Homeostasis Model Assessment Ratio Research Articles

Ingestion of a collagen peptide containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine reduces advanced glycation end products levels in the skin and subcutaneous blood vessel walls: a randomized, double-blind, placebo-controlled study.

In this randomized, double-blind, placebo-controlled study, we investigated the effects of collagen peptides (CP) containing high concentrations of prolyl-hydroxyproline and hydroxyprolyl-glycine on advanced glycation end products (AGEs) levels in the skin and subcutaneous blood vessel walls. A total of 31 individuals aged 47-87 years were randomly assigned to receive either 5g/day of fish-derived CP or a placebo for 12 weeks. Body and blood compositions and AGEs levels were measured at the beginning and end of the study. No adverse events were observed, and both groups' blood and body compositions did not change significantly. However, the CP group had significantly lower AGEs levels and a slightly lower insulin resistance index (homeostasis model assessment ratio [HOMA-R]) than the placebo group. In addition, the percentage changes in AGEs and HOMA-R levels were positively and strongly correlated in both groups. These findings suggest that fish-derived CP may be effective in reducing AGEs levels and improving insulin resistance.

Changes in urinary glucose concentration and body weight in patients treated with the selective SGLT2 inhibitor luseogliflozin

AimsWe investigated the effects of the SGLT2 inhibitor luseogliflozin on blood and urinary glucose and body weight. MethodsLuseogliflozin 2.5 mg was administered once daily for 24 weeks to 30 outpatients with type 2 diabetes. Urinary glucose concentration, continuous glucose monitoring values, HbA1c, fasting glucose, and body weight were evaluated. Correlations with urinary glucose, subcutaneous/visceral fat mass, insulin, EPA/AA ratio, plasma free fatty acids, ghrelin, blood ketones, plasma 1,5-anhydro-D-glucitol were evaluated. ResultsUrinary glucose significantly increased from 11.1 ± 11.8 g at Week −4 to 84.5 ± 46.8 g at Week 24. HbA1c significantly declined from 7.88 ± 0.88% to 7.36 ± 1.13% at Week 24. Mean blood glucose significantly decreased from 149.6 ± 41.8 to 131.6 ± 31.1 mg/dL at Week 24. Subcutaneous and visceral fat mass was also significantly decreased, as were AST and ALT (P < 0.01). Blood urea nitrogen was significantly increased, and urate significantly decreased from 5.04 ± 1.07 to 4.53 ± 0.94 mg/dL. The homeostasis model assessment ratio remained significantly improved throughout the treatment period. Acyl ghrelin levels remained constant but des-acyl ghrelin increased significantly. ConclusionsLuseogliflozin monotherapy resulted in an improvement in blood glucose, a decrease in body weight, and decreased insulin resistance. Luseogliflozin appears to be an effective therapy for obese diabetics.

Polysorbate 80-induced leaky gut impairs skeletal muscle metabolism in mice.

Impaired intestinal permeability can induce systemic inflammation and metabolic disturbance. However, the effect of impaired intestinal permeability on metabolic function in the skeletal muscle is unknown. Dietary polysorbate 80 (PS80), a common emulsifier, has been shown to impair intestinal permeability in mice. Here, we investigated the effect of PS80‐induced intestinal permeability on glucose tolerance with metabolic signaling in the skeletal muscle. Male ICR mice were divided into control and PS80 groups. In the PS80 group, PS80 was contained in the drinking water at 1% (w/v). After 4 weeks, plasma fluorescein isothiocyanate (FITC) intensity was measured after orally administering FITC‐dextran. Half of the mice in each group underwent running exercises. Metabolic and inflammatory parameters were examined in the blood and skeletal muscle. Plasma FITC and lipopolysaccharide levels were higher in the PS80 group than the control group (p < .01, p = .085). The expression of tumor necrosis factor‐α in the skeletal muscle was increased upon PS80 administration (p < .05). Although the homeostasis model assessment ratio was higher in the PS80‐fed mice (p < .05), insulin‐signaling activity in the muscle did not differ between groups. Muscular pH, mitochondrial cytochrome oxidase activity, and glycogen content after exercise were lower in the PS80 group (p < .05) than the control group. There was a negative correlation between plasma FITC and muscle glycogen levels in the exercised groups (r = −.60, p < .05). These results suggest that daily PS80 intake induces intestinal permeability, leading to glucose intolerance and mitochondrial dysfunction in the skeletal muscle.

Impact of Impaired Pancreatic β-Cell Function on Cardiovascular Prognosis in Heart Failure Patients Without Diabetes Mellitus.

Background: Insulin resistance as assessed using homeostasis model assessment ratio (HOMA-R) is associated with latent myocardial damage in apparently healthy subjects in health check. Meanwhile, diabetes mellitus (DM) is an unfavorable prognostic risk factor in patients with heart failure (HF). We examined the impact of pancreatic β-cell dysfunction on clinical outcomes in HF patients without DM.Methods and Results: This study enrolled 312 HF patients without DM. Pancreatic β-cell dysfunction was defined as HOMA-β <30%. A total of 108 patients (35%) had β-cell dysfunction. Plasma brain natriuretic peptide was higher in patients with pancreatic β-cell dysfunction compared with those without (625.2 vs. 399.0 pg/mL, P<0.001). On Kaplan-Meier analysis, a significantly higher cardiovascular events rate was observed in patients with pancreatic β-cell dysfunction (log-rank test, P=0.001), but there was no significant difference between patients with and without insulin resistance. On Cox hazard analysis, pancreatic β-cell dysfunction was independently associated with cardiovascular events after adjustment for confounding factors (HR, 1.58; 95% CI: 1.02–2.45), whereas insulin resistance was not associated with cardiovascular events.Conclusions: Pancreatic β-cell dysfunction, but not insulin resistance, was associated with unfavorable outcome in HF patients without DM.

Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial.

BackgroundBased on non-clinical data, it is expected that azilsartan, an angiotensin II receptor blocker, will help improve insulin resistance in addition to its hypotensive action. The present study is aimed to explore the effect of azilsartan compared to telmisartan on insulin sensitivity in hypertensive patients in the clinical setting.MethodsThis multicenter, randomized, open-label, parallel-group exploratory study was conducted in Japan. We randomized adult patients (≥20 years old) with grade I or II essential hypertension and coexisting type 2 diabetes (1:1) to receive either oral azilsartan (20 mg/day;17 patients) or telmisartan (40 mg/day;16 patients) for 12 weeks. The primary endpoint was the change in the homeostasis model assessment ratio of insulin resistance (HOMA-R) from the baseline at the end of the treatment period. We also evaluated its safety and efficacy on other diabetes-related variables and blood pressure.FindingsThe mean changes in HOMA-R at the end of treatment were 0.22 (95% CI, −1.09–1.52) in the azilsartan group and −0.23 (95% CI, −0.72–0.27) in the telmisartan group. We found no clinically remarkable changes between the groups in diabetes-related variables such as fasting blood glucose, fasting insulin, HbA1c (NGSP), HOMA-β, or 1,5-anhydroglucitol. Reductions in clinic systolic and diastolic blood pressure were observed at week 4 and the reduced levels were maintained throughout the treatment period in both groups. No serious treatment-emergent adverse events (TEAEs) were observed. Only one drug-related TEAE (mild decrease in blood pressure) was reported in one patient in the azilsartan group.ConclusionNeither azilsartan nor telmisartan had any clinically remarkable effects on insulin resistance parameters when administered for 12 weeks to patients with grade I or II essential hypertension and coexisting type 2 diabetes mellitus. Azilsartan (20 mg/day) and telmisartan (40 mg/day) exerted comparable antihypertensive effects.Trial registrationClinicalTrials.gov NCT02079805

Cardiovascular risk may be increased in women with unexplained infertility.

ObjectiveGrowing evidence suggests that increased cardiovascular disease (CVD) risk is associated with female infertility caused by conditions such as polycystic ovarian disease, obesity, thyroid dysfunction, and endometriosis. The aim of this study was to evaluate whether any relationship exists between CVD and unexplained infertility.MethodsSixty-five women with unexplained infertility and 65 fertile controls were enrolled in the study. CVD risk markers such as low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG), insulin resistance (defined by the homeostasis model assessment ratio), and high-sensitivity C-reactive protein (hs-CRP) were assessed.ResultsTG, TC, LDL, and hs-CRP levels were higher and HDL levels were lower in patients with unexplained infertility than in fertile controls (p<0.05 for all). Positive associations were found between unexplained infertility and TG, TC, LDL, and hs-CRP levels, and a negative correlation was found for HDL (p<0.05 for all). Multivariate logistic regression analysis showed that TG, HDL, and hs-CRP were independent variables associated with unexplained infertility.ConclusionOur study showed that women with unexplained infertility had an atherogenic lipid profile and elevated hs-CRP levels, suggesting a higher risk of developing CVD in the future. Further studies with larger groups are needed to investigate the nature of this link.

The Characteristics of Hepatic Gsα-cAMP Axis in HSHF Diet-Fed Obese Insulin Resistance Rats and Genetic Diabetic Mice.

Stimulatory G protein α-subunit (Gsα) mediated cAMP signal is required for elevated hepatic glucose production (HGP) in diabetic patients. However, it remains obscure of the exact characteristics of hepatic Gsα-cAMP signal axis (including Gsα, glucagon receptor, β2-adrenergic receptor, cAMP, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). In current study, we investigated the changing characteristics of hepatic Gsα-cAMP signal axis and blood glucose in high-sugar-high-fat (HSHF)-diet-induced IR Wistar rats and db/db diabetic mice. As expected, the HSHF-diet rats were characterized by hyperinsulinemia, hyperglycemia and impaired glucose tolerance. According to a threshold (1.7) of homeostasis model assessment ratio (HOMA-R), the process of IR in HSHF-diet rats could be divided into slight and high IR stages, with the week-23 as the cut-off point. In early slight IR stage, key molecules expressions of hepatic Gsα-cAMP signal axis in HSHF-diet rats were up-regulated with significantly elevated fasting blood glucose (FBG) from 18 to 23 weeks. Unexpectedly, in high IR stage, hepatic Gsα-cAMP signal axis was recovered comparatively to that of normal chow-diet rats, and no significant differences in FBG levels were found. However, in diabetic db/db mice, up-regulation of hepatic Gsα-cAMP signal axis was responsible for its severely increased fasting hyperglycaemia. Our data revealed a positive correlation between hepatic Gsα-cAMP signal axis and FBG in slight IR stage of HSHF-diet rats and diabetic db/db mice. The current finding thus suggested hepatic Gsα-cAMP signal axis plays a central role in regulating of FBG during the developing and development of T2DM.

Gene-environment interactions in obesity: implication for future applications in preventive medicine.

Obesity is associated with environmental factors; however, information about gene-environment interactions is lacking. We aimed to elucidate the effects of gene-environment interactions on obesity, specifically between genetic predisposition and various obesity-related lifestyle factors, using data from a population-based prospective cohort study. The genetic risk score (GRS) calculated from East Asian ancestry single-nucleotide polymorphisms was significantly associated with the body mass index (BMI) at baseline (P<0.001). Significant gene-environment interactions were observed for six nutritional factors, alcohol intake, metabolic equivalents-hour per day and the homeostasis model assessment ratio. The GRS altered the effects of lifestyle factors on BMI. Increases in the BMI at baseline per unit intake for each nutritional factor differed depending on the GRS. However, we did not observe significant correlations between the GRS and annual changes in BMI during the follow-up period. This study suggests that the effects of lifestyle factors on obesity differ depending on the genetic risk factors. The approach used to evaluate gene-environment interaction in this study may be applicable to the practice of preventive medicine.

Low antimullerian hormone levels may be associated with cardiovascular risk markers in women with diminished ovarian reserve

There is growing evidence that diminished ovarian reserve (DOR) may be associated with cardiovascular disease (CVD). The aim of the study was to investigate whether there was any relationship between antimullerian hormone (AMH) and CVD risk markers in the study.Ninety women with DOR and 90 women with normal ovarian reserve (NOR) attending the infertility unit at XXXX, were enrolled in the study. CVD risk markers such as insulin resistance [defined by the homeostasis model assessment ratio (HOMA-IR)], C-reactive protein (CRP), low density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) were assessed. HOMA-IR, CRP, TG, LDL levels were higher and HDL and AMH were lower among patients with DOR compared with controls (p < 0.05, for all). There were positive associations between low AMH and HOMA-IR, CRP, TG, LDL levels and a negative correlation with HDL (p < 0.05, for all). However, multivariate logistic regression analysis showed that HOMA-IR, CRP, TG and HDL were independent variables that were associated with low AMH.There was a close relationship between low AMH and CVD risk markers in the study. Further studies with larger groups are needed to investigate the nature of this link in these patients.

Insulin resistance and β-cell function influence postprandial blood glucose levels in Japanese patients with gestational diabetes mellitus

Aims/introduction: The aim of this study in patients with gestational diabetes mellitus (GDM) was to evaluate the relationship of insulin resistance and secretion to area-under-the-sensor glucose concentration–time curve from before to 120 min postmeal (CGM-AUC0–120 min) as determined with continuous glucose monitoring (CGM).Materials and methods: Immunoreactive insulin and HbA1c were determined in 22 Japanese patients with GDM undergoing a 75 g oral glucose tolerance test. Patients underwent CGM within 3 weeks of receiving a diagnosis of GDM.Results: HbA1c (NGSP) was 5.5 ± 0.4%, BMI was 24.8 ± 5.3 kg/m2, mean sensor glucose by CGM was 94.2 ± 10.3 mg/dL, standard deviation was 17.5 ± 4.4 mg/dL, and CGM-AUC0–120 min was 204.2 ± 23.8 h mg/dL. The insulin resistance indices the homeostasis model assessment ratio (HOMA-R), quantitative insulin sensitivity check index (QUICKI), and the Matsuda Index were correlated with CGM-AUC0–120 min. The disposition index (DI), which was used to evaluate insulin secretion, was negatively correlated with CGM-AUC0–120 min.Conclusions: Not only insulin resistance but also beta cell dysfunction contributes to postprandial hyperglycemia in Japanese patients with GDM.

Development of an ultrasensitive immunoassay using affinity maturated antibodies for the measurement of rodent insulin

The measurement of plasma insulin is important for clinical diagnosis of diabetes and for preclinical research of metabolic diseases, especially in rodent models used in drug discovery research for type 2 diabetes. Fasting immunoreactive insulin (F-IRI) concentrations are used to calculate the homeostasis model assessment ratio (HOMA-R), an index of insulin sensitivity. However, even the most sensitive commercially available enzyme-linked immunosorbent assay (ELISA) kits cannot measure the very low F-IRI concentrations in normal rats and mice. Therefore, we sought to develop a new rodent insulin ELISA with greater sensitivity for low F-IRI concentrations. Despite repeated efforts, high-affinity antibodies could not be generated by immunizing mice with mouse insulin (self-antigen). Therefore, we generated two weak monoclonal antibodies (13G4 and 26B2) that were affinity maturated and used to develop a highly sensitive ELISA. The measurement range of the sandwich ELISA with the affinity maturated antibodies (13G4m1 and 26B2m1) was 1.5 to 30,000pg/ml, and its detection limit was at least 10 times lower than those of commercially available kits. In conclusion, we describe the development of a new ultrasensitive ELISA suitable for measuring very low plasma insulin concentrations in rodents. This ELISA might be very useful in drug discovery research in diabetes.

Abstract 11598: Increased Advanced Glycation End-Products Accelerate the Progress of Left Ventricular Hypertrophy Under Condition of Elevated Oxidative Stress or Insulin Resistance in Patients With Hypertension

Background: Elevated oxidative stress or insulin resistance has been shown to promote the production of advanced glycation end-products (AGEs) in patients with hypertension (HT). Because AGEs enhance left ventricular hypertrophy (LVH) via the activation of nuclear factor-kappa B, it is considered that increased AGEs contribute to LVH in HT patients. The aim of this study was to investigate the effect of increased AGEs on LVH in them. Methods: Eighty five HT patients aged 65 ± 9 years were prospectively followed up for a year, whose blood pressure was controlled under 140/90mmHg. We assessed patients’ glucose and lipid metabolism and neurohumoral factors including plasma noradrenaline and renin activity as clinical characteristics. We measured serum malondialdehyde-modified LDL-cholesterol (MDA-LDL) and plasma pentosidine as parameters of oxidative stress and AGEs, respectively. Homeostasis model assessment ratio (HOMA-R), estimate glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) were assessed as parameters of insulin resistance, renal function and LVH, respectively. All parameters were assessed before and after one-year observation period. We examined the change in each parameter from baseline to the value measured after the observation period ([[Unable to Display Character: &amp;#8895;]]MDA-LDL, [[Unable to Display Character: &amp;#8895;]]pentosidine, [[Unable to Display Character: &amp;#8895;]]HOMA-R and [[Unable to Display Character: &amp;#8895;]]LVMI). We divided patients into two groups based on the median of baseline pentosidine: high AGEs and low AGEs groups. We compared baseline values between the two groups. We analyzed the relationships among [[Unable to Display Character: &amp;#8895;]]MDA-LDL, [[Unable to Display Character: &amp;#8895;]]HOMA-R, [[Unable to Display Character: &amp;#8895;]]Pentosidine and [[Unable to Display Character: &amp;#8895;]]LVMI, and performed stepwise multiple regression analysis using parameters of clinical characteristics and AGEs to detect the predictors for the LVH progress after one year. Results: Baseline LVMI was significantly higher in the high AGEs group than in the low AGEs group (P&lt;0.05). [[Unable to Display Character: &amp;#8895;]]Pentosidine was positively correlated with [[Unable to Display Character: &amp;#8895;]]MDA-LDL (r=0.34, P&lt;0.01),[[Unable to Display Character: &amp;#8895;]]HOMA-R (r=0.37, P&lt;0.01) and [[Unable to Display Character: &amp;#8895;]]LVMI (r=0.39, P&lt;0.05). Multiple regression analysis detected pentosidine as a significant independent predictor for the LVH progress (β=0.407, P=0.005) (R2=0.315). Conclusion: Increased AGEs accelerated the LVH progress under condition of elevated oxidative stress or insulin resistance in HT patients.

Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes.

To analyse the effects of thyroid hormones on β-cell function and glucose metabolism in people with prediabetes who are euthyroid. A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of β-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic β-cell function. In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic β-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of β-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.

Is there any relationship between cardiovascular risk markers and young women with diminished ovarian reserve?

Objective: It has been widely known that cardiovascular disease (CVD) risk is increased in menopause. The aim of the study was to evaluate whether this risk was elevated in young women with diminished ovarian reserve (DOR).Methods: A hundred women with DOR and 100 women with normal ovarian reserve (NOR) attending the infertility unit at Suleymaniye Maternity, Research &Training Hospital, were enrolled in the study. CVD risk markers such as insulin resistance (defined by the homeostasis model assessment ratio [HOMA-IR]), C-reactive protein (CRP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) were assessed.Results: HOMA-IR, CRP, TG, LDL levels were higher and HDL was lower among patients with DOR compared to the controls (p < 0.05 for all). There were positive associations between DOR and HOMA-IR, CRP, TG, LDL levels and a negative correlation with HDL (p < 0.05 for all). However, multivariate logistic regression analysis showed that HOMA-IR, CRP, TG, and HDL were independent variables that were associated with DOR.Conclusions: CVD risk markers were increased in women with DOR. Further studies with larger groups are needed to investigate the nature of the link in these patients.

Effect of Bridelia ferruginea Benth (Euphorbiaceae) ethyl acetate and acetone fractions on insulin resistance in fructose drinking mice

Ethnopharmacological relevanceThe root of Bridelia ferruginea is traditionally used as a treatment for type 2 diabetes. The present study was investigated to evaluate the effect of Bridelia ferruginea root bark fractions on some markers of type 2 diabetes on fructose drinking mice. Materials and methodsMice received a solution of fructose 15% during 42 days ad libitum; at the 15th day to the 42nd day, they received distilled water for fructose drinking control group, metformin 50mg/kg per day or fractions 50mg/kg per day for treatment groups. The normal control group received only distilled water during the experiment. After 6 weeks of experiment, OGTT, fasting blood glucose, plasma insulin, triglycerides (TG), total cholesterol, AST and ALT levels were measured. ResultsFructose drinking control group (F) showed significant (p<0.001) increase of glucose tolerance, plasma levels of total cholesterol, triglycerides and insulin index for insulin resistance (Homeostasis Model Assessment ratio HOMA-IR) as compared to normal control mice. In treated groups, there was a significant reduction of glucose intolerance respectively 74% (p<0.001), 25% (p<0.5) and 92% (p<0.001) for ethyl acetate fraction, acetone fraction and metformin at the same dose of 50mg/kg per day during 4 weeks administration. In ethyl acetate fraction and metformin treated groups, biochemical parameters and insulin index were significantly (p<0.001) lower than that of fructose drinking control group. ConclusionsThis indicates that Bridelia ferruginea root bark ethyl acetate fraction improved insulin resistance as metformin significantly in type 2 diabetes.

Increased epicardial adipose tissue volume predicts insulin resistance and coronary artery disease in non-obese subjects without metabolic syndrome

Background/objectivesEpicardial adipose tissue (EAT) reportedly secretes various adipokines that evoke insulin resistance in patients with obesity or metabolic syndrome. However, it remains unclear whether EAT also plays a role in the development of insulin resistance in lean subjects. The purpose of this study was to investigate the impact of EAT volume on the presence of insulin resistance and coronary artery disease in non-obese subjects without metabolic syndrome. MethodsWe prospectively studied 624 consecutive patients who underwent multidetector computed tomography (MDCT) and measured EAT volume between January 2009 and June 2011. Obesity was defined as body mass index ≥25kg/m2, and metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria. After we excluded 385 patients with obesity or metabolic syndrome, 239 patients were enrolled in the present study. ResultsThere were 102 (42.7%) subjects with insulin resistance (homeostasis model assessment ratio [HOMA-R] >2.5) and 88 (36.8%) subjects with coronary artery disease. After adjusting for age, gender, and body mass index, increased EAT volume (≥35ml mean EAT volume) was independently associated with insulin resistance (odds ratio 2.6, 95% confidence interval 1.5–4.8). Furthermore, increased EAT volume was also associated with coronary artery disease (odds ratio 1.9, 95% confidence interval 1.0–3.6) after adjustment of age, gender, body mass index, and the presence of insulin resistance. ConclusionIncreased EAT volume may play a key role in the development of insulin resistance and coronary artery disease, even in non-obese subjects without metabolic syndrome.

Association Between Glycemic Control and Morning Blood Pressure Surge With Vascular Endothelial Dysfunction in Type 2 Diabetic Patients

Morning blood pressure surge (MBPS) is an independent predictor of cardiovascular events. However, little is known about the association between glycemic control and MBPS, and its effect on vascular injury in patients with type 2 diabetes mellitus (T2DM). The current study examined the association between glycemic control and MBPS, and the involvement of MBPS in the development of vascular dysfunction in T2DM patients. We examined MBPS in T2DM patients (25 male patients/25 female patients; mean age, 60.1 ± 13.2 years; n = 50) using 24-h ambulatory blood pressure monitoring, and assessed vascular function by brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). HbA1c (ρ = 0.373, P = 0.009) and triglyceride (TG) (ρ = 0.375, P = 0.009) levels correlated significantly and positively with MBPS. In multiple regression analysis, including TG and HbA1c levels in addition to age and 24-h systolic blood pressure (SBP) as independent variables, HbA1c (β = 0.328, P = 0.016) and TG (β = 0.358, P = 0.014) were associated significantly in a positive manner with MBPS. In a noninsulin user, when homeostasis model assessment ratio (HOMA-R) was included in place of TG, HOMA-R emerged as a significant factor. MBPS (ρ = -0.289, P = 0.043) and HbA1c (ρ = -0.301, P = 0.035) correlated significantly and negatively with FMD, whereas 24-h SBP correlated with both FMD (ρ = -0.359, P = 0.012) and NMD (ρ = -0.478, P = 0.004). In multiple regression analysis, including age, gender, 24-h SBP, MBPS, LDL cholesterol, and HbA1c, MBPS (β = -0.284, P = 0.044) alone associated significantly in a negative manner with FMD, but not with NMD. The current study demonstrated that poor glycemic control and insulin resistance are independently associated with the occurrence of MBPS in T2DM patients, which might be significantly associated with endothelial dysfunction.

A refined-JinQi-JiangTang tablet ameliorates prediabetes by reducing insulin resistance and improving beta cell function in mice

Ethnopharmacological relevanceRefined-JQ (JQ-R) is a mixture of refined extracts from three major herbal components of JinQi-JiangTang tablet: Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae), and Lonicera japonica (Caprifoliaceae). Our previous studies have indicated that JQ-R could decrease fasting blood glucose levels in diabetic mice and insulin resistance mice. Investigating the hypoglycemic effect of JQ-R on prediabetes has practical application value for preventing or delaying insulin resistance, impaired glucose tolerance and possibly the development of clinical diabetes. Materials and methodsThe anti-diabetic potential of JQ-R was investigated using a high fat-diet (HFD)-induced obesity mouse model. C57BL/6J mice (HFD-C57 mice) were fed with high-fat diet for 4 months. HFD-C57 mice were treated with either JQ-R (administered intragastrically once daily for 4 weeks) or metformin (as positive control), and the effects of JQ-R on body weight, blood lipids, glucose metabolism, insulin sensitivity, and beta cell function were monitored. ResultsThe body weight, serum cholesterol, and the Homeostasis Model Assessment ratio (insulin resistance index) were significantly reduced in JQ-R or metformin-treated mice, and the glucose tolerance was enhanced and insulin response was improved simultaneously. Moreover, both JQ-R and metformin could activate liver glycogen syntheses even under a relatively high glucose loading. Although glyconeogenesis was inhibited in the metformin treated mice, it was not observed in JQ-R treated mice. Similar to metformin, JQ-R could also improve the glucose infusion rate (GIR) in hyperglycemic clamp test. JQ-R was also shown to increase the levels of phosphorylated AMPKα and phosphorylated acetyl CoA carboxylase (ACC), similar to metformin. ConclusionJQ-R could reduce HFD-induced insulin resistance by regulating glucose and lipid metabolism, increasing insulin sensitivity through activating the AMPK signaling pathway, and subsequently improving β cell function. Therefore, JQ-R may offer an alternative in treating disorders associated with insulin resistance, such as prediabetes and T2DM.

Decreased perivascular CGRP-containing nerves in Otsuka Long–Evans Tokushima Fatty rats with insulin resistance and hypertension

We previously reported that chronic hyperinsulinemia induced by drinking fructose elicited an abnormal neuronal regulation of vascular tone, which contributed to the development of hypertension. This study was designed to elucidate the possible mechanisms underlying the dysfunctional neuronal regulation of vascular tone induced by chronic hyperinsulinemia by comparing isolated mesenteric vascular beds from Otsuka Long-Evans Tokushima Fatty (OLETF) rats with those of control Long-Evans Tokushima Otsuka rat (LETO) rats. Insulin, triglyceride and total cholesterol levels in plasma, blood glucose concentrations, a glucose-insulin index, systolic blood pressure and perivascular innervations were assessed using biochemical and immunohistochemical methods. Mesenteric vascular beds isolated from OLETF and LETO rats were perfused with a Krebs solution containing methoxamine, and changes in perfusion pressure in response to periarterial nerve stimulation (PNS) and the perfusion of vasoactive agents were measured. OLETF rats (8-25 weeks old) showed age-related increases in insulin, triglycerides, total cholesterol, blood glucose, the glucose-insulin index (homeostasis model assessment ratio (HOMA-IR)) and systolic blood pressure compared with LETO rats. In perfused mesenteric vascular beds, the PNS-induced adrenergic nerve-mediated vasoconstrictor responses in OLETF rats were significantly greater than those in LETO rats, whereas the PNS-induced calcitonin gene-related peptide (CGRP) nerve-mediated vasodilator responses in OLETF rats were significantly smaller than those in LETO rats. In immunohistochemical experiments, the density of CGRP-immunopositive nerves in the mesenteric arteries of OLETF rats decreased significantly with age. The present findings suggest that the abnormal innervation of perivascular nerves in mesenteric resistance arteries induced by chronic hyperinsulinemia disturbs the neuronal regulation of vascular tone and may cause hypertension in OLETF rats.

Increased insulin resistance decreases exercise tolerance in patients with hypertension and/or dyslipidemia

Background: It is considered that increased insulin resistance is closely correlated with the exercise capacity in patients with hypertension (HT) and/or dyslipidemia (DL), because it is known to impair the energy metabolism in skeletal muscles. The aim of this study was to investigate the influence of insulin resistance on the exercise capacity in patients with HT and/or DL. Methods: We recruited 45 patients with HT and/or DL and assessed their homeostasis model assessment ratio (HOMA-R)as a parameter of insulin resistance. Patients were defined to have insulin resistance, if their HOMA-R showed >2.50. Patients were divided into low and high HOMA-R groups based on 2.50 of HOMA-R. Oxygen uptake (VO2) at anaerobic threshold (VO2 AT) and peak VO2 were measured by cardiopulmonary exercise testing (CPX) using a treadmill. The exercise capacity was assessed using ratios of measured VO2 to predicted VO2 AT and predicted peak VO2 (%VO2 AT and %peak VO2, respectively). The number of steps per day was counted for 2 weeks as a parameter of physical activity. We compared %VO2 AT, %peak VO2 and physical activity between the two groups and determined correlations of %VO2 AT and %peak VO2 with HOMA-R using a single regression analysis. Results: There were no significant differences in clinical characteristics and physical activity between the two groups. The %VO2 AT and %peak VO2 were 93% and 90% in the low HOMA-R group and 76% and 72% in the high HOMA-R group, respectively. They were significantly lower in the high HOMA-R group than in the low HOMA-R group (P<0.05, respectively), and negatively correlated with HOMA-R (r=0.339, P<0.05 and r=0.522,P<0.001, respectively) (Figure). ![Figure][1] Conclusion: The present study showed that increased insulin resistance decreased exercise capacity in patients with HT and/or DL. [1]: pending:yes