Diabetic Ketoacidosis

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1 Diabetic Ketoacidosis CS Kim, MD, PhD Associate Professor Endocrinology Div., HUMC

2 Case 1 환자 : 여자 20세 주소 : 복통 현병력 : 과거특이질환이없었던환자로내원저녁식사후시작된심와부통증및오심, 구토증상으로응급실로내원하였다. 환자는 2일전운동중넘어져서다리에찰과상을입었다. 증상발생전체중감소, 심계항진, 다음, 다뇨등의증상은없었고, 복용중인약물도없었다. 과거력 : 특이사항없었다. 가족력 : 특이사항없었다. 내원시혈압 105/65 mmhg, 심박수분당 142회, 호흡수분당 28회, 체온 37.8 C 였다. 빈호흡및구강호흡으로혀는말라있는상태였다. 환자는키 165 cm, 체중 61 kg이었다.

Debut DKA 혈당은 485 mg/dl, Na + 135 meq/l, K + 4.0 meq/l였으며, BUN/Cr 32/1.2 mg/dl, 동맥혈검사상 ph 6.

3 Debut DKA 혈당은 485 mg/dl, Na meq/l, K meq/l였으며, BUN/Cr 32/1.2 mg/dl, 동맥혈검사상 ph 6.95, PaO 2 91 mmhg, PaCO mmhg, HCO meq/l, 소변검사결과당 (++++), 케톤 (++++) 소견보였다. 좌측하지에사진과같은소견이관찰되었다.

4 다음중적절치못한치료는? 1. Fluid therapy 2. Insulin therapy 3. Potassium therapy 4. Bicarbonate therapy 5. Antibiotics therapy

5 Management of adult patients with DKA Hyperglycemic Crises in Adult Patients With Diabetes / ADA Statements, Diabetes Care. 2009;32:

6 Bicarbonate therapy in severe diabetic ketoacidosis Severe metabolic acidosis can lead to impaired myocardial contractility, cerebral vasodilatation and coma, and several gastrointestinal complications. A prospective randomized study in 21 patients failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with an admission arterial ph between 6.9 and small studies in a total of 434 patients with DKA support the notion that bicarbonate therapy for DKA offers no advantage in improving cardiac or neurologic functions or in the rate of recovery of hyperglycemia and ketoacidosis. However severe acidosis may lead to a numerous adverse vascular effects, it is recommended that adult patients with a ph < 6.9 should receive sodium bicarbonate. Viallon A, et al., Crit Care Med 1999;27: Mitchell JH, et al., Kidney Int 1972;1: Morris LR, et al., Ann Intern Med 1986;105: Hyperglycemic Crises in Adult Patients With Diabetes / ADA Statements, Diabetes Care. 2009l;32:

7 Case 2 환자 : 여자 22세 주소 : 심계항진, 오심, 구토 현병력 : 본환자는내원하루전심계항진, 오심, 구토증상으로응급실로내원하였다. 환자는 4년전제1형당뇨병을진단받고타병원에서다회인슐린요법을하는중이며몇주부터시작된전신쇠약감이있었다고한다. 최근직장일로과로중이었으며, 점심전인슐린을거르는일이많았다고한다. 최근 1달동안 8kg 정도의체중감소가있었다고한다. 내원시혈압 120/80 mmhg, 심박수분당 142회, 호흡수분당 20회, 체온 37.0 C 였다. 환자의의식은명료하였다. 환자는키 165 cm, 체중 51 kg으로체질량지수 (body mass index, BMI) 는 21.2 kg/m 2 이었다. 경부진찰상중등도의갑상선종대가관찰되었다.

8 혈당은 323 mg/dl, Na meq/l, K meq/l 였으며, BUN/Cr 22/1.1 mg/dl, 동맥혈검사상 ph 7.12, PaO 2 93 mmhg, PaCO 2 24 mmhg, HCO meq/l, 소변검사결과당 (+++), 케톤 (+) 소견보였다. 갑상선기능검사결과 T ng/dl, Free T ng/dl, TSH <0.01 uiu/ml 였다. 한편 Anti-TPO >600.0 IU/mL, Anti-thyroglobulin IU/ml, Anti-TSH receptor 14.2 IU/L 였다.

9 이환자에서 DKA 를유발한가장가능한원인은? 1. Infection 2. Inadequate insulin therapy 3. Thyrotoxicosis 4. Pregnancy 5. Eating disorders

10 Precipitating factors in the development of DKA Noncompliance with insulin therapy Infection Pancreatitis Pregnancy Myocardial infarction, cerebrovascular accident More insulin resistant Psychological problems complicated by eating disorders Drugs Others Components of the comprehensive diabetes evaluation Lab. part A1C, if results not available within past 2 3 months If not performed/available within past year: Fasting lipid profile, including total, LDL, and HDL cholesterol and TG Liver function tests Test for UAE with spot urine albumin-to-creatinine ratio Serum creatinine and calculated GFR Thyroid-stimulating hormone in T1DM, dyslipidemia, or women over age 50 years Standards of Medical Care in Diabetes 2012 / Diabetes Care 2012; 35: S11-63

11 Case 3 환자 : 여자 36세 주소 : 복통 현병력 : 본환자는외래를방문하여수일전부터발생한오심, 구토증상을호소하였다. 환자는 5년전당뇨병을진단받았으나약물삼키기가어려워복용을제대로하지못해왔으며, 3년전부터하루 2회인슐린요법을불규칙적으로해오던중이었다. 최근가정문제로스트레스가많았으며음주를하는경우가많았다고한다. 내원시혈압 115/75 mmhg, 심박수분당 112회, 호흡수분당 20회, 체온 36.5 C 였다. 환자의의식은명료하였다. 환자는키 151 cm, 체중 51 kg이었다.

12 소변검사결과당 (++), 케톤 (+) 소견보였다. HbA1c 10.5%, 공복혈당은 323 mg/dl, Na meq/l, K meq/l였으며, BUN/Cr 17/1.0 mg/dl, ketone positive 였다. 한편 C-peptide 0.40 ng/ml였다. 동맥혈검사상 ph 7.14, PaO 2 92 mmhg, PaCO 2 23 mmhg, HCO meq/l, 5년전당뇨병진단당시 C-peptide는 3.76 ng/ml였으며 3년전시행한 C- peptide는 0.83 ng/ml, anti-gad (glutamic acid decarboxylase) antibody 62.7 U/mL ( 정상범위, 0-9), anti-islet cell Ab는음성이었다. Year C-peptide (ng/ml)

13 진단은? 1. 제2형당뇨병과동반된 DKA 2. 제1형당뇨병과동반된 DKA 3. 전격성당뇨병과동반된 DKA 4. LADA (Latent Autoimmune Diabetes in Adults) 와동반된 DKA 처음진단시어떠한방법으로관리를해야하는가? 1. 인슐린투여 2. 경구용혈당강하제 3. 면역요법

14 Definition of Latent Autoimmune Diabetes in Adults (Immunology of Diabetes Society) Patients should be at least 30 yr of age Positive for at least one of the 4 antibodies commonly found in type 1 diabetic patients (ICAs and autoantibodies to GAD65, IA-2, and insulin) Not treated with insulin within the first 6 months after diagnosis. Therapeutic Interventions for LADA Immunomodulatory therapies Insulin treatment Thiazolidinedione Others Glucagon-like peptide-1 analogs, IL-1 receptor antagonist J Clin Endocrinol Metab 94: , 2009

15 Case 4 환자 : 남자 41세 주소 : 오심, 구토 현병력 : 본환자는내원 3일전부터발생한오심, 구토로내원하였다. 과거특이질환이없었으며몇주전부터감기증상이있었다고한다. 만성적인요통으로인하여일주일전개인의원에서진통주사를투여하였다고한다. 과거력 : 특이사항없었다. 가족력 : 특이사항없었다. 내원시혈압 130/80 mmhg, 심박수분당 96회, 호흡수분당 20회, 체온 37.3 C 였다. 환자는키 169 cm, 체중 75 kg이었다.

16 동맥혈검사상 ph 7.218, PaO mmhg, PaCO 2 26 mmhg, HCO meq/l, 소변검사결과당 (++), 케톤 (+++) 소견보였다. 혈액검사결과 HbA1c 6.7%, 혈당은 628 mg/dl, Na meq/l, K meq/l 였으며, BUN/Cr 32.3/1.1 mg/dl, Osmolality 332 mosm/kg, amylase 250 U/L ( 정상범위, 0-220), Lipase 29 U/L ( 정상범위, 13-26), ketone positive였다. 혈액검사상 WBC 16,500/uL (neutrophil 80.5%), Hb 13.9 g/dl였다. 공복및식후 2시간 C-peptide는각각 0.09, 0.23 ng/ml였다. 혈당이안정화된이후에측정값은각각 0.08, 0.15 ng/ml였다. 한편 anti-gad (glutamic acid decarboxylase) antibody 0.26 U/mL ( 정상범위, 0-9), anti-insulin 4.3% ( 정상범위, 0-7) anti-islet cell Ab는음성이었다

17 진단은? 1. 제2형당뇨병과동반된 DKA 2. 제1형당뇨병과동반된 DKA 3. 전격성당뇨병과동반된 DKA 4. LADA (Latent Autoimmune Diabetes in Adults) 와동반된 DKA 이러한환자에서흔히나타나는선행요인은? 1. 상기도감염 2. 장염 3. 심한스트레스

18 Criteria for definite diagnosis of fulminant type 1 diabetes Fulminant T1DM is confirmed when all the following 3 findings are present. 1. Occurrence of diabetic ketosis or ketoacidosis soon (around 7 days) after the onset of hyperglycaemic symptoms (elevation of urinary or serum ketone bodies at first visit) 2. Plasma glucose level 288 mg/dl (16.0 mmol) and hemoglobin A1c level <8.5% at first visit 3. Urinary C-peptide excretion <10 μg/day or fasting serum C-peptide level <0.3 and <0.5 ng/ml after intravenous glucagon (or meal) load at onset Typical features of fulminant type 1 diabetes Severe hyperglycemia DKA shortly after the onset of diabetic symptoms and normal HbA1c levels A rapid and almost complete destruction of beta cells leads to low C-peptide levels, no remission period, and a complete insulin dependency. High frequency of flu-like symptoms Elevated pancreatic enzymes, pointing perhaps to a primary infection of the exocrine pancreatic tissue Journal of Diabetes Investigation 2010; 1(5): Diabetes Metab Res Rev. 2011;27:959-64

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