阿醜 2010-5-4 11:40
人工胰臟可能有助於控制第一型糖尿病
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
April 14, 2010 — 根據一項線上發表於4月14日科學轉譯醫學（Science Translational Medicine）的研究結果與主編評論，一種以電腦流程方式控制之雙荷爾蒙、封閉迴路的人工胰臟，可能協助第一型糖尿病嚴密地控制血糖，且降低低血糖風險。
麻州波士頓大學的Firas H. EI-Khatib博士與其同事們表示，自動化控制血糖（BG）濃度是第一型糖尿病治療長期以來的目標。我們已經發展出一種以電流程頻繁監測血糖濃度並且經皮下投予速效胰島素相似物lispro與glucagon（以模仿正常生理）的封閉迴路控制系統。該流程僅對血糖濃度有反應，且與lispro的藥物動力學模式結合。
在27小時的實驗期間，包括3次富含碳水化合物的餐點，研究者們針對11位第一型糖尿病、且沒有內生性胰島素分泌的病患研究封閉迴路系統的效果。6位受試者的平均血糖為140 mg/dl，低於平均血糖目標的154 mg/dl以下，達到美國糖尿病醫學會的建議。
相較於6位不需要治療低血糖的病患，5位在治療期間未發生低血糖的病患，其lispro吸收速度較慢。沒有低血糖患者，達到lispro最高血中濃度的時間為56至72分鐘（平均為64±6分鐘），低血糖患者則是71至191分鐘（平均117±48分鐘）。總結平均分別延長了31與84分鐘，相較於電腦流程預估的33分鐘（P=0.07）。
在另一項實驗中，研究者們校正流程的藥物動力學（PK）參數。設定到達lispro尖峰濃度時間為65分鐘，以避免兩組發生低血糖，且達到總結平均血糖濃度為164 mg/dl。
研究者們寫到，這些研究結果顯示，以雙荷爾蒙、封閉迴路人工內分泌胰臟在安全血糖控制上的可行性。對胰島素藥物動力學（吸收）較快的受試者，不需以非常高碳水化合物飲食預先治療、且沒有前饋控制資訊的情況下達到將近正常的血糖控制，且沒有發生低血糖。對胰島素吸收較慢的受試者，校正流程的PK參數可以避免低血糖，但是換來些微較高的平均血糖濃度。
在隨後的主編評論中，來自麻州劍橋哈佛MIT健康科技與技術部門的Larry Brown博士與Elazer R. Edelman博士描述使用雙荷爾蒙人工胰臟作為一例，針對嚴格血糖控制的治療挑戰與潛在好處。
Brown博士與Edelman博士寫到，多重荷爾蒙輸注可能可以讓研究者回答有關糖尿病生理學與最佳化其治療的關鍵問題。其他研究者可以檢驗同樣病患根據嚴密控制或是寬鬆控制（血糖）流程僅接受胰島素、或是升糖素、澱粉素、或體制素的效果，直到有一天，胰島素依賴型糖尿病是可以治癒的，在那之前，控制他或是她的糖尿病所帶來的影響都將是很重要的。
青少年糖尿病研究基金會、Wallace H. Coulter基金會糖尿病創新研究、以及國家衛生研究院贊助這項研究。試驗作者中2位擁有密閉迴路流程正在申請中的專利。Edelman博士部分接受國家衛生研究院的贊助。
Artificial Pancreas May Help Control Type 1 Diabetes
By Laurie Barclay, MD
Medscape Medical News
April 14, 2010 — A bihormonal closed-loop artificial pancreas using a computer algorithm may tighten glycemic control in patients with type 1 diabetes while lowering risk for hypoglycemia, according to the results of a study and editorial published online April 14 in Science Translational Medicine.
"Automated control of blood glucose (BG) concentration is a long-sought goal for type 1 diabetes therapy," write Firas H. El-Khatib, PhD, from Boston University in Massachusetts, and colleagues. "We have developed a closed-loop control system that uses frequent measurements of BG concentration along with subcutaneous delivery of both the fast-acting insulin analog lispro and glucagon (to imitate normal physiology) as directed by a computer algorithm. The algorithm responded only to BG concentrations and incorporated a pharmacokinetic [PK] model for lispro."
During 27-hour experiments, which included 3 carbohydrate-rich meals, the investigators studied the effects of a closed-loop system in 11 patients with type 1 diabetes and no endogenous insulin secretion. Mean BG concentration of 140 mg/dL, which is below the mean BG concentration target of 154 mg/dL or less that is recommended by the American Diabetes Association, was achieved in 6 participants.
Compared with 6 patients who had no episodes of hypoglycemia requiring treatment, 5 patients who did have hypoglycemia requiring treatment had slower lispro absorption kinetics. Times to peak plasma lispro concentrations were 56 to 72 minutes (mean, 64 ± 6 minutes) in patients who had no hypoglycaemia vs 71 to 191 minutes (mean, 117 lusmn; 48 minutes) in patients who had hypoglycemic episodes. Aggregate mean was 31 minutes longer vs 84 minutes longer, respectively, than the algorithm's assumption of 33 minutes (P = .07).
In another experiment, the investigators adjusted the algorithm's PK parameters. Setting the time-to-peak plasma lispro concentration to 65 minutes prevented hypoglycemia in both groups and achieved an aggregate mean BG concentration of 164 mg/dL.
"These results demonstrate the feasibility of safe BG control by a bihormonal artificial endocrine pancreas," the study authors write. "Near-normal mean BG concentrations without hypoglycaemia were achieved without feedforward information or pretreatment for very high carbohydrate meals in the subjects with faster insulin PKs. In subjects with slower insulin absorption, adjustment of the algorithm's PK parameters prevented hypoglycemia at the cost of modestly higher average BG concentrations."
In an accompanying perspective, Larry Brown, ScD, and Elazer R. Edelman, PhD, MD, from Harvard MIT Division of Health Sciences and Technology in Cambridge, Massachusetts, describe the potential benefits and challenges of therapy targeting tight glycemic control, using the bihormonal artificial pancreas described here as an example.
"Multihormonal infusion may allow investigators to address critical questions regarding the pathobiology of diabetes mellitus and optimization of its therapy," Dr. Brown and Dr. Edelman write. "One could well examine studies of the same patients treated with insulin alone or with glucagon, amylin, and somatostatin dispensed according to tight-control or loose-control algorithms.... Until there is a cure for insulin-dependent diabetes, the influence of the patient on controlling his or her diabetes will remain significant."
The Juvenile Diabetes Research Foundation, Wallace H. Coulter Foundation, Charlton Fund for Innovative Research in Diabetes, and National Institutes of Health supported this study. Two of the study authors have a pending patent on the closed-loop algorithm.Dr. Edelman is supported in part by grants from the National Institutes of Health.
Sci Transl Med. Published online April 14, 2010