Prediabetes and Type 2 Diabetes
2021 vs 2022:
2.6 無症狀成人應考慮通過對危險因素的非正式評估或經過驗證的工具 風險計算器 篩查前驅糖尿病和 2 型糖尿病。 B
2.6 Screening for prediabetes and type 2 diabetes with an informal assessment of risk factors or validated tools risk calculator should be considered done in asymptomatic adults. B
2021: -> 2022 沒有這段
2.8 對於計劃懷孕的超重或肥胖和/或有一個或多個其他糖尿病危險因素的女性，應考慮檢測前驅糖尿病和/或 2 型糖尿病（表 2.3）。 C
2.8 Testing for prediabetes and/or type 2 diabetes should be considered in women with overweight or obesity planning pregnancy and/or who have one or more additional risk factor for diabetes (Table 2.3). C
2021 vs 2022: 提早至於35歲篩檢
2.9 對所有的人來說，檢測篩查應該從 45 35歲開始。
2.9 For all people, testing screening should begin at age 45 35years. B
2021 vs 2022:
2.10 如果測試正常，至少每隔 3 年進行一次重複測試是合理的，越早出現症狀, 或風險變化（即體重增加）。 C
2.10 If tests are normal, repeat testing carried out at a minimum of 3-year intervals is reasonable, sooner with symptoms, or change in risk (i.e., weight gain). C
2022 新增：
2.12 當使用 OGTT 作為糖尿病篩查時，應確保在測試前 3 天攝入足夠的碳水化合物（至少 150 克/天）。 A
2.12 When using oral glucose tolerance testing as a screen for diabetes, adequate carbohydrate intake (at least 150 g/day) should be assured for 3 days prior to testing. A
Prediabetes
2021 vs 2022: pre-DM: risk factors of CVD-> 需對心血管危險因素進行全面篩查
“Prediabetes” is the term used for individuals whose glucose levels do not meet the criteria for diabetes but are too high to be considered normal yet have abnormal carbohydrate metabolism (35,36). Patients with prediabetes are defined by the presence of IFG and/or IGT and/or A1C 5.7–6.4% (39–47 mmol/mol) (Table 2.5). Prediabetes should not be viewed as a clinical entity in its own right but rather as an increased risk for risk factor for progression to diabetes and cardiovascular disease (CVD). Criteria for testing for diabetes or prediabetes in asymptomatic adults is outlined in Table 2.3. Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. The presence of prediabetes should prompt comprehensive screening for cardiovascular risk factors. (2022增）
Screening and Testing for Prediabetes and Type 2 Diabetes in Asymptomatic Adults
2022: screen pre-DM -> benefit/risk 個別化考量，找最大風險族群
建議通過對風險因素的非正式評估（表 2.3）或使用評估工具篩查糖尿病前期和 2 型糖尿病風險，以指導提供者進行診斷測試（表 2.2）是否合適。糖尿病前期和 2 型糖尿病符合通過篩查進行早期檢測的條件標準。這兩種情況都很常見，會給臨床和公共衛生帶來巨大的負擔。在診斷 2 型糖尿病之前，通常有一個較長的症狀前階段。檢測臨床前疾病的簡單測試很容易獲得 (99)。血糖負擔的持續時間是不良結果的一個強有力的預測因素。有有效的干預措施可以防止從前驅糖尿病發展為糖尿病。對糖尿病前期患者進行正式介入的風險/益處需要個別化考量，並考慮以患者為中心的目標。風險模型已經探索了介入的好處，總體上發現對高風險人群進行介入的好處更高（100）（2022增）
Screening for prediabetes and type 2 diabetes risk through an informal assessment of risk factors (Table 2.3) or with an assessment tool, such as the ADA risk test (Fig. 2.1) (online at diabetes.org/socrisktest), is recommended to guide providers on whether performing a diagnostic test (Table 2.2) is appropriate. Prediabetes and type 2 diabetes meet criteria for conditions in which early detection via screening is appropriate. Both conditions are common and impose significant clinical and public health burdens. There is often a long presymptomatic phase before the diagnosis of type 2 diabetes. Simple tests to detect preclinical disease are readily available (99). The duration of glycemic burden is a strong predictor of adverse outcomes. There are effective interventions that prevent progression from prediabetes to diabetes. It is important to individualize risk/benefit of formal intervention for patients with prediabetes and consider patient-centered goals. Risk models have explored the benefit, in general finding higher benefit of intervention in those at highest risk (100) (2022增）
Posttransplantation Diabetes Mellitus
2022：
OGTT 被認為是診斷 PTDM（移植後 1 年）的黃金標準測試 (143,144,154,155)。 hs-CRP 的移植前升高與腎移植情況下的 PTDM 相關 (156,157)。 然而，篩查空腹血糖和/或 A1C 的患者可以識別需要進一步評估的高危患者，並可能減少所需的總體 OGTT 數量。
The OGTT is considered the gold-standard test for the diagnosis of PTDM (1 year posttransplant) (143,144,154,155).Pretransplant elevation in hs-CRP was associated with PTDM in the setting of renal transplant (156,157). (2022增） However, screening patients with fasting glucose and/or A1C can identify high-risk patients requiring further assessment and may reduce the number of overall OGTTs required.
Neonatal Diabetes
2021 vs 2022:
發生在 6 個月以下的糖尿病被稱為“新生兒”或“先天性”糖尿病，大約 80-85% 的病例可以發現有潛在的單基因病因 (134-137)。新生兒糖尿病在 6 個月大後發生的頻率要低得多，而自身免疫性 1 型糖尿病很少在 6 個月大之前發生。新生兒糖尿病可以是暫時的或永久性的。暫時性糖尿病最常見的原因是染色體 6q24 上的基因過度表達，大約一半的病例會復發，並且可以用胰島素以外的藥物治療。永久性新生兒糖尿病最常見的原因是編碼 β 細胞 KATP 通道的 Kir6.2 亞基 (KCNJ11) 和 SUR1 亞基 (ABCC8) 的基因的常染色體顯性突變。最近的一份報告詳細介紹了 EIF2B1 的從頭突變影響與永久性新生兒糖尿病和肝功能障礙相關的 eIF2 信號傳導，類似於 Wolcott-Rallison 綜合徵，但幾乎沒有嚴重的合併症 (138)。
最近的 ADA-EASD of Diabetes 1 型糖尿病共識報告建議無論當前年齡如何，診斷為 6 個月以下的個體都應該進行基因檢測 (8) 正確診斷具有重要意義，因為大多數 30-50%患有 KATP 相關新生兒糖尿病的患者在使用大劑量口服磺脲類藥物而不是胰島素治療時會表現出更好的血糖控制。胰島素基因 (INS) 突變是導致新生兒永久性糖尿病的第二大常見原因，雖然強化胰島素管理是目前首選的治療策略，但有重要的遺傳諮詢考慮，因為大多數導致糖尿病的突變是顯性遺傳的。
Diabetes occurring under 6 months of age is termed “neonatal” or “congenital” diabetes, and about 80–85% of cases can be found to have an underlying monogenic cause (134–137). Neonatal diabetes occurs much less often after 6 months of age, whereas autoimmune type 1 diabetes rarely occurs before 6 months of age. Neonatal diabetes can either be transient or permanent. Transient diabetes is most often due to overexpression of genes on chromosome 6q24, is recurrent in about half of cases, and may be treatable with medications other than insulin. Permanent neonatal diabetes is most commonly due to autosomal dominant mutations in the genes encoding the Kir6.2 subunit (KCNJ11) and SUR1 subunit (ABCC8) of the β-cell KATP channel. A recent report details a de novo mutation in EIF2B1 affecting eIF2 signaling associated with permanent neonatal diabetes and hepatic dysfunction, similar to Wolcott-Rallison syndrome but with few severe comorbidities (138). The recent ADA-European Association for the Study of Diabetes type 1 diabetes consensus report makes the recommendation that regardless of current age, individuals diagnosed under 6 months of age should have genetic testing (8). 2022增 Correct diagnosis has critical implications because most30-50% patients with KATP-related neonatal diabetes will exhibit improved glycemic control when treated with high-dose oral sulfonylureas instead of insulin. Insulin gene (INS) mutations are the second most common cause of permanent neonatal diabetes, and, while intensive insulin management is currently the preferred treatment strategy, there are important genetic counseling considerations, as most of the mutations that cause diabetes are dominantly inherited.
Maturity-Onset Diabetes of the Young
2021 vs 2022:
MODY 的特徵通常是在早期出現高血糖（通常在 25 歲之前，儘管診斷可能發生在年齡較大的年齡）。 MODY 的特徵是胰島素分泌受損，而胰島素作用的缺陷很少或沒有（在沒有共存肥胖的情況下）。它以常染色體顯性遺傳模式遺傳，迄今為止鑑定的不同染色體上至少有 13 個基因異常。最常見的報告形式是 GCK-MODY (MODY2)、HNF1A-MODY (MODY3) 和 HNF4A-MODY (MODY1)。 MODY 的特徵通常是在早期出現高血糖（通常在 25 歲之前，儘管診斷可能發生在年齡較大的年齡）。 MODY 的特徵是胰島素分泌受損，而胰島素作用的缺陷很少或沒有（在沒有共存肥胖的情況下）。它以常染色體顯性遺傳模式遺傳，迄今為止鑑定的不同染色體上至少有 13 個基因異常（172）。最常見的報告形式是 GCK-MODY (MODY2)、HNF1A-MODY (MODY3) 和 HNF4A-MODY (MODY1)。
對於 MODY 患者，治療意義重大，需要進行基因檢測 (139,140)。臨床上，GCK-MODY 患者表現出輕度、穩定的空腹高血糖，除有時在 通常在懷孕期間外不需要降糖治療。 HNF1A-或 HNF4A-MODY 患者通常對低劑量磺脲類藥物反應良好，這被認為是一線治療, 在某些情況下，隨著時間需要使用胰島素。 HNF1B 的突變或缺失與腎囊腫和子宮畸形（腎囊腫和糖尿病 [RCAD] 綜合徵）有關。據報導，其他極為罕見的 MODY 形式涉及其他轉錄因子基因，包括 PDX1 (IPF1) 和 NEUROD1。
MODY is frequently characterized by onset of hyperglycemia at an early age (classically before age 25 years, although diagnosis may occur at older ages). MODY is characterized by impaired insulin secretion with minimal or no defects in insulin action (in the absence of coexistent obesity). It is inherited in an autosomal dominant pattern with abnormalities in at least 13 genes on different chromosomes identified to date. The most commonly reported forms are GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1). MODY is frequently characterized by onset of hyperglycemia at an early age (classically before age 25 years, although diagnosis may occur at older ages). MODY is characterized by impaired insulin secretion with minimal or no defects in insulin action (in the absence of coexistent obesity). It is inherited in an autosomal dominant pattern with abnormalities in at least 13 genes on different chromosomes identified to date (172). The most commonly reported forms are GCK-MODY (MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1).
For individuals with MODY, the treatment implications are considerable and warrant genetic testing (139,140). Clinically, patients with GCK-MODY exhibit mild, stable fasting hyperglycemia and do not require antihyperglycemic therapy except sometimes commonly during pregnancy. Patients with HNF1A- or HNF4A-MODY usually respond well to low doses of sulfonylureas, which are considered first-line therapy, in some instances insulin will be required over time.(2022增） Mutations or deletions in HNF1B are associated with renal cysts and uterine malformations (renal cysts and diabetes [RCAD] syndrome). Other extremely rare forms of MODY have been reported to involve other transcription factor genes including PDX1 (IPF1) and NEUROD1.
Diagnosis of Monogenic Diabetes
2021 vs 2022: HNFIA-MODY & HNF4A-MODY -> CV risk similar as T1DM/T2DM
對於患有非典型糖尿病的個體和多個家庭成員患有非 1 型或 2 型糖尿病特徵的糖尿病，應考慮對 MODY 的診斷，儘管不可否認，“非典型糖尿病”在沒有明確的一組明確定義的情況下變得越來越困難。測試任一類型的糖尿病 (135–137, 139–145)。在大多數情況下，1 型糖尿病自身抗體的存在排除了對單基因糖尿病的進一步檢測，但已有報導稱單基因糖尿病患者存在自身抗體 (146)。疑似單基因糖尿病的個體應轉診至專科醫生處進行進一步評估（如果有），並可從多個中心諮詢。遵循下列標準的現成商業基因檢測現在可以實現具有成本效益的 (147)，通常是節省成本的基因診斷，並且越來越多地得到健康保險的支持。生物標誌物篩查途徑，例如結合尿 C 肽/肌酐比和抗體篩查可能有助於確定誰應該接受 MODY 基因檢測 (148)。正確診斷其中一種單基因糖尿病至關重要，因為這些患者可能被錯誤地診斷為 1 型或 2 型糖尿病，從而導致治療方案不理想，甚至可能有害，並延遲診斷其他家庭成員 (149)。對於 GCK-MODY 突變的患者，正確的診斷尤其重要，因為多項研究表明，在沒有降糖治療的情況下不會出現並發症 (150)。HNFIA-和 HNF4A-MODY 引起的微血管和大血管並發症的風險與在 1 型和 2 型糖尿病患者中觀察到的風險相似 (185,186)。(2022增） 建議進行遺傳諮詢，以確保受影響的個體了解遺傳模式和正確診斷的重要性，和解決綜合心血管風險的重要性。
A diagnosis of MODY should be considered in individuals who have atypical diabetes and multiple family members with diabetes not characteristic of type 1 or type 2 diabetes, although admittedly “atypical diabetes” is becoming increasingly difficult to precisely define in the absence of a definitive set of tests for either type of diabetes (135–137, 139–145). In most cases, the presence of autoantibodies for type 1 diabetes precludes further testing for monogenic diabetes, but the presence of autoantibodies in patients with monogenic diabetes has been reported (146). Individuals in whom monogenic diabetes is suspected should be referred to a specialist for further evaluation if available, and consultation is available from several centers. Readily available commercial genetic testing following the criteria listed below now enables a cost-effective (147), often cost-saving, genetic diagnosis that is increasingly supported by health insurance. A biomarker screening pathway such as the combination of urinary C-peptide/creatinine ratio and antibody screening may aid in determining who should get genetic testing for MODY (148). It is critical to correctly diagnose one of the monogenic forms of diabetes because these patients may be incorrectly diagnosed with type 1 or type 2 diabetes, leading to suboptimal, even potentially harmful, treatment regimens and delays in diagnosing other family members (149). The correct diagnosis is especially critical for those with GCK-MODY mutations where multiple studies have shown that no complications ensue in the absence of glucose-lowering therapy (150). The risks of microvascular and macrovascular complications with HNFIA- and HNF4A-MODY are similar to those observed in patients with type 1 and type 2 diabetes (185,186). Genetic counseling is recommended to ensure that affected individuals understand the patterns of inheritance and the importance of a correct diagnosis and addressing comprehensive cardiovascular risk.
Pancreatic Diabetes or Diabetes in the Context of Disease of the Exocrine Pancreas
2021 vs 2022:
胰腺型糖尿病包括在胰腺外分泌功能障礙的情況下葡萄糖正常化胰島素分泌的結構和功能喪失，通常被誤診為 2 型糖尿病。由一般胰腺功能障礙引起的高血糖症被稱為“3c 型糖尿病”，而最近，與胰腺外分泌疾病相關的糖尿病被稱為缺胰性糖尿病 (1)。多種病因包括胰腺炎（急性和慢性）、創傷或胰腺切除術、瘤形成、囊性纖維化（本章其他部分討論）、血色素沉著症、纖維結石性胰腺病、罕見遺傳疾病 (152) 和特發性形式 (1)，這是首選術語 因此，胰腺糖尿病是首選的總稱。胰腺炎，即使是一次發作，也可能導致胰腺炎後糖尿病 (PPDM)。 急性和慢性胰腺炎均可導致 PPDM，並且反復發作的風險最高。
一個顯著特徵是並發胰腺外分泌功能不全（根據單克隆糞便彈性蛋白酶 1 測試或直接功能測試）、病理性胰腺成像（內鏡超聲、MRI、計算機斷層掃描），以及沒有 1 型糖尿病相關的自身免疫 (153-157) .胰島素和胰高血糖素分泌均減少，胰島素需求量通常高於預期。微血管並發症的風險與其他形式的糖尿病相似。在胰腺切除術的情況下，可以進行胰島自體移植以保留胰島素分泌 (158,159)。在某些情況下，自體移植可導致胰島素依賴。在其他情況下，它可能會減少對胰島素的需求（160）。
Pancreatic diabetes includes both structural and functional loss of glucose-normalizing insulin secretion in the context of exocrine pancreatic dysfunction and is commonly misdiagnosed as type 2 diabetes. Hyperglycemia due to general pancreatic dysfunction has been called “type 3c diabetes” and, more recently, diabetes in the context of disease of the exocrine pancreas has been termed pancreoprivic diabetes (1). The diverse set of etiologies includes pancreatitis (acute and chronic), trauma or pancreatectomy, neoplasia, cystic fibrosis (addressed elsewhere in this chapter), hemochromatosis, fibrocalculous pancreatopathy, rare genetic disorders (152), and idiopathic forms (1), which is the preferred terminologyas such, pancreatic diabetes is the preferred umbrella terminology. Pancreatitis, even a single bout, can lead to postpancreatitis diabetes mellitus (PPDM). Both acute and chronic pancreatitis can lead to PPDM, and the risk is highest with recurrent bouts.
A distinguishing feature is concurrent pancreatic exocrine insufficiency (according to the monoclonal fecal elastase 1 test or direct function tests), pathological pancreatic imaging (endoscopic ultrasound, MRI, computed tomography), and absence of type 1 diabetes–associated autoimmunity (153–157). There is loss of both insulin and glucagon secretion and often higher-than-expected insulin requirements. Risk for microvascular complications is similar to other forms of diabetes. In the context of pancreatectomy, islet autotransplantation can be done to retain insulin secretion (158,159). In some cases, autotransplant can lead to insulin independence. In others, it may decrease insulin requirements (160).