1. Obesity 2. Obesity Big Data 1) Genetics 2) Environment 3) Electrical Health Record 4) Imaging 5) Mobile/Sensor 6) National Health Record 7) Social Network Service 3. Research 4. Clinical Application

1. 최형진

2. 2015 Nature Immunology. A vision and a prescription for big data–enabled medicine

3. Contents
1. Obesity
2. Obesity Big Data
3. Research
4. Clinical Application
3

4. 왜?

5. Whole-Organism Physiology
Food Availability Growth
Fertility

6. Lab Research Theme
Central Regulation of Metabolism
Pancreas
Gut MuscleLiver
Fat

8. Translational Research
Animal + Human Research
How?
Animal
Genetics
Human
Data Science
Surgical Model
Physiology Study
College of Medicine
Imaging
Biobank
Clinical Insight
Pharmacological Model
Genetic Model
Clinical Trial
Mechanistic Insight
Tools
Understanding of
Biology and Mechanism
Understanding of
Human Metabolism and
Disease
Brain Imaging
Cadaver Study

9. 2012 JCEM Regulation of food intake, energy balance, and body fat mass- implications for the pathogenesis and treatment of obesity

10. Modern Environment
Physiologic Control of Energy Metabolism
Appetite Energy Expenditure
Obesity
T2DM
Hypertension

11. 비만 치료?
Psychotherapy
동기부여
식사요법+운동요법
Pharmacotherapy

12. 2012 JCEM Regulation of food intake, energy balance,
and body fat mass- implications for the pathogenesis
and treatment of obesity
Appetite
Appetite
Appetite
Calorie Restriction

13. 2012 Nature Medicine Shedding pounds after going under the knife
↑Agrp
↑NPY
↓POMC
↑Agrp
↑NPY
↓POMC

14. 식욕촉진 호르몬
Ghrelin
식전 ↑
체중 감소시↑
2002 NEJM Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery

15. 2011 NEJM Long-term persistence of hormonal adaptations to weight loss.
N=50

16. 2013 NRE The endocrinology of food intake

17. Determination of the settling point
for food intake
Food
Availability
Palatability
Leptin Resistance↑Adiposity↑ Leptin↑
2010 Trends in Endocrinology and Metabolism- Obesity and leptin resistance- distinguishing cause from effect
New Set Point

18. 2013 NRE The endocrinology of food intake

19. Hunger
Physiological desire
Appetite
Psychological desire

20. “Obesity and drug addiction may share common hedonic mechanisms”
2011 Neuron. Reward mechanisms in obesity- new insights and future directions

21. Liking and Wanting
• “Liking” (hedonic impact)
• “Wanting” (incentive motivation)
• Learning (associations and predictions)
• “Wanting” without “liking”
– Addictive incentive-sensitization
• A mechanism of drug addiction
• Sensitized “wanting” can rise even if “liking” declines for the same reward
– Hypothetically, if a similar brain mechanism applies to obesity and eating
disorders, some individuals could compulsively crave and seek food, but not derive
higher pleasure from it.
2010 Brain Research- The tempted brain eats- Pleasure and desire circuits in obesity and eating disorders

22. 2009 Liking’ and ‘wanting’ food rewards- Brain substrates and roles in eating disorders

23. 2013 The Addictive
Dimensionality of Obesity
Addictive Dimensionality
of Obesity

24. 2012 Ghrelin signalling and obesity- At the interface of stress, mood and food reward

25. 2009 Nat Rev Endocrinol. Stress and disorders of the stress system

26. Stress and Food Intake
2009 Trends in Endocrinology and Metabolism- Stress-induced obesity and the emotional nervous system

27. 2013 Stress as a Common Risk Factor for Obesity and Addiction

28. Model of insulin resistance, regional brain
activation, and food craving in obese individuals
2012 Diabetes Care. Neural Correlates of Stress- and Food- Cue-Induced Food Craving In Obesity
Viscous cycle driving weight gain

29. Model
Food Reward and Obesity
2009 Relation of obesity to consummatory and anticipatory food reward
2012 Feed-forward mechanisms- Addiction-like behavioral and molecular adaptations in overeating

30. BELVIQ

32. Bupropion for
Smoking Cessation

33. Fast-food habits and Weight Gain
2005 Lancet Fast-food habits, weight gain, and insulin resistance (the CARDIA study)- 15-year prospective analysis

34. 2014.10.27.

35. Soda School
No-Soda School
Obese Family Lean Family

36. 36
Environment
Gene
Eat
Exercise
Metabolism
Brain
Glucose
DM
Blood Pressure
HTN
Cardiovascular
Disease
Cognitive
Hormone
Behavior
Psychotherapy
Behavior Therapy
Policy Making
Genetic Testing
Neuroimaging
Neuromodulation
Drug
Drug
Lab
Survey
Survey
Sensor
DrugDiagnosis
EMR
Government
Data
Mining

37. Contents
1. Obesity
2. Obesity Big Data
① Genetics
② Environment
③ Electrical Health Record
④ Imaging
⑤ Mobile/Sensor
⑥ National Health Record
⑦ Social Network Service
3. Research
4. Clinical Application
37

38. Contents
1. Obesity
2. Obesity Big Data
① Genetics
② Environment
③ Electrical Health Record
④ Imaging
⑤ Mobile/Sensor
⑥ National Health Record
⑦ Social Network Service
3. Research
4. Clinical Application
38

39. 39

40. (출처: 금창원 대표님 블로그)
$99
TV CF
40

41. 30만원-200만원
41

42. CPIC Pharmacogenetic Tests: 최형진
No
Drug
(N= 10)
Gene
(6 genes=8 bioma
rkers)
Target SNPs
(N=12)
#5
(HJC)
Genotype Interpretation Clinical Interpretation
1 Clopidogrel CYP2C19
rs4244285 (G>A) GG
*1/*1
(EM)
Use standard dosers4986893 (G>A) GG
rs12248560 (C>T) CC
2 Warfarin
VKORC1 rs9923231 (C>T) TT
Low dose
(higher risk of bleeding)
Warfarin dose=0.5~2 mg/day
CYP2C9
rs1799853 (C>T) CC
rs1057910 (A>C) AC
3 Simvastatin SLCO1B1 rs4149056 (T>C) TT Normal
4
Azathioprine (AP),
MP, or TG
TPMT rs1142345 (A>G) AA Normal
5
Carbamazepine
or Phenytoin
HLA-B*1502
rs2844682 (C>T) CT
Normal
rs3909184 (C>G) CC
6 Abacavir HLA-B*5701 rs2395029 (T>G) TT Normal
7 Allopurinol HLA-B*5801 rs9263726 (G>A) GG Normal
Clopidogrel1)
: UM/EM=standard dose, IM/PM= consider alternative antiplatelet agent (eg. prasugrel/ticagrelor)
Warfarin2)
: high dose=5~7 mg/day, medium dose=3~4 mg/day, low dose=0.5~2 mg/day

43. Future of Genomic Medicine?
Test when neededWithout information Know your type
Blood
type
Geno
type
Here is my
sequence
43

44. 44

45. 45

46. 46

47. 47

48. 48

49. Genetics of eating behavior
2011 Genetics of eating behavior

50. Per-allele effect of BMI-associated
loci on body weight
2012 Genetic determinants of common obesity and their value in prediction50

51. 2011 Hum Genet. Type 2 diabetes and obesity- genomics and the clinic51

52. GWAS
N=339,224 individuals
97 BMI-associated loci

53. 2015 Nature Genetic studies of
body mass index yield new
insights for obesity biology
Blue: Previous
Red: Novel

54. Tissue Specific Gene Expression
2015 Nature Genetic studies of body mass index yield new insights for obesity biology
- Hypothalamus, Pituitary gland
(appetite regulation)
- Hippocampus, Limbic system
(learning, cognition, emotion,
memory)

55. Gene Set Enrichment Analysis
2015 Nature Genetic studies of body mass index yield new insights for obesity biology

56. Genetic Prediction of Obesity
2015 Nature Genetic studies of body mass index yield new insights for obesity biology

57. Gene-Environment Interaction
Gene Environment
Disease
Genetic Predisposition Score Sugar-Sweetened Beverages

58. 2010 PLoS Med Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study
Gene-Environment Interaction
Exercise X Genetic Predisposition

59. Sugar Beverages X Genetic Predisposition
High Sugar Intake
Low Sugar Intake
Genetic Predisposition Score
10 4020 30
BMI Slope = 2.43
Slope = 1.46
Slope = ΔBMI / Δ10 alleles
2012 NEJM Sugar-
Sweetened Beverages
and Genetic Risk of
Obesity

60. Contents
1. Obesity
2. Obesity Big Data
① Genetics
② Environment
③ Electrical Health Record
④ Imaging
⑤ Mobile/Sensor
⑥ National Health Record
⑦ Social Network Service
3. Research
4. Clinical Application
60

61. Electronic Health Records
2012 NRG Mining electronic health records- towards better research applications and clinical care
61

62. PCA Analysis혈당
신장기능
62

63. Machine Learning
2014 Big data bioinformatics63

64. Clinical Notes
64

65. 밤동안 저혈당수면 Lt.foot rolling Keep떨림,
식은땀, 현기증, 공복감, 두통, 피로감등의 저혈
당 에 저혈당 이 있을 즉알려주도록 밤사이 특
이호소 수면유지상처와 통증 상처부위 출혈
oozing, severe pain 알리도록 고혈당 처방된 당
뇨식이의 중요성과 간식을 자제하도록 .고혈
당 ,,관리 방법 .당뇨약 이해 잘 하고 수술부위
oozing Rt.foot rolling keep드레싱 상태를 고혈
당 고혈당 의식변화 BST 387 checked.고혈당
으로 인한 구강 내 감염 위해 식후 양치, gargle
등 구강 위생 격려.당뇨환자의 발관리 방법에 .
목표 혈당, 목표 당화혈색소에 .식사를 거르거
나 지연하지 않도록 .식사요법, 운동요법, 약물
요법을 정확히 지키는 것이 중요을 .처방된 당
뇨식이의 중요성과 간식을 자제하도록 .고혈
당 ,,관리 방법 .혈당 정상 범위임rt foot rolling
중으로 pain호소 밤사이 수면양호걱정신경 예
민감정변화 중임감정을 표현하도록 지지하고
경청기분상태 condition 조금 나은 듯 하다고 혈
당 조절과 관련하여 신경쓰는 모습 보이며 혈당
self로 측정하는 모습 보임혈당 조절에 안내하
고 불편감 지속알리도록고혈당 고혈당 의식변
화 고혈당 허약감 지남력 혈당조절 안됨고혈당
으로 인한 구강 내 감염 위해 식후 양치, gargle
등 구강 위생 격려.당뇨환자의 정기점검 내용과
빈도에 .BST 140 으로 저혈당 호소 밤동안 저
혈당수면 Lt.foot rolling Keep떨림, 식은땀, 현
기증, 공복감, 두통, 피로감등의 저혈당 에 저
혈당 이 있을 즉알려주도록 pain 및 불편감 호
소 WA 잘고혈당 고혈당 의식변화 고혈당 허
약감 지남력 혈당조절 안됨식사요법, 운동요법,
약물요법을 정확히 지키는 것이 중요을 .저혈당
/고혈당 과 대처법에 .혈당정상화, 표준체중의
유지, 정상 혈중지질의 유지에 .고혈당 ,,관리
방법 .혈당측정법,인슐린 자가 투여법, 경구투
약,수분 섭취량,대체 탄수화물,의료진의 도움이
필요한 사항에 교혈당 정상 범위임수술부위
oozing Rt.foot rolling keep수술 부위 (출혈, 통
증, 부종)수술부위 출혈 상처부위 oozing
Wound 당겨지지 않도록 적절한 체위 취하기
설명감염 발생 위험 요인 수술부위 출혈 밤동안
간호기록지 Word Cloud
Natural Language Processing (NLP)65

66. Contents
1. Obesity
2. Obesity Big Data
① Genetics
② Environment
③ Electrical Health Record
④ Imaging
⑤ Mobile/Sensor
⑥ National Health Record
⑦ Social Network Service
3. Research
4. Clinical Application
66

67. Department of Anatomy
Functional Neuroanatomy of Metabolism Regulation Lab
Jae-Chang Kim, Hyung Jin Choi
67

68. BOLD signal
Blood-Oxygen-Level Dependent

70. fMRI analysis
2013 Science Functional interactions as big data in the human brain

71. Functional Connectivity
2013 Science Functional interactions as big data in the human brain
N=50,000 voxels
N(N – 1)/2 = 1,249,975,000 Pairs
Seed Region Based Analysis

72. 2013 Science Functional interactions as big data in the human brain

73. N=20
Age=24 year
BMI=22 kg/m2
73

74. 2008 Cell Met. Ghrelin modulates brain activity in areas that control appetitive behavior74

75. Neural Activation with Food Stimuli
2008 Cell Met. Ghrelin modulates brain activity in areas that control appetitive behavior
Food > SceneryOnly with Ghrelin Infusion
75

76. 2008 Cell Met. Ghrelin modulates
brain activity in areas that control
appetitive behavior76

77. Contents
1. Obesity
2. Obesity Big Data
① Genetics
② Environment
③ Electrical Health Record
④ Imaging
⑤ Mobile/Sensor
⑥ National Health Record
⑦ Social Network Service
3. Research
4. Clinical Application
77

78. 78

79. 79

80. 80

81. 81

82. Overview of secondary data in
public health by data source
보험청구자료 건강검진
NHIS (National Health Insurance Corporation): 국민건강보험공단 (보험공단)
HIRA (Health Insurance Review and Assessment Service) :건강보험심사평가원 (심평원)
통계청 암센터
J Korean Med Assoc 2014 May; 근거중심 보건의료의 시행을 위한 빅데이터 활용82

83. Social Network and
Obesity Prevalence
2013 PLOS One. Assessing the Online Social Environment for Surveillance of Obesity Prevalence83

84. 84

85. 85
Environment
Gene
Eat
Exercise
Metabolism
Brain
Glucose
DM
Blood Pressure
HTN
Cardiovascular
Disease
Cognitive
Hormone
Behavior
Psychotherapy
Behavior Therapy
Policy Making
Genetic Testing
Neuroimaging
Neuromodulation
Drug
Drug
Lab
Survey
Survey
Sensor
DrugDiagnosis
EMR
Government
Data
Mining

86. Contents
1. Obesity
2. Obesity Big Data
3. Research
4. Clinical Application
86

87. Impact Factor = 6.31

88. Yale Food Addiction Scale

90. 음식 중독 점수
A U C
과다섭취 0 0 1
지속적 탐식 혹은 중단 실패 1 1 1
음식 관련 과도한 시간/행위 소요 2 0 1
음식 관련 사회적, 직업적, 여가 제약 0 2 4
해로운 결과 알면서 계속 탐닉 1 1 1
내성 (점점 더 큰 자극 탐닉) 0 1 2
금단증상 1 0 1
신체적 손실 초래 0 0 2
종합 중독 점수 5 5 11

91. /표준
/표준
/표준
/표준
/표준
/표준
/표준
총콜레스테롤 LDL콜레스테롤 중성지방
A
U
C
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
A U C
인슐린저항성
/표준
/표준
/표준
/표준
/표준
/표준
/표준
/표준
/표준
/표준
A U C
Leptin
/표준
/표준
/표준
/표준
/표준
/표준
/표준
공복혈당 간기능수치(AST) 간기능수치(ALT)
A
U
C
혈액 검사

92. 2011 Nature. Brain buzz
Transcranial direct current stimulation (tDCS)
Treatment for cravings for alcohol, cigarettes and
sweets

93. Neuronal Mechanims of
Transcranial Direct Current Stimulation (tDCS)
Time
Membranepotential(mV)
-70
-55
Threshold
40
Stimulus
tDCS
Resting state
Failed action potential
Action potential
Refractory period
Background

94. Background

95. tDCS Disease Treatment Indications
Obesity
Background

96. tDCS Decreases Food Craving
Real tDCS
Sham tDCS
Real tDCS
Sham tDCS
Craving Trouble resisting
2011 Appetite. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces
food cravings and increases the self-reported ability to resist food in adults with frequent food craving
Background

97. Long-term tDCS Treatment
Decreases Food Intake
2014 AJCN Repetitive electric brain stimulation reduces food intake in humans
Background

98. 2015 Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity
Spectrum of
Personalized Obesity Treatment
FDA approval
JAMA February 24, 2015
Background

99. Neurotherapeutic Strategies against
Obesity and/or Eating Disorders
2015 Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity
Background

100. Objective
Neuromodulation Brain Activity Feeding Behavior

101. Methods
• Study Design
– Cross-over design
• Real tDCS or sham tDCS
• Subjects
– N=15
– BMI > 28 kg/m2
• Brain Activity
– Functional MRI with visual food cues
• Behavior Measurement
– Visual analog scale: appetite, desire for food, mood
3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
1 2 3 4 5 6 7

102. Experimental Protocol
3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
Time
tDCS or sham
stimulation
Visual task
(food image
ratings)
Blood test/survey
Resting MRI
T1 structure MRI
5-6min
7min
5-6min
20min
Blood test/survey

103. Results
Effect of tDCS Neuromodulation
on Brain Activity
High calories > Low calories
Lt.parahippocampus
Active < Sham
p<0.0001 (k=16.1)
Lt./Rt. hippocampus Rt. insula precuneus
Lt./Rt. orbitofrontal Lt./Rt. pallidum
p<0.0001 (k=21.3)

104. Results
p<0.05
Treatment
(RealtDCS)
Control
(Sham tDCS)
Effect of tDCS Neuromodulation
on Feeding Behavior
Before treatment
After treatment
Fullness score

105. Brain Functional Connectivity
-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
-4 -2 0 2 4 6
R=0.648
p=0.043
tDCS effect on
right dlPFC - right thalamus
connectivity
tDCS effect on fullness score
Spearman’s correlation
Results
dlPFC (dorsolateral prefrontal cortex)
Thalamus

106. Green Lines: orexigenic pathways
Red lines: dopaminergic pathways
2013 The contribution of brain reward circuits to the obesity epidemic
2014 Obesity – A neuropsychological disease- Systematic review and neuropsychological mode
A, amygdala;
H, hypothalamus;
NA, nucleus accumbens,
PFC, prefrontal cortex;
VTA, ventral tegmental area
106
Conclusion
tDCS Neuromodulation Controls
Feeding Behavior via
Food Reward Activity and Connectivity
Neuromodulation Brain Activity Feeding Behavior
Brain Connectivity

107. 3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
Obesity related
visual stimulus
fMRI
107

108. Experimental Protocol
3
+
Food presentation
max 4sec
Feedback
1sec
Fixation
1~10sec
Time
tDCS stimulation
Visual task
(food image ratings)
Blood test/survey
Resting MRI
T1 structure MRI
Taste task
(food intake rating)
Diffusion tensor
imaging (DTI)
MR spectroscopy
(MRS)
5-6min
6min
10min
7min
5-6min
20min
4min
108

109. 연구 대상
비만환자 (42명) 정상체중 피험자 (13명)
성별 남자 32, 여자 10 남자 10, 여자 3
나이(년) 26.4±8.3 23.9±1.4
키(cm) 173.6±7.1 174.3±6.9
체중(kg) 88.2±10 66.4±8.4
BMI(kg/m2) 29.3±2.6 21.8±1.8
109

110. 희귀호르몬질환 수술전후 비교
• 질환
– 부갑성선기능항진증
– 갈색세포종: 불안
– 쿠싱: 우울
• 검사
– fMRI
– EEG
– PET
– Hormone

111. 스마트폰 활용 당뇨병 통합관리
의사
상담 교육
조회/
분석
교육간호사
매주/필요시
진료 처방
2-3달 간격
평가 회의
매주/필요시
식사/
운동
스마트폰
데이터베이스 서버
자가관리
전송
분석
혈당
측정
혈당측정기

112. 식사량 실시간 모니터링
0
100
200
300
400
500
600
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
아침
아침간식
점심
점심간식
저녁
저녁간식
2014-08-09 2014-08-10 2014-08-11 2014-08-12 2014-08-13 2014-08-14 2014-08-15
점심 과식
저녁 금식
112

113. 운동량 실시간 모니터링
0
5000
10000
15000
20000
25000
걸음 수
운동X
113

114. 114

115. 운동
식사
115

117. 비만정복 뇌인지행동 HT-IT 융합연구단

118. Contents
1. Obesity
2. Obesity Big Data
3. Research
4. Clinical Application
118

119. Environment Survey
NeuroimagingGenetics Lab/Hormone Hospital
Cognitive
Personalize
Psychotherapy
Dietary
Intervention
Exercise
Intervention
Food
Exercise
Glucose
Mobile
Drug
Neuromodulation
Monitoring