Insulin resistance assessed by short insulin tolerance test and its association with obesity and insulin resistance-related parameters in humans

The aim of this study was to examine the association of insulin resistance (evaluated by the short insulin tolerance test [SITT]) with parameters related to obesity and insulin resistance. We prospectively recruited controls and patients with type 2 diabetes mellitus (T2DM), subjected them to the SITT, and calculated the K indices of the intravenous insulin tolerance test (KITT(iv)) and the subcutaneous insulin tolerance test (KITT(sc)). We compared KITT(iv) between the volunteers and patients, and examined its correlation with KITT(sc). We also examined the association of KITT(iv) with obesity, insulin resistance-related parameters, and the insulin dose required for glycemic control. A total of 24 participants (seven controls and 17 patients with T2DM) were studied. The mean KITT(iv) was significantly lower in patients with T2DM than in the controls (2.5%±2.1% vs. 4.5±1.8%). In all participants, KITT(iv) was significantly correlated with the HOMA-IR values (r=−0.601, p<0.05) but not with KITT(sc) (p=0.62). KITT(iv) was correlated positively with the serum adiponectin concentration, but negatively with the visceral fat area and serum concentrations of tumor necrosis factor-α and branched-chain amino acids. In patients with T2DM, KITT(iv) and HOMA-IR values were significantly correlated with the total insulin dose required for glycemic control. Insulin resistance evaluated using intravenous insulin (KITT(iv)) was correlated with the HOMA-IR values, but not with the resistance evaluated using subcutaneous insulin (KITT(sc)). The degree of insulin resistance was associated with biomarkers, such as adiponectin, and with the dose of insulin required for glycemic control. ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: Taku Watanabe received lecture fees from Sumitomo Pharma co. Ltd. Ichizo Tsujino receives funding from Janssen Pharmaceutical K.K. for a Joint Research and funding from Nippon Shinyaku Co Ltd, Mochida Pharmaceuticals Co Ltd, Boehringer Ingelheim Japan Co Ltd, Takeyama Co Ltd, Kaneka Co Ltd, and Medical System Network Co Ltd for endowed department. Isao Yokota reports grants from KAKENHI, AMED, and Health, Labour and Welfare Policy Research Grants, research fund by Nihon Medi-Physics, and speaker fees from Chugai Pharmaceutical Co, AstraZeneca, and Pfizer outside the submitted work. ### Clinical Trial approval no. 016-0014 the University Hospital Medical Information Network (UMIN000024453). ### Funding Statement The author(s) received no specific funding for this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: the ethics committee of the Hokkaido University Hospital I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All relevant data are within the manuscript and its Supporting Information files.