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Update in Diabetes Care Exercise and Bariatric Surgery Ted Adams, PhD, MPH Intermountain LiVe Well Center Salt Lake October 6, 2017
Update in Diabetes Care
Exercise and Bariatric Surgery
Ted Adams, PhD, MPH
Intermountain LiVe Well Center Salt Lake
October 6, 2017
“There is no drug in current or perspective use that holds as much promise for sustained
health as a lifetime program of physical activity.”
American Medical Association
Physical Activity/Exercise and Diabetes:A Position Statement of the American Diabetes Association
Benefits of exercise/physical activity in diabetic patients
• Improve blood glucose control in type 2 diabetes
• Reduced cardiovascular risk factors
• Contributes to weight loss
• Improves well-being
• May prevent or delay type 2 diabetes
• Improve cardiovascular fitness, muscle strength, insulin sensitivity, etc.
Diabetes Care 2016;39:2065-2079
Rx Exercise/physical activity should be tailored to meet specific needs of each individual patient
• Refer to Table 3, page 2070, for specific recommendations related to types, intensity, duration and progression of exercise prescription.
• Refer to Table 5, page 2073, for physical activity considerations. Precautions and recommended activities for exercising with health-related complications.
• Be mindful of pregnancy, hypo- and hyper-glycemia, medication effects and heat-related illness
Diabetes Care 2016;39:2065-2079
ADA – Abridged Standards of Care, 2017*
Rx Exercise/physical prescription -children and adolescents
*Clinical Diabetes published online 12/15/2016
Type 1, type 2 or prediabetes – 60 min/day of moderate or vigorous intensity activity, with vigorous, muscle strengthening and bone-strengthening activities included at least 3
days/week
ADA – Abridged Standards of Care, 2017*
Rx Exercise/physical prescription -most adults, Type 1 and 2
*Clinical Diabetes published online 12/15/2016
• Type 1 or type 2 –150 min or more of moderate-to-vigorous intensity activity per week (spread out over at least 3 days/wk, not missing more than 2 days in a row
• 2-3 sessions/wk or resistance exercise (not in a row)• Decrease time spent in sedentary behavior; interrupt
prolonged sitting every 30 min• Flexibility and balance training 2-3 times/wk for older
adults (yoga and tai chi - flexibility, strength, balance
Prospective and retrospective observational studies in bariatric surgery
• Can contribute (in a unique way) to the understanding of long-term outcomes of bariatric surgery.
• Electronic medical record
• Health plans claims data
• Combined health plans claims data
• RCTs in bariatric surgery have some limitations
• Difficult to recruit participants
• May be under-powered for adequate analyses
Reduction of Micro- and Macrovascular Complications (Johnson BJ et al.; 2013)
• Pre-bariatric surgical patients (BAR) with T2DM(n=2580); surgery, 1996-2009
• Moderate and obese non-bariatric surgical patients (No-BAR) with T2DM (n=13,371)
• Both groups without MI, angina, CHF, stroke, or advanced microvascular disease
• Study outcome: First major macrovascular or microvascular event BAR to No-BAR
Johnson BJ et al. J Am Coll Surg 2013;216:545-58
Disease HR
Macrovascular 0.39; 95% CI, 0.29-0.51
Microvacular 0.22; 95% CI, 0.09-0.49
Multisite Study of Long-term Remission and Relapse of T2DM (Arterburn; 2013)
Pre-bariatric surgical patients with T2DM (n=4,434); 1995-2008
• Initial T2DM remission within 5 years post-surgery:
68.2% (95% CI, 66-70%)
• Remitters who redeveloped T2DM remission within 5 years
• 35.1% (95% CI, 32-38%)
Arterburn DE et al. Obes Surg 2013;23(1):93
• Two large Swedish registries merged – National Diabetes
Registry & Scandinavian Obesity Surgery Registry
• 6132 RYGB patients and 6132 non-surgery control patients –
all patients with T2DM
• Matched on sex, age, BMI, calendar time
• 3.5 years follow-up
Eliasson, B, Lancet Diabetes Endocrinol, 2015;3:847
Retrospective – Pre-surgery T2DM andCVD Incidence and Mortality (Eliasson; 2015)
EventsRYGB
Patients (N)
Non-operated
(N)HR (95% CI)
All-cause mortality 82 288 0.42 (0.3-0.6)
CVD-caused mortality
13 67 0.41 (0.2-0.9)
Fatal or non-fatal MI 24 67 0.51 (0.3-0.91)
Eliasson cont. – all patients with T2DM (n=6132; each group, )
Eliasson, B, Lancet Diabetes Endocrinol, 2015;3:847
PROMISE study– NIH Funded (Arterburn; 2016)
Joint collaboration between 4 U.S. health care systems:
• Kaiser Permanente Northern California (KPNC)
• Kaiser Permanente Southern California (KPSC)
• HealthPartners Research Foundation in Minnesota (HPRF)
• Group Health Cooperative (GHC)
Approximately 10,000 bariatric surgical patients who were
diabetic prior to surgery (surgery – 2001 through 2011; 40%
racial/ethnic minority)
PROMISE study (continued)
First manuscript – Long-term microvascular disease (first occurrence ofretinopathy, neuropathy, and/or nephropathy)
• Those who remitted T2DM = 29% lower risk of microvascular
disease compared to never-remitted (HR 0.71 [95% CI 0.60, 0.85])
• For those who remitted T2DM and later relapsed, the longer the
remission time inversely related to risk for incident microvascular
disease
• Every additional year of remittance = reduced risk of 19% (HR 0.81
[95% CI 0.67, 0.99])
Coleman KJ et al. Diab Care 2016 (online pub)
Geisinger Obesity Institute – CVD Risk Factors and CHF (Benotti; 2017)
• RYGB group and matched controls, n=1724
• Matched on: age, BMI, sex, Framingham Risk Score, smoking
Hx, HTN meds, T2DM and date of surgery
• Primary end points: MI, stroke and CHF
• Secondary end points: CVD risk factors (risk score, lipids,
SBP, and T2DM)
• Follow-up: 12 years post-surgery (mean = 6.3 years)
Benotti PN et al. J Am Heart Assoc 2017;6:e005126
Geisinger Obesity Institute – results
• Reduction in major composite CV events (63 in RYGB group
and 110 in control group) – HR 0.58 (95% CI: 0.42, 0.82)
• Reduction in CHF in RYGB compared to controls (p=0.0077)
but not significantly different for MI and stroke alone
• Improvements in CV risk factors (p<0.0001)
Benotti PN et al. J Am Heart Assoc 2017;6:e005126
Groups MI (N) Stroke (N) CHF
RYGB 12 31 24
Matched Controls 17 49 55
• French health care system database, SNIRAM, linked to
French medical discharge database, PMSI
• 1633 bariatric surgery patients and 1633 matched controls
• Follow-up of 6 years; greatest benefit in RYGB subgroup
Thereaux, J et al, data presented at IFSO London, 2017.
Thereaux J et al. – Retrospective Nationwide Matched Cohort Study
EventsBariatric Surgery
PatientsNon-operated (N)
Remitted T2DM 50% 9%
T2DM Incidence 1% 12%
SOS Long-term Micro- and Macro-vascular Complications (Sjöström L et al.)
Macrovascular complications of BAR vs. No-BAR
• BAR – 20.6 per 1000 person–years
• No-BAR – 41.8 per 1000 person-years
• HR 0.44; 95% CI, 0.34-0.5; p<0.001
Microvascular complications of BAR vs. No-BAR
• BAR – 31.7 per 1000 person–years
• No-BAR – 44.2 per 1000 person-years
• HR 0.68; 95% CI, 0.54-0.85; p=0.001
Sjöström L et al. JAMA 2014;311:2297
One RCT - Micorvascular & Macrovascular Outcomes - STAMPEDE (Schauer, P. et al.)
Reduction in urinary albumin-to-creatinine ratio (UACR) of SURG vs. No-SURG (p<0.04) for both GBP and sleeve groups
Patients with baseline albuminuria who returned to normal values:
• 62% (8 of 13; p=0.04 within group comparison)
• 80% (8 of 10; p=0.11 within group comparison)
• 25% (1 of 4; p=1.00 within group comparison)
Schauer, P. et al. NEJM 2014;370:2002
Utah Study - Hypothesis
Does Roux-en-Y gastric bypass (RYGB) surgery
result in improved morbidity when severely obese
non-surgical groups (population-based and
denied-surgery) are compared to RYGB patients?
Note: Gastric banding was not approved in USat time of study initiation (2001).
Health plan approves RYGB or patient provides self-pay and
RYGB surgery performed
Recruitment Scheme:RYGB Group and Non-surgery Group 1
Patients come to surgeon’s clinic to learn about RYGB and get health insurance advice. Patients informed of study.
Patient agrees to participate
Patient undergoes baseline testing
Patient assigned toRYGB Group
Patient assigned toNon-surgical group 1
Health plan denies coverage of RYGB or patient chooses not to
have RYGB performed
Recruitment Scheme:Non-surgery Group 2
• Severely obese participants not seeking bariatric surgery.
• Randomly selected from the Utah Health Family Tree
program database:
• 150,000+ families (>1 million family members)
• Health data, including reported weight status.
Recruitment Hypothesis
• Denied surgery patients (Non-surgical Group 1) represent
characteristics associated with seeking surgery (potentially
self-selected for significant comorbidities and other
conditions).
• Population-based severely obese participants (Non-surgical
Group 2) represent characteristics associated with severely
obese subjects in the general population.
Long-term Prospective Utah Study(NIH-funded 2001-2015)
387
388
Exam 3
410
400
Exam 2Exam 1
2 Years 6 YearsBaseline
417
No
RYGB
418
RYGBSurgical
Center
12 Years
315319321
Utah
Health
Family
Tree
Program301
388
364
Exam 4
Adams et al. Obesity 2010;18:121-30
RYGB Surgery
Non-Surgery 1
Non-Surgery 2
Adams et al. JAMA 2012;308:1122-31
12-year Results – Follow-up
End Point RYGB Surgery Group
(minus deaths)
Non-surgery Group 1
(minus deaths)
Non-surgery Group 2
(minus deaths)
Potential Participation, n 392 378 303
Any data source, n (%) 388 (98.7%) 364 (96.3%) 301 (99.3%)
Minimum of Weight, SBP, and either glucose or
HbA1c, n (%)353 (90.1%) 342 (90.5%) 285 (94.1%)
Later had bariatric surgery, n (%)
--- 147 (35%) 39 (12%)
Adams, T. et al. NEJM 2017;377:1143-55
12-year Results – Mortality
End Point
RYGB Surgery Group
(minus deaths)
Non-surgery Group 1
(minus deaths)
Non-surgery Group 2
(minus deaths)
All-cause, n (%) 26 (6.2%) 39 (9.4%) 18 (5.6%)
CVD, (n) (%) 3 17 8
Cancer, n (%) 4 5 7
Suicide, n (%) 5 (1.2%) 2 (0.5%)* 0
Poisoning, n (%) 4 (1.0%) 2 (0.5%) 0
* = Death subsequent to bariatric surgery
Adams, T. et al. NEJM 2017;377:1143-55
-50
-40
-30
-20
-10
0
10
BL 2 Years 6 Years 12 Years
% C
hange
Control 2
Control 1
Surgery
*
* *
% Change in Baseline Body Weight (mean adjusted)
* = Surgery group differs significantly from non-surgery groups; p<0.001 Adams, T. et al. NEJM 2017;377:1143-55
# of participants Baseline 2 Years 6 Years 12 Years
RYGB patients 418 409 379 387
Deaths --- 3 9 14
Total 418 412 388 401
% Change in Baseline Body Weight RYGB Group
-70
-60
-50
-40
-30
-20
-10
0
10
20
2001 2004 2006 2009 2012 2014 2017
Perc
ent
weig
ht
change f
rom
baseline Baseline
2-yr
6-yr
12-yr
% weight lost
% Change in Baseline Body WeightNon-Surgery Group 1
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
40
50
60
70
2001 2004 2006 2009 2012 2014 2017
Perc
ent
weig
ht
change f
rom
baseline
Baseline
2-yr
6-yr
12-yr
2-yr surgery
6-yr surgery
12-yr surgery
Non-surgical controls
All controls including surgeries
# of participants Baseline 2 Years 6 Years 12 Years
Non-surgery group 1 417 373 294 217
Had surgery later --- 28 89 146
Deaths --- 3 11 25
Total 417 404 394 388
-70
-60
-50
-40
-30
-20
-10
0
10
20
30
40
50
60
70
2001 2004 2006 2009 2012 2014 2017
Perc
ent
weig
ht
change f
rom
baseline
Baseline
2-yr
6-yr
12-yr
2-yr surgery
6-yr surgery
12-yr surgery
Population controls
All controls including surgeries
# of participants Baseline 2 Years 6 Years 12 Years
Non-surgery group 2 321 312 294 262
Had surgery later --- 8 19 39
Deaths --- --- 3 15
Total 321 320 316 316
% Change in Baseline Body WeightNon-Surgery Group 2
Weight Loss Maintenance at 12 Years: RYGB Group
• 360 of 387 RYGB patients (93%) maintained at least a 10% weight loss from baseline to year 12
• 271 (70%) maintained at least 20% weight loss
• 155 (40%) maintained at least 30% weight loss
• Only 4 of 387 (1%) had regained all postsurgical
weight loss
Adams, T. et al. NEJM 2017;377:1143-55
Diabetes remission after RYGB
Group 2 years 6 years 12 years
Surgery, % 74% 62% 51%
Surgery, n 66/88 54/87 43/84
Adams, T. et al. NEJM 2017;377:1143-55
Diabetes and Hypertension:12-year Remission
End
Point
Surgery
%
NS 1, % NS 2, % Adj. OR
S vs NS 1
Adj. OR
S vs NS 2
T2D 51% 10% 5%8.9***
(2.0, 40.0)
14.8***(2.9, 75.5)
HTN 36% 10% 14%5.1***
(1.7, 15.6)
2.4(0.9, 5.9)
*** = P<0.001
Adams, T. et al. NEJM 2017;377:1143-55
Diabetes and Hypertension: 12-year Incidence
End
Point
Surgery
%
NS 1, % NS 2, % Adj. OR
S vs NS 1
Adj. OR
S vs NS 2
T2D 3% 26% 26%0.08***
(0.03, 0.24)
0.09***(0.03, 0.24)
HTN 16% 41% 47%0.23***
(0.11, 0.49)
0.09***(0.11, 0.51)
*** = P<0.001
Adams, T. et al. NEJM 2017;377:1143-55
30
35
40
45
50
55
60
65
BL 2 Years 6 Years 12 Years
mg
/dL
Surgery Group Non-S Group 1 Non-S Group 2
**
*
Unadjusted Mean HDL-Cholesterol
*Surgery group mean (adjusted for medication use) differs significantly from non-surgery groups; p<0.05
Adams et al. JAMA 2012;308:1122-31Adams et al. Obesity 2010;18:121-30Adams, et al. NEJM 2017;377:1143-55
0
50
100
150
200
250
BL 2
Years
6
Years
12
Years
gra
ms
Surgery Group Non-S Group 1 Non-S Group 2
** *
Left Ventricular Mass
Adams et al. JAMA 2012;308:1122-31Adams et al. Obesity 2010;18:121-30Adams, et al. NEJM 2017;377:1143-55
Conclusions
• Long-term durability of weight loss after RYGB with minimal
weight increase between the 6- and 12-year follow-up
• Very minimal incidence of T2DM
• Remission rate 51% at the 12-year follow-up
• Marked improvement in systolic hypertension and lipid levels
Acknowledgement: Funding from NIH-NIDDK
Thank You
“There is no drug in current or perspective use that holds as much promise for sustained
health as a lifetime program of physical
activity.”
Journal of the American Medical Association
Benefits of Physical Activity
Lower death rates
Prevents or reduces risk of:
• High blood pressure
• Osteoporosis
• Overweight and obesity
• Depression and anxiety
• Diabetes
• Some cancers (i.e. colon)
Benefits of Physical Activity
Improves structure and function of ligaments, tendons and joints
Improves:
• Muscular strength
• Sleep patterns
• Health-related quality of life
• Independent living with increasing age
Rx Structured Exercise
Program
Frequency: 3-5 days/week
Intensity: 55/65% - 90% max heart rate
Rx Structured Exercise
Program continued
Duration: 20-60 min (continuous or intermittent - minimum 10 min. bouts accumulated over the day)
Mode: Large muscle groups, continuous, aerobic in nature
Modes for Structured Exercise
Walking-hiking
Running-jogging
Cycling-bicycling
Aerobic dance
Stair climbing
Swimming
Endurance games
Resistance training: One set, 8-10 exercises, 8-12 reps, 2-3 days/wk
Rx Structured Exercise
Program continued
Examples of Using YourOwn Weight
Flexibility training: 2-3
days/wk of stretching
major muscle groups
Rx Structured Exercise
Program continued
Flexibility Exercises
Rx Lifestyle Physical Activity
Accumulate 30 minutes or more of moderate-intensity physical activity on most, preferably all days of the week.
Resistance training 2 times per week
Examples: Moderate Intensity Activities
Walking
Yard Work
Stair Climbing
Housework
Dancing
Resting Metabolic Rate (RMR)
• Indirect calorimetry using a Parvomedics TrueOne 2400 metabolic cart.
• Measurements taken in the morning after a 12-hour fast, minimal exercise in prior 24 hours, and participants having rested in a supine position for at least 30 minutes.
• 24-hour estimates based on at least 10 minutes of stable resting values.
• 986 participants had at least one assessment
Mixed model regression was used to determine group-wise differences at each time point.
1500
1600
1700
1800
1900
2000
2100
2200
2300
2400
2500
BL 2 Years 6 Years 12 Years
kcals
/day
Non-Surgery 2
Non-Surgery 1
Surgery
Resting Metabolic Rate (RMR)
†‡ †‡
‡
*
*
**
*
*/*/* Within-group change from previous assessment is significant (p<0.05)† Surgery value differs significantly from Non-Surgery 1 group (p<0.05)‡ Surgery value differs significantly from Non-Surgery 2 group (p<0.05)
†‡
*
• RMR has an expected drop with weight loss in Surgery group
• Long-term rate of RMR decrease mirrors age-related drop in controls
12
13
14
15
16
17
18
19
20
21
22
BL 2 Years 6 Years 12 Years
kcals
/day
Non-Surgery 2
Non-Surgery 1
Surgery
Resting Metabolic Rate (RMR) per kg body weight
†‡
†‡
‡
*/*/* Within-group change from previous assessment is significant (p<0.05)† Surgery value differs significantly from Non-Surgery 1 group (p<0.05)‡ Surgery value differs significantly from Non-Surgery 2 group (p<0.05)
†‡
*
*
*
**
**
• Per kilogram RMR remains improved long-term, perhaps explaining maintenance of post-op weight loss
• Difference begins to wane by 12 years
RYGB: influence of Fat and FFM on RMR
0
500
1000
1500
2000
2500
0
20
40
60
80
100
120
140
160
BL 2 yrs 6 yrs 12 yrs
kilo
gra
ms
FFM
FM
Weight
RMR
*
*
* **
*/*/*/* Change is significant (p<0.05) compared with previous assessment
*
**
*
**
• RMR does not decrease as much as expected with weight loss
• FFM constitutes 1/3rd of weight loss, but is only 11% of regain
RYGB: influence of Fat and FFM on RMR/kg
0
5
10
15
20
0
20
40
60
80
100
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BL 2 yrs 6 yrs 12 yrs
Kcals
/kg/d
ay
kilo
gra
ms
FFM
FM
Weight
RMR/kg
**
* **
*
** *
**
*
• RMR/kg changes reflect increased FFM relative to FM
*/*/*/* Change is significant (p<0.05) compared with previous assessment
Cardiorespiratory fitness: time on treadmill
Time Test type RYGB
(seconds)
NS 1
(seconds)
NS 2
(seconds)
BaselineSubmax
(80%)602±13 593±14 582±13
2 years Maximal 873±13 623±16*** 586±14***
6 years Maximal 828±14 641±17*** 679±13***
12 yearsSubmax
(80%)643±14 598±16* 556±17***
• Graded exercise test with 12-lead ECG
• Submaximal tests at baseline and 12 years (maximal tests at 2 and 6 years)
• Means are seconds to test completion
• After surgical weight loss, RYGB patients are able to last significantly longer on the treadmill 10-12 years after surgery
• The effect is lost when controlling for weight
* = (p<0.05)*** = (p<0.0001)
