Rosiglitazone Intervention Study in Patients With Type 1.5 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Changes in Beta Cell Function Assessed by Fasting and Stimulated C-peptide Measured at 36 Months.
研究概览
简要总结
The purpose of this research was to test whether one treatment was superior over another in the management of type 1.5 diabetes. Specifically we tested recently diagnosed antibody positive type 2 diabetic patients to determine whether treatment with rosiglitazone results in greater preservation of beta cell function compared to treatment with glyburide.
详细描述
Type 1 diabetes and Type 2 diabetes have different underlying pathophysiologic processes. The disease process in classical Type 1 diabetes is an autoimmune destruction of the pancreatic beta cells. In contrast, the disease process in classical Type 2 diabetes is not autoimmune in nature, a decreased sensitivity to insulin action is central to the disease process, and a poorly understood but non-inflammatory beta cell lesion occurs which diminishes insulin secretion. In clinical practice, the diagnosis of Type 1 versus Type 2 diabetes is made phenotypically using variables such as age at onset, apparent abruptness of onset of hyperglycemia, presence of ketosis, degree of obesity (especially central and intra abdominal), prevalence of other autoimmune diseases, and apparent need for insulin replacement. This clinical distinction of Type 1 versus Type 2 diabetes is recognized to be imperfect.
There is also a third group of individuals, who phenotypically are usually like classic Type 2 diabetics but who are positive for one or more of the autoantibodies commonly seen in the Type 1 disease process, namely islet cell antibodies (ICA) and/or insulin autoantibodies (IAA) and/or autoantibodies to glutamic acid decarboxylase (GAD Ab) and/or autoantibodies to the tyrosine phosphatase islet cell autoantibody 512 (IA 2 Ab).
These patients, autoantibody positive [Ab(+)] Type 2 or Type 1.5 diabetes, were the focus of our study. Compared to antibody negative Type 2 diabetics, patients with Type 1.5 diabetes have a more rapid decline in beta cell function, fail sulfonylurea therapy and require insulin therapy earlier (4-13).
Hypothesis: Rosiglitazone treatment will ameliorate or slow the underlying disease process in antibody positive Type 2 diabetes.
Patients meeting the inclusion criteria came in for a baseline visit. The nature of the study was explained and informed consent obtained. A fasting blood sample was obtained for autoantibodies, glucose, C peptide of proinsulin molecule (C-peptide), glycosylated hemoglobin (HbA1c), genetic typing, and T lymphocyte (T cell) responses to islet antigens. The beta cell function test was performed. Patients were then randomized to either rosiglitazone or glyburide.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age at onset of diabetes - 35-69 years old.
- •No history of ketonuria or ketoacidosis.
- •Not requiring insulin to achieve glycemic control.
- •Not receiving more than two oral hypoglycemic agents.
- •Not taking a thiazolidinedione agent.
- •HbA1c in established patients (on an oral hypoglycemia agent for over 4 months) of greater than 6% and under 10%.
- •Fasting c-peptide greater than or equal to 0.8 ng/ml.
- •Women must be either post-menopausal or on adequate birth control (i.e. oral contraceptives, tubal ligation, hysterectomy, condoms, or diaphragm) or use abstinence.
排除标准
- •Patients with history of chronic pancreatitis or other secondary causes of diabetes.
- •Patients receiving systemic corticosteroids.
- •Patients with severe systemic illness (e.g. recent MI, CHF or cerebral vascular disease).
- •Creatinine greater than 1.4 or liver enzymes greater than 2 times the upper limits of normal.
- •Not able to adhere to the protocol.
研究组 & 干预措施
rosiglitazone
Rosiglitazone is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. The rosiglitazone treatment group commenced therapy with 4 mg once per day and increase to twice per day if adequate glycemic control was not achieved.
干预措施: rosiglitazone (Drug)
glyburide
Glyburide is a sulfonylurea. Glyburide therapy was initiated with 2.5 mg in the morning or the patient was maintained on the dose they had been receiving prior to starting the study. This starting dose was raised by 2.5 in the evening and further up to a maximum of 10 mg twice a day if necessary to achieve desired glycemic control.
干预措施: glyburide (Drug)
结局指标
主要结局
Changes in Beta Cell Function Assessed by Fasting and Stimulated C-peptide Measured at 36 Months.
时间窗: 36 months
Changes in beta cell function assessed by fasting and stimulated C-peptide measured at 36 months.
次要结局
- Patients Positive for T Cell Responses to Islet Proteins at 36 Months.(36 months)