The full content of Annals is available to subscribers

Subscribe/Learn More  >
Mechanisms of Diabetic Complications: The Glucose Hypothesis |

The Pathophysiology of Diabetic Complications: How Much Does the Glucose Hypothesis Explain?

David M. Nathan, MD
[+] Article, Author, and Disclosure Information

From Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. For the current author address, see end of text. Note: This article is one of a series of articles comprising an Annals of Internal Medicine supplement entitled “Risks and Benefits of Intensive Management in Non-Insulin-dependent Diabetes Mellitus: The Fifth Regenstrief Conference.” To view a complete list of the articles included in this supplement, please view its Table of Contents. Grant Support: In part, by the Diabetes Control and Complications Trial (NIDDK UO1 DK30643-13) and the Mallinckrodt General Clinical Research Center (RR01066-18). Requests for Reprints: David M. Nathan, MD, Diabetes Unit, Massachusetts General Hospital, Boston, MA 02114.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1996;124(1_Part_2):86-89. doi:10.7326/0003-4819-124-1_Part_2-199601011-00002
Text Size: A A A

Objective: To examine the putative pathogenetic mechanisms of the long-term, specific complications of diabetes mellitus.

Data Sources: Literature review relevant to long-term diabetic complications and their pathogenesis.

Study Selection: Studies of animal models of diabetes, epidemiologic investigations of diabetes and its long-term complications, and interventional studies examining intensive treatment of diabetes and its effect on the development and progression of complications.

Data Synthesis: Diabetic retinopathy, nephropathy, and neuropathy occur in all clinical forms of diabetes mellitus, regardless of the cause of the diabetes. Hyperglycemia appears to be the major variable shared among these different clinical forms; and epidemiologic data, studies in animal models of diabetes, and the results of recent interventional studies such as the Diabetes Control and Complications Trial, all support an important and perhaps dominant role of hyperglycemia in the pathogenesis of complications. However, the diverse complications may not share the same pathogenesis. Different pathogenetic mechanisms may operate in different types of diabetic complications or at different stages of specific complications, or both.

Conclusions: The level of chronic glycemia is the best established concomitant factor associated with diabetic complications. The mechanism by which hyperglycemia might cause complications remains unknown, and evidence for a uniform pathogenetic mechanism is far from established.





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 $32.00

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.