第1型糖尿病的預測與預防


  【24drs.com】根據發表於美國臨床內分泌科醫師協會第21屆年會與臨床研討會的研究,目的為制止β細胞分子破壞的藥物,可能是阻止自體免疫第1型糖尿病的下一步。
  
  科羅拉多大學醫學院小兒醫學、免疫科教授、Barbara Davis兒童糖尿病中心執行長George Eisenbarth博士表示,我們做的試驗大多數是在最近發生的第1型糖尿病,當時已經有至少達20%的β細胞流失;如果可以加以預防,將可以更容易地控制病況;很像是蜜月期。
  
  目前,檢測抗體可以預測個人發生第1型糖尿病的風險,甚至是發生疾病的年紀—有朝一日可以用這些資訊於預防治療。
  
  Eisenbarth博士在最近的一篇報告(Endocr Pract. 線上發表於2010年5月1日)中寫道,在隨機取樣之大體進行的這類檢測結果認為,美國有50萬人屬於發生第1型糖尿病的初期階段,強調發現預防性藥物的迫切性。
  
  因為第1型糖尿病的發展病程緩慢,必須依據β細胞的逐漸流失,確認遺傳易感性和誘發因子,可以實現預防目標。
  
  他解釋,有第1型糖尿病的遺傳易感性者,在生命中的任何階段都可能發生,如果一個人是第1A型糖尿病患者的同卵雙胞胎,勢必有相同風險 — 自體抗體可能較晚出現、糖尿病比較晚爆發。這個疾病的第二波發生率高峰期在70-80歲時。
  
  迄今,與發生第1型糖尿病有關的自體抗體有4種:胰島鋅傳導子(ZnT8)、胰島素瘤相關抗原、麩胺酸脫羧酶、胰島素自體抗體。
  
  現在,這4種自體抗體都有商用分析方法,用於有疾病家族史者的篩選。
  
  發現單一種抗體表示發生第1型糖尿病風險約為5%,而一般人的發生風險約0.3%;不過,有兩種以上自體抗體者,這風險更高— 從出生追蹤到10歲,風險高達90%。
  
  Eisenbarth博士表示,我們不只可以預測風險,現在還可以預測幾歲時會發生第1型糖尿病,有兩個因素可以預測發生年紀,如果你同時有這兩種參數,可以解釋發生第1型糖尿病之年紀時變化的三分之一狀況。
  
  第一個因素是發現自體抗體時的年紀;如果我們認為自體免疫過程始於第一次自體抗體出現時,這有其道理。整體而言,當你第一次出現自體抗體時的年紀越大,發生糖尿病的年紀也越大。
  
  第二個預測因子是第一次發現胰島素自體抗體時的濃度。他表示,這是特別針對胰島素自體抗體,其他自體抗體的濃度都無關於何時發生第1型糖尿病。
  
  目前,口服胰島素(以誘發耐受性)與免疫抑制或免疫調節藥物顯示可保留β細胞,延緩6個月至1年發生糖尿病,不過,Eisenbarth博士的團隊著眼於更特定的標靶療法,針對以下三種分子的複合體:胜肽間的互動、T-細胞受體、以及主要組織相容性複合體分子。
  
  他指出,這代表我們可以有許多不同方式針對這個三分子複合體,可望發展一個特定且安全的療法。我們不常有這樣好的機會可以來預防一種疾病,暸解其自體免疫而不是自體免疫療法。
  
  根據Pinnacle健康體系的內分泌科醫師Shivani Narasimhan和Parul Kakaria醫師表示,擁有第1型糖尿病自體抗體檢測方式對執業醫師而言相當重要。Narasimhan醫師表示,Eisenbarth醫師的實驗室會篩檢2-45歲家人的自體抗體;這篇研究相當實用。
  
  Narasimhan醫師表示,她的第1型糖尿病成年病患相當相當擔心家人和子代發生該病的風險;如果想生孩子或已經有孩子,會希望知道這些,只是因為我們掌握到它,並不意味著有預防方法。
  
  Kakaria醫師表示,不過,篩檢有其他幫助。如果病患願意,可以納入臨床試驗,他們會進行一系列驗血,由小兒內分泌科醫師追蹤。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6834&x_classno=0&x_chkdelpoint=Y
  

Prediction and Prevention of Type 1 Diabetes

By Kate Johnson
Medscape Medical News

May 27, 2012 (Philadelphia, Pennsylvania) — Drugs aimed at halting the molecular destruction of beta cells are likely the next step in the quest to stop the progression of autoimmune type 1 diabetes, according to research presented here at the American Association of Clinical Endocrinologists 21st Annual Meeting and Clinical Congress by a pioneer in the field.

"Most of the trials we do in are in recent-onset type 1 diabetes, when there are plenty of beta cells left — probably at least 20%.... If one could preserve them, it would be much easier to control patients; it's like the honeymoon phase," said George Eisenbarth, MD, PhD, executive director of the Barbara Davis Center for Childhood Diabetes and professor of pediatrics, medicine, and immunology at the University of Colorado at Denver School of Medicine.

Today, autoantibody testing can predict an individual's risk of developing autoimmune type 1 diabetes, and even the age of onset of the disorder — information that could one day guide the use of such preventive therapy, said Dr. Eisenbarth.

Such testing in random cadaveric donors suggests that half a million people in the United States might be in the early stages of developing type 1 diabetes, Dr. Eisenbarth wrote in a recent paper (Endocr Pract. Published online May 1, 2012), underscoring the urgency of finding preventive drugs.

Because the development of type 1 diabetes is a slow process, requiring genetic predisposition and a precipitating trigger followed by the gradual development of beta cell loss, prevention is a realistic goal.

People with genetic predispositions can develop type 1 diabetes at any stage in life, he explained. "If one is an identical twin of someone with type 1A diabetes, you're never out of the woods — autoantibodies can appear later in life and full-blown diabetes even later," he said. A second peak in the incidence of the disorder is seen in people 70 to 80 years of age, he added.

To date, 4 autoantibodies are implicated in the development of type 1 diabetes: the islet zinc transporter (ZnT8), insulinoma associated antigen, glutamic acid decarboxylases, and insulin autoantibodies.

Commercial assays are available for all 4 autoantibodies, enabling the screening of people with a family history of the disorder.

Detection of a single antibody suggests a risk of developing type 1 diabetes of about 5%, compared with 0.3% in the general population. However, in people with 2 or more autoantibodies, the risk is much higher — up to a 90% by the age of 10 in children followed from birth.

"Not only can we predict risk, now we can also predict the age at which type 1 diabetes will occur," said Dr. Eisenbarth, explaining that there are 2 factors that predict age at onset. "If you combine these 2 parameters, you can explain about a third of the variation in age at which type 1 diabetes develops," he said.

The first factor is the person's age at autoantibody detection; "that makes sense if we think that the autoimmune process begins when that first autoantibody appears," he said. "Overall, the older you are when the first autoantibody appears, the older you are when diabetes occurs."

The second predictive factor is the level of insulin autoantibody at first detection. "This is specific for insulin [autoantibody]," he said. "The levels of none of the other autoantibodies correlated at all with how long it takes to develop type 1 diabetes."

Currently, oral insulin (to induce tolerance) and immunosuppressive or immunomodulating drugs have been shown to preserve beta cells and to delay diabetes onset for 6 months to 1 year. However, work by Dr. Eisenbarth's team is directed at more specific therapies that target the trimolecular complex: the interaction of peptides, T-cell receptors, and major histocompatibility complex molecules.

"I bet...we're going to be able to — in many different ways — target this trimolecular complex, and hopefully develop a very specific and safe therapy," he said. 'It's unusual to have a disease that we can predict so well, and know the autoimmunity, and not have an immunologic therapy in our armamentarium."

The availability of autoantibody testing for type 1 diabetes autoantibodies is important to practicing clinicians, according to endocrinologists Shivani Narasimhan, MD, and Parul Kakaria, MD, from the Pinnacle Health System in Harrisburg, Pennsylvania, who attended the session.

Dr. Eisenbarth's lab "will screen family members between the ages of 2 and 45 for autoantibodies; that is very practical to me," said Dr. Narasimhan.

Physicians and patients who want to know more can call 1-800-HALT-DM1 (1-800-425-8361) or visit the TrialNet Web site.

Dr. Narasimhan said that her adult patients with type 1 diabetes are "very much concerned" about the risk of other family members and offspring developing the disease. "If they're planning on having children or have just had children, they want to know," she told Medscape Medical News. "Just because we catch it doesn't mean we have the treatment to prevent it."

Still, screening has other benefits, said Dr. Kakaria. "Patients can potentially enroll in a clinical trial if they choose, they can have the blood tests done serially, and could be followed by a pediatric endocrinologist if they choose."

Dr. Eisenbarth reports being on 2 university provisional patents for treating autoimmunity with small molecules and receiving a research grant from Novartis for work in this area. Dr. Kakari and Dr. Narasimhan have disclosed no relevant financial relationships.

American Association of Clinical Endocrinologists (AACE) 21st Annual Meeting and Clinical Congress. Presented May 26, 2012.

    
相關報導
FDA核准第1型糖尿病幹細胞治療孤兒藥
2010/5/13 下午 05:56:00
第1型糖尿病婦女常見性功能障礙
2009/5/8 下午 01:54:00
免疫系統蛋白可能是早期肺癌的信號
2007/10/22 上午 08:07:00

上一頁
   1   2   3   4  




回上一頁