268-OR: Insulin Resistance in the Liver, but Not Muscle or Adipose, Is Essential for Remission from Newly Diagnosed Type 2 Diabetes by Short-Term Insulin Intensive Therapy

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.