Undernutrition-Associated Diabetes Mellitus: Pathophysiology of a Global Problem

Abstract

Early-life undernutrition is known to be a potentially important risk factor for the development of diabetes mellitus in adult life. Additionally, some literature suggests that undernutrition during later life or adulthood may lead to metabolic consequences, including diabetes, despite an individual's normal nutritional status earlier in life. Notably, individuals with diabetes and undernutrition show some unique features that do not fit the usual phenotype of type 2 diabetes mellitus, such as a low body mass index of <18.5 kg/m², resistance to ketosis, and low serum C-peptide levels. Many global descriptions of this unique phenotype have led to a controversy that "undernutrition-associated diabetes mellitus" is a distinct form of diabetes, deserving a separate diabetes category in the WHO classification of diabetes. However, a few investigators argue that undernutrition-associated diabetes mellitus is one of the variants of the classical forms of diabetes. The second controversy is whether adult undernutrition is independently associated with metabolic abnormalities. Its pathophysiology has been difficult to determine, given confounding factors such as infections that can complicate the direct effects of malnutrition. Studies have shown that insulin deficiency due to pancreatic β-cell impairment is likely to contribute to the development of undernutrition-associated diabetes. To examine these controversies, further research is warranted to understand the role of undernutrition in the pathogenesis of undernutrition-associated diabetes. This review aims to shed more light on these controversies, focusing on whether diabetes in malnourished individuals represents a distinct diabetes category and the association between malnutrition and diabetes in adults.

Keywords: insulin deficiency; insulin secretion; lean diabetes; low BMI; undernutrition.

Figure 1:

Global Map of Countries Reporting Undernutrition-associated Diabetes

Figure 2:

The proposed pathophysiological mechanisms of undernutrition-associated diabetes mellitus

Figure 3:

The proposed vicious cycle of insulin deficiency