본발표와관련된이해관계 없음 대한당뇨병학회학술위원회

Clinical Characteristics of latent autoimmune diabetes in adults in Korea 경희의대내분비대사내과 이상열

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

너무단순한건아닐까? 2 형당뇨병임상연구센터 (KNDP). 한국인을위한당뇨병임상진료지침 2015.

Considerable overlaps between the phenotypes of T1DM and T2DM Holt RIG, et al. Textbook of Diabetes,4 th ed.

Definition of LADA No unified criteria exist for LADA but three criteria have often been used - GAD antibody (+) - 35 yrs at diagnosis - no insulin therapy in the first 6 12 mo. after Dx. Tuomi T et al. Lancet 383: 1084-1094, 2014.

A definition of LADA WHO classify LADA a Type 1 diabetes. Study Age Antibody Ketoacidosis[K] Time to insulin Agardh 2005 30-70 GAD - Not requiring insulin Cabrera-Rode 2002 - GAD and ICA No K at 1 month - Kobayasahi 1996 - ICA No K - Maruyama 2003 - GAD No K No insulin for 6 months Zhou 2005 25+ GAD No K within 6 months - Fourlanos 2006 30-75 GAD - No insulin for 6 months Weslley Souza Rosario 2005 35+ GAD - No insulin for 1 year Vatay 2002 35+ GAD or ICA - No insulin for 6 months Isomaa 1999 35+ GAD No K - Yang 2005 25+ GAD No K for 6 months -

Eponyms for autoimmune diabetes in adults Eponym Reference Latent type 1 diabetes Groop LC, et al. Diabetes, 1986. Latent autoimmune diabetes in adults (LADA) Tuomi T, et al. Diabetes, 1993. Slowly progressive IDDM (SPIDDM) Kobayashi, T et al. Diabetes Care, 1993. Slow-onset IDDM Lohmann, T et al. Diabetes Care, 1997. Slowly progressive type 1 diabetes Seissler J, et al. Diabetologia, 1998. Type 1 1/2 diabetes Juneja R, et al. Autoimmunity, 1999. LADY-like Lohmann T, et al. Diabetes Care, 2000. Autoimmune diabetes not requiring insulin at diagnosis Pozzilli P, et al. Diabetes Care, 2001. LADA type 1 and type 2 Lohmann T, et al. Diabetologia, 2001. Slowly progressive β-cell failure Borg H, et al. JCEM, 2001. Slowly progressive adult-onset type 1 diabetes Hosszufalusi N, et al. Diabetes Care, 2003. Antibody-positive phenotypic type 2 diabetes with obesity Palmer JP, et al. Diabetes Care, 2003. Latent autoimmune diabetes in children (LADC) Aycan Z, et al. J Pediatr Endo Metab, 2004

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

Global Epidemiology Tuomi T et al. Lancet 383: 1084-1094, 2014.

Epidemiology in Asia n Ethnicity Age (yr) Age at onset (yr) Duration (yr) BMI (kg/m 2 ) GADA (+) (n, %) ICA (+) (n, %) Ko et al. 140 T1 and T2 Asian 30.8 ±5.8 25.9 ±7.2 4.6 ±4.7 25.6 ±5.1 17 (12.1%) - Thai et al. 168 T2 Asian 40.6 ±15.3 38.4 ±15.3 2.3 ±4.4 24.4 ±4.0 27 (16.1%) 8 (4.8%) Tsuruoka et al. 680 T2 Asian 46.9 ±19.49 - - - 29 (4.3%) - Park et al. 121 New T2DM Asian 57.4 ±12.5 - - 25.2 ±3.8 2 (1.7%) - Huang et al. 40 T2 Asian 36.9 ±3.4 34.4 ±2.5 2.4 ±1.8 24.6 ±3.7 2 (5.0%) 1 (2.5%) Modified Huang C.-Y. et al. Journal of Internal Medicine of Taiwan 15:12-18, 2004

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

Gender distribution 70 60 * 50 40 30 20 Female Male 10 0 Ab positive Ab negative * p=0.029 vs Ab negative Genovese S, Pozzilli P et al. Eur J Endocrinol 154:441-7, 2006

HbA1c values in screened patients according to antibody positivity 12 * 10 8 % 6 4 2 0 Ab positive (n=68) Ab negative (n=857) * p=0.008 vs Ab negative Genovese S, Pozzilli P et al. Eur J Endocrinol 154:441-7, 2006

Body Mass Index in screened patients according to antibody positivity BMI 34 32 30 28 26 24 22 20 * ** >2 Abs 1 Ab No Ab (n=21) (n=68) (n=857) ** p=0.024 vs 1 Ab * p<0.001 vs No Ab Genovese S, Pozzilli P et al. Eur J Endocrinol 154:441-7, 2006

Prevalence of patients treated with insulin according to antibody positivity 100 80 60 % 40 20 ** * 0 >2 abs 1 ab No ab ** p=0.036 vs 1 Ab * p<0.001 vs No Ab Genovese S, Pozzilli P et al. Eur J Endocrinol 154:441-7, 2006

DRB1-DQB1 association is age-related in LADA Prevalence of the DR3/DR4-DQB1*0302 combination according to age of diagnosis in LADA (n= 255) and in controls (n= 200): 100 DR3/DR4-DQB1*0302 others 80 60 p<0.006 2 trend 40 20 0 25-34 35-44 45-54 55-65 Controls Age at diagnosis (years) UKPDS 43: Horton et al, 1999

β-cell function in LADA Stenström G et al. Diabetes 54: S68-S72, 2005.

LADA, truly Latent? Though not as severe as in classic type 1 diabetic patients, LADA patients have an early impairment in β- cell function. LADA is not a latent form of autoimmune diabetes. Hence, we favor the use of ADA (autoimmune diabetes in adults) rather than LADA for this type of patient in the future. Stenström G et al. Diabetes 54: S68-S72, 2005.

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

Son HS, et al. Korean J Med 40: 670-676, 1991.

Park M. et al. J Kor Diabetes Assoc 30: 190-197, 2006.

Treatment Modality Park M. et al. J Kor Diabetes Assoc 30: 190-197, 2006.

Park YS et al. Diabetes Care 19: 241-245, 1996.

Lee SH et al. DRCP 83: e62-e65, 2009.

Roh M, et al. Acta Diabetol 50: 129-134, 2013.

5.2% Roh M, et al. Acta Diabetol 50: 129-134, 2013.

Roh M, et al. Acta Diabetol 50: 129-134, 2013.

Park YS et al. DMRR 27: 975-979, 2011.

Insulin dependency and Auto-Ab titer Park YS et al. DMRR 27: 975-979, 2011.

한국인특성? 비비만형 phenotype, 큰차이없음 Prevalence of Autoantibodies Insulin dependency Prevalence 증가예상

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

General treatment strategy Diet treatment in LADA is similar Obese LADA patients benefit calorie restriction and increased physical activity. Issues from glibenclamide promote the autoimmune process?? Thiazolidinediones seem to prevent diabetes Stenström G et al. Diabetes 54: S68-S72, 2005.

General treatment strategy Metformin is probably useful Esp. in obese patients. Insulin therapy is the treatment of choice. β-cell function is impaired at diagnosis of LADA patients, irrespective of the clinical phenotype. Early insulin treatment may improve β-cell dysfunction no reason to postpone the commencement of insulin Stenström G et al. Diabetes 54: S68-S72, 2005.

Approach to the treatment of the Asian adolescent with diabetes Park YS. J Korean Diabetes 15: 190-195, 2014.

Antigen-specific intervention trials in T1DM Holt RIG, et al. Textbook of Diabetes,4 th ed.

순서 정의 역학 병태생리 한국인데이터 치료 생각해볼문제 요약, 정리

인슐린분비감소가당뇨병발생에가장중요 Korean Data (n=322) Rhee SY et al. DRCP 76: 397-403, 2007.

SS Schwartz, et al. Diabetes Care 39: 179-186, 2016.

Dysfunctional β-cell: the final common denominator in all DM SS Schwartz, et al. Diabetes Care 39: 179-186, 2016.

Spectrum of factors associated with different forms of DM SS Schwartz, et al. Diabetes Care 39: 179-186, 2016.

Egregious Eleven SS Schwartz, et al. Diabetes Care 39: 179-186, 2016.

Targeted Treatment Strategy SS Schwartz, et al. Diabetes Care 39: 179-186, 2016.

요약및정리 정의 역학 병태생리 한국인데이터 치료 생각해볼문제

경청해주셔서감사합니다