Bariatric Surgery in diabetes mellitus type 2

Josephine Carlos- Raboca M.D.

Weight Wellness Center

Bariatric Surgery

1995 the number of bariatric surgeries performed was well over 20000

2003 - 103,000

2004 - 144,000

Average age of patient – 30 years old

Length of Hospital Stay – 3.9 days

Bariatric surgeons – increased by 500%

Complication rate – 10%

Deaths <1% CDC, 2006

Long-term Effect of Gastric Bypass Surgery on Body Weight

Poiries et al. Ann Surg 1995;222:339.

BMI (kg/m2): 50 34 35 35

We

igh

t Los

s(%

of E

xces

s W

eig

ht)

Years After Surgery

0

20

40

60

80

1000 2 4 6 8 10 12 14

-30

-25

-20

-15

-10

-5

0

Obrien et al. Ann Intern Med. 2006;144:625-33

Wei

ght L

oss,

%

Baseline

Surgical

Nonsurgical

*(VLCD, behavioral modification, and pharmacotherapy)

6 mo 12 mo 18 mo 24 mo

LLaparoscopic aparoscopic AAdjustable djustable GGastric astric BBanding anding Produces Produces Greater Weight Loss than CGreater Weight Loss than Comprehensive omprehensive MMedical edical TTherapyherapy** in in PPatients with Class I Obesity (BMI 30-35 kg/matients with Class I Obesity (BMI 30-35 kg/m22))

ApproximateLoss of Excess

Procedure Weight (%)

Laparoscopic gastric banding 45–65

Gastric bypass procedure 55–65

Biliopancreatic diversion 60–75

with duodenal switch

Effect of Different Bariatric Surgical Procedures on Weight Loss

Klein et al. Gastroenterology. 2002;123:882-932

BARIATRIC SURGERY IN ST LUKE’S

PATIENT PROFILE*MALE FEMALE TOTAL

Number (%) 18 (36%) 32 (64%) 50

Age group

14-18 1 (6%) 1(3%) 2 (4%)

19-59 15 (83%) 30 (94%) 45 (90%)

>60 2 (11%) 1 (3%) 3 (6%)

BMI (mean)

14-18 57 46.8 51.9

19-59 47.07 46.15 46.5

>60 39.45 39 39.3

Obesity Types

Obese (30-40)

7 (39%) 10 (31%) 17 (34%)

Morbidly obese (40-50)

4 (22%) 12 (38%) 16 (32%)

Super obese

7(39) 10(21%) 17 (34%)*Dineros, Obesity Surgery, 2007

COMPLICATIONS

• Early Complications• Wound infection 2/50• Pneumonia 1/50• Dehydration 1/50• Gastritis 1/50• Leakage 1/50

COMPLICATIONS

• Late Complications• Band Slippage 2/20 (10%)• Stomal Stenosis 1/20 (5%)• Ventral Hernia 1/5 (20%)

0

25

50

75

100

Patents with Type 2 Diabetes

Patients with IGT

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Hb

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(%)

Gastric Bypass Surgery Improves Glycemic Control in Impaired Glucose Tolerance or Type 2

Diabetes

Pories et al. Ann Surg 1995;222:339.

4.7

18.5

0.0

3.6

0.0

4.0

8.0

12.0

16.0

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2 8Follow-up After Surgery (y)

Inci

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Control Bariatric surgery

Prevention of Type 2 Diabetes at 8 Years After Bariatric Surgery (94% Restrictive)

Sjostrom et al. Hypertension 2000;36:20.

Control Surgery Initial BMI (kg/m2) 41 5 41 4Weight change at year 8: 1 11% -16 12%

0

20

40

60

80

100

2 yr 10 yr 2 yr 10 yr 2 yr 10 yr

Effect of Bariatric Surgery on Obesity-related Metabolic Complications

Sjöström: N Engl J Med 2004;351:2683.

Rat

io o

f Rec

over

y (%

of s

ubje

cts)

21

72

Diabetes Hypertension Hypertriglyceridemia

13

36

21

34

11

19 22

62

24

46

Control Surgery

Adams et al., NEJM 2007

• 15850 gastric bypass patients and matched controls (Utah)

• 7.1 year mean follow-up

• Gastric bypass group exhibited overall 40% reduction in mortality

• Specific-cause mortality after gastric bypass

– 56% reduction from CAD

– 92% reduction from Type 2 diabetes

– 60% reduction from Cancer

0

1

2

3

4

5

6

7

Control Bariatric Surgery

Long-term Survival: Canada

Rel. Risk = 0.11 (.04-.27)

89% reduction in risk ofdeath over 5 years

Christou et al. Ann Surg 2004;240:416-424

% M

ort

alit

y

Gastric Banding in morbid obese DM2

• 905 consecutive patients followed up for a median of 12.5mos

• 78 DM2• 64 IGT• 100 MS• patients on OHA: 81% remission• patients on OHA+insulin:• 43% ceased or reduced OHA• 93% ceased or reduced insulin• Patients on insulin: only 75% reduced or ceased insulin

• 88% of MS remission or improved

• 100% IGT did not progress to DM

Meta-analysis of Bariatric Surgeries

• 1990-2006

• 621 studies

• 145,246 patients

• Mean age 40.2 years

• BMI 47.9 kg/m2

• 80% female

• weight loss was 38.5kg (55.9%)

• 78.1% of diabetic patients had complete resolution

• Diabetes improved or resolved in 86.6%• Resolution rate: biliopancreatic

diversion/duodenal switch>gastric bypass> gastric banding

• More pronounced with greater weight loss and maintained for 2 years or more

• Am J Med 2009

Major Obesity-related Comorbidities That Have Been Improved by Bariatric Surgery

• Type 2 diabetes• Hypertension• Obstructive sleep apnea• Obesity hypoventilation• GERD• NALD, NASH• Pseudotumor cerebri• Depression

• Dyslipidemias• Coronary artery disease• Cardiac dysfunction• Venous stasis disease• Polycystic ovary syndrome• Infertility• Cancers• Degenerative joint disease• Quality of life

Results of Different Types of Results of Different Types of Bariatric SurgeryBariatric Surgery

ResultResult MalabsorptiveMalabsorptive

(BPD)(BPD)

RestrictiveRestrictive

(LAGB. VBG)(LAGB. VBG)

CombinedCombined

(RYGB)(RYGB)

Excess weight Excess weight loss, %loss, %

7272 48-6848-68 6262

Resolution of Resolution of Comorbid Comorbid Conditions. %Conditions. %

Type 2 DMType 2 DM 9898 48-7248-72 8484

HypertensionHypertension 8181 28-7328-73 7575

Dyslipidemia, Dyslipidemia, improved improved

100100 71-8171-81 9494

Operative Mortality Operative Mortality rate, %rate, %

1.101.10 0.10.1 0.50.5

Marion L. Vetter, MD, RD; Serena Cardillo, MD; Michael R. Rickels, MD, MS; and Nayyar Iqbal, MD, MSCE, Effect of Bariatric Surgery on Type 2 Diabetes Mellitus. Ann Intern Med. 2009;150:94-103. www.annals.org

PROPOSED MECHANISMS FOR IMPROVED GLYCEMIC CONTROL AFTER BARIATRIC SURGERY

Effects of Decreased Caloric Intake on Fasting Glycemia

• Decreased caloric intake affects glucose metabolism

• Rate of diabetes remission are not the same – Complete remission within days of intestinal

bypass procedures (Porries, 1995)– Takes months to occur in LAGB (Dixon, 2008)

GLP-1 and GIP Are the Two Major Incretins

GLP-1 GIP• Produced by L cells mainly located

in the distal gut (ileum and colon) • Stimulates glucose-dependent

insulin release

• Produced by K cells in the proximal gut (duodenum)

• Stimulates glucose-dependent insulin release

Other effects• Suppresses hepatic glucose output

by inhibiting glucagon secretion in a glucose-dependent manner

• Inhibition of gastric emptying; reduction of food intake and body weight

• Enhances beta-cell proliferation and survival in animal models and isolated human islets

• Minimal effects on gastric emptying; no significant effects on satiety or body weight

• Potentially enhances beta-cell proliferation and survival in islet cell lines

GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide.

Drucker DJ. Diabetes Care. 2003;26:2929–2940; Ahrén B. Curr Diab Rep. 2003;3:365–372; Drucker DJ. Gastroenterology. 2002;122:531–544; Farilla L et al. Endocrinology. 2003;144:5149–5158; Trümper A et al. Mol Endocrinol. 2001;15:1559–1570; Trümper A et al. J Endocrinol. 2002;174:233–246; Wideman RD et al. Horm Metab Res. 2004;36:782–786.

Nonincretin Gut Peptides

• GHRELIN– Secreted by gastric fundus and proximal small intestine

and acts on the hypothalamus to regulate appetite

– Inhibits insulin secretion by a paracrine mechanism

– Systemic ghrelin levels increase before a meal and decrease afterward

– Ghrelin stimulates appetite and food intake and suppresses energy expenditure and fat catabolism

– Inversely proportional to body weight

– Weight loss increases ghrelin levels suggests that ghrelin affects long term regulation of body weight

Nonincretin Gut Peptides

• Peptide YY (PYY)– Secreted by the L cells of the distal intestine– Present in 2 molecular forms: PYY(1-36) and

PYY (3-36), a cleavage product– PYY increases satiety and delays gastric

emptying through neuropeptide Y-receptor subtypes in the central and peripheral nervous system

– IV PYY(3-36) increases satiety and decreases food intake in humans

FOREGUT EXCLUSION THEORY ( Hypothesis of the Proximal Bowel)

• Exclusion of the duodenum and jejunum prevents the secretion of a “putative signal” that promotes insulin resistance and Type 2 DM

• Bypass of proximal gut prevents secretion of “Anti-incretin factor” or “decretin”

• May be implicated in the pathogenesis of diabetes

HINDGUT HYPOTHESIS (HYPOTHESIS of distal bowel)

• Intestinal rearrangement speeds the delivery of nutrients to the distal intestines

• Causes exaggerated GLP-1 and PYY levels and improves glucose tolerance and insulin secretion

Cummings, et al, 2007

Rat Experiments

• Simple gastrojejunostosmy without bypassing proximal intestine did not improve diabetes

• GJB + proximal intestinal bypass improved diabetes

• Supports Proximal Bowel Hypothesis

Gut Peptide Response to Different Bariatric Surgical Procedures*

HORMONE

Cell Type (Location)

Effect on Insulin Secretion

BPD RYGB LAGB

Ghrelin X/A cells Stomach

Decrease Increase Increase/Decrease

Increase/No Change

GIP K cells duodenum

Increase Decrease Decrease No change

GLP-1 L cellsDistal ileum

Increase Increase Increase No change

Peptide YY L cellsDistal ileum

Decrease Increase Increase No change

*Folli, 2007

Markers for remission

• Post op dietary behaviour

• Beta cell dysfunction

• Insulin resistance

• More recent onset <5years

• Satisfactory control on diet or oral hypoglycemic agents

• Greater weight loss

CLINICAL PRACTICE RECOMMENDATIONS, 2009 ADA

• Bariatric surgery should be considered for

adults with BMI 35 kg/m2 and type 2 diabetes, especially if the diabetes is difficult to control with lifestyle and pharmacologic therapy. (B)

• Patients with type 2 diabetes who have undergone bariatric surgery need life-long lifestyle support and medical monitoring. (E)

Surgery for nonobese DM2

• 24 week interventional prospective trial

• BMI 25-29.9 kg/m2

• DM<15 years

• Insulin treated

• No history of major complications

• Preserved beta cell function

• Absence of autoimmunity

12 open duodenal-jejunal exclusion surgery vs 12 standard medical care

• Results reductions in • FBS 14% vs 7%• A1c 8.78 to 7.84 p<0.01• vs 8.93 to 8.71 p<0.05 between groups• Insulin requirements 93% vs 29% p<0.01• 10 patients stopped insulin but continued oral

medications in surgical patients.

• Conclusion: duodenal jejunal exclusion was an effective treatment for nonobese T2DM patients and superior to medical treatment in achieving better glycemic control along with reduction in insulin requirements.

Clinical improvement after duodenojejunal bypass for nonobese type 2 diabetes despite minimal

improvement in glycemic homeostasis

• 7 patients T2DM with BMI<35 - LDJB

• 12 month prospective study

Results: At 12 months after surgery, all subjects consistently felt relief from fatigue pain and/or numbmess in the extremeties, polyuria and polydipsia

Conclusion

• Although this is a small series data showed that at 12 months after surgery, clinical improvement was obvious, LDJG may not be effective at inducing remission of T2DM and the Metabolic Syndrome in certain patients . This suggests that larger patient studies should be conducted before conlcuding that surgery may offer clinical and biochemical resolution to a disease once treated medically. Longer follow up is required for better evaluation.

• Until better approaches become available, bariatric surgery is the therapy of choice for patients with severe obesity

• Pories WJ JCEM 2008 Nov; 93(11 Supp 1) S89-96.

• While indiscriminate use of bariatric surgery to treat diabetes is potentially harmful, ignoring an opportunity offered by surgery is not an option either at a time when medical cure is not available.