手術治療糖尿病的趨勢 體重管理中心 宋天洲主任
“Diabetes is a public health emergency in slow motion” Ban Ki-Moon, UN Secretary-General
Where do nations rank in the global obesity stakes?
OECD Predictions for Future Overweight Rates
Obesity main driver for type 2 diabetes 80
Age 40-49 years Age 50-59 years
70 60 50 40 30 20 10 0
< 23
23 -23. 9
24-24.9
25-26.9
27-28. 9
29 -30. 9
31 -32. 9
33-34.9
> 35
Chan JM et al Diabetes Cars 1994
Diabetes Prevalence Rates in Selected Natios:1970-1989 & 1990-2005
Yoon KH et al. lancet 2006, 368 168 1-16888
Mauritius: Increase in Diabetes Prevalence over 22 yrs
Standardised to 2008 population structure of Mauritius
Global Projections for the Diabetes Epidemic:2010-2030 (millions) Wold 2010=285 million 2030=438 million Increase 54%
2011- a staggering 366 million 2030-552 million Shaw J. Diab ess & Clin Practice. 2009 IDF Atias 2009 www.idf org.
Conclusions • Diabetes continues to rise exponentially in Asia globally • Ageing, lifestyle change urbanisation have been targetted as the main drivers but in Asian nations, the story may be very different • A greater focus on early life risk factors eg maternal nutrition may lead to more effective strategies to halt this global “perfect storm” of diabetes • By 2020, diabetes is set to bankrupt the economies of many Asian nations
Diabetes “Cure” or Not
A surgical ‘cure’ for Diabetes??
N=168,146 with T2DM,152 with IFG
ANNALS OF SURGERY Vol.222,No. 3,339~352
â&#x20AC;˘ Rubinoâ&#x20AC;&#x2122;s idea boils down to one impolite word used to refer to the excrement of steers
ADA Expert Consensus Statement
Diabetes Care 32:2133(2009)
Definition of “cure”
Surgeons and Endocrinologists
“The surgeon perspective”
“My daddy is a doctor and he treats diabetes.” “My daddy is a surgeon and he cures it.”
â&#x20AC;Ś..but things can change
• Fist time that ADA acknowledgers surgery among “diabetes therapies”
The IDF Position Statement on Bariatric Surgery in obese type 2 diabetes
IDF Taskforce Consensus Panel Conveners: * Professor George Albert * Professor John B. Dixon * Professor Francesco Rubino * Professor Paul Zimmet Attendees: * Professor Stephanie Amiel * Professor Louise A. Baur * Professor Nam H. Cho * Dr. Bruno Geloneze * Professor Jan Willem Greve
* Professor Linong J. * Dr. Muffazal Lakdawala * Professor Wei-Jei Lee * Professor Pierre Lefebvre * Dr. Carel Ie Rour * Professor Jean-Claude Mbarrya * Professor Gertrude Mingrone * Dr. Philip R. Schauer * Professor Luc Van Gaal * Dr. David Whinng * Professor Bruce M. Wolfe
Management Algorithm for Metabolic Control in Type 2 Diabetes Lifestyle modification Diet modification Weight control Physical activity Metformin Bariatric sugary BMI >25 legible BMI >40 prioritized
FAILURE sulphonylureas
Acarbose
Dpp-4 inhibitor
glitazone insulin Basel
Premixed
Gabee insulin
Management Algorithm for Metabolic Control in Type 2 Diabetes Lifestyle modification Diet modification Weight control Physical activity Metformin Bariatric sugary BMI >25 legible BMI >40 prioritized
sulphonylureas Acarbose Barriatric surgery BMI >30 ebbic & BMI >25 Pefionitaed â&#x20AC;&#x153;It HbA1c-7.5% daspite Optinpend conventional Therapy espscially d weight is ie operative comobidities are Potreaathing farger on coventonal therapy
Dpp-4 inhibitor glitazone In Asian, and some other ethnicities of increased risk, BMI action points may be lower, e.g. BMI 27.5 to 32.5
insulin Basel
Premtaed
Gabee insulin
Bariatric surgery for obese adolescents with type 2 diabetes *An Australian report recommends surgery be considered if adolescents have BMI > 40, or >35 with severe co-morbidities, are 15 years or over & can provide informed consent. *This IDF position statement advises that only 2 procedures. Roux en Y gastric bypass & laparoscopic gastric banding are currently conventional bariatric surgical procedures for adolescents.
The idf position statement on bariatric surgery in obese type2 diabetes
Surgeons and Endocrinolongists
Glycemic and Metabolic Outcomes with Bariatric/Metabolic Surgery: Overview
Bariatric Surgery
What is the Evidence for Surgery as a Treatment for T2DM? BMI ≥ 35 • Retropective Studies • Prospective, Matched Controlled Studies • Prospective, Randomized Controlled Studies • Meta-analysis Studies
Weight and Type 2 Diabetes after Bariatric Surgery Systematic Review and Meta-analysis â&#x20AC;˘ 1990-2006:19 Studies, 4,070 diabetic patients
The American Journal of Medicine(2009) 122,248-256
Prospective, Matched Controlled Studies
Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 years after Bariatric Surgery “SOS STUDY”
Sjo¨stro¨m L, et al. N Engl J Med 2004. 351.2683-93
Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 years after Bariatric Surgery “SOS STUDY”
Sjo¨stro¨m L, et al. N Engl J Med 2004. 351.2683-93
Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 years after Bariatric Surgery “SOS STUDY”
Sjo¨stro¨m L, et al. N Engl J Med 2004. 351.2683-93
Prospective, Randomized Controlled Studies
RCT: LAGB vs Med Rx of DM • • • • • • •
T2DM (< 2 yrs, Ha1c 7.7% no insulin) 60 patient (30 med RX. 30 surg RX follwed for 2 years) BMI 30-40 Med RX+ lifestyle vs. LAGB + Med Rx + lifestyle Remission @ 2 yrs 13% vs 73% (p<0.001) Wt. loss (%lnitial BW) @ 2 yrs 1.7% vs 20.7% (p<0.001) No serious side effects in either group
Dixon et al. JAMA. Jan 23,2008
LSG v RYGB BMI <35 • RCT LSG vs. RYGB • N=60, BMI 25-35, Age 30-59, A1c>7.5% • Remission: LSG 47% vs. RYGB 93% P<0.05 Lee WJ et.al Arch Surg. March 2011
Is Diabetes only about sugar? *What about all 3 endpoints? *HTN *Hypertriglyceridemia *HbA1C
Effects of Bariatric Surgery on CV Disease: Systematic Review Systematic Review -All types of bariatric -Effects on CV risk factors -DM .HTN. Bp CV risk score -FRS Novel CVD biomaker -CRP - 52 studies included Heneghan HM . Eldar S. Brethauer.S schauer PR. Young J:Am J Cardiol 2011
Effects on CV risk factors: Objective evidence *Mean follow up of 34 months Changes in blood pressure and laboratory measurements of CVD risk factors Baselin
postoperatively
Systolic
139
124
Diastolic
87
77
Fasting blood glucose (mg/dL)
125.99
91.85
HbA1C(%)
7.45
5.98
Total cholesterol
205
169
LDL
118
94
Triglycerides
169
103
HDL
49
52
Blood pressure (mm Hg)
Diabeted Mellitus
Lipid profile (mg/dL)
Heneghan HM. Eldar S. Brethance S. Schauce PR. Young J Am J Cardiol 2011
Effect on CV Risk • Data from J studies • Mean follow-up 34 months
40% relative risk Reduction after Bariatric surgery
Heneghan HM. Eldar S. Brethance S. Schauce PR. Young J Am J Cardiol 2011
Effect on CV Biomarkers: CRP â&#x20AC;˘Mean follow-up 34 months 5
CRP level
4 3 2 1 0
Preoperative CRP
Postoperative CRP*
Heneghan HM. Eldar S. Brethance S. Schauce PR. Young J Am J Cardiol 2011
What about effect of surgery on Longterm Clinical Outcomes?
Sjostrom: NEJM 2007; 357:741-52
Unadjusted Cumulative Mortality Swedish Obesity Study
Sjostrom: NEJM 2007:357:741-52
Effect on Long-term Mortality Compared to Non-Operated Controls Study
Procedure
F/U
Mortality Reduction
MacDonald.1997
RYGB
9 yrs
88%
Flum. 2004
RYGB
4.4 yrs
33%
Christou.2004
RYGB
5 yrs
89%
Sowemimo. 2007
RYGB
4.4 yrs
50%
Oâ&#x20AC;&#x2122;brien.2006
LAGB
12 yrs
73%
Adams. 2007
RYGB
8.4 yrs
40%
Sjostrom 2007
VBG/other
14 yrs
31%
Perry, 2008(Medicare)
RYGB.VBG LAGB
2 yrs
48% age <65 34% age >65
SOS JAMA 2012
Will Early Surgical Intervention Reduce progression of Microvascular and macrovascular disease?
Change in Nephropathy
DIABETES CARE, VOLUME 34,MARCH 2011
BMI <35 ?
Studies of “Metabolic Surgery” BMI <35
Fried M, Ribaric G et al. (2010) Obes surg 20(6):776-790
GI SURGERY for TYPE 2 DIABETES in ASIAN PATIENTS with BMI <35
1nd ADSS,2010.07.15-16 Taiwan, Taoyuan
2nd ADSS,2011.07.07 Taiwan, Taoyuan
ASIAN DIABETES SURGERY STUDY Wei-Jei Lee MD&hD1 Kyung Yul Hur MD2 Muffatal Lakadawala MD5; Yi-Chin Lee PH.D.,1 1.Department of surgery, Mi-Sheng General Hospital. Taiwan. 2.Department of Surgery, Soonchunhyang University hospital, Seoul, korea 3.Department of Surgery, Saifee hospital , Mumbai, India 4.Department of Surgery Yotsuya Medical Cube. Tokyo, Japan 5.Department of surgery. Dance of wales Hospital, Hong Kong
ASIAN DIABETES SURGERY STUDY Inclusion Criteria • • • • •
1.Asian, Age >18 years. 2.T2DM,Hba1c>7% 3.BMI ≤ 34.9 kg/m2 4.Receive gastro-intestinal Metabolic Surgery . 5.Complete pre- operative clinical data and post operation annual follow-up data.
Gastrointestianal Metabolic Surgery for the Treatment of Diabetic Patients: A multi-institutional International Study Befere (n=200)
After (n=87)
P_value
BMI (kg/m2)
28.5±3.3
23.4±3.1
0.027*
Waist (cm)
103.4±7.1
91.9±7.3
0.002*
Weight loss(%)
19.4%
SBP (mmHg)
130.1±14.8
128.8±18.2
0.003*
Olucose (mg/dl)
188.0±10.3
115.3±41.4
0.041*
Total cholesterol (mg/di)
202.0±44.7
119.9±58.8
0.000*
Triglyceride (mg/dl)
233.6±265.8
119.9±58.8
0.016&
LDL (mg/dr)
119.3±37.8
105.4±33.2
0.000*
HbA1c %
9.3±8
6.3±1.5
0.002*
C-peptide (ng/ml)
20±8
1.9±1.0
0.048*
HOMA
9.5±1.5.7
2.3±2.7
0.021*
p=0.05, BMI. Body mass index. SBP systolic blood pressure. DBP disease blood pressure HDL-C high-density lipoprotein cholesterol Lee WJ et al. J Gastrointst Surg 2012:16:45-52
Gastrointestianal Metabolic Surgery for the Treatment of Diabetic Patients: A multi-institutional International Study
BMI body mass index *p<0.05,
Lee WJ et al. J Gastrointst Surg 2012:16:45-52
Effects of â&#x20AC;&#x153;Bariatricâ&#x20AC;? Operations on Gut Hormones, Insulin Secretion, Insulin sensitivity
Cummings De overdulin J ,J Clin inveset 2007
Ghrelin â&#x20AC;˘ Peptide hormone produced primarily by stomach & proximal small intestine â&#x20AC;˘ Powerfully stimulates appetite and food intake in many species, including humans
ACTH & Cortisol Epinephrine GHRELIN
Glucagon? Adiponectin Insulin Action Insulin Secretion Food Intake
counter. regulatory
GH
GLUCOSE
Plasma Ghrelin Increases After Diet-Induced Weight Loss
Cummings. et al. NEJM 346:1623
Lower Intestinal Hormones
Roux-en-Y Gastric Bypass (RYGB) Ingested food bypasses the duodenal site of nutrient mediated GLP-1 stimulation
Does gastric bypass Increase GLP-1 And/or PYY levels?
Increase in Postprandial GLP-1 and PYY After RYGB
Meal
Meal
Korner J, et al ,JCEM 90:359 Korner J, et al ,SOARD 3:597
GLP-1 For Up To 3 Years After RYGB
Laferrere et al ,unpublished
Operation That Rapidly Reverse DM All Expedite Nutrient Delivery to the Ileum
Roux-en-Y Gastric Bypass
…and All
Biliopancreatic Diversion
GLP-1 Levels
Jejuon-ileal Bypass GPT @20yrs
Are elevated GLP-1 levels after RYGB associated with an increased incretin effect?
Effects on Glucose Homeostasis of Equivalent Weight Loss from RYGB vs. Diet Type2 diabetes patients Matched for BMI, age, degree of diabetes
RYGB Studied at 9.7 kg
Diet Studied at 9.2 kg
Incretin Effect on Insulin Secretion Remains Normal up to One year After RYGB
No change in incretin Effect from equal Dietary weight loss
Bose M & Laferrere B. J Diabetes 2:47 (2010)
Higher C-Peptide Response to Oral Glucose After RYGB vs. Equivalent Dietary weight loss
Prandial GLP-1 response Increases immediately after RYGB, along with insulin
GLP-1 Meal Responses by 3 Days After RYGB
C-Peptide Responses by 3 Days After RYGB
Glucose Tolerance by 3 Days After RYGB
Acute Improvement in β-Cell Functin 4 Weeks After RYGB vs. Gastric Restriction Gastric Restriction
RYGB
Kashyap SR….Schauer PR. IJO 34:465 (2010)
Intestinal Bypass Operations That Increase Postprandial GLP-1 and Insulin Responses • Gastric bypass – e.g. LaFerrere. LeRoux. Korner. Holst. Schauer Mingrone. Morinigo. Peterli, Cummings • Biliopancreatic …but Diversion not seen with gastric banding or Dietary Efrrannini weight loss – e.g. Briatore, Mingrone, • Duodenal-Jejunal Bypass – e.g. Ramos
Bariatric Metabolic Surgery “An overview of safety”
Mortality Rates –Common GIT Surgical Procedures Procedure
Discharge
Mean Age
Mortality Rate
Small bowel resection
51,569
59
8.1%
Gastrostomy- temporary and permanent
93,693
73
7.9%
Gastrectomy – Partial and total
19,605
63
7.0%
Gastrointestinal therapeutic OR procedures
94,202
52
4.5%
Colorectal resection
280,969
64
4.2%
Lower GI Therapeubc OR procedures
113,271
52
2.5%
Hemia Repak
101,256
58
0.9%
Cholecystectomy and common duct exploration
407,582
53
0.8%
Fundoplic anti rethc Surgery
86,400
NR
0.8%
Gastric Bypass obesity Surgery
9,258
NR
0.5%**
Lap adjustable Gastric Band –Obesity surgery
5,780
NR
0.5%*
Mortality Rates â&#x20AC;&#x201C; Common GIT Surgical Procedures Procedure
Number of Patients
Perioperative Mortality Rate
Gastric Bypass (Open)
437
2.1%
Cholecystectomy and common duct exploration
407,582
0.8%
fundoplication
86,400
0.8%
Appendectomy (Open
3,025
0.3%
Gastric Bypass (Laparoscopic)
2,975
0.2%
Appendectomy (Laparoscopic)
14,174
0.1%
LAGB-obesity surgery
5,780
0.05%
America College of surgeons National Surgical Quality Improvement Program LRYGB =3,580 LAGB =1,176 * 2006 included 4,756 patients * LAGB experienced an equivalent 30-day mortality ( 0.09% vs. 0.14%, P=10) * Lower rate of major complications(1.0% vs. 3.3%; p <0.0001) * Any complication (2.6% vs. 6.7% ; p<0.0001) * Return visits to the OR( 0.94% vs. 3.6%; p<0.0001) * Shorter postoperative LOS (median 1 vs. 2 days; p <0.0001)
Risk factors for major complications *History of VTE, mobility limitations, coronary artery disease, age over 50, pulmonary disease, male gender, smoking history and procedure type *Reference LAGB: * Duodenal switch (OR 9.68. CI 6.05-15.49) * Laparoscopic gastric bypass (OR 3.58,CI 2.79-4.64) * Open gastric bypass (OR3.51, CI 2.38-5.22); * Sleeve gastrectomy (OR 2.46, CI 1.73-3.50) Finks, J. F. K L.. Kole. et al. (2011), Ann Surg 254(4):633-640 â&#x20AC;&#x153;Predichng risk for complications with bariatric surgery : results from the Michigan Bariatiric Surgery Collaborative â&#x20AC;&#x153;
Combine rather than stop therapy • LDL – cholesterol • Hypertension • Diabetes treatment and prevention • Obstructive sleep apnea
Stopping therapy can put your patients at risk
Predictor factors ?
ABCE Score- DIABETES SURGERY SCORE The relative importance of pre-operative predictor variables Variables and point Values Used for the Computation of the Age. Body-Mass index. C-peptide and Duration of Diabetes (ABCD) index. Variable
Points on ABCD Index 0
1
2
3
Age
â&#x2030;Ľ40
<40
BMI (kg/m2)
<30
30-39
40-49
>50
C-peptide (mmol/L) 0.9-1.9
2-3.9
4-6
>6
Duration of DM (years)
5-10
2-4.9
<2
>10
ABCE Score- DIABETES SURGERY SCORE The relative importance of pre-operative predictor variables Variables and point Values Used for the Computation of the Age. Body-Mass index. C-peptide and Duration of Diabetes (ABCD) index. ABCD index Sore
Patient No
Remission No
Remission %
0
3
1
33%
1
9
3
33%
2
30
13
43%
3
24
11
46%
4
17
7
41%
5
14
8
57%
6
24
20
83%
7
23
20
87%
8
15
15
100%
9
13
13
100%
10
4
4
100%
Overall
176
115
65.3%
From the Bariatric and Metabolic InstituteCleveland Clinic The mean (±SD) age of the patients at baseline was 48±8 years, HbA1c(%) level was 9.3±1.5%, BMI was 36.0±3.5.
HbA1c(%)
-0.6%
-2.5% -2.5%
BMI
-1.6
-6.9
-9.2
RAND 36-Item Health Survey
Conclusions *Including body weight, use of glucoselowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. *Obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone.
台灣代謝及減重外科醫學會 Taiwan Society for Metabolic and Bariatric Surgery (TSMBS)
26.4% 25.2%
*Patient Character Male/Female Age (mean) BMI (mean) Hospital days (mean) Mortality Major complication 30 days Readmission 30 days Re-operation
849/1455 36.2 38.4 5.4 -> 4.8 0.17%( 4/2304) 1.5% 1.17%(27/2304) 1% (23/2304)
* 台灣代謝及減重外科醫學會 Taiwan Society for Metabolic and Bariatric Surgery (TSMBS)
2010~2014 嘉義基督教醫院
2014~2015 高雄阮綜合醫院
Characteristics of the Bariatric Surgery Patients (2014~2015) Total No. Female sex — no. (%) Male sex — no. (%) Age — yr Body weight — kg BodyBody-mass index ( BMI )
150 98 (63 (63.3%) 52 (36.7%) 37.2 ± 10.9 106.5 ± 24.2
Value < 32 — no. (%) 32 ≤ BMI < 40— 40— no. (%) 40 ≤ BMI < 50— 50— no. (%) ≥ 50— 50— no. (%) Hospitalized — day Diabetes— Diabetes— no. (%) Hypertension— Hypertension— no. (%) Hyperuricemia Hyperuricemia— uricemia— no. (%) Hepatic Steatosis— Steatosis— no. (%)
39.1 ± 7.4 8 (5.3%) 75 (5 (50.0%) 59 (3 (39.4%) 8 (5.3%) 4.5 ± 1.5 48 (32.0%) 56 (37.3%) 23 (15.3%) 96 (64%)
Thanks a lot for your attentionďź Sung,Tienchou. Tel: 0933153320
2015.08.14