Cerebrospinal Fluid Changes in Insulin-Resistant Men
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Abnormal concentrations of CSF biomarkers related to Alzheimer's disease
研究概览
简要总结
Type 2 diabetes mellitus has been associated with an about 2-fold increase in risk of Alzheimer's disease (AD). Patients with AD have been reported to have reduced insulin sensitivity. It may be hypothesized that, compared to insulin sensitive subjects otherwise similar in general health and body habitus, insulin resistant subjects are more likely to have cerebrospinal fluid (CSF) indicators of incipient AD pathology, abnormalities in CSF peptides related to insulin signaling and glucose homeostasis, and possibly other metabolites that are associated with a risk of AD. The objective of this study is to examine the relation of insulin resistance and the concentrations of CSF biomarkers. The results of this study may be useful in the detection of the subjects who are at risk for cognitive decline and AD.
详细描述
Type 2 diabetes mellitus has been associated with an approximately 2-fold increase in risk of Alzheimer's disease (AD). Patients with AD have been reported to have reduced insulin sensitivity, and to have insulin concentrations that are elevated in plasma and decreased in cerebrospinal fluid (CSF). Cognitively normal individuals with insulin resistance are thus of interest in our effort to gain an understanding of the antecedents of this problem. It may be hypothesized that, compared to insulin sensitive subjects otherwise similar in general health and body habitus, insulin resistant subjects are more likely to have CSF indicators of incipient Alzheimer pathology, abnormalities in CSF peptides related to insulin signaling and glucose homeostasis, and possibly other metabolites that are associated with a risk of AD.
The objectives are to 1) assess the concentrations of biomarkers of Alzheimer pathology in the CSF of cognitively normal men with and without insulin resistance, and 2) assess the concentrations of other CSF biomarkers of potential relevance to insulin resistance and AD in the CSF of cognitively normal men with and without insulin resistance.
All subjects with eligibility will have had an oral glucose tolerance test performed within the past 3 months that revealed a normal fasting blood level and normal glucose tolerance. In addition, they will have had no history of significant cognitive disorders, no prior diagnosis of diabetes mellitus, and will not be receiving insulin or oral hypoglycemic. Eligibility for inclusion in the insulin-resistant group will be defined by scores on the Matsuda Index; non-insulin resistant controls will have normal values on the Matsuda Index. An effort will be made to ensure that both groups (i.e., those with insulin resistance and those without insulin resistance) will be similar in age, weight, BMI, and Apo E4 genotype (APOE).
All procedures will be performed on a single visit. The subjects will undergo a Mini-Mental Status Examination (MMSE) performed by a qualified examiner. In addition, a blood sample will be obtained for measurements of basic blood chemistry (electrolytes, creatinine, glucose, total protein, and albumin), hematology, thyroid function, metabolic function (e.g. fasting plasma glucose and insulin levels) and for proteomic analysis. The APOE genotype will be determined from the blood samples, if it has not been assessed earlier. A lumbar puncture will be performed to obtain CSF samples that will be used to determine concentrations of biomarkers of AD pathology and to find out new biomarkers that may reflect AD pathology.
All materials will be used according to national ethical guidelines for Good Clinical Practice. Analyses of the CSF for levels of beta-Amyloid biomarkers, total tau and phosphorylated tau will be done using a sandwich ELISA. Descriptive statistics will be provided for each analyte, comparing the 2 groups of subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 55 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Males 55-70 years in age
- •Normal cognitive function, as evidenced by the following:
- •Living independently in the community,
- •No memory complaints; Score on Mini Mental State Examination >= 25 (Folstein 1975),
- •Score on Functional Activities Questionnaire < 9
- •Has had oral glucose tolerance test including determination of plasma glucose and insulin levels at baseline and 30 and 120 minutes within the past 3 months, meeting the following criteria:
- •Normal fasting blood glucose (<7.0 mmol/l),
- •Normal glucose tolerance at 120 minutes (<11.1 mmol/l),
- •Meets criteria for either normal insulin sensitivity or insulin resistance, based upon the Matsuda insulin sensitivity index
- •Willing to have lumbar puncture
排除标准
- •Evidence of significant neurological disease, including
- •Abnormal neurological examination,
- •History of stroke (other than lacunar infarction),
- •prior diagnosis of mild cognitive impairment, significant head injury with impairment of consciousness > 24h, brain tumor, multiple sclerosis, epilepsy, or hydrocephalus,
- •Diagnosis or family history consistent with autosomal dominantly inherited AD
- •Prior diagnosis of diabetes mellitus type 1 or 2
- •Evidence of significant metabolic or endocrine disorder associated with risk of cognitive impairment, e.g., hypothyroidism or B12 deficiency
- •Major psychiatric disorder, including psychosis
- •Evidence of significant systemic disease, including: congestive heart failure, renal failure, hepatic cirrhosis, significant chronic obstructive pulmonary disease, cancer within the past 5 years (other than nonmetastatic basal cell and squamous cell carcinoma of the skin)
- •Excluded concomitant medications:
- •Acetylcholinesterase inhibitors, Memantine (Alzheimer's disease medications),
- •Insulin or oral hypoglycemics,
- •Anticoagulants (excluding aspirin, clopidogrel, dipyridamole, or other antiplatelet drugs),
- •Neuroleptic drugs, including risperidone, olanzapine, quetiapine, and ziprasidone,
- •Receipt of an investigational drug within the past 30 days (or within 5 half-lives of an investigational drug, whatever is longest)
结局指标
主要结局
Abnormal concentrations of CSF biomarkers related to Alzheimer's disease
时间窗: during a single visit, i.e., day 1
次要结局
- Abnormal concentrations of other CSF biomarkers of potential relevance to insulin resistance and Alzheimer's disease(during a single visit, i.e., day 1)
研究者
Hilkka Soininen
Professor
University of Eastern Finland