Mechanism Underlying Beta-cell Failure in Obese African Americans With History of Hyperglycemic Crises
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- First-Phase Insulin Release (FPIR)
研究概览
简要总结
Obesity is common in African American (AA) patients with newly diagnosed diabetes who present with diabetic ketoacidosis (DKA). Despite the presentation with severe symptoms of insulinopenia and ketoacidosis, clinical and immunogenetic observations indicate that most obese AA patients with DKA have type 2 diabetes. In such patients, previous studies reveal that: a) at presentation, obese AA patients with DKA have markedly decreased pancreatic insulin secretion, lower than in obese non-DKA patients admitted with comparable hyperglycemia, but significantly greater than in lean patients with DKA; b) aggressive diabetic management results in significant improvement in beta-cell function and insulin sensitivity sufficient to allow discontinuation of insulin therapy within 3 months of follow-up. Based on these observations the researchers conclude that similar to obese patients with hyperglycemia, most obese AA with DKA have type 2 diabetes, and that although defects in both insulin secretion and insulin action are present, transient b-cell failure is the primary defect in the development of ketoacidosis.
详细描述
Obese AA patients with a history of DKA who later experience near-normoglycemia remission represent an ideal population in which to define the sequence of events that lead to b-cell dysfunction in type 2 diabetes. The researchers hypothesize that obese AA with DKA will prove particularly susceptible to beta-cells dysfunction due to sustained elevations of plasma glucose (glucose toxicity) and/or free fatty acid levels (lipotoxicity). This study will test beta-cell response by administering a glucose infusion to diabetic African Americans with a history of DKA, diabetic African Americans without a history of DKA, and non-diabetic African Americans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Obese African American subjects (body mass index (BMI) equal or greater than 30)
- •Age 18-65
- •Patients with a history of diabetic ketoacidosis as defined by the American Diabetes Association (ADA) criteria
- •Patients admitted with hyperglycemia but without ketoacidosis (blood glucose greater than 400ml/dl without evidence of ketosis/ketones
- •Obese nondiabetic controls (BMI >30; ruled out for diabetes with a 75g oral glucose tolerance test)
排除标准
- •Patients with positive autoimmune markers (islet cell or glutamic acid decarboxylase (GAD) autoantibodies)
- •Patients with significant medical or surgical illness, including but not limited to myocardial ischemia, congestive heart failure, chronic renal insufficiency, liver failure, and infectious processes
- •Patients with recognized or suspected endocrine disorders associated with increased insulin resistance, such as hypercortisolism, acromegaly, or hyperthyroidism
- •Patients with bleeding disorders, thrombocytopenia, or abnormalities in coagulation studies
- •Patients with fasting hyperglycemia (blood glucose > 120 mg/dl) after discontinuation of insulin therapy
- •Pregnancy
研究组 & 干预措施
Participants with ketosis-prone diabetes
Obese African Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA) receiving Intralipid 20% and a glucose infusion.
干预措施: Intralipid 20% (Drug)
Participants with ketosis-prone diabetes
Obese African Americans with type 2 diabetes with history of diabetic ketoacidosis (DKA) receiving Intralipid 20% and a glucose infusion.
干预措施: Glucose infusion (Drug)
Participants with ketosis-resistant diabetes
Obese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion.
干预措施: Intralipid 20% (Drug)
Participants with ketosis-resistant diabetes
Obese African American with type 2 diabetes with hyperglycemia without ketosis receiving Intralipid 20% and a glucose infusion.
干预措施: Glucose infusion (Drug)
Non-diabetic control group
Obese African Americans without diabetes receiving a glucose infusion.
干预措施: Glucose infusion (Drug)
结局指标
主要结局
First-Phase Insulin Release (FPIR)
时间窗: Hour 0, Hour 20
An arginine stimulation test was used to evaluate beta-cell function and insulin secretion. Increased glucose in the blood causes insulin to be released, beginning with a spike in insulin in the first 10 minutes and plateauing 2 to 3 later. Diminished first-phase insulin release is an early indicator of beta-cell dysfunction. Two sequential arginine stimulation tests were performed, the first set before and the second after completion of the 20-hour dextrose infusion. The first-phase insulin release (FPIR) was calculated as the sum of the insulin levels at 2, 3, 4, and 5 minutes after the arginine infusion. FPIR is expected to rise after the dextrose (glucose) infusion and FPIR generally rises less in persons with impaired glucose tolerance.
次要结局
- Number of Participants With Beta-cell Failure(Hour 20)
研究者
Guillermo Umpierrez, MD
Professor
Emory University