Gestational Diabetes Mellitus: Classification and Diagnosis of Diabetes
2021:
2.25 對有危險因素的人，在第一次產前檢查時，使用標準診斷檢測未確診的前驅糖尿病和糖尿病。 B
2.25 Test for undiagnosed prediabetes and diabetes at the first prenatal visit in those with risk factors using standard diagnostic criteria. B
2022 修正和新增：
2.26a 在計劃懷孕的女性中，篩查具有風險因素的女性 B，並考慮對所有女性進行未確診糖尿病的檢測。 E
2.26b 在妊娠15週之前，對有風險因素的婦女進行檢測 B，如果孕前沒有篩查，考慮在第一次產前檢查時用標準診斷標準對所有婦女進行未診斷的糖尿病檢測 E。
2.26c 被確定患有糖尿病的女性應該接受這樣的治療。 A
2.26d 在妊娠 15 週之前，篩查血糖代謝異常，以確定哪些婦女有較高的不良妊娠和新生兒結局的風險，更有可能需要胰島素，並且有較高的妊娠期糖尿病診斷風險。 B 治療可能會帶來一些好處。 E
2.26e 使用空腹血糖 110–125 mg/dL 或 A1C 5.9–6.4% 來篩查早期血糖代謝異常。 B
2.26a In women who are planning pregnancy, screen those with risk factors B and consider testing all women for undiagnosed diabetes. E
2.26b Before 15 weeks of gestation, test women with risk factors B and consider testing all women E for undiagnosed diabetes at the first prenatal visit using standard diagnostic criteria, if not screened preconception.
2.26c Women identified as having diabetes should be treated as such. A
2.26d Before 15 weeks of gestation, screen for abnormal glucose metabolism to identify women who are at higher risk of adverse pregnancy and neonatal outcomes, are more likely to need insulin, and are at high risk of a later gestational diabetes mellitus diagnosis. B Treatment may provide some benefit. E
2.26e Screen for early abnormal glucose metabolism using fasting glucose of 110–125 mg/dL or A1C 5.9–6.4% . B
2021 vs 2022:
2.27 在妊娠 24-28 週對以前未發現糖尿病或在本次妊娠早期時發現高危險血糖代謝異常的孕婦進行妊娠期糖尿病檢測。
2.27 Test for gestational diabetes mellitus at 24–28 weeks of gestation in pregnant women not previously found to have diabetes or high-risk abnormal glucose metabolism detected earlier in the current pregnancy. (2022 新增） A
Definition
2021 vs 2022:
多年來，GDM 被定義為在懷孕期間首次發現的任何程度的葡萄糖耐受不良 (60)，無論高血糖的程度如何。這個定義促進了 GDM 檢測和分類的統一策略，但這個定義有嚴重的局限性（161）。首先，現有的最佳證據表明，許多（也許是大多數）GDM 病例代表妊娠期常規篩查發現的預先存在的高血糖症，因為常規篩查並未在非妊娠育齡婦女中廣泛進行。高血糖的嚴重程度對於短期和長期母體和胎兒風險具有臨床意義。由於缺乏關於適當診斷閾值和結果以及成本效益的數據和共識，普遍的孕前和/或孕早期篩查受到阻礙 (162,163)。在該領域開展進一步研究的一個令人信服的論據是，在妊娠期以外可診斷糖尿病並在受孕時出現的高血糖症與先天性畸形風險增加相關，而這種風險在血糖水平較低時不會出現（164,165 ).
2021 vs 2022:
For many years, GDM was defined as any degree of glucose intolerance that was first recognized during pregnancy (60), regardless of the degree of hyperglycemia. This definition facilitated a uniform strategy for detection and classification of GDM, but this definition has serious limitations (161). First, the best available evidence reveals that many, perhaps most,cases of GDM represent preexisting hyperglycemia that is detected by routine screening in pregnancy, as routine screening is not widely performed in nonpregnant women of reproductive age. It is the severity of hyperglycemia that is clinically important with regard to both short- and long-term maternal and fetal risks. Universal preconception and/or first trimester screening is hampered by lack of data and consensus regarding appropriate diagnostic thresholds and outcomes and cost-effectiveness (162,163). A compelling argument for further work in this area is the fact that hyperglycemia that would be diagnostic of diabetes outside of pregnancy and is present at the time of conception is associated with an increased risk of congenital malformations that is not seen with lower glucose levels (164,165).(2022 刪）
2021 vs 2022:
肥胖和糖尿病的持續流行導致育齡婦女出現更多 2 型糖尿病，妊娠早期未確診 2 型糖尿病的孕婦人數增加 (166-169)。由於未確診 2 型糖尿病的孕婦人數眾多，因此有理由在初次產前檢查時使用標準診斷標準（表 2.2）對有 2 型糖尿病危險因素的女性進行檢測（170）（表 2.3）。根據妊娠以外使用的標準診斷標準發現患有糖尿病的婦女應歸類為妊娠合併糖尿病（最常見的是 2 型糖尿病，很少有 1 型糖尿病或單基因糖尿病）並進行相應管理。符合 GDM 較低血糖標準的女性應被診斷為患有該疾病並進行相應管理。
The ongoing epidemic of obesity and diabetes has led to more type 2 diabetes in women of reproductive age, with an increase in the number of pregnant women with undiagnosed type 2 diabetes in early pregnancy (166–169). Because of the number of pregnant women with undiagnosed type 2 diabetes, it is reasonable to test women with risk factors for type 2 diabetes (170) (Table 2.3) at their initial prenatal visit, using standard diagnostic criteria (Table 2.2). Women found to have diabetes by the standard diagnostic criteria used outside of pregnancy should be classified as having diabetes complicating pregnancy (most often type 2 diabetes, rarely type 1 diabetes or monogenic diabetes) and managed accordingly. Women who meet the lower glycemic criteria for GDM should be diagnosed with that condition and managed accordingly.
2022 新增：
理想情況下，在有危險因素的婦女或高危險人群中，應在孕前發現未診斷的糖尿病(202-207)，因為對已有糖尿病的婦女進行孕前護理，可降低A1C，減少出生缺陷、早產、周產期死亡率、胎兒小於妊娠年齡和新生兒重症入院的風險(208)。
如果婦女在懷孕前沒有進行篩查，可以考慮在懷孕<15週時對未診斷的糖尿病進行普遍的早期篩查，而不是選擇性的篩查（表2.3），特別是在育齡婦女危險因素和未診斷的糖尿病高盛行人群。
在未確診的糖尿病發病率方面存在著強烈的種族和民族差異。因此，早期篩查提供了識別這些健康差異的最初步驟，從而可以開始解決這些差異（204-207）。確認懷孕早期未診斷的糖尿病的標準診斷標準與非懷孕人群使用的標準相同（見表2.2）。根據懷孕以外的標準診斷標準，發現有糖尿病的婦女應被歸類為妊娠並發糖尿病（最常見的是2型糖尿病，很少是1型糖尿病或單基因糖尿病）並進行相應的管理。
2022 新增：Ideally, undiagnosed diabetes should be identified preconception in women with risk factors or in high-risk populations (202–207), as the preconception care of women with preexisting diabetes results in lower A1C and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age births, and neonatal intensive care unit admission (208). If women are not screened prior to pregnancy, universal early screening at <15 weeks of gestation for undiagnosed diabetes may be considered over selective screening (Table 2.3), particularly in populations with high prevalence of risk factors and undiagnosed diabetes in women of childbearing age. Strong racial and ethnic disparities exist in the prevalence of undiagnosed diabetes. Therefore, early screening provides an initial step to identify these health disparities so that they can begin to be addressed (204–207). Standard diagnostic criteria for identifying undiagnosed diabetes in early pregnancy are the same as those used in the nonpregnant population (see Table 2.2). Women found to have diabetes by the standard diagnostic criteria used outside of pregnancy should be classified as having diabetes complicating pregnancy (most often type 2 diabetes, rarely type 1 diabetes or monogenic diabetes) and managed accordingly.
Ref:
2022 新增：
早期血糖代謝異常，定義為空腹血糖閾值為 110 mg/dL 或 A1C 為 5.9% ，可識別出妊娠和新生兒不良結局風險較高的女性（子癇前症、 巨嬰、肩難產、周產期死亡），更有可能需要胰島素治療，並且後期診斷為 GDM 的風險很高（209-215）。 A1C 5.7% 的閾值與不良周產期結局沒有相關 (216,217)。
2022 新增： Early abnormal glucose metabolism, defined as fasting glucose threshold of 110 mg/dL (6.1 mmol/L) or an A1C of 5.9% (39 mmol/mol) may identify women who are at higher risk of adverse pregnancy and neonatal outcomes (preeclampsia, macrosomia, shoulder dystocia, perinatal death), are more likely to need insulin treatment, and are at high risk of a later GDM diagnosis (209–215). An A1C threshold of 5.7% has not been shown to be associated with adverse perinatal outcomes (216,217).
2021 vs 2022：
如果早期篩查結果為陰性，女性應在妊娠 24 至 28 週之間重新篩查 GDM。 國際糖尿病與妊娠研究組協會 (IADPSG) 75g OGTT 的 GDM 診斷標準以及兩步法中使用的 GDM 篩查和診斷標準並非來源於妊娠前半期的數據， 因此，通過 FPG 或 OGTT 值對妊娠早期 GDM 的診斷不是基於證據的 (171)，需要進一步的工作 並且不應用於早期篩查 (218)。迄今為止，大多數早期血糖代謝異常治療的隨機對照試驗的結果都不足。因此，早期血糖代謝異常的治療益處仍不確定。建議每週進行營養諮詢和定期“分段”血糖測試，以確定高血糖的女性。如果在妊娠 18 週之前空腹血糖>110 mg/dL，則測試頻率可能會增加到每天，並且可能會加強治療。(2022新增）
2022 新增：
空腹血糖和 A1C 都是低成本測試。 A1C 的一個優點是它的方便性，因為它可以添加到產前實驗室並且不需要清晨禁食預約。 缺點包括存在紅血球更新和血色素病變增加而不準確（通常讀數較低），以及因貧血和紅血球更新減少而造成A1c數值較高（219）。 A1C 在妊娠 15 週或之後篩查 GDM 或預先存在的糖尿病並不可靠。
Both the fasting glucose and A1C are low-cost tests. An advantage of the A1C is its convenience, as it can be added to the prenatal laboratories and does not require an early-morning fasting appointment. Disadvantages include inaccuracies in the presence of increased red blood cell turnover and hemoglobinopathies (usually reads lower), and higher values with anemia and reduced red blood cell turnover (219). A1C is not reliable to screen for GDM or for preexisting diabetes at 15 weeks of gestation or later. See Recommendation 2.3 above.
One-Step Strategy
2021 vs 2022：
然而，最近的一項隨機試驗在妊娠 24-28 週通過使用 IADPSG 標準的一步法與使用 1 小時 50 克葡萄糖負荷試驗 (GLT) 的兩步法檢測 GDM，如果陽性，根據 Carpenter-Coustan 標准進行的 3 小時 OGTT，與兩步法相比，一步法確定的 GDM 女性人數是兩步法的兩倍。儘管使用一步法治療了更多的 GDM 女性，但在妊娠和圍產期並發症方面沒有差異 (234)。
一步法確定孕婦 pre-DM 和 DM 風險以及後代血糖代謝異常和肥胖的長期風險。在 HAPO 隊列中通過一步法診斷的GDM女性之後與較高的 IGT 患病率相關； OGTT 期間 30 分鐘、1 小時和 2 小時的血糖升高；與沒有 GDM 的母親的後代相比，其後代在 10-14 歲時的胰島素敏感性和 disposition index降低。母親在 75 g OGTT 的空腹、1 小時和 2 小時值與後代代謝結果是有連續相關 (231,235)。此外，HAPO 追縱研究 (HAPO FUS) 數據表明，新生兒肥胖和胎兒高胰島素血症（臍帶 C-peptide）在母親高血糖的連續過程中都比較高，是兒童體脂肪的中介因素 (236)。
However, a recent randomized trial of testing for GDM at 24–28 weeks of gestation by the one-step method using IADPSG criteria versus the two-step method using a 1-h 50-g glucose loading test (GLT) and, if positive, a 3-h OGTT by Carpenter-Coustan criteria identified twice as many women with GDM using the one step-method compared with the two-step. Despite treating more women for GDM using the one-step method, there was no difference in pregnancy and perinatal complications (234).
The one-step method identifies the long-term risks of maternal prediabetes and diabetes and offspring abnormal glucose metabolism and adiposity. Post hoc GDM in women diagnosed by the one-step method in the HAPO cohort was associated with higher prevalence of IGT; higher 30-min, 1-h, and 2-h glucoses during the OGTT; and reduced insulin sensitivity and oral disposition index in their offspring at 10–14 years of age compared with offspring of mothers without GDM. Associations of mother’s fasting, 1-h, and 2-h values on the 75-g OGTT were continuous with a comprehensive panel of offspring metabolic outcomes (231,235). In addition, HAPO Follow-up Study (HAPO FUS) data demonstrate that neonatal adiposity and fetal hyperinsulinemia (cord C-peptide), both higher across the continuum of maternal hyperglycemia, are mediators of childhood body fat (236).
Preconception Counseling
2022 新增：
對既往患有糖尿病的婦女進行孕前護理的觀察性研究的系統回顧和薈萃分析表明，較低的A1C 和出生缺陷、早產、周產期死亡率、小於胎齡兒分娩和新生兒重症加護病房入院的風險降低有關。 8）。
A systematic review and meta-analysis of observational studies of preconception care for women with preexisting diabetes demonstrated lower A1C and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age births, and neonatal intensive care unit admission (8).
Continuous Glucose Monitoring in Pregnancy
2021 vs 2022：
關於 Time in range 的國際共識 (50) 同意使用 CGM，如動態血糖曲線報告的那樣，對第 1 型糖尿病患者設定妊娠目標範圍和目標； 但是，它沒有指定設備的類型或準確性或警報和警報的需要。 CGM 設備的選擇應根據患者情況進行個體化。
The international consensus on time in range (50) endorses pregnancy target ranges and goals for TIR for patients with type 1 diabetes using CGM as reported on the ambulatory glucose profile; however, it does not specify the type or accuracy of the device or need for alarms and alerts. Selection of CGM device should be individualized based on patient circumstances. (2022 新增)
Management of Gestational Diabetes Mellitus
2022 新增：
15.16 與標準的面對面護理相比，妊娠期糖尿病孕婦的遠程醫療訪問改善了結果。 A
(15.16 Telehealth visits for pregnant women with gestational diabetes mellitus improve outcomes compared with standard in-person care. A)
2022 新增：
對 11 項 RCT 的薈萃分析表明，在肥胖、多囊卵巢綜合徵或胰島素阻抗的高危險女性，妊娠期使用 metformin 治療不會降低GDM風險 (56)。
一項對 32 項 RCT 進行的薈萃分析評估了遠距醫療 vs. 標準的面對面護理的有效性，結果顯示，與標準照護相比，剖腹產、新生兒低血糖、羊膜早破、巨嬰、妊娠高血壓或子癇前症、早產、新生兒窒息和羊水過多的發生率在遠距醫療降低。 (57)。
A meta-analysis of 11 RCTs demonstrated that metformin treatment in pregnancy does not reduce the risk of GDM in high-risk women with obesity, polycystic ovary syndrome, or preexisting insulin resistance (56). A meta-analysis of 32 RCTs evaluating the effectiveness of telehealth visits for GDM demonstrated reduction of incidences of cesarean delivery, neonatal hypoglycemia, premature rupture of membranes, macrosomia, pregnancy-induced hypertension or preeclampsia, preterm birth, neonatal asphyxia, and polyhydramnios compared with standard in-person care (57).
Medical Nutrition Therapy and Exercise
2021：
單醣的碳水化合物會導致更高的餐後高血糖
Simple carbohydrates will result in higher postmeal excursions.
2022：
目前推薦的碳水化合物量為 175 克，或 2,000 卡路里飲食的 35%。 釋放更高質量、營養豐富的碳水化合物可控制空腹/餐後葡萄糖、降低游離脂肪酸、改善胰島素作用和血管益處，並可能減少嬰兒過度肥胖。
用脂肪代替碳水化合物的母親可能會無意中增強脂肪分解，促進游離脂肪酸升高，並惡化母體胰島素抵抗 (63,64)。 空腹尿酮測試可能有助於識別嚴格限制碳水化合物以控制血糖的女性。 簡單或單醣的碳水化合物會導致更高的餐後血糖波動。
The current recommended amount of carbohydrate is 175 g, or ∼35% of a 2,000-calorie diet. Liberalizing higher quality, nutrient-dense carbohydrates results in controlled fasting/postprandial glucose, lower free fatty acids, improved insulin action, and vascular benefits and may reduce excess infant adiposity. Mothers who substitute fat for carbohydrate may unintentionally enhance lipolysis, promote elevated free fatty acids, and worsen maternal insulin resistance (63,64). Fasting urine ketone testing may be useful to identify women who are severely restricting carbohydrates to control blood glucose. Simple carbohydrates will result in higher postmeal excursions.
2022 新增
- 運動
一項系統評價表明，通過運動干預可以改善血糖控制並減少開始胰島素或胰島素劑量需求的需求。 有效運動類型（有氧運動、阻力運動或兩者兼有）和運動持續時間（每天 20-50 分鐘，中等強度每週 2-7 天）存在異質性 (65)。
Physical Activity
A systematic review demonstrated improvements in glucose control and reductions in need to start insulin or insulin dose requirements with an exercise intervention. There was heterogeneity in the types of effective exercise (aerobic, resistance, or both) and duration of exercise (20–50 min/day, 2–7 days/week of moderate intensity) (65).
Management of Preexisting Type 1 Diabetes and Type 2 Diabetes in Pregnancy
Insulin Use Recommendations
2021:
最近的 Cochrane 系統評價未能推薦任何特定的胰島素治療方案來治療妊娠期糖尿病（90）。
A recent Cochrane systematic review was not able to recommend any specific insulin regimen over another for the treatment of diabetes in pregnancy (90).
2022 修正：
在RCT研究的胰島素（96-99）優於cohort 研究中研究的胰島素（100），cohort 研究優於僅在病例報告中研究的胰島素。
Insulins studied in RCTs are preferred (96–99) over those studied in cohort studies (100), which are preferred over those studied in case reports only.
2022 新增：
目前的混合 closed-loop insulin pump 都沒有達到妊娠目標。 然而，預測性低血糖暫停 (PLGS) 技術已在非妊娠人群中顯示出優於傳感器增強技術 (SAP) 以減少低血糖 (103)。 它可能適合懷孕，因為暫停胰島素的預測低葡萄糖閾值在懷孕期間的餐前和過夜葡萄糖目標範圍內，並且可能允許更積極的餐時給藥。
None of the current hybrid closed-loop insulin pump systems achieve pregnancy targets. However, predictive low glucose suspend (PLGS) technology has been shown in nonpregnant people to be better than sensor augment technology (SAP) for reducing low glucoses (103). It may be suited for pregnancy because the predict low glucose threshold for suspending insulin is in the range of premeal and overnight glucoses targets in pregnancy and may allow for more aggressive prandial dosing.
- Type 2 Diabetes
2021 vs 2022：
在薈萃分析和系統綜述中，Glyburide與胰島素或Metformin相比，具有更高的新生兒低血糖率、巨嬰症和新生兒腹圍增加率。
Glyburide was associated with a higher rate of neonatal hypoglycemia, macrosomia, and increased neonatal abdominal circumference than insulin or metformin in meta-analyses and systematic reviews (72,73).
2022 新增：
胰島素是妊娠期 2 型糖尿病的首選治療方法。 一項在胰島素中添加 metformin 治療 2 型糖尿病的隨機對照試驗發現，產婦體重增加較少，剖腹產次數較少。 巨嬰的數量較少，但小於胎齡兒的數量增加了一倍 (104)。
Insulin is the preferred treatment for type 2 diabetes in pregnancy. An RCT of metformin added to insulin for the treatment of type 2 diabetes found less maternal weight gain and fewer cesarean births. There were fewer macrosomic neonates, but there was a doubling of small-for-gestational-age neonates (104).
Gestational Diabetes MellitusInitial Testing
2022 新增：
在沒有明確的高血糖症狀的情況下，糖尿病的陽性篩查需要兩個異常值。 如果空腹血糖（≥126 mg/dL）和 2 h 血糖（≥200 mg/dL ）在單次篩查中均異常，則診斷為 糖尿病。 如果 OGTT 中只有一個異常值符合糖尿病標準，則應重複測試以確認異常持續存在。
In the absence of unequivocal hyperglycemia, a positive screen for diabetes requires two abnormal values. If both the fasting plasma glucose (≥126 mg/dL [7.0 mmol/L]) and 2-h plasma glucose (≥200 mg/dL [11.1 mmol/L]) are abnormal in a single screening test, then the diagnosis of diabetes is made. If only one abnormal value in the OGTT meets diabetes criteria, the test should be repeated to confirm that the abnormality persists.
2022 新增：
在沒有明確的高血糖症狀的情況下，糖尿病的陽性篩查需要兩個異常值。 如果空腹血糖（≥126 mg/dL）和 2 h 血糖（≥200 mg/dL ）在單次篩查中均異常，則診斷為 糖尿病。 如果 OGTT 中只有一個異常值符合糖尿病標準，則應重複測試以確認異常持續存在。
In the absence of unequivocal hyperglycemia, a positive screen for diabetes requires two abnormal values. If both the fasting plasma glucose (≥126 mg/dL [7.0 mmol/L]) and 2-h plasma glucose (≥200 mg/dL [11.1 mmol/L]) are abnormal in a single screening test, then the diagnosis of diabetes is made. If only one abnormal value in the OGTT meets diabetes criteria, the test should be repeated to confirm that the abnormality persists.