Gale E A M, Bingley P J, Emmett C L, Collier T
University of Bristol, UK.
Lancet. 2004 Mar 20;363(9413):925-31. doi: 10.1016/S0140-6736(04)15786-3.
Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of beta-cell NAD depletion. We aimed to assess whether high dose nicotinamide prevents or delays clinical onset of diabetes in people with a first-degree family history of type 1 diabetes.
We did a randomised double-blind placebo-controlled trial of nicotinamide in 552 relatives with confirmed islet cell antibody (ICA) levels of 20 Juvenile Diabetes Federation (JDF) units or more, and a non-diabetic oral glucose tolerance test. Participants were recruited from 18 European countries, Canada, and the USA, and were randomly allocated oral modified release nicotinamide (1.2 g/m2) or placebo for 5 years. Random allocation was done with a pseudorandom number generator and we used size balanced blocks of four and stratified by age and national group. Primary outcome was development of diabetes, as defined by WHO criteria. Analysis was done on an intention-to-treat basis.
There was no difference in the development of diabetes between the treatment groups. Of 159 participants who developed diabetes in the course of the trial, 82 were taking nicotinamide and 77 were on placebo. The unadjusted hazard ratio for development of diabetes was 1.07 (95% CI 0.78-1.45; p=0.69), and the hazard ratio adjusted for age-at-entry, baseline glucose tolerance, and number of islet autoantibodies detected was 1.01 (0.73-1.38; p=0.97). Of 168 (30.4%) participants who withdrew from the trial, 83 were on placebo. The number of serious adverse events did not differ between treatment groups. Nicotinamide treatment did not affect growth in children or first-phase insulin secretion.
Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.
动物和人类研究结果表明1型糖尿病是可预防的。烟酰胺可预防动物模型中的自身免疫性糖尿病，可能是通过抑制DNA修复酶聚-ADP-核糖聚合酶并防止β细胞NAD耗竭。我们旨在评估高剂量烟酰胺是否能预防或延缓有1型糖尿病一级家族史人群的糖尿病临床发病。
我们对552名亲属进行了一项随机双盲安慰剂对照试验，这些亲属的胰岛细胞抗体（ICA）水平经确认达到20青少年糖尿病联盟（JDF）单位或更高，且口服葡萄糖耐量试验结果为非糖尿病。参与者从18个欧洲国家、加拿大和美国招募，随机分配口服缓释烟酰胺（1.2 g/m²）或安慰剂，为期5年。随机分配使用伪随机数生成器进行，我们使用大小为4的平衡区组，并按年龄和国家组进行分层。主要结局是根据WHO标准定义的糖尿病发生情况。分析采用意向性分析。
治疗组之间糖尿病的发生情况没有差异。在试验过程中发生糖尿病的159名参与者中，82人服用烟酰胺，77人服用安慰剂。糖尿病发生的未调整风险比为1.07（95%CI 0.78-1.45；p=0.69），调整入组年龄、基线葡萄糖耐量和检测到的胰岛自身抗体数量后的风险比为1.01（0.73-1.38；p=0.97）。在退出试验的168名（30.4%）参与者中，83人服用安慰剂。治疗组之间严重不良事件的数量没有差异。烟酰胺治疗不影响儿童生长或第一相胰岛素分泌。
旨在预防1型糖尿病发病的干预措施的大规模对照试验是可行的，但我们使用的剂量的烟酰胺无效。
