Journal of Personalized Medicine
Normoglycemic Diabetes—A New Disease Concept Complementary to Type 2 Diabetes Mellitus Based on Early Beta-Cell Dysfunction
By Julia Jantz, Petra Wiechel, Uwe Nixdorff and 1 others.
Abstract
Background
The conventional definition of diabetes mellitus is based on the presence of hyperglycemia. However, growing evidence indicates that key pathophysiological processes—particularly β-cell dysfunction—occur well before any measurable increase in blood glucose. These early changes remain undetected by standard diagnostics but are clinically significant.
Objective
This work introduces the proposed concept of normoglycemic diabetes, defined as a pathophysiological state in which conventional glucose criteria remain normal while measurable evidence of early β-cell dysfunction is already present. Particular emphasis is placed on intact proinsulin as a marker of impaired proinsulin processing and β-cell secretory stress.
Methods
A staged model of declining functional β-cell mass is presented, ranging from compensated β-cell stress during normoglycemia to overt secretory failure and dysglycemia, incorporating genetic, epigenetic, and environmental influences. Diagnostic strategies, including extended OGTT assessment and intact proinsulin quantification, and their potential preventive implications are discussed.