Subgroups of Adult‐Onset Diabetes: A Prospective Follow‐Up Study of Progression of Insulin Resistance and Deficiency and Association With Liver Steatosis and Fibrosis

AIMS: To assess progression of insulin deficiency and resistance in diabetes, the stability of cluster-based subgrouping, and the association between steatotic liver disease (SLD), liver fibrosis (LF), and tissue insulin resistance. MATERIALS AND METHODS: Participants from a regional diabetes register were studied within 3 years from diagnosis and 2-10 years later with fasting laboratory tests (n = 547). A subset (n = 194) participated in an investigation with i.v. glucagon-insulin tolerance test, and elastography. RESULTS: , HbA1c: +0.1[0.7]%, +1.0[8.0]mmol/mol, HOMA2-B: -2.5[35.9], HOMA2-IR -0.1[1.1]; p < 0.001). Overall, the differences between the subgroups diminished and < 25% in the smaller groups characterized by insulin deficiency or resistance retained the same cluster compared with > 76% in the obesity- and age-related subgroups. HOMA2-IR decreased significantly, but remained highest in the group initially characterized by insulin resistance. In the whole cohort, SLD was mainly related to BMI, while LF was associated with insulin resistance in liver (HOMA2-IR: OR 3.90 [95% CI 2.05-7.42]) and adipose tissue (1.14 [1.06-1.22]) and insulin sensitivity in muscle (0.33 [0.17-0.64]). There were no statistically significant differences between subgroups in SLD/LF after adjusting for confounders. CONCLUSIONS: Subgrouping should be performed near diagnosis, as the more severe phenotypic features attenuate with time (or treatment). To assess the risk of LF, the degree of insulin resistance should be evaluated, not only BMI.