Insulin Secretion in Diabetes Before and After Glycemic Control
Condition: Diabetes; Hyperglycemia
MeSH terms: Diabetes Mellitus; Hyperglycemia
Study type: Interventional

Summary: 
      The objective of this project is to understand defects in insulin secretion that contribute
      to abnormal glucose metabolism in patients with diabetes. In particular the effects of
      signals released from the intestine to stimulate insulin secretion will be tested. Patients
      with type 2 diabetes will have insulin secretion in response to glucose and intestinal
      factors before and after insulin treatment to lower their blood glucose. It is expected that
      the results of this work will provide valuable information for treating diabetic people.
    

Detailed description: 
      The objective of this project is to understand defects in insulin secretion that contribute
      to abnormal glucose metabolism in patients with diabetes. Diabetes is a major problem for
      patients receiving care at VA medical centers among whom 20% are affected. Specifically, this
      project will seek to determine the mechanism(s) by which the incretin effect is impaired in
      diabetic patients. The incretin effect refers to the action of GI hormones and neural stimuli
      to increase insulin secretion after food intake, and accounts for approximately 50% of
      postprandial insulin secretion in nondiabetic humans. There are several studies indicating
      that this response is severely impaired in patients with type 2 diabetes. The mechanism(s) by
      which this occurs has not been explained. There is some evidence to suggest that secretion of
      the important incretins, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic
      polypeptide (GIP), may be impaired in diabetic individuals. There is also some data to
      suggest that the beta-cells in persons with diabetes are insensitive to the incretins. The
      problem with the current state of knowledge in this area is that previous work has involved
      small numbers of diabetic subjects, and did not directly test mechanisms by which the
      incretin effect is altered in diabetes.

      In this project we will determine the role of hyperglycemia to impair the incretin effect.
      Type 2 diabetic subjects will have the incretin effect measured before and after intensified
      diabetes treatment. This study will test the effect of chronic hyperglycemia on incretin
      mediated insulin secretion. In all studies, the incretin effect will be measured before and
      after these interventions using studies with a within subjects design. A combined glucose
      clamp/meal tolerance test protocol will be used to quantify the incretin effect.

      These studies will allow the role of incretin secretion, incretin action, and overall
      metabolic milieu, on postprandial insulin secretion to be defined. The results of these
      studies will add important new information for understanding abnormal beta-cell function in
      diabetes. By identifying the sites where the incretin effect is impaired this project will
      provide the basis for new approaches to treat diabetic patients. This is especially relevant
      with the recent availability of new medications that target the incretin pathways to lower
      blood glucose.

      The blood samples will be drawn and processed in the GCRC. The samples will be frozen and
      stored in Building 15, Room 401. Samples will be shipped to the Genome Research Institute by
      staff trained in IATA shipping procedures.
    

Intervention name(s): insulin glargine
Intervention type(s): Drug
Intervention description(s): Diabetic subjects will be treated with insulin glargine once daily for 2 months. Subjects will monitor their blood glucose and have their insulin dose adjusted in steps of 4-6 units to achieve a goal of less than or equal to 120 mg/dl for fasting blood glucose.
Other intervention name(s): Basal insulin; Long-acting insulin; Lantus
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin, Long-Acting
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes; Glucose Tolerance; Incretin; Insulin