Increased Glucagon Secretion Not Indispensable Prerequisite for the Development of Diabetes

Only one subgroup of type 2 diabetes (T2D) has elevated glucagon levels. This is the finding of a study conducted by DZD researchers in Munich. The scientists studied glucagon levels in young women with different levels of risk for T2D during an oral glucose tolerance test*. They discovered four patterns of glucagon dynamics that did not match the metabolic phenotypes. The results have now been published in the “Journal of Clinical Endocrinology & Metabolism”.

Four patterns of glucagon curves during oral glucose tolerance testing. (Colors: blue = controls, gray = metabolically healthy high risk, red = prediabetes/diabetes). © JCEM/Group Lechner

It is known that glucagon is the main antagonist of insulin, but just what role the hormone plays in the onset of type 2 diabetes is still under debate among scientists. A research team compared glucagon secretion in young women with three different metabolic phenotypes during an oral glucose tolerance test. The groups were: a healthy control group (93 women),  metabolically healthy women after gestational diabetes (high-risk group for type 2 diabetes, 121 women) and 71 women who were newly diagnosed with diabetes or prediabetes.

The analysis showed that there are four patterns of glucagon dynamics but that the found patterns did not match the three different metabolic groups. However, one pattern elevated fasting glucagon levels with delayed glucagon suppression – was particularly common in women with diabetes and prediabetes (21 percent), but this cluster was also discovered in 8 percent of healthy women. Conversely, the majority of women in the prediabetes / diabetes group (n = 39; 55%) had glucagon levels in the normal range with low fasting glucagon and rapid suppression. In addition, in the cluster of high fasting glucagon and poor glucagon suppression, there were increased symptoms of metabolic syndrome (high blood pressure, visceral obesity, and high blood lipids).

The authors of the study therefore assume that increased glucagon secretion in a subgroup can contribute to the development of type 2 diabetes, but this is not an indispensable prerequisite for the development of diabetes.

The study of the DZD, the Medical Center of the University of Munich and Helmholtz Zentrum München was published in the March issue of Journal of Clinical Endocrinology & Metabolism.

Original Publication:
Gar, C. et al. (2018): Patterns of Plasma Glucagon Dynamics Do Not Match Metabolic Phenotypes in Young Women. J Clin Endocrinol Metab; DOI: 10.1210/jc.2017-02014

*Background Information:
Oral Glucose Tolerance Test (oGTT)
The oGTT provides evidence of the body's ability to break down a defined amount of glucose within a given period of time. For this purpose, 75 g of glucose are consumed as a sugar solution on an empty stomach. Subsequently, blood is taken at certain intervals and tested for sugar content.