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1 KYUNG HEE UNIVERSITY HOSPITAL at GANGDONG Postprandial Glucose & Glycemic Variability 이론적근거 강동경희대학병원당뇨병교육실이정화

2 당뇨병과혈당유지 혈당조절유지의목표 정상혈당을유지 당뇨병성급성, 만성합병증의예방

3 당뇨병성만성합병증모식도 DYSGIYCEMIA Substained chronic hyperglycemia Acute glucose fluctuations FPG PPG Increased glycation + Activation of oxidative stress Diabetic complication

4 가장적절한혈당유지는? HbA1C(%) MBG HbA1C(%)=8% MBG HbA1C(%)=7% MBG= Mean Blood Glucose

5 당화혈색소와만성합병증 The intensive glucose control policy maintained a lower HbA 1c by mean 0.9 % over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk Albuminuria at 12 years -33 Diabetes related endpoint -12 Microvascular endpoint -25 Myocardial infarction -16 Cataract extraction -24 Retinopathy at 12 years -21 Reduction risk(%) UK Prospective Diabetes Study Lancet 1998;352:837-53

6 당화혈색소 [ HbA1C] From 0 to 3months = 0 3months FPG(t) dt + 0 3months PPG(t) dt

7 당화혈색소와식후혈당 DCCT: Diabetes 1995;44:

공복혈당과식후혈당의공헌도 100% Contribution(%) 80% 60% 40% 30 70 50 55 60 70 FBS PPG 20% 50 45 40 30 0% <7.3 7.

8 공복혈당과식후혈당의공헌도 100% Contribution(%) 80% 60% 40% FBS PPG 20% % < >10.3 HbA1C range(%) Monnier L, Lapinski H, Colette Diabetes Care 2003;26:881-5

9 Daliy glycemic variation <6.5 L MONNIER, C Colette, G. Dunseath, D. Owens, Diabetes Care Feb;30(2):263-9

10 당화혈색소하루의변화 300 Glycemia(mg/dL) Type 2 diabetes patient with HbA1C = 8 % % Hours Basal + Postprandial Hyperglycemia = 2% of HbA1c

11 식후혈당의의미 Acute glucose fluctucation Duration of PPG Chronic hyperglycaemia

12 식후고혈당과합병증 Factor Mechanism Outcomes Basal hyperglycemia HbA1c (Chronic Hyperglcemia) Excess of glycemia Microangio -pathy PPG Hypoglycemia Glycaemic variablity Oxdative stress Macroangiopath

13 식후혈당의상승기전 1 제 2 형당뇨병발생초기결함으로식후혈당상승주축이되는인슐린분비의초기반응소실 정상인과제 2 형당뇨병환자의혈당증가에따른인슐린분비반응

14 식후혈당의상승기전 2 인슐린저항성으로인한근육으로의포도당섭취및간의포도당생산조절의실패로인한식후혈당상승 글루카곤분비억제의실패

15 근거수준 LEVEL Level 1++ Level 1+ Level 1- TYPE OF EVIDENCE 무작위실험연구 (RCT) 결과들에대한체계적인문헌고찰또는메타분석, 근거기반임상실무가이드라인 설계가잘된메타분석, 체계적인문헌고찰혹은낮은위험도의 bias 를가진 RCT 결과들 메타분석, 체계적인문헌고찰혹은고위험의 bias 를가진 RCT 결과들 Level 2++ 정교화된비무작위유사실험연구로부터얻은근거 Level 2- 조사연구또는질적연구에대한체계적문헌고찰에서얻은연구 Level 3 단순사례연구또는질적연구에서얻은근거 Level 4 전문가의의견또는전문가집단의보고서

study centre,according to the fasting gluco se and 2 h glucose classifications in individuals

16 식후고혈당과합병증 1. 식후고혈당은대혈관합병증의강력한예측인자이다 [Level 1+] Hazard ratios for death (95% CI) adjusted for age, sex, and study centre,according to the fasting gluco se and 2 h glucose classifications in individuals not known as diabetic mg/dl < ~ ~139 Fasting glucose 140 mg/dl < ~199 Postprandal glucose DECODE study group:lancet ;

17 식후고혈당과합병증 1. 식후고혈당은대혈관합병증의강력한예측인자이다 [Level 1+] Relative Risk of Cardiovascular (CV) or Coronary Heart Disease (CHD) Mortality in Patients with Elevated Postprandial Glucose Levels Study Population Duration(y) RR* risk Hoorn Study 2,363 명의네덜란드남성 & 여성 ; 50~ in patients with 2hPG 200 mg/dl vs. normoglycaemic patients Cardiovascular Health Study 4,515 명의미국남성 & 여성 : > in glucose intolerant vs. normoglycaemic patients Paris prospective Study 7,018 명의남성 in patients with 2hPG mg/dl vs. normoglycaemic patients 4.29 in patients with 2hPG 200 mg/dl vs. normoglycaemic patients Rancho Berado study 1,704 명의남성과여성 ; 50~ in womens patients with 2hPG 200mg/dL vs. normoglycaemic patients Baltimore Longitudinal Study 1236 명의남성 13.4 RR Increased in patients with 2hPG 140mg/dL vs.normoglycaemic patients RR : Relative risk /hpg, hours post-glucose challenge.

18 식후고혈당과합병증 1. 식후고혈당은대혈관합병증의강력한예측인자이다 [Level 1+] Incidence of MI and mortality according to categories of the NIDDM Policy Group :11-year follow-up Rate per Rate per * MI Mortality * * MI Mortality > mg/dl > 180 Fasting glucose Postprandal glucose Hanefeld M, Fischer S, Julius U, et al: : the Diabetes Intervention Study. Diabetologia 39(12)1996 ;

analyzed by tertiles of 2-h post-prandial insulin concentrations and 2-h

19 식후고혈당과합병증 2. 식후고혈당은 retinopathy 의위험도와연관성이있다 [Level 2+] Incidence of diabetic retinopathy analyzed by tertiles of 2-h post-prandial insulin concentrations and 2-h post-prandial glucose concentrations Shiraiwa T, Kaneto H, Miyatsuka T, Kato K, Yamamoto K, Kawashima A et al. Biochem Biophys Res Commun 2005; 336(1):

intima 2 h-media thickness mean to possible atherosclerosis risk factors and pp

20 식후고혈당과합병증 3. 식후고혈당은 carotid intima-media thickness (IMT) 와연관성이있다 [Level 2+] Correlations of intima 2 h-media thickness mean to possible atherosclerosis risk factors and pp plasma glucose adjusted by age and gender Hanefeld M, Koehler C, Schaper F, Fuecker K, Henkel E, Temelkova-Kurktschiev T. Atherosclerosis 1999;144(1):

21 식후고혈당과합병증 4. 식후고혈당은 oxidative stress, inflammation 과 endothelial dysfunction 의원인이다 [Level 2+] Linear Correlation Between 24-Hour Urinary Excretion Rates of 8-Iso Prostaglandin F2α (PGF2α) and Mean Amplitude of Glycemic Excursions (MAGE) r = 0.86; P<.001. Monnier, L. et al. JAMA 2006;295:

22 식후고혈당과합병증 5. 식후고혈당은 myocardial blood volume 와 myocardial blood flow 감소와연관이있다 [Level 2+] Scognamiglio, R. et al. Circulation 2005;112:

23 식후고혈당과합병증 6. 식후고혈당은암의위험도와연관성이있다 [Level 2++] Multivariable-Adjusted Relative Risk of Pancreatic Cancer Mortality in the Chicago Heart Association D etection Project in Industry*. Gapstur, S. M. et al. JAMA 2000;283:

24 식후고혈당과합병증 7. 식후고혈당은 2 형노인당뇨병환자에서인지장애와연관성이있다 [Level 2+] repaglinide glibenclamide CV-PPG Changes in hemoglobin A1c (HbA1c), coefficient of variation for postprandial plasma glucose (CV-PPG), and fasting plasma glucose (FPG) over time in drug groups. Abbatecola AM, Rizzo MR, Barbieri M, Grella R, Arciello A, Laieta MT et al. Neurology 2006; 67(2):

25 식후고혈당과합병증 1. 식후고혈당은대혈관합병증의강력한예측인자이다 [Level 1+] 2. 식후고혈당은 retinopathy 의위험도와연관성이있다 [Level 2+] 3. 식후고혈당은 carotid intima-media thickness (IMT) 와연관성이있다 [Level 2+] 4. 식후고혈당은 oxidative stress, inflammation 과 endothelial dysfun ction 의원인이다 [Level 2+] 5. 식후고혈당은 myocardial blood volume 와 myocardial blood flow 감소와연관이있다 [Level 2+] 6. 식후고혈당은암의위험도와연관성이있다 [Level 2++] 7. 식후고혈당은 2 형노인당뇨병환자에서인지장애와연관성이있다 [Level 2+]

26 식후혈당조절목표와어떻게식후고혈당을알수있나. 식후혈당을 140mg/dL 이하로유지하고식후 2 시간혹은 3 시간이후에는정상혈당을유지하도록한다 [Level 2++] 75G 경구당부하후에도혈당이 140mg/dL 한다 [Level 4] 의료기간에서는식후 2 시간혈당도혈장검사로체크하여야한다 [Level 4] 혈장혈당검사를잘사정하기위해 SMBG 를정확하게체크하도록한다 [Level 1++]. 인슐린을사용하는사람에게는하루에적어도세번이상 SMBG 수행하도록하고인슐린을사용하지않더라고 SMBG 는치료방식에맞게자주체크하도록한다 [Level 4]

27 식후고혈당을조절하기위해서는 1. 식후고혈당을조절하기위해서는효과적인식이조절을해야한다. [Level 1+] 2. 식후고혈당을낮추기위해적절한 medication 을사용한다. [Level 1++] - α-glucosidase inhibitors, Amylin analogues, Insulins Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glinides glucagon-like peptide-1 (GLP-1) derivatives

28 어떻게 comment 하시겠습니까? HbA1C(%) MBG HbA1C(%)=8% MBG HbA1C(%)=7% MBG= Mean Blood Glucose

29 식후혈당과고혈당 TEXT Post Prandial HERE Glycemia Fasting Glycemia TEXT HERE Glinides or Acarbose Diet Exercise Sulfonylureas Diet Exercise

30 적절한혈당유지를위해서는 Your text here HbA1C Long-term average glucose level Your text here FFPG Basal glucose level PPG Peak glucose level

31 결론 1. HbA1C 는당뇨병합병증을예방하는데있어중요한인자중의하나이다. 2. HbA1C 만으로는당뇨병합병증을설명할수없다. 3. 당뇨병합병증을설명하는다른요소로식후고혈당및혈당변동성이있다. 4. 식후고혈당은대혈관합병증의강력한예측인자일뿐아니라여러합병증과도연관성이있다. 5. 식후고혈당을빠르게인지할수있는교육이필요하다.

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract