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Randomized Controlled Trial
. 2024 Jun 21;19(6):e0297718.
doi: 10.1371/journal.pone.0297718. eCollection 2024.

Insulin resistance assessed by short insulin tolerance test and its association with obesity and insulin resistance-related parameters in humans: A pilot randomized trial

Akiko Hayashishita  1 , Taku Watanabe  1 , Naoko Suzuki  1 , Toshitaka Nakaya  1 , Ayako Sugimoto  1 , Isao Yokota  2 , Hiroshi Ohira  1 , Masaharu Nishimura  1 , Ichizo Tsujino  1
Affiliations
Randomized Controlled Trial

Insulin resistance assessed by short insulin tolerance test and its association with obesity and insulin resistance-related parameters in humans: A pilot randomized trial

Akiko Hayashishita et al. PLoS One. .

Abstract

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) results 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 homeostasis model assessment for insulin resistance (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 KITT(iv) was correlated with the HOMA-IR values, but not with the resistance evaluated using KITT(sc). The degree of insulin resistance was associated with biomarkers, such as adiponectin, tumor necrosis factor-α, branched-chain amino acids, the visceral fat area, and the dose of insulin required for glycemic control.

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Conflict of 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. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flow diagram of the allocation.
The 24 subjects were registered using a central registration system and were assigned on 1:1 basis by the research office. The participants were assigned to undergo either of the following pathways:1) the SITT first, followed by the ITTsc or 2) the ITTsc first, followed by the SITT.
Fig 2
Fig 2. Relationship of KITT(iv) with the HOMA-IR value and KITT(sc).
(a) KITT(iv) was significantly correlated with the HOMA-IR value (ρ = −0.520). (b) KITT(iv) was not correlated with KITT(sc). KITT(iv), K index of the intravenous insulin tolerance test; HOMA-IR, homeostasis model assessment for insulin resistance; KITT(sc), K index of the subcutaneous insulin tolerance test.
Fig 3
Fig 3. Relationship of KITT(iv) with other parameters.
(a) KITT(iv) was negatively correlated with the visceral fat area (ρ = −0.466), (b) fasting plasma glucose (ρ = −0.798), (c) fasting serum C-peptide (ρ = −0.436), (e) TNF-α (ρ = −0.680), and (f) BCAA/total AA (ρ = −0.683). (d) It was positively correlated with the adiponectin level (ρ = 0.532). KITT(iv), K index of the intravenous insulin tolerance test; TNF-α, tumor necrosis factor-α; BCAA, branched-chain amino acid; AA, amino acid.
Fig 4
Fig 4. Relationship of KITT(iv) and the HOMA-IR value with the mean total insulin dose/kg.
(a) KITT(iv) was significantly correlated with the mean total insulin dose per body weight (ρ = −0.656); this was estimated using with the following regression equation: total insulin dose/kg = 0.78–0.10 × KITT(iv). (b) The HOMA-IR value was also significantly correlated with the mean total insulin dose per body weight (ρ = 0.756); this was estimated using with the following regression equation: total insulin dose/kg = 0.23+0.15 × HOMA-IR. KITT(iv), K index of the intravenous insulin tolerance test; HOMA-IR, homeostasis model assessment for insulin resistance.
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