Allostasis and the origins of adult-onset diabetes

Abstract

Physiological plasticity enables homeostasis to be maintained in biological systems, but when such allostasis fails, then disease can develop. In a new population-based study by Rolandsson et al (https://doi.org/10.1007/s00125-019-05016-3), autoimmunity, defined by an immunogenotype, predicted adult-onset non-insulin requiring diabetes. Type 1 diabetes is no longer viewed as a disease confined to children, with a significant proportion, maybe the majority, presenting in adulthood. Such cases masquerade as type 2 diabetes and their identification has clinical utility. Nevertheless, in this study, autoimmunity had a limited effect on the overall risk of adults developing diabetes.

Keywords: Autoantibodies; Autoimmunity; C-peptide; Diabetes; Diabetes heterogeneity; Diabetes risk; Genetics.

Fig. 1

Prevalence of detectable C-peptide by age at diabetes onset and disease duration (in years). The plot shows the prevalence of detectable C-peptide by age at onset and duration (years) of the disease. The prevalence of C-peptide was 19% in those who were <15 years old at disease onset and with a disease duration of ≥15 years vs 72% for those who were >35 years old at disease onset, with a disease duration of <15 yeasrs. The diffrence in detectable C-peptide both at baseline and years after diagnosis between younger patients (<15 years old) and older patients (>35 years old) is clear since differences in persistent C-peptide relate to disease age at onset and duration, especially the former. Data from Mckeigue et al [21]

Fig. 2

HRs for incident diabetes comparing GADA⁺ with GADA^– cases within categories of tertiles of BMI and type 1 diabetes mellitus GRS (T1DMGRS). The plot shows the HR for incident diabetes comparing GADA⁺ with GADA^–. High HR has been associated with low BMI (<25 kg/m²); the opposite trend is seen with a high HR for values shown for T1DMGRS. This shows that GADA⁺ cases tend to be both genetically and phenotypically closer to type 1 diabetes than type 2 diabetes. Data from Rolandsson et al [4]