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。
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.
