Classification
2021 vs 2022: 新增 T1DM 特徵
1 型糖尿病和 2 型糖尿病是異質性疾病，其臨床表現和疾病進展可能有很大差異。分類對於確定治療很重要，但有些人在診斷時無法明確分類為 1 型或 2 型糖尿病。僅在成人中發生的 2 型糖尿病和僅在兒童中發生的 1 型糖尿病的傳統範例不再準確，因為這兩種疾病都發生在兩個年齡組中。 1 型糖尿病兒童通常出現多尿/煩渴的標誌性症狀，大約三分之一 一半的兒童出現糖尿病酮症酸中毒 (DKA) (2)。 1 型糖尿病的發病在成人中可能更加多變；他們可能不會出現在兒童中看到的典型症狀，並且可能會暫時緩解對胰島素的需求 (3-5)。對鑑別 1 型糖尿病最有用的特徵包括診斷時年齡較小（<35 歲）、BMI 較低（<25 kg/m2）、無意體重減輕、酮症酸中毒和葡萄糖 >360 mg/dL（20 mmol/L）在演示文稿 (8) 中. 偶爾，2 型糖尿病患者可能會出現 DKA (6)，尤其是少數族裔和種族 (7)。對於提供者來說，重要的是要認識到糖尿病類型的分類在就診時並不總是簡單明了，而且誤診很常見（例如，患有 1 型糖尿病的成人被誤診為患有 2 型糖尿病；患有成年發病的年輕糖尿病患者 [MODY] ] 誤診為 1 型糖尿病等）。儘管所有年齡組在發病時都可能難以區分糖尿病類型，但隨著時間的推移，β細胞缺乏症患者的診斷會變得更加明顯。
Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical presentation and disease progression may vary considerably. Classification is important for determining therapy, but some individuals cannot be clearly classified as having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms of type 2 diabetes occurring only in adults and type 1 diabetes only in children are no longer accurate, as both diseases occur in both age-groups. Children with type 1 diabetes typically often present with the hallmark symptoms of polyuria/polydipsia, and approximately one-thirdhalf present with diabetic ketoacidosis (DKA) (2). The onset of type 1 diabetes may be more variable in adults; they may not present with the classic symptoms seen in children and may experience temporary remission from the need for insulin (3–5). The features most useful in discrimination of type 1 diabetes include younger age at diagnosis (<35 years) with lower BMI (<25 kg/m2), unintentional weight loss, ketoacidosis, and glucose >360 mg/dL (20 mmol/L) at presentation (8). Occasionally, patients with type 2 diabetes may present with DKA (6), particularly ethnic and racial minorities (7). It is important for the provider to realize that classification of diabetes type is not always straightforward at presentation and that misdiagnosis is common (e.g., adults with type 1 diabetes misdiagnosed as having type 2 diabetes; individuals with maturity-onset diabetes of the young [MODY] misdiagnosed as having type 1 diabetes, etc.). Although difficulties in distinguishing diabetes type may occur in all age-groups at onset, the diagnosis becomes more obvious over time in people with β-cell deficiency.
2021 vs 2022:
1 型糖尿病的潛在病理生理學特徵比 2 型糖尿病更準確。現在從對 1 型糖尿病患者一級親屬的前瞻性研究中可以清楚地看出，兩種或多種胰島自身抗體的持續存在幾乎是臨床高血糖和糖尿病的一定預測因素。進展速度取決於首次檢測自身抗體的年齡、自身抗體數量、自身抗體特異性和自身抗體滴度。葡萄糖和 A1C 水平在糖尿病臨床發作之前就升高了，這使得在 DKA 發作之前就可以進行診斷。可以確定 1 型糖尿病的三個不同階段（表 2.1），並作為未來研究和監管決策的框架 (8,10)。關於成人發病的緩慢進展性自身免疫性糖尿病是否應稱為成人潛伏性自身免疫性糖尿病（LADA）或 1 型糖尿病，存在爭議。檢測 LADA 的臨床重點是意識到成人可能會發生緩慢的自身免疫性 β 細胞破壞，從而導致長期的邊緣胰島素分泌能力。就這一分類而言，由自身免疫性 β 細胞破壞介導的所有形式的糖尿病都包括在 1 型糖尿病的標題下。 LADA 一詞的使用在臨床實踐中很常見並且可以接受，並且具有提高對可能發生明顯自身進行性免疫性 β 細胞破壞的成年人群體的認識的實際影響 (11)，從而在血糖控製或發育惡化之前加速胰島素的啟動DKA (4,12)。
Characterization of the underlying pathophysiology is more precisely developed in type 1 diabetes than in type 2 diabetes. It is now clear from prospective studies of first-degree relatives of patients with type 1 diabetes that the persistent presence of two or more islet autoantibodies is a near certain predictor of clinical hyperglycemia and diabetes. The rate of progression is dependent on the age at first detection of autoantibody, number of autoantibodies, autoantibody specificity, and autoantibody titer. Glucose and A1C levels rise well before the clinical onset of diabetes, making diagnosis feasible well before the onset of DKA. Three distinct stages of type 1 diabetes can be identified (Table 2.1) and serve as a framework for future research and regulatory decision-making (8,10). There is debate as to whether slowly progressive autoimmune diabetes with an adult onset should be termed latent autoimmune diabetes in adults (LADA) or type 1 diabetes. The clinical priority with detection of LADA is awareness that slow autoimmune β-cell destruction can occur in adults leading to a long duration of marginal insulin secretory capacity. For the purpose of this classification, all forms of diabetes mediated by autoimmune β-cell destruction are included under the rubric of type 1 diabetes. Use of the term LADA is common and acceptable in clinical practice and has the practical impact of heightening awareness of a population of adults likely to develop overthave progressive autoimmune β-cell destruction (11), thus accelerating insulin initiation prior to deterioration of glucose control or development of DKA (4,12).
Diagnostic Tests for Diabetes
1。A1c
2022: 新增 Prepare for OGTT
2.4 在作為糖尿病篩查的口服葡萄糖耐量試驗前 3 天，應確保攝入足夠的碳水化合物（至少 150 克/天）。 A
2.4 Adequate carbohydrate intake (at least 150 g/day) should be assured for 3 days prior to oral glucose tolerance testing as a screen for diabetes. A
2021 vs 2022:
A1C 測試應使用經 NGSP (www.ngsp.org) 認證並標準化或可追溯至 DCCT 參考測定的方法進行。 儘管即時 A1C 檢測可能已獲得美國 FDA 的 NGSP 認證和批准，可用於在臨床實驗室改進修正案 (CLIA) 監管和 CLIA 豁免的環境中監測糖尿病患者的血糖控制 ，只有那些也被 FDA 批准用於糖尿病診斷的即時 A1C 測定才應該用於此目的，並且只能在它們被批准的臨床環境中使用 尚未對床旁 A1C （Point-of-care A1C ）檢測進行糖尿病診斷的前瞻性研究，因此不推薦用於糖尿病診斷；如果使用，則應使用經過驗證的措施對其進行確認。在美國，即時 A1C 是一種限制 CLIA 監管的實驗室測試。
The A1C test should be performed using a method that is certified by the NGSP (www.ngsp.org) and standardized or traceable to the Diabetes Control and Complications Trial (DCCT) reference assay. Although point-of-care A1C assays may be NGSP certified and cleared by the U.S. Food and Drug Administration (FDA) for use in monitoring glycemic control in people with diabetes in both Clinical Laboratory Improvement Amendments (CLIA)-regulated and CLIA-waived settings, only those point-of-care A1C assays that are also cleared by the FDA for use in the diagnosis of diabetes should be used for this purpose, and only in the clinical settings for which they are cleared. Point-of-care A1C assays have not been prospectively studied for the diagnosis of diabetes and are not recommended for diabetes diagnosis; if used, they should be confirmed with a validated measure. In the U.S., point-of-care A1C is a laboratory test that limits CLIA regulation.
2021 vs 2022:
與 FPG 和 OGTT 相比，A1C 具有幾個優勢，包括更方便（不需要禁食）、更高的分析前穩定性以及在壓力、飲食變化或疾病期間的日常乾擾更少。 然而，這些優勢可能會被指定切割點的 A1C 敏感性較低、成本較高、發展中國家某些地區 A1C 檢測的可用性有限以及某些個體的 A1C 與平均血糖之間的不完美相關性所抵消。 根據國家健康和營養檢查調查 (NHANES)，A1C 測試的診斷閾值≥6.5% (48 mmol/mol)，僅診斷出使用 A1C、FPG 或 2 小時 PG 共同確定的糖尿病病例的 30% ) 數據 (22)。儘管 A1C 存在這些限制，但國際專家委員會在 2009 年將 A1C 添加到診斷標準中，目的是增加篩查
A1C has several advantages compared with FPG and OGTT, including greater convenience (fasting not required), greater preanalytical stability, and less day-to-day perturbations during stress, changes in diet, or illness. However, these advantages may be offset by the lower sensitivity of A1C at the designated cut point, greater cost, limited availability of A1C testing in certain regions of the developing world, and the imperfect correlation between A1C and average glucose in certain individuals. The A1C test, with a diagnostic threshold of ≥6.5% (48 mmol/mol), diagnoses only 30% of the diabetes cases identified collectively using A1C, FPG, or 2-h PG, according to National Health and Nutrition Examination Survey (NHANES) data (22).Despite these limitations with A1C, in 2009 the International Expert Committee added A1C to the diagnostic criteria with the goal of increased screening (21). 2022增
2。Age
2021 vs 2022: 年齡和性別與男性 A1C 升高 in Taiwan
對於任何給定的平均血糖水平，具有常見血紅蛋白變體 HbS 雜合子的非裔美國人與沒有該特徵的人相比，A1C 可能降低約 0.3% (26)。 另一種遺傳變異，X-連鎖葡萄糖-6-磷酸脫氫酶 G202A，由 11% 的非洲裔美國人攜帶，與沒有該變異的人相比，純合子男性和純合子女性的 A1C 降低約 0.8% 和 0.7%。 27)。例如，在坦桑尼亞，HIV 感染者極有可能發生血紅蛋白病，A1C 可能低於基於葡萄糖的預期，從而限制了其在篩查中的用途 (35)。
即使沒有血紅蛋白變異體，A1C 水平也可能隨種族/民族而變化，與血糖無關 (28-30)。例如，非洲裔美國人的 A1C 水平可能高於非西班牙裔白人，空腹和葡萄糖負荷血糖水平相似 (31)。儘管存在相互矛盾的數據，但非洲裔美國人的果糖胺和糖化白蛋白水平也可能較高，而 1,5-脫水葡萄糖醇水平較低，這表明他們的血糖負擔（尤其是餐後）可能更高 (32,33)。類似地，當通過連續血糖監測進行測量時，對於給定的平均葡萄糖濃度，A1C 水平可能更高 (34)。最近一份針對非洲裔加勒比人的報告顯示，A1C 低於葡萄糖水平的預測值 (43). 儘管存在這些和其他報導的差異，但 A1C 與並發症風險的關聯在非洲裔美國人和非西班牙裔白人中似乎相似 (35,36)。據報導，在台灣人群中，年齡和性別與男性 A1C 升高有關（46）；目前尚不清楚這一發現的臨床意義。
(Ref 46: 男性和女性的 HbA1c 水平存在顯著差異; 在 30-39 歲和 40-49 歲年齡組中，男性的HbA1c明顯高於女性)
African Americans heterozygous for the common hemoglobin variant HbS may have, for any given level of mean glycemia, lower A1C by about 0.3% compared with those without the trait (26). Another genetic variant, X-linked glucose-6-phosphate dehydrogenase G202A, carried by 11% of African Americans, was associated with a decrease in A1C of about 0.8% in homozygous men and 0.7% in homozygous women compared with those without the variant (27). For example, in Tanzania, where there is a high likelihood of hemoglobinopathies in people with HIV, A1C may be lower than expected based on glucose, limiting its usefulness for screening (35).
Even in the absence of hemoglobin variants, A1C levels may vary with race/ethnicity independently of glycemia (28–30). For example, African Americans may have higher A1C levels than non-Hispanic Whites with similar fasting and postglucose load glucose levels (31). Though conflicting data exists, African Americans may also have higher levels of fructosamine and glycated albumin and lower levels of 1,5-anhydroglucitol, suggesting that their glycemic burden (particularly postprandially) may be higher (32,33). Similarly, A1C levels may be higher for a given mean glucose concentration when measured with continuous glucose monitoring (34). A recent report in Afro-Caribbean people demonstrated a lower A1C than predicted by glucose levels (43). Despite these and other reported differences, the association of A1C with risk for complications appears to be similar in African Americans and non-Hispanic Whites (35,36). In the Taiwanese population, age and sex have been reported to be associated with increased A1C in men (46); the clinical implications of this finding are unclear at this time.
Confirming the Diagnosis
2021 vs 2022: prepare OGTT 的重要性
每個篩查測試都具有分析前和分析可變性，因此當重複測試產生異常結果（即高於診斷閾值）時，可能會產生低於診斷臨界點的值。 如果葡萄糖樣品保持在室溫並且沒有立即離心，這種情況很可能發生在 FPG 和 2-h PG 中。 由於分析前可能存在變異性，因此在提取血漿葡萄糖樣品後立即對其進行旋轉和分離至關重要。 如果患者的檢測結果接近診斷閾值，醫療保健專業人員應與患者討論體徵和症狀，並在 3-6 個月內重複檢測。
人們應該在口服葡萄糖耐量測試前 3 天食用至少 150 克碳水化合物的混合飲食 (55-57)。 禁食和限制碳水化合物可能會在口服葡萄糖挑戰時錯誤地升高葡萄糖水平。
Each of the screening tests has preanalytic and analytic variability, so it is possible that a test yielding an abnormal result (i.e., above the diagnostic threshold), when repeated, will produce a value below the diagnostic cut point. This scenario is likely for FPG and 2-h PG if the glucose samples remain at room temperature and are not centrifuged promptly. Because of the potential for preanalytic variability, it is critical that samples for plasma glucose be spun and separated immediately after they are drawn. If patients have test results near the margins of the diagnostic threshold, the health care professional should discuss signs and symptoms with the patient and repeat the test in 3–6 months.
People should consume a mixed diet with at least 150 g of carbohydrate on the 3 days prior to oral glucose tolerance testing (55–57). Fasting and carbohydrate restriction can falsely elevate glucose level with an oral glucose challenge. (2022增）
Type 1 DiabetesRecommendations
2021 vs 2022 要驗 4 種抗體； Ab 不只作為診斷； 也作為干預或篩檢工具
2.4 目前建議在研究試驗中使用一組胰島自身抗體 使用檢測胰島素、 GAD、胰島抗原 2 或鋅轉運蛋白 8 自身抗體篩查 1 型糖尿病風險，或者可以作為 1 型糖尿病先證者的一級家庭成員的選擇。 B
2.4 Screening for presymptomatic type 1 diabetes risk with a panel of islet autoantibodies using screening tests that detect autoantibodies to insulin, glutamic acid decarboxylase (GAD), islet antigen 2, or zinc transporter 8 is currently recommended in the setting of a research trial or can be offered considered as an option for first-degree family members of a proband with type 1 diabetes. B
2.5 多種胰島自身抗體的產生和持續存在是臨床糖尿病的危險因素，可作為臨床試驗干預或篩查 Stage 2 第 1 型糖尿病的指徵。 B
2.5 Persistence of Development of and persistence of multiple islet autoantibodies is a risk factor for clinical diabetes and may serve as an indication for intervention in the setting of a clinical trial or screening for stage 2 type 1 diabetes. B
Immune-Mediated Diabetes
2021 vs 2022: T1DM和 DQB1有關, 可以篩檢易感族群
這種形式，以前稱為“胰島素依賴型糖尿病”或“幼年型糖尿病”，佔糖尿病的 5-10%，是由於細胞介導的胰腺 β 細胞自身免疫性破壞所致。自身免疫標誌物包括胰島細胞自身抗體和針對 GAD (GAD65)、胰島素、酪氨酸磷酸酶 IA-2 和 IA-2β 以及鋅轉運蛋白 8 (ZnT8) 的自身抗體。正在進行大量臨床研究，以測試在有胰島自身免疫證據的患者中預防 1 型糖尿病的各種方法（www.clinicaltrials.gov 和 www.trialnet.org/our-research/prevention-studies）(12,45–49) . 1 型糖尿病的第 1 階段定義為存在兩種或多種這些自身免疫標誌物。該疾病與 DQA 和 DQB 基因有很強的 HLA 關聯。與 DQB1 和 DRB1 單倍型有關，並且在一些研究中使用基因篩查來識別高危人群。這些基因中的特定等位基因可以是易感性的或保護性的（表 2.1）。
This form, previously called “insulin-dependent diabetes” or “juvenile-onset diabetes,” accounts for 5–10% of diabetes and is due to cellular-mediated autoimmune destruction of the pancreatic β-cells. Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (GAD65), insulin, the tyrosine phosphatases IA-2 and IA-2β, and zinc transporter 8 (ZnT8). Numerous clinical studies are being conducted to test various methods of preventing type 1 diabetes in those with evidence of islet autoimmunity (www.clinicaltrials.gov and www.trialnet.org/our-research/prevention-studies) (12,45–49). Stage 1 of type 1 diabetes is defined by the presence of two or more of these autoimmune markers. The disease has strong HLA associations, with linkage to the DQA and DQB DQB1 and DRB1 haplotypes, and genetic screening has been used in some research studies to identify high risk populations. Specific alleles in these genes can be either predisposing or protective (Table 2.1). These HLA-DR/DQ alleles can be either predisposing or protective (Table 2.1). There are important genetic considerations, as most of the mutations that cause diabetes are dominantly inherited. The importance of genetic testing is in the genetic counseling that follows. Some mutations are associated with other conditions, which then may prompt additional screenings.
2021 vs 2022: 更多兒童和青少年T1DM in US
β 細胞破壞的速度變化很大，在某些個體（主要是特別是但不限於嬰兒和兒童）中較快，而在其他個體（主要是但不限於成人）中較慢（50）。兒童和青少年可能通常以 DKA 作為該疾病的首發表現, 並且在過去 20 年中，美國的發病率急劇增加 (2-4)。其他人有適度的空腹高血糖，可迅速轉變為嚴重的高血糖和/或 DKA，並伴有感染或其他壓力。成人可能會保留足夠的β細胞功能來預防 DKA 多年；這些人可能會在數月或數年內緩解或減少對胰島素的需求，並最終依賴胰島素生存，並有患 DKA 的風險 (3–5,51,52)。在疾病的後期，胰島素分泌很少或沒有，表現為血漿 C 肽水平低或檢測不到。免疫介導的糖尿病是兒童和青春期最常見的糖尿病形式，但它可以發生在任何年齡，甚至在 8 歲和 9 歲時。
The rate of β-cell destruction is quite variable, being rapid in some individuals (mainly particularly but not exclusively in infants and children) and slow in others (mainly but not exclusively adults) (50). Children and adolescents may often present with DKA as the first manifestation of the disease the rates in the U.S. have increased dramatically over the past 20 years (2–4). Others have modest fasting hyperglycemia that can rapidly change to severe hyperglycemia and/or DKA with infection or other stress. Adults may retain sufficient β-cell function to prevent DKA for many years; such individuals may have remission or decreased insulin needs for months or years and eventually become dependent on insulin for survival and are at risk for DKA (3–5,51,52). At this latter stage of the disease, there is little or no insulin secretion, as manifested by low or undetectable levels of plasma C-peptide. Immune-mediated diabetes is the most common form of diabetes in childhood and adolescence, but it can occur at any age, even in the 8th and 9th decades of life.
2021 vs 2022:
β細胞的自身免疫性破壞具有多種遺傳傾向，並且還與仍不清楚的環境因素有關。 雖然患者在出現 1 型糖尿病時通常並不肥胖，但肥胖在普通人群中越來越普遍，並且有證據表明它也可能是 1 型糖尿病的危險因素。 因此，肥胖不應排除診斷。 1 型糖尿病患者還容易出現其他自身免疫性疾病，如橋本甲狀腺炎、格雷夫斯病、乳糜瀉、艾迪生病、白癜風、自身免疫性肝炎、重症肌無力和惡性貧血
2022新增： 1 型糖尿病可能與單基因多腺體自身免疫綜合徵相關，包括免疫失調、多內分泌病、腸病和 X 連鎖 (IPEX) 綜合徵，這是一種由叉頭盒蛋白 3 (FOXP3) 突變引起的早發性全身性自身免疫性遺傳疾病 基因，另一個是由自身免疫調節因子 (AIRE) 基因突變引起的 (66,67)。 如名稱所示，這些疾病與其他自身免疫性疾病和風濕病有關。
Autoimmune destruction of β-cells has multiple genetic predispositionsfactors and is also related to environmental factors that are still poorly defined. Although patients are not typically obese when they present with type 1 diabetes, obesity is increasingly common in the general population, and there is evidence that it may also be a risk factor for type 1 diabetes. As such, obesity should not preclude the diagnosis. People with type 1 diabetes are also prone to other autoimmune disorders such as Hashimoto thyroiditis, Graves disease, celiac disease, Addison disease, vitiligo, autoimmune hepatitis, myasthenia gravis, and pernicious anemia.
Type 1 diabetes can be associated with monogenic polyglandular autoimmune syndromes including immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is an early-onset systemic autoimmune genetic disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene, and another caused by the autoimmune regulator (AIRE) gene mutation (66,67). As indicated by the names, these disorders are associated with other autoimmune and rheumatological diseases.
2022 新增：PD-1/PD-L1 -> T1DM
用於癌症治療的免疫療法，特別是檢查點抑製劑的引入導致了意想不到的不良事件，包括免疫系統激活導致自身免疫性疾病。 1 型糖尿病可暴發，DKA 和低水平或無法檢測到的 C 肽水平可作為內源性 β 細胞功能的標誌物 (68,69)。 這些患者中只有不到一半有 1 型糖尿病患者的自身抗體，這支持了替代病理生物學。 這種與免疫相關的不良事件發生在檢查點抑製劑治療的患者中不到 1%，但最常見於單獨阻斷 PD-1/PD-L1 途徑的藥物或與其他檢查點抑製劑聯合使用的藥物 (70) . 迄今為止，家族史或自身抗體無法預測風險，因此所有使用這些藥物的提供者都應注意這種不良反應並適當地教育患者。
Introduction of immunotherapy, specifically checkpoint inhibitors, for cancer treatment has led to unexpected adverse events including immune system activation precipitating autoimmune disease. Fulminant onset of type 1 diabetes can develop, with DKA and low or undetectable levels of C-peptide as a marker of endogenous β-cell function (68,69). Fewer than half of these patients have autoantibodies that are seen in type 1 diabetes, supporting alternate pathobiology. This immune-related adverse event occurs in just under 1% of checkpoint inhibitor–treated patients but most commonly occurs with agents that block the programmed cell death protein 1/programmed cell death ligand 1 pathway alone or in combination with other checkpoint inhibitors (70). To date, risk cannot be predicted by family history or autoantibodies, so all providers administering these medications should be mindful of this adverse effect and educate patients appropriately.
Screening for Type 1 Diabetes Risk
2021 vs 2022: T1DM family; Ab+ childroon + s/s教育 + 追縱-> 有效篩檢T1DM
1 型糖尿病的發病率和患病率正在增加 (53)。 1 型糖尿病患者經常出現糖尿病急性症狀和顯著升高的血糖水平，大約三分之一40–60% 的患者被診斷出患有危及生命的 DKA (2)。多項研究表明，測量具有 1 型糖尿病遺傳風險的個體（例如，1 型糖尿病患者的親屬或具有 1 型糖尿病相關遺傳因素的普通人群的個體）的胰島自身抗體測量 1 型糖尿病患者親屬 (15) 或普通人群兒童 (73,74) 的胰島自身抗體可以有效識別將患 1 型糖尿病的患者 10）。這種檢測，加上有關糖尿病症狀的教育和密切隨訪，可以更早地識別 1 型糖尿病的發病。
一項研究報告了來自芬蘭、德國和美國的三個兒科隊列從血清轉化為自身抗體陽性時進展為 1 型糖尿病的風險。在產生兩種以上自身抗體的 585 名兒童中，近 70% 在10 年和 84% 在 15 年內 (45)。這些發現非常重要，因為雖然德國組是從患有 1 型糖尿病的父母的後代中招募的，但芬蘭和美國組是從普通人群中招募的。值得注意的是，所有三組的研究結果都是相同的，這表明在“散發性”和家族性 1 型糖尿病病例中，相同的事件序列導致了臨床疾病。事實上，隨著檢測到的相關自身抗體數量的增加，1 型糖尿病的風險也會增加 (48,54,55)。在青年糖尿病的環境決定因素 (TEDDY) 研究中，363 名受試者中有 21% 在 3 歲時至少患有一種自身抗體 (56)。此類測試，加上有關糖尿病症狀的教育和密切隨訪，已被證明可以早期診斷和預防 DKA (78,79)。
The incidence and prevalence of type 1 diabetes is increasing (53). Patients with type 1 diabetes often present with acute symptoms of diabetes and markedly elevated blood glucose levels, and approximately one-third40–60% are diagnosed with life-threatening DKA (2).
Multiple studies indicate that measuring islet autoantibodies in individuals genetically at risk for type 1 diabetes (e.g., relatives of those with type 1 diabetes or individualsor in children from the general population can effectively identify those who will develop type 1 diabetes (10). Such testing, coupled with education about diabetes symptoms and close follow-up, may enable earlier identification of type 1 diabetes onset. (2022 刪)
A study reported the risk of progression to type 1 diabetes from the time of seroconversion to autoantibody positivity in three pediatric cohorts from Finland, Germany, and the U.S. Of the 585 children who developed more than two autoantibodies, nearly 70% developed type 1 diabetes within 10 years and 84% within 15 years (45). These findings are highly significant because while the German group was recruited from offspring of parents with type 1 diabetes, the Finnish and American groups were recruited from the general population. Remarkably, the findings in all three groups were the same, suggesting that the same sequence of events led to clinical disease in both “sporadic” and familial cases of type 1 diabetes. Indeed, the risk of type 1 diabetes increases as the number of relevant autoantibodies detected increases (48,54,55). In The Environmental Determinants of Diabetes in the Young (TEDDY) study, type 1 diabetes developed in 21% of 363 subjects with at least one autoantibody at 3 years of age (56).Such testing, coupled with education about diabetes symptoms and close follow-up, has been shown to enable earlier diagnosis and prevent DKA (78,79).
2021 vs 2022:
Individuals who test positive should be counseled about the risk of developing diabetes, diabetes symptoms, and DKA prevention. Numerous clinical studies are being conducted to test various methods of preventing and treating stage 2 type 1 diabetes in those with evidence of autoimmunity with promising results (see www.clinicaltrials.gov and www.trialnet.org).
2022 新增：
2019 年報導了在 2 期 1 型糖尿病中使用抗 CD3 抗體 teplizumab 在有 1 型糖尿病風險的親屬中延遲明顯的糖尿病發展，並在 2021 年延長了隨機對照試驗 (80,81)。 基於這些數據，該藥物已提交給 FDA，用於指示高危人群延遲或預防臨床 1 型糖尿病。 該藥物和該類別中的其他藥物目前都不能用於臨床。
Delay of overt diabetes development in stage 2 type 1 diabetes with the anti-CD3 antibody teplizumab in relatives at risk for type 1 diabetes was reported in 2019, with an extension of the randomized controlled trial in 2021 (80,81). Based on these data, this agent has been submitted to the FDA for the indication of delay or prevention of clinical type 1 diabetes in at-risk individuals. Neither this agent nor others in this category are currently available for clinical use.