[Endocrinology] 성인 발병 제1형 당뇨병과 제2형 당뇨병 구분, Differentiate adult-onset T1DM from T2DM

당뇨병의 원인에 따른 ADA 분류 표를 보면, 당뇨병을 type 1 DM, type 2M, specific types of diabetes, gestatioal DM으로 구분합니다. 그리고 specific types of diabetes의 여러 유형 중에 MODY가 있습니다.

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Etiologic classification of diabetes mellitus

Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)

A. Immune-mediated

B. Idiopathic

Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

Other specific types

A. Genetic defects of beta cell function

Chromosome 12, HNF-1-alpha (MODY3)

Chromosome 7, glucokinase (MODY2)

Chromosome 20, HNF-4-alpha (MODY1)

Chromosome 13, insulin promoter factor-1 (IPF-1; MODY4)

Chromosome 17, HNF-1-beta (MODY5)

Chromosome 2, NeuroD1 (MODY6)

Mitochondrial DNA

Others

B. Genetic defects in insulin action

Type A insulin resistance

Leprechaunism

Rabson-Mendenhall syndrome

Lipoatrophic diabetes

Others

C. Diseases of the exocrine pancreas

Pancreatitis

Trauma/pancreatectomy

Neoplasia

Cystic fibrosis

Hemochromatosis

Fibrocalculous pancreatopathy

Others

D. Endocrinopathies

Acromegaly

Cushing's syndrome

Glucagonoma

Pheochromocytoma

Hyperthyroidism

Somatostatinoma

Aldosteronoma

Others

E. Drug or chemical induced

Vacor

Pentamidine

Nicotinic acid

Glucocorticoids

Thyroid hormone

Diazoxide

Beta-adrenergic agonists

Thiazides

Atypical antipsychotics

Dilantin

Alpha interferon

Others

F. Infections

Congenital rubella

Cytomegalovirus

Others

G. Uncommon forms of immune-mediated diabetes

"Stiff man" syndrome

Anti-insulin receptor antibodies

Others

H. Other genetic syndromes sometimes associated with diabetes

Down syndrome

Klinefelter syndrome

Turner syndrome

Wolfram syndrome

Friederich's ataxia

Huntington's chorea

Laurence-Moon-Biedl syndrome

Myotonic dystrophy

Porphyria

Prader-Willi syndrome

Others

Gestational diabetes mellitus

Patients with any form of diabetes may require insulin treatment at some stage of their disease. Such use of insulin does not, of itself, classify the patient.

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당뇨병은 제1형 당뇨병과 제2형 당뇨병으로 확실히 구분할 수 없는 경우도 있습니다.

LADA, fulminant DM, ketosis prone diabetes, Type 1 DM 관련 항체가 음성인 type 1 DM 등입니다.

성인 발병 제1형 당뇨병과 제2형 당뇨병을 구분하기 위한 노력은 ketosis prone diabetes와 LADA와 같은 일련의 새로운 질병 분류를 낳았습니다. 확실한 진단 기준의 부족은 새로운 범주로서 당뇨병의 새로운 질병 실체를 채택하려는 노력을 위축시킵니다. 또한 제1형당뇨병 환자들이 제2형 당뇨병 환자들의 특징인 인슐린 저항성을 발현할 수 있다는 개념 또한 중요합니다. 특히 제1형 당뇨병 환자들은 (자가항체 양성을 포함하여) 높은 농도의 공복 인슐린 또는 C-peptide, 그러나 소실된 자극 인슐린 분비가 특징인 당뇨병으로 내원하기도 합니다. ​ Efforts to differentiate adult-onset T1DM from T2DM ( Table) have also resulted in a series of proposed new disease classifications, most notably ketosis prone diabetes and latent autoimmune disease of adults . The lack of firm diagnostic criteria dampens enthusiasm for adopting these presumed new disease entities as novel categories for diabetes. It is also important to note that T1DM patients can manifest insulin resistance, a feature most often associated with T2DM. Specifically, T1DM patients (including those who are autoantibody-positive) may present with diabetes characterized by high serum levels of fasting insulin or C-peptide but loss of stimulated insulin secretion. ​ Williams Textbook of Endocrinology, 14th edition

일부 코코시안 소아 (~10%)는 진단 당시 (고혈당 발병 당시)에 T1DM 관련 자가항체가 없습니다. 이것은 그와 같은 환자들이 진단 당시에 자가 항체 표현을 못하는 것인지 (아니면 적어도 혈액검사로 이것을 발견하지 못하는지) 아니면 제1형 당뇨병 진단이 정확한 것인지에 대한 의문을 제기합니다. 자가항체를 소실한 것이냐 다른 형태의 당뇨병이 존재한 것인가에 대한 것도 또한 확실히 하기 어렵습니다. 그 이유는 많은 환자들인 제1형 당뇨병 감수성과 관련된 HLA alleles을 가지고 있고, 인슐린 저항성이 없으며, DKA가 존재하고, 진단 당시에 C-peptide 분비 기능을 잃기 때문입니다. 적절한 검사 검사가 이루어진다면, 그와 같은 환자들을 T1DM patients negative for T1DM-associated autoantibodies로 인식하는 것이 적절한 진단일 수 있습니다. ​ As noted previously, some Caucasian children (∼10%) are devoid of a T1DM-associated autoantibody at disease diagnosis (i.e., time of hyperglycemic onset), raising questions as to whether such persons lost their autoantibody expression (or at least the ability to detect it with laboratory testing) by the time of diagnosis, or whether a diagnosis of T1DM is accurate. The notion of autoantibody loss versus the presence of a different form of diabetes is also difficult to ascertain because many have HLA alleles associated with susceptibility for T1DM; are not insulin resistant; present with DKA; and, with time, lose their C-peptide secretion. With appropriate laboratory testing, notation of such persons as T1DM patients negative for T1DM-associated autoantibodies can be an appropriate diagnosis. This said, advances in understanding the heretofore underappreciated disease classifications of monogenic diabetes, including those of maturity onset of diabetes in youth, warrant genetic testing of diabetes cases diagnosed in the very young (i.e., <1 year of age). ​ Williams Textbook of Endocrinology, 14th edition

더 이상 IDDM 또는 NIDDM이라는 용어를 사용하지 않으며 그 이유에 대한 설명입니다.

Two features of the current classification of DM merit emphasis from previous classifications. First, the terms insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) are no longer used. Because many individuals with type 2 DM eventually require insulin treatment for control of glycemia, the use of the term NIDDM generated considerable confusion. A second difference is that age or treatment modality is not a criterion. Although type 1 DM most commonly develops before the age of 30, autoimmunity against beta cells can develop at any age. It is estimated that between 5 and 10% of individuals who develop DM after age 30 have type 1 DM. Although type 2 DM more typically develops with increasing age, it is now being diagnosed more frequently in children and young adults, particularly in obese adolescents.

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그리고 fulminant DM 보고가 일본에서 있었다는 내용이 있습니다.

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DISTINGUISHING TYPE 1 FROM TYPE 2 DIABETES ​ 제1형 당뇨병과 비전형 제2형 당뇨병을 구분하는 것은 때때로 어렵습니다. 많은 제2형 당뇨병 환자들이 시간이 지나면서 베타세포 기능을 잃고 혈당 조절을 위해 인슐린을 필요로 합니다 따라서 인슐린 필요성이 제1형 당뇨병과 제2형 당뇨병을 구분시켜 주지 못합니다. 당뇨병성 케톤산증이 완전한 인슐린 결핍상태에서 발생할 수 있고 제2형 당뇨병의 특징이 아닌 것으로 알려져 있지만, 특정 상황 (심각한 감염 또는 질환)에서 제2형 당뇨병의 일부 환자들이 DKA를 나타내므로 케톤산증이 제 1형 당뇨병인지 아니면 인슐린 치료를 장기적으로 필요로 한 것인지 판별하는 절대적인 표지는 아닙니다. It is occasionally difficult to distinguish between type 1 and atypical presentations of type 2 diabetes. Patients with type 1 diabetes have an absolute requirement for insulin therapy. However, many patients with type 2 diabetes lose beta cell function over time and require insulin for glucose control. Thus, need for insulin per se does not distinguish between type 1 and type 2 diabetes. While it is known that diabetic ketoacidosis (DKA) can occur in the presence of complete insulin deficiency and it is not a typical feature of type 2 diabetes, some patients with type 2 diabetes develop DKA under certain circumstances (usually severe infection or other illness). Thus, ketoacidosis cannot be relied upon as an absolute indicator that the patient has type 1 diabetes or that long-term insulin therapy will be required. ​ 게다가 제1형 당뇨병 환자들을 제2형 당뇨병 환자의 병태생리학적 요소들을 동시에 가지고 있기도 합니다. 과거에는 제1형 당뇨병 환자들의 혈당조절이 잘 되었었고 그로 인하여 이 환자들이 체중이 늘지 않았으나 요즈음은 제1형 당뇨병 환자들도 적극적인 혈당 조절로 인하여 고혈당으로 인한 체중 감량이 없어 약 20-30% 환자에서 과체중 또는 비만합니다. 인슐린 저항성과 제2형 당뇨병 환자들의 다른 특징들이 제1형 당뇨병 환자들에서 나타나기도 하며 특히 제2형 당뇨병 환자 가족력이 있는 환자에서 그렇습니다. In addition, patients with type 1 diabetes may coincidentally have pathophysiologic elements of type 2 diabetes. In the past, poor metabolic control of type 1 diabetes prevented most of these patients from gaining weight. Intensive therapy now commonly used to manage type 1 diabetes has resulted in approximately 20 to 30 percent of type 1 diabetic patients becoming overweight or obese. Insulin resistance and other features of type 2 diabetes may be exhibited in overweight patients with type 1 diabetes, especially those who also have a family history of type 2 diabetes. ​ 제2형 당뇨병으로 추정되는 환자에서 glutamic acid decarboxylase (GAD), islet cell, insulin, the tyrosine phosphatases (insulinoma-associated protein 2 [IA-2] and IA-2 beta), zinc transporter (ZnT8)에 대한 항체의 존재는 제1형 당뇨병이 있을 수 있고 인슐린 치료를 필요로 할 가능성이 더 높은 환자를 식별시켜 줍니다. The presence of antibodies to glutamic acid decarboxylase (GAD), islet cell, insulin, the tyrosine phosphatases (insulinoma-associated protein 2 [IA-2] and IA-2 beta), and zinc transporter (ZnT8) in patients with presumed type 2 diabetes can identify patients who may have type 1 diabetes (latent autoimmune diabetes in adults [LADA]) and are more likely to require insulin. Based upon a review of clinical features in 102 adult diabetic patients who did not initially require insulin but who were positive for anti-GAD antibodies, a screening tool was developed to identify adult patients with newly diagnosed diabetes who should be considered for antibody testing. These features included: age of onset <50 years, acute symptoms, body mass index (BMI) <25 kg/m2, and personal or family history of autoimmune disease. The presence of two or more criteria had a 90 percent sensitivity and 71 percent specificity for identifying patients positive for anti-GAD antibodies. ​ 내원시 제1형 당뇨병 또는 제2형 당뇨병 진단이 불확실 할 때 자가항체를 측정합니다 . We measure autoantibodies when the diagnosis of type 1 or type 2 diabetes is uncertain by clinical presentation: ● Thin patient with poor response to initial therapy with sulfonylureas or metformin ● Personal or family history of autoimmune disease ● Overweight or obese children or adolescents presenting with apparent type 2 diabetes, who actually may have an early presentation of type 1 diabetes ​ 2주 이상 인슐린 치료를 받은 환자에서는 인슐린 자가항체는 측정해서는 안되는데 인슐린 치료가 인슐린 항체를 생성하기 때문입니다. 1가지 이상의 자가항제가 양성이라면, 특히 2가 이상이 양성, 환자는 제1형 당뇨병이 있는 것으로 추정하고 식이와 경구 혈당강하제로 혈당 조절이 되지 않으면 인슐린 치료를 시작해야 합니다. 게다가 제1형 당뇨병이 발생할 초기 단계에 적극적 인슐린 치료는 베타세포기능을 지연시킵니다. Measuring more than one antibody will increase the likelihood of a positive value, but it is also more costly. Two (ie, islet cell and GAD65) or three (insulin, GAD65, and IA-2 or GAD65, IA-2, and ZnT8) antibodies can be measured. Insulin antibodies should not be measured if the patient has received insulin therapy for ≥2 weeks, because this will generate insulin antibodies. If one or more of the antibodies is present, and especially if two or more are positive, the patient should be presumed to have type 1 diabetes and should be treated with insulin replacement therapy, as these patients respond poorly to diet and oral hypoglycemic drug therapy. In addition, during early stages in the development of type 1 diabetes, intensive insulin therapy prolongs beta cell function. ​ 케톤산증의 위험이 있는 경우 제1형 당뇨병 또는 제2형 당뇨병 여부와 상관 없이 인슐린 치료를 시작해야 하는데 그와 같은 경우는 체중 감소 또는 고혈당에서 탈수 상황 또는 케톤뇨나 산증과 같은 케톤산증의 증거가 있는 경우에 그렇습니다. Given the risk of ketoacidosis, insulin should also be started in any patient, regardless of whether they are thought to have type 1 or type 2 diabetes, who is catabolic (weight loss or dehydration in the setting of hyperglycemia), or who has evidence of increased ketogenesis (ketonuria or acidosis). ​ UpToDate 2020.08.02

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REF. Williams Textbook of Endocrinology, 14th edition

Harrsion's Internal Medicine, 20th edition

UpToDate 2020.08.02