Clinical Research on Insulin Resistance

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 15407

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Department of Endocrinology and Diabetes, INI Institute, Rome, Italy
Interests: diabetes; endocrinology; OSAS
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ASSL Olbia, Via Bazzoni-Sircana 2, 07026 Olbia, Italy
Interests: hypertension; diabetes complications; cardiovascular system; metabolic syndrome; clinical nutrition; diabetes; cardiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Insulin sensitivity (also defined by its reciprocal value “insulin resistance”) is the main regulator of the metabolic processes of the body, and, consequently, its derangement leads to metabolic disorders, the most well-known being type 2 diabetes mellitus and so-called “metabolic syndrome”. The level of insulin sensitivity is in turn regulated by other hormones, e.g., catecholamines and GH, by the nervous system, and by many local molecules. We also know that the level of insulin sensitivity varies among different tissues, and this may have an important impact on our physiology and on the pharmacokinetics of most drugs, notably insulin. At present, we have simple measures of insulin resistance that can help us in our clinical work. The most well-used, HOMA-IR, is mostly useful in the follow-up of patients, but still has a level of uncertainty and does not identify the level of insulin sensitivity of different tissues. The same is true for the Matsuda Index and many others. We need a simple index and a robust algorithm that can at least help us determine the insulin sensitivity of the most relevant organs, such as the liver, heart, and adipose tissue. The aim of this Special Issue is to invite all researchers in the field of insulin resistance to contribute with their work to define where we are, the strengths and the limitations of what we have, and to pave the way for better knowledge on and a new therapy of this critical physiologic process and its derangement.

Prof. Dr. Patrizio Tatti
Prof. Dr. Giancarlo Tonolo
Guest Editors

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Keywords

  • insulin-resistance
  • insulin sensitivity
  • metabolic syndrome
  • type 2 diabetes
  • insulin receptor
  • insulin action

Published Papers (8 papers)

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Editorial

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4 pages, 206 KiB  
Editorial
Insulin Resistance: An Unresolved Riddle
by Patrizio Tatti and Pavandeep Singh
J. Clin. Med. 2023, 12(19), 6394; https://doi.org/10.3390/jcm12196394 - 7 Oct 2023
Viewed by 673
Abstract
Insulin resistance (IR) is a rather common condition that is often diagnosed on the basis of an arbitrary “increased insulin value” or the presence of symptoms indicative of the Metabolic Syndrome [...] Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)

Research

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11 pages, 648 KiB  
Article
Indirect Insulin Resistance Indices and Their Cut-Off Values for the Prediction of Post-Transplantation Diabetes Mellitus in Kidney Transplant Recipients
by Sara Sokooti, Tamás Szili-Török, Hiddo J. L. Heerspink, Robin P. F. Dullaart and Stephan J. L. Bakker
J. Clin. Med. 2023, 12(23), 7296; https://doi.org/10.3390/jcm12237296 - 24 Nov 2023
Viewed by 961
Abstract
Background: Insulin resistance plays an important role in the development of post-transplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTRs). Current methods for the direct determination of insulin resistance are complicated and invasive. Therefore, this study aimed to investigate the relevance of indirect [...] Read more.
Background: Insulin resistance plays an important role in the development of post-transplantation diabetes mellitus (PTDM) in kidney transplant recipients (KTRs). Current methods for the direct determination of insulin resistance are complicated and invasive. Therefore, this study aimed to investigate the relevance of indirect insulin resistance indices in relation to the development of PTDM in KTRs. Methods: We included 472 stable outpatient KTRs without diabetes at baseline from a prospective cohort study. Four indirect insulin resistance indices, namely homeostasis model assessment–insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), and triglycerides–glucose (TyG) index, were assessed. We analyzed each measure using the receiver operating characteristic (ROC) curve for PTDM development. The optimal cut-off value for each parameter was determined using the Youden index. Results: After a median of 9.6 years (interquartile range (IQR) 6.6–10.2) of follow-up, 68 (14%) KTRs developed PTDM. In Cox regression analyses, all indirect insulin resistance indices associated with incident PTDM were independent of potential confounders. ROC curve was 0.764 (95% CI, 0.703–0.826) for HOMA-IR, 0.685 (95% CI, 0.615–0.757) for VAI, 0.743 (95% CI, 0.678–0.808) for LAP, and 0.698 (95% CI, 0.629–0.766) for TyG index, with respective optimal cut-off values of 2.47, 4.01, 87.0, and 4.94. Conclusions: Indirect insulin resistance indices can be used to predict incident PTDM in KTRs. In addition to HOMA-IR, insulin-free surrogates of insulin resistance might serve as useful methods to identify KTRs at risk of PTDM, thus obviating the necessity to measure insulin. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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11 pages, 1425 KiB  
Article
Gamma-Glutamyltransferase Is a Predictor for Future Changes of Diabetogenic Factors in Aged Chinese—A Four-Year Follow-Up Study
by Man Sze Wong, Chun Yen Jun Lo, Yen-Lin Chen, Fang-Yu Chen, Chun-Heng Kuo, Jin-Shuen Chen, Dee Pei, Pietro Pitrone and Chung-Ze Wu
J. Clin. Med. 2023, 12(17), 5606; https://doi.org/10.3390/jcm12175606 - 28 Aug 2023
Viewed by 851
Abstract
Glucose homeostasis in the body is determined by four diabetes factors (DFs): insulin resistance (IR), glucose effectiveness (GE), and the two phases of insulin secretion—first phase (FPIS) and second phase (SPIS). Previous research points to a correlation between elevated levels of gamma-glutamyl transferase [...] Read more.
Glucose homeostasis in the body is determined by four diabetes factors (DFs): insulin resistance (IR), glucose effectiveness (GE), and the two phases of insulin secretion—first phase (FPIS) and second phase (SPIS). Previous research points to a correlation between elevated levels of gamma-glutamyl transferase (γGT) and an increased risk of type 2 diabetes. This study investigates the relationship between γGT and the four DFs in older Chinese individuals. This study involved 2644 men and 2598 women, all of whom were relatively healthy Chinese individuals aged 60 years or more. The DFs were calculated using formulas developed by our research, based on demographic data and factors related to metabolic syndrome. Pearson’s correlation was utilized to assess the relationship between γGT and the four DFs. The findings suggested a positive correlation between γGT and IR, FPIS, and SPIS, but a negative correlation with GE in men. Among women, only SPIS and GE were significantly correlated with γGT. The factors showed varying degrees of correlation, listed in descending order as follows: GE, SPIS, FPIS, and IR. This study confirms a significant correlation between γGT and DFs in this population, highlighting the noteworthy role of GE. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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19 pages, 2191 KiB  
Article
A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men
by Satoshi Kadowaki, Yoshifumi Tamura, Daisuke Sugimoto, Hideyoshi Kaga, Ruriko Suzuki, Yuki Someya, Nozomu Yamasaki, Motonori Sato, Saori Kakehi, Akio Kanazawa, Ryuzo Kawamori and Hirotaka Watada
J. Clin. Med. 2023, 12(12), 4084; https://doi.org/10.3390/jcm12124084 - 16 Jun 2023
Cited by 2 | Viewed by 2106
Abstract
A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and [...] Read more.
A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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11 pages, 1038 KiB  
Article
Association between Sleep Duration and Incident Diabetes Mellitus in Healthy Subjects: A 14-Year Longitudinal Cohort Study
by Jin ha Jang, Wonjin Kim, Jin Sil Moon, Eun Roh, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm and Ji Hye Huh
J. Clin. Med. 2023, 12(8), 2899; https://doi.org/10.3390/jcm12082899 - 16 Apr 2023
Cited by 3 | Viewed by 2588
Abstract
Background: This study aimed to investigate whether sleep duration and/or quality are associated with incident diabetes mellitus (DM). Methods: A total of 8816 of 10,030 healthy participants were enrolled in a prospective cohort study. Sleep duration and quality questionnaires were completed. Sleep quality [...] Read more.
Background: This study aimed to investigate whether sleep duration and/or quality are associated with incident diabetes mellitus (DM). Methods: A total of 8816 of 10,030 healthy participants were enrolled in a prospective cohort study. Sleep duration and quality questionnaires were completed. Sleep quality was assessed using the Epworth Sleepiness Scale (ESS), which measures excessive daytime sleepiness in individuals. Results: During the 14-year follow-up period, 18% (1630/8816) were diagnosed with DM. A U-shaped relationship was observed between sleep duration and incident DM, with the highest risk observed when sleep duration was ≥10 h/day (hazard ratios (HR) 1.65 [1.25–2.17]). This group exhibited decreased insulin glycogenic index, a marker of insulin secretory function, during the study period. Among study participants who slept less than 10 h/day, the risk of incident DM increased when the ESS score was >10. Conclusions: We found that the association between sleep duration and incident DM was U-shaped; both short (≤5 h) and long (≥10 h) sleep durations were associated with an increased risk for the occurrence of incident DM. When sleep duration was 10 h or longer per day, there was a tendency to develop DM due to decreased insulin secretory function. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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13 pages, 592 KiB  
Article
The Burden of Non-Alcoholic Fatty Liver Disease in Adolescents with Polycystic Ovary Syndrome: A Case–Control Study
by Aikaterini Giannouli, Vasiliki Efthymiou, Marianna Konidari, Iliana Mani, Leon Aravantinos, Spyridon P. Dourakis, Aristeidis Antoniou, Efthymios Deligeoroglou and Flora Bacopoulou
J. Clin. Med. 2023, 12(2), 557; https://doi.org/10.3390/jcm12020557 - 10 Jan 2023
Cited by 6 | Viewed by 3181
Abstract
The aim of this case–control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian [...] Read more.
The aim of this case–control study was to assess the burden of non-alcoholic fatty liver disease (NAFLD) in adolescents with polycystic ovary syndrome (PCOS) and its associations with insulin resistance, hyperandrogenism, and other metabolic characteristics of the syndrome. A total of 87 Caucasian adolescent girls (47 with PCOS and 40 controls), aged 12.3–20.4 years, underwent blood sampling for glucose metabolism, hormonal and lipid profile, gynecological and liver ultrasound, and liver elastography. Indices of insulin resistance, liver steatosis, and liver fibrosis were calculated. NAFLD diagnosed by ultrasound was more prevalent in adolescents with PCOS than controls (22.7% vs. 6.1%, p = 0.046), and was also verified by liver steatosis indices. The latter was not apparent for hepatic fibrosis, as assessed by Fibroscan® and calculated indices. The homeostatic model assessment for insulin resistance (HOMA-IR) was found to predict NAFLD diagnosis by the liver fat score (LFS) index (β = 0.709, p = 0.002). Adolescents with PCOS and high free androgen index (FAI) presented worse NAFLD than those adolescents with PCOS and lower FAI. In addition, adolescents with PCOS and concurrent NAFLD had worse insulin sensitivity indices (HOMA-IR, QUICKI, and glucose to insulin ratio) than adolescents with PCOS alone. Adolescent insulin resistance could be considered a confounder of the association between PCOS and NAFLD. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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14 pages, 524 KiB  
Article
Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
by Gladys Maribel Hidalgo-Lozada, Angélica Villarruel-López, Esperanza Martínez-Abundis, Olga Vázquez-Paulino, Manuel González-Ortiz and Karina Griselda Pérez-Rubio
J. Clin. Med. 2022, 11(19), 5741; https://doi.org/10.3390/jcm11195741 - 28 Sep 2022
Cited by 4 | Viewed by 2334
Abstract
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, usually with a common pathophysiological origin in insulin resistance and abdominal obesity. Considering the reported effects of ellagic acid (EA) on insulin resistance and abdominal obesity, the aim of this study was to [...] Read more.
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, usually with a common pathophysiological origin in insulin resistance and abdominal obesity. Considering the reported effects of ellagic acid (EA) on insulin resistance and abdominal obesity, the aim of this study was to evaluate the effect of EA on the components of MetS, insulin sensitivity and insulin secretion by conducting a randomized, double-blind, placebo-controlled, clinical trial with 32 volunteers diagnosed with MetS. Sixteen patients were randomly allocated, received 500 mg of EA orally twice a day for 12 weeks, and the other 16 received a placebo. Clinical and laboratory determinations were obtained at baseline and at the end of the study. After EA administration, patients reduced their waist circumference (females: 102.2 ± 4.2 to 99.5 ± 3.2 cm (p < 0.05); males: 99.8 ± 6.7 to 96.0 ± 4.7 cm (p < 0.01)), systolic blood pressure (118.1 ± 10.1 to 113.7 ± 7.8 mmHg (p < 0.01)), diastolic blood pressure (118.1 ± 10.1 to 113.7 ± 7.8 mmHg (p < 0.01)), triglycerides (2.8 ± 1.1 to 2.1 ± 0.7 mmol/L (p < 0.01)), fasting plasma glucose (6.5 ± 0.5 to 5.7 ± 0.6 mmol/L (p < 0.01)), fasting plasma insulin (p < 0.01), and insulin secretion (p < 0.05), with an increase of insulin sensitivity (p < 0.01). In male patients, high-density lipoprotein cholesterol increased (p < 0.05). In conclusion, EA improved the components of MetS, reduced hyperinsulinemia, and improved insulin sensitivity. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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9 pages, 432 KiB  
Article
Relationship between Leptin and Insulin Resistance among Community—Dwelling Middle-Aged and Elderly Populations in Taiwan
by Yu-Lin Shih, Tzu-Cheng Huang, Chin-Chuan Shih and Jau-Yuan Chen
J. Clin. Med. 2022, 11(18), 5357; https://doi.org/10.3390/jcm11185357 - 13 Sep 2022
Cited by 4 | Viewed by 2089
Abstract
The relationship between leptin and insulin resistance among middle-aged and elderly populations in Asia is seldom reported. Our research included 398 middle-aged and elderly Taiwanese individuals. First, we divided participants into three groups according to the tertiles of the homeostasis model assessment of [...] Read more.
The relationship between leptin and insulin resistance among middle-aged and elderly populations in Asia is seldom reported. Our research included 398 middle-aged and elderly Taiwanese individuals. First, we divided participants into three groups according to the tertiles of the homeostasis model assessment of insulin resistance (HOMA-IR) to analyze the parameters between each group. Pearson’s correlation was then applied to calculate the correlation between HOMA-IR and cardiometabolic risk factors after adjusting for age. A scatter plot indicated a relationship between serum leptin levels and the HOMA-IR index. Finally, the coefficients of the serum leptin level and HOMA-IR were assessed by multivariate linear regression. The participants in the high HOMA-IR index group were more likely to have higher serum leptin levels. Meanwhile, the HOMA-IR index was positively correlated with serum leptin levels, even after adjusting for age. Serum leptin levels were positively correlated with the HOMA-IR index (β = 0.226, p < 0.01) in the multivariate linear regression after adjusting for age, sex, smoking, drinking, BMI, triglycerides, systolic blood pressure, fasting plasma glucose, uric acid, ALT, and creatinine. Furthermore, the leptin–creatinine ratio also showed a significantly positive relationship with HOMA-IR in the same multivariate linear regression model. In conclusion, serum leptin levels showed a positive relationship with insulin resistance in middle-aged and elderly people in Taiwan. Furthermore, serum leptin levels may be an independent risk factor for insulin resistance according to our study. Full article
(This article belongs to the Special Issue Clinical Research on Insulin Resistance)
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