To clarify the effects of insulin resistance from different tissues on the remission from newly diagnosed type 2 diabetes (T2DM) following short-term insulin intensive therapy (SIIT). This study enrolled 37 healthy controls and 160 patients with newly diagnosed type 2 diabetes mellitus (n=160, HbA1c11±2.1%). They were randomly divided to four groups, CSII alone for 2 weeks, or combination with an insulin sensitizer (CSII + metformin or CSII + rosiglitazone), or an antioxidant (CSII + α-lipoic acid). HOMA-IR, Adipo-IR and intramyocellular lipid (IMCL), were compared before and after termination of CSII. After short-term intensive treatment, 77.5% patients achieved normal HOMA-IR but little change in the Adipo-IR. The IMCL were nearly normalized except for those in metformin group, impacted by the lower insulin dose. The improvement of HOMA-IR and FFA, not IMCL or Adipo-IR, statistically related to the percentage declines of FPG (r=0.317 and 0.275), while only the HOMR-IR was associated with ΔPPG% (r=0.284). And 40.6% patients achieved sustained normal HOMA-IR in the first 3 months after CSII and attained 50% remission rate at the 5-year, far beyond 8.9% in the other patients (HR = 2.82 95% CI is1.813-4.388, p<0.001). Besides, slight superiority has occurred with HOMA-IR, Adipo-IR and IMCL in the CSII+ rosiglitazone group. In brief, short-term CSII therapy, with or without insulin sensitizers, is extremely effective in improving insulin resistance, even normalizing the HOMA-IR and IMCL. Sustained normal hepatic insulin resistance is essential for remission from T2DM. Insulin reversed ectopic fat in muscle with dose effect and the combination therapy with rosiglitazone is superior.
X. Wan: None. Z. Huang: None. Y. Li: None.