Methods of normalizing metabolic parameters in diabetics

• US 5,468,727 A
• Filed: 02/16/1993
• Issued: 11/21/1995
• Est. Priority Date: 12/13/1990
• Status: Expired due to Term

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Green, Gary M., Schwartz, Joyce G., Phillips, William T.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): SALATA, CAROL
• Application Number:
  US08/019,159
• Time in Patent Office: 1,008 Days
• Field of Search: 514/12, 514/13, 514/14, 514/15, 514/16, 530/324
• US Class Current: 514/5.9
• CPC Class Codes: A61K 2123/00 Preparations for testing in vivo
• CPC Class Codes: A61K 38/168 from plants
• CPC Class Codes: A61K 38/2207 Gastrins; Cholecystokinins [CCK]
• CPC Class Codes: A61K 38/55 Protease inhibitors
• CPC Class Codes: A61K 51/0493 Steroids, e.g. cholesterol, testosterone

Abstract

The invention relates to a method of diagnosing and treating individuals with diabetes or at risk to develop diabetes mellitus. In particular, gastric emptying determinations are used to assess risk. Risk or early symptoms associated with subsequent development of diabetes mellitus may be controlled or alleviated by delaying gastric emptying. Delay or inhibition of gastric emptying is sufficient to restore gastric emptying within normal ranges as determined by restoration of typical glucose metabolic parameters such as blood glucose and insulin levels to normal or near normal ranges. The method is also useful in prophylactic treatment of individuals at high risk to develop diabetes mellitus, such as the obese, those with a family history of diabetes and those of particular ethnic and minority groups.

Claims

1. A method of maintaining the following glucose metabolic indicators at or near normal levels;

blood glucose, C-peptide and insulin levels at fasting and during oral glucose tolerance tests, hemoglobin A1C, insulin sensitivity and GIP levels in a human having a early non-insulin dependent diabetic condition and exhibiting rapid grastric emptying, comprising administering to said individual a therapeutically effective dose of POT II, cholecystokinin, cholestyramine or camostat to effectively raise plasma cholecystokinin levels to about 2-3 fold of basal fasting levels of cholecystokinin in said human.

2. The method of claim 1 wherein the early diabetic condition is an impaired glucose tolerance, hyperinsulinemia or insulin resistance.

3. The method of claim 1 wherein the early diabetic condition is borderline diabetes, characterized by at least one of glycosuria, increased thirst, abnormally high blood glucose or insulin, insulin resistance and increased susceptibility to infection.

4. The method of claim 1 wherein the early diabetic condition is non-insulin dependent diabetes mellitus.

5. The method of claim 1 wherein the administered compound comprises POT II and a protein obtained from milk or egg white.

6. The method of claim 5 wherein the POT II effective therapeutic dose is between about 15 to about 25 mg/kg.

7. The method of claim 1 where the administration is oral or by intravenous administration.

8. The method of claim 1 wherein camostat has the structure:

##STR1## and wherein R₁ and R₂ are independently H or lower alkyl and R₃ is O or NH.

9. The method of claim 8 wherein the lower alkyl is methyl, ethyl, or propyl.

10. The method of claim 8 wherein R₁ and R₂ are H and R₃ is O.