ~ 30%
Anderson JW, Kendall CWC, et al. J Am Coll Nutr. 2003;22(5):

18. Joslin New Nutrition Guidelines
Reduce Daily Caloric Intake by calories
~40% Carbohydrates, LGI, High Fiber
20-30% Protein
30% Fat (no TF, 7-10% SF, 20% Mono & Poly UF)
Lower CHO; higher protein. Increasing protein increases satiety; thermogenic effect; greater LBM in maintenance. Higher protein produces greater weight loss, due to effect on REE (editorial Li & Heber, JAMA 2010
CHO intake drives insulin production; A powerful way to lower insulin levels is to reduce dietary CHO; then metabolism shifts to fat catabolism. CHO restriction very effective method to control diabetes; dietary CHO drives insulin.
Dietary CHO primary insulin secretagogue; Nutritional ketosis: Insulin inhibits adipocyte lipolysis
CHO restriction lowers endogenous insulin production, allowing lipolysis
Metabolism directed from fat storage to fat mobilization & oxidation

19. Bariatric Surgery

20. Bariatric surgery Most effective treatment for sustained weight loss
Most patients have complete resolution of T2DM, HTN, OSA, dyslipidemia
Criteria to qualify:
Ages 16* – 65
BMI ≥ 40
BMI ≥ 35 with serious comorbidities
(T2DM, OSA, HTN, cardiovascular disease)

21. Surgical Procedures
BPD rarely done; significant malabsorption (protein and lipid) and complications. Vertical (sleeve) gastrectomy and duodenal switch: long-limb bypass (distal common channel). Sleeve gastrectomy; pyloris preserved (duodenal switch). Duodenum transected and duodenal stump made (sewn) small bowel transected 250 cm from ileocecal valve, anastomosed to stomach/duodenal bulb (duodeno-ileostomy) . most of small intestine bypassed, common channel cm. Biliopancreatic limb (BP) 150 cm, 150 cm alimentary (Roux) limb,

22. Roux-en-Y gastric bypass (RYGB)
Gold Standard
Laparoscopic
Both restrictive and malabsorptive
Metabolic effect
Most common bariatric surgery in US
Primarily restrictive procedure

23. Roux-en-Y gastric bypass
Upper stomach transected, creating a 15 ml pouch. Upper jejunum is transected, and the distal end anastomosed to the gastric pouch, creating the alimentary (roux) limb. The proximal end of the transected jejunum (the biliopancreatic limb) is anastomosed to the side of the alimentary (roux) limb 50 to 150 cm distal to the gastrojejunostomy, creating a common channnel, where food meets the bile and pancreatic juices
Stomach before bariatric surgery. (B) Stomach after Roux-en-Y gastric bypass procedure; food is redirected to the middle portion of the small intestine, limiting absorption of calories.
American Family Physician - April 15, 2006

24. Adjustable gastric banding (AGB)
Laparoscopic
Primarily restrictive
Potentially reversible
Most common bariatric surgery in Australia and Europe
Commercial sponsorship heavy marketing (Allergan)
Potentially reversible but adhesions and a thick capsule form around the band; in reality ?

25. Adjustable Gastric Banding
Inflatable tube placed around stomach just below gastroesophageal junction; size of outlet adjusted with saline through subcutaneous port; limits food intake
Inflatable ring inserted laparoscopically; adjusted via subcutaneous access port
American Family Physician – April 15, 2006

26. AGB: poor long-term outcomes
151 consecutive patients ; 82 followed:
Reoperation rate 60%
1/3 experienced band erosions
~50% require band removal
Laparoscopic adjustable gastric banding: 82 patients followed; 22% minor complications (incisional hernia, port-tubing disconnections, port infection); 39% major complications (pouch dilatation, erosion, repositioning). EWL 43% (Complete weight-loss data were available for 70 patients). The 36 patients who still had their band in place had lost 48% of their excess weight, compared with 64% for patients who underwent LRYGB
Reported patient satisfaction favors RYGB: 80% report being very satisfied, in contrast to only 46% LB; 19% LB unsatisfied or even regretted having the procedure
Himpens, Cadiere et al. Arch Surg. March 22, 2011

27. RYGB has better risk-benefit profile than LB
RYGB greater weight loss, increased resolution of diabetes, improved QOL
Low complication rate similar to LB
Lower rate late complications (reoperations)
Campos, Rabl et al. Arch Surg. 2011;146(2):
Performed in high-volume centers by expert surgeons. Self-esteem, physical and social measures significantly better for RYGB group. RYGB higher patient satisfaction; superior results, lower long term complications

28. Vertical Sleeve Gastrectomy (VSG)
Vertical Sleeve Gastrectomy (VSG) (Sleeve Gastrectomy; Vertical Gastrectomy)
2/3 of stomach removed; remaining stomach 3-4 oz (~ 100 cc)
Ghrelin not produced (loss of appetite)
Irreversible
Purely restrictive although has metabolic effect
Easy to modify; sometimes done as staged procedure
Weight loss superior to Band
Portion of resected stomach secretes Ghrelin: responsible for appetite and hunger (orexigen). Pylorus preserved: little or no dumping. Still considered experimental by many insurance companies. Once a patient’s BMI goes above 60kg/m2, it is increasingly difficult to safely perform a Roux-en-Y gastric bypass or a Duodenal Switch using the laparoscopic approach. It can usually be done laparoscopically even in patients weighing over 500 pounds. The stomach restriction that occurs allows these patients to lose more than 100 pounds. This dramatic weight loss allows significant improvement in health and resolution of associated medical problems such as diabetes and sleep apnea, and therefore effectively “downstages” a patient to a lower risk group. Once the patients BMI is lower (35-40) they can return to the operating room for the “second stage” of the procedure, which can either be the Duodenal Switch, Roux–en-Y gastric bypass or even a Lap-Band®. 

29. Vertical Sleeve Gastrectomy
                         
Greater curvature resected. Remaining stomach shaped like hotdog or thin banana.
Preserves functions of stomach while drastically reducing volume (nerves and pylorus remain intact). Physiology preserved.
The removed section of the stomach is actually the portion that “stretches” the most.  The long vertical tube shaped stomach that remains is the portion least likely to expand over time and it creates significant resistance to volumes of food.  Remember, resistance is greatest the smaller the diameter and the longer the channel.  Not only is appetite reduced, but very small amounts of food generate early and lasting satiety).

30. Resolution of T2 diabetes
RYGB, VSG, BPD/DS associated with rapid metabolic improvements
Resolution of T2 diabetes
% EBWL % DM resolved
Band
Gastroplasty (VSG)
Gastric Bypass
BPD/DS
Malabsorptive surgeries have greater weight loss and resolution of T2DM. Meta-analysis 135,246 patients.
Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med Mar;122(3):
Buchwald, Estok et al. Am J Med 2009;122(3):

31. Metabolic improvements
Metabolic surgery (RYGB, VSG, BPD/DS) state of negative energy balance and rapid weight loss:
decreased appetite & early satiety, not hunger
Suggests resetting of weight set point to a lower level
After metabolic surgery,
rapid improvement in glycemic control in T2DM patients
diabetes remission occurs almost immediately before significant weight loss has occurred
alterations in gut hormones seem to underlie glucose homeostasis
Bariatric surgery (RYGB, VSG, DS) associated with dramatic & rapid metabolic improvements, Alterations in gut hormone expression. sustained for long periods of time. Diabetes remission in days to weeks; precedes weight loss. Gastric banding doesn’t affect the intestine at all and lacks metabolic benefits (surgery not the intervention; weight loss, lifestyle changes). Impact of bariatric surgery on GI tract investigated; 2 hypothesis: action of upper (foregut; proximal) hormones reduced or enhanced action of lower (hindgut) intestinal hormones

32. Energy homeostasis & weight regulation highly complex
Energy homeostasis/weight regulation is regulated by multiple peripheral hormonal signals effecting the CNS, especially the hypothalamus. Short-term polypeptide hormonal signals from the periphery stimulate hunger and food-seeking behavior before a meal (orexigens; eg, ghrelin), whereas others promote satiety and meal cessation during and after a meal (anorectics; eg, glucagon-like peptide-1 [GLP-1], peptide tyrosine tyrosine [PYY]3–36 [PYY3–36], cholecystokinin [CCK], oxyntomodulin [OXM], and several others). Hormonal signals from adipose tissue (adipokines), including leptin and adiponectin, provide feedback signals to the brain (adipose-brain axis), whereas feedback signals from the intestinal tract (the gut-brain axis) include polypeptide hormones (enterokines) and neuronal signals via the vagus and other autonomic afferents.
Stanley, Physiol. Review 85:1131, 2005 32

33. Key hormones in energy homeostasis
Hormone expression altered by metabolic surgery:
Ghrelin
GLP-1
PYY1–36
GIP
Insulin
Leptin
Adiponectin

34. Metabolic adaptations after RYGB, VSG & BPD/DS
gut hormones mediate glucose metabolism
after bariatric surgery; reduce food intake
Ghrelin (appetite stimulating & prodiabetic hormone produced by stomach and duodenum) may decrease *
Incretin hormones increased (enhance insulin secretion, decrease glucagon secretion, inhibit gastric emptying; exert trophic effects on beta cells in response to meals), CNS effect to reduce food intake
Glucagon-like peptide-1 (GLP-1)
Gastric inhibitory peptide (GIP)
Peptide YY (PYY)
Incretins: hormones produced by GI tract in response to nutrients/enteral glucose; enhance insulin secretion by pancreas; also act in CNS to reduce food intake.
Decreased appetite. Strohmayer et al. Mt Sinai J Med. 2010;77: Postoperative changes in hormonal signal pathways that mediate glucose-energy metabolism also play an important and possibly dominant role in the resolution of T2DM following bariatric surgery.
Improvements in insulin resistance, as well as restoration of the first-phase insulin response These changes were not seen in patients who underwent gastric restrictive procedures, indicating that the rearrangement of the intestine is partly responsible for these alterations in beta-cell function and insulin sensitivity
Ghrelin levels have considerable physiologic variations; some studies measured only a single level; some measured “active” ghrelin; a lot of variability between studies and differences between assays (Harvey et al; Mount Sinai J of Medicine 2010; 77: ). Kohli R, Stefater MA, Inge TH. Rev Endocr Metab Disord 2011.
*early decrease; inconsistent long-term; variable methods used in studies (Harvey et al, 2010)

35. . Alimentary limb (roux); biliopancreatic limb
©2010 by Cleveland Clinic
KASHYAP S R et al. Cleveland Clinic Journal of Medicine 2010;77:

36. Summary of IDF Position Statement for T2DM
Obesity and diabetes epidemics are serious chronic diseases & major global public health issues
Prejudices about severe obesity, which also exist within the health care system, should not be a barrier to effective treatment options
Bariatric surgery can significantly improve T2DM
Effective, safe, cost-effective therapy
Bariatric surgery is an appropriate treatment for people with T2DM and obesity not achieving recommended treatment targets with medical therapies especially when there are other major co-morbidities
International Diaabetes Federation Taskforce

37. IDF Position Statement for T2DM
Surgery accepted option in people with T2DM & BMI ≥ 35
Surgery should be considered as treatment option in persons with BMI when diabetes not adequately controlled by optimal medical regimen especially in the presence of other major cardiovascular diseases risk factors
Procedures must be performed within accepted guidelines
Requires comprehensive approach and ongoing multidisciplinary care, patient education and follow up
Surgery should be considered complementary to medical therapies
International Diabetes Federation Taskforce.

38. Post-op requirements (Bariatric program requirements vary)
Maintain good nutrition
60-80 g protein daily
B12 supplementation:
500 mcg SL/d;
mcg oral/d;
500 mcg/wk nasal;
1000 mcg/month IM
OR B complex
Calcium citrate mg/d (divided doses; separate from iron)
Most common deficiencies are B12, Ca, iron, vit D (thiamine/B1 if vomiting); menstruating women highest risk for iron deficiency
Many lose taste for meat; will need to get protein from lean dairy, fish, protein supplements. Separate calcium and MV (fe). Calcium citrate preferred: superior bioavailability and decreased gastric acid production.DO NOT RECOMMEND PNV.B12/folate combination (B complex)
Eat small amounts (2-3 ounces of food) slowly over 30 minutes; focus on protein

39. Post-op requirements *Ca and Fe need to be separated
Complete multivitamin (with iron): 1-2/d*
Menstruating women may need additional iron: mg elemental Fe daily divided
May develop anemia refractory to oral Fe and require parenteral Fe infusions
Vitamin D if deficient
Do not recommend prenatal vitamins
If become pregnant, one complete MV + one PNV daily
NO GTT!!!
*Ca and Fe need to be separated
menstruating women highest risk for iron deficiency; Many lose taste for meat; will need to get protein from lean dairy, fish, protein supplements. Separate calcium and MV (fe). Ca can decreases fe absorption 50-60% (Jacques). Check a FBS, and then a 2 hour post prandial after a high CHO breakfast. B12/folate combination (B complex). PNV do not supply adequate vitamins and minerals (deficient in vit A, zinc/selenium). Increase D until PTH normal; target 25(OH)D ng/dL Avoid pregnancy until weight and nutrition stable (at least one year; some recommend 18 months)
80-90% vit D deficiency/insufficiency pre-op; 50% secondary hyperparathyroidism, fe def, vit. C

40. Post-op lab parameters
Every 6 months for 1st yr; then yearly
CBC with differential
CMP
B12
B1 (thiamine)
25(OH) D
Ferritin
Serum iron
RBC folate (most reliable indicator of folate tissue stores; steadier value)
Pre albumin (most sensitive laboratory indicator of protein status)
Lipid profile
PTH intact
*Hgb A1c, TSH (If h/o DM or hypothyroid)
Basic labs; variations; RBC folate most reliable indicator of folate tissue stores; steadier value. Pre-albumin most sensitive laboratory indicator of protein status (albumin relatively insensitive to dietary changes and is greatly affected by other factors such as dehydration and kidney function). Remember ferritin reflects iron stores; Regular comprehensive lab evaluation, Continued care at Bariatric Center; Regular aerobic activity: 150 min/wk, Long term dietary, lifestyle, behavior modification and follow-up required

41. Recommendations for pre- and post-operative diabetic care
Optimize glycemic control peri-operatively & closely monitor after surgery
Tips from IU Health Bariatric Center Diabetic Educator Angela Marsden, RD, MS, CHES, CD, CDE:
Check A1c and lipids pre-op; A1c should be < 8% for surgery
If A1c > 7.5%, patient contacted and asked what they are doing for BS control
If A1c ≥ 8%, PCP notified to assist in achieving good control pre-op
On-going, long-term supplementation & support. Poorly controlled DM increases risk of peri-operative complications and poor wound healing. Similarly correct nutritional deficiencies before surgery (very common: overweight but undernourished)
Pts asked about monitoring BS, dietary restrictions, exercise habits, hypoglycemic episodes

42. Pre- and post-operative diabetic care Tips from IU Health Bariatric Center Diabetic Educator Angela Marsden, RD, MS, CHES, CD, CDE:
Patients educated during pre-op class:
Managing glucose during clear liquid diet
Maintaining diabetes self-care behaviors after surgery
How to treat low blood sugar after surgery
Potential causes of hypoglycemia (too many carbs; poorly timed meals)
Ongoing support and monitoring
Data collection following post-op progress: BMI, BP, LDL, A1c
Address post-op individual concerns: hypoglycemia, dumping syndrome
Continued care at Bariatric Center; Regular aerobic activity: 150 min/wk, Long term dietary, lifestyle, behavior modification and follow-up required

43. Is there a difference between surgical and medical weight loss?

44. Weight loss: surgical vs medical
Surgery is the most effective treatment for sustained weight loss RYBG, VSG  metabolic effect
Surgery is the most effective treatment for diabetes
Difficult to lose >100# without surgery
Nonsurgical typical maximum weight loss 1/3:
If 300 #; getting to 200 # good result
if 400 #; 270# best result
Realistic goals: Need to decide if you would be satisfied with this approach. With most aggressive dietary intervention, can lose approximately 1/3 of weight (if 300#, around 100#, if 250#, around 80#) 44

45. Surgical vs. medical weight loss
Observational study comparing people who lost large amounts of weight through surgery vs non-surgical means (NWCR data)
Possible to have massive weight loss through intensive lifestyle/behavioral efforts sometimes comparable to surgery
Marked behavioral differences: non-surgical worked much harder in terms of diet and exercise
Bond DS et al. Int J Obes 2009;33:173-80
105 surgical; 210 non-surgical; average weight loss 56 kg (123 #) in both groups; no significant regain in either group at 2 years.
Surgical group reported less physical activity, more fast food and fat consumption, less dietary restraint, higher depression and stress. More dietary indiscretions: medical: physiologic drive to regain; unfavorable change in hormones
Exercise: 33% surgical vs. 62% non-surgical expended ≥2000 kcal/wk PA per ACSM recommendations for maintenance 45

46. What happens after medical weight loss?
Unfavorable metabolic adaptations occur
Neuroendocrine changes convey “energy deficit signal”
Decreased leptin, PYY, cholecystokinin, insulin, amylin (anorexigenic hormones satiety)
Increased ghrelin, pancreatic peptide (oxeigenic hormones increase appetite
MacLean et al; Am J Physiol Regulatory Integrative Comp Physiol 2009;297
Opposite changes compared to after metabolic surgery. No increase in incretins. Factors contributing to weight regain include: Reduced resting energy expenditure (REE); Reduction in leptin (anorexigenic) and insulin; Increase in ghrelin (orexigenic); The obesogenic environment. Weight loss produces compensatory metabolic responses and a physiologic and hormonal drive to regain, which are attenuated by high levels of activity. in a 10-week weight-loss program for which a very-low-energy diet was 50 overweight or obese patients without diabetes prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). N ENGL J MED 2011; 365: ; October 27, 2011
MacLean PS, Higgins JA, et al. Regular exercise attenuates the metabolic drive to regain weight after long-term weight Loss. Am J Physiol Regulatory Integrative Comp Physiol 2009;297:R793-R802.
Sumithran et al; NEJM 2011;365;Oct 27, 2011 46

47. What happens after medical weight loss?
Increased drive to eat
Decreased energy expenditure/REE
 large energy gap between appetite and expenditure
~8 kcal/# lost/day less energy
MacLean et al; 2009
Sumithran et al; NEJM 2011;365; Oct 27, 2011
Factors contributing to weight regain include: Reduced resting energy expenditure (REE); Reduction in leptin (anorexigenic) and insulin; Increase in ghrelin (orexigenic); The obesogenic environment. Weight loss produces compensatory metabolic responses and a physiologic and hormonal drive to regain, which are attenuated by high levels of activity. in a 10-week weight-loss program for which a very-low-energy diet was 50 overweight or obese patients without diabetes prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite. One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001). N ENGL J MED 2011; 365: ; October 27, 2011
Position of the American Dietetic Association: Weight Management. J Am Diet Assoc. 2009;109(2):
ADA position: weight management; J Am Diet Assoc. 2009 47

48. Summary
Weight management is most important therapy for patients with T2DM obesity promotes diabetes; weight loss counteracts it
Comprehensive lifestyle intervention can produce sustainable clinically significant weight loss
Metabolic surgery most effective intervention
Therapeutic lifestyle changes cornerstone of therapy for all approaches
adiposity is one of the physiological determinants of insulin sensitivity. Weight loss has been shown to enhance insulin sensitivity under all circumstances
Comprehensive lifestyle intervention can produce sustainable clinically significant weight loss

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