The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Slow Glucose Removal Rate and Hyperinsulinemia Precede the Development of Type II Diabetes in the Offspring of Diabetic Parents

James H. Warram, MD, SCD; Blaise C. Martin, MD; Andrzej S. Krolewski, MD, PhD; J. Stuart Soeldner, MD; and C. Ronald Kahn, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by grants from the Diabetes Association of Fall River and the American Diabetes Association, grants DK-36836 and DK-33201 from the National Institutes of Health, and a grant from the Joslin Diabetes Center.

Requests for Reprints: James H. Warram, MD, ScD, Section on Epidemiology and Genetics, Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.

Current Author Addresses: Drs. Warram, Krolewski, and Kahn: Research Division, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215.

Dr. Martin: Institut für Sozial- und Päventivmedizin der Universitat Zurich, Sumatrastrasse 30, CH-8006 Zurich, Switzerland.

Dr. Soeldner: Division of Endocrinology, University of California Davis Medical Center, 1625 Alhambra Boulevard, Room 2901, Sacramento, CA 95816.

© 1990 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1990;113(12):909-915. doi:10.7326/0003-4819-113-12-909
Text Size: A A A

Objective: To determine whether insulin resistance or insulin deficiency is primary in the pathogenesis of type II diabetes.

Design: Cohort analytic study of persons with normal glucose tolerance but with a high risk for developing type II diabetes (average follow-up time, 13 years).

Setting: Outpatients had an intravenous glucose tolerance test and were contacted periodically to ascertain diagnoses of diabetes.

Participants: One hundred and fifty-five normal offspring, ranging in age from 16 to 60 years, of two parents with type II diabetes and 186 normal control subjects in the same age range who had no family history of diabetes.

Measurements and Main Results: Two phenotypic characteristics distinguished the offspring of diabetic parents from control subjects. They had slower glucose removal rates (Kg) (P < 0.01) and higher insulin levels (fasting and during the second phase of insulin response to intravenous glucose; P < 0.0001) than did control subjects, even after adjustment for differences in obesity. Sixteen percent of the offspring developed type II diabetes. Mean Kg at baseline was 1.7%/min among offspring who subsequently developed diabetes, 2.2%/min among offspring who remained nondiabetic, and 2.3%/min among control subjects. Corresponding means for first-phase insulin were 498, 354, and 373 pM, respectively, whereas second-phase insulin means were 329, 117, and 87 pM, respectively. In multivariate analysis, low Kg and high serum insulin levels independently increased the risk for developing diabetes among the offspring of diabetic parents.

Conclusions: One to two decades before type II diabetes is diagnosed, reduced glucose clearance is already present. This reduced clearance is accompanied by compensatory hyperinsulinemia, not hypoinsulinemia, suggesting that the primary defect is in peripheral tissue response to insulin and glucose, not in the pancreatic beta cell.





Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $42.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.