Association Between Insulin Resistance, Oxidative Stress, Sympathetic Activity and Coronary Microvascular Function in Patients With Early Stage Impaired Glucose Metabolism

Abstract Objective To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

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Association of Insulin Resistance, Plasma Glucose Level, and Serum Insulin Level With Hypertension in a Population With Different Stages of Impaired Glucose Metabolism

Journal of the American Heart Association ◽

10.1161/jaha.119.015546 ◽

2020 ◽

Vol 9 (7) ◽

Author(s):

Nobuo Sasaki ◽

Ryoji Ozono ◽

Yukihito Higashi ◽

Ryo Maeda ◽

Yasuki Kihara

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Glucose Level ◽

Plasma Glucose ◽

Plasma Glucose Level ◽

Serum Insulin ◽

Insulin Level ◽

Serum Insulin Level ◽

Impaired Glucose Metabolism

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Association of elevated serum ferritin concentration with insulin resistance and impaired glucose metabolism in Korean men and women

Metabolism ◽

10.1016/j.metabol.2010.03.007 ◽

2011 ◽

Vol 60 (3) ◽

pp. 414-420 ◽

Cited By ~ 94

Author(s):

Chul-Hee Kim ◽

Hong-Kyu Kim ◽

Sung Jin Bae ◽

Joong-Yeol Park ◽

Ki-Up Lee

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Serum Ferritin ◽

Elevated Serum ◽

Impaired Glucose Metabolism ◽

Ferritin Concentration ◽

Men And Women ◽

Serum Ferritin Concentration

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Heme oxygenase system enhances insulin sensitivity and glucose metabolism in streptozotocin-induced diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90783.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. E829-E841 ◽

Cited By ~ 61

Author(s):

Joseph Fomusi Ndisang ◽

Ashok Jadhav

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Heme Oxygenase ◽

Soleus Muscle ◽

Insulin Biosynthesis ◽

Model Assessment ◽

Antidiabetic Effects

Hyperglycemia-induced oxidative stress is a common phenomenon in diabetes. Since oxidative stress depletes adiponectin and insulin levels, we investigated whether an upregulated heme oxygenase (HO) system would attenuate the oxidative destruction of adiponectin/insulin and improve insulin sensitivity and glucose metabolism in streptozotocin (STZ)-induced type 1 diabetes. HO was upregulated with hemin (15 mg/kg ip) or inhibited with chromium mesoporphyrin (CrMP, 4 μmol/kg ip). Administering hemin to STZ-diabetic rats reduced hyperglycemia and improved glucose metabolism, whereas the HO inhibitor CrMP annulled the antidiabetic effects and/or exacerbated fasting/postprandial hyperglycemia. Interestingly, the antidiabetic effects of hemin lasted for 2 mo after termination of therapy and were accompanied by enhanced HO-1 and HO activity of the soleus muscle, along with potentiation of plasma antioxidants like bilirubin, ferritin, and superoxide dismutase, with corresponding elevation of the total antioxidant capacity. Importantly, hemin abated c-Jun NH2-terminal kinase (JNK), a substance known to inhibit insulin biosynthesis, and suppressed markers/mediators of oxidative stress including 8-isoprostane, nuclear-factor (NF)-κB, activating protein (AP)-1, and AP-2 of the soleus muscle. Furthermore, hemin therapy significantly attenuated pancreatic histopathological lesions including acinar cell necrosis, interstitial edema, vacuolization, fibrosis, and mononuclear cell infiltration. Correspondingly, hemin increased plasma insulin and potentiated agents implicated in insulin sensitization and insulin signaling such as adiponectin, adenosine monophosphate-activated protein kinase (AMPK), cAMP, cGMP, and glucose transporter (GLUT)4, a protein required for glucose uptake. These were accompanied by improved glucose tolerance [intraperitoneal glucose tolerance text (IPGTT)], decreased insulin intolerance [intraperitoneal insulin tolerance test (IPITT)], and reduced insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR) index], whereas CrMP nullified the hemin-dependent antidiabetic and insulin-sensitizing effects. In conclusion, by concomitantly enhancing insulin and paradoxically potentiating insulin sensitivity, this study unveils a novel, unique, and long-lasting antidiabetic characteristic of upregulating HO with hemin that could be exploited against insulin-resistant and insulin-dependent diabetes.

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Retinol-binding protein 4 levels are elevated in polycystic ovary syndrome women with obesity and impaired glucose metabolism

Acta Endocrinologica ◽

10.1530/eje-07-0143 ◽

2007 ◽

Vol 157 (2) ◽

pp. 201-207 ◽

Cited By ~ 28

Author(s):

Susanne Hahn ◽

Manuel Backhaus ◽

Martina Broecker-Preuss ◽

Susanne Tan ◽

Tiina Dietz ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Metabolism ◽

Polycystic Ovary Syndrome ◽

Body Fat ◽

Polycystic Ovary ◽

Retinol Binding Protein ◽

Healthy Controls ◽

Impaired Glucose Metabolism ◽

Ovary Syndrome ◽

Retinol Binding Protein 4

Objective: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4), a new fat-derived adipokine, has been described to be elevated in obesity and type 2 diabetes. The aim of the present study was to investigate whether serum RBP4 levels are correlated with metabolic parameters, indices of insulin resistance, and endocrine variables in German PCOS women. Design: We assessed the correlation between metabolic and endocrine parameters with RBP4 levels in 200 PCOS patients and 64 healthy controls. Methods: Serum RBP4 was measured by enzyme-linked immunosorbent assay (Immundiagnostik AG, Bensheim, Germany). In addition, anthropometric variables, clinical signs of hyperandrogenism, and body fat were evaluated, and a glucose tolerance test was performed to assess parameters of insulin resistance and glucose metabolism. Results: Taking the entire PCOS cohort, RBP4 levels were positively correlated with body mass index (BMI), body fat, waist circumference, fasting glucose, and area under the curve for glucose (all P<0.05), but not with indices of insulin resistance. On the other hand, PCOS women with impaired glucose metabolism had higher RBP4 levels than PCOS women with normal glucose metabolism (median 30.6, range 23.3–73.9 versus median 26.3, range 6.4–61.4, P<0.05). Furthermore, no differences were found in RBP4 levels between lean PCOS women and BMI-matched healthy controls. Conclusion: In German PCOS women, serum RBP4 levels are associated with obesity and parameters of glucose metabolism but not with PCOS per se.

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