A Possible Role for Pioglitazone in the Management of Depressive Symptoms in Metabolic Syndrome Patients (EPICAMP Study): A Double Blind, Randomized Clinical Trial

The present trial aimed to evaluate the effects of pioglitazone on the mental status of nondiabetic metabolic syndrome patients. From 145 patients screened, 104 eligible volunteers (57% female; age 20–70 years) were enrolled and randomly assigned to receive either pioglitazone (uptitrated to 30 mg/day; P=53) or matching placebo (P=51) for 24 weeks. Depression and anxiety were quantified using the hospital anxiety and depression scale and stress level using the general health questionnaire 12 at baseline, week 12, and endpoint. Homeostasis model assessment was used to estimate insulin resistance. At week 24, pioglitazone was superior in mitigating depression score (P=0.011). In trend analysis, the effect of time (P<0.001) and group (P=0.023) as well as the time by group interaction (P=0.032) on the mean depression score was considerable. In contrast, significant decrements in anxiety and stress levels (P<0.001 and P=0.012, resp.) were comparable between two groups. With respect to our findings, alterations in depression severity were not correlated with changes in insulin resistance level (P=0.145). In conclusion, our findings suggest that pioglitazone might be able to improve mood in nondiabetic insulin resistant patients. (Registered at Australian New Zealand Clinical Trials Registry; ACTRN12611000351910.)

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Long-term Effect of Glimepiride and Rosiglitazone on Non-conventional Cardiovascular Risk Factors in Metformin-treated Patients Affected by Metabolic Syndrome: A Randomized, Double-blind Clinical Trial

Journal of International Medical Research ◽

10.1177/147323000503300303 ◽

2005 ◽

Vol 33 (3) ◽

pp. 284-294 ◽

Cited By ~ 16

Author(s):

G Derosa ◽

AV Gaddi ◽

L Ciccarelli ◽

E Fogari ◽

M Ghelfi ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Cardiovascular Risk ◽

Plasma Glucose ◽

Double Blind Study ◽

Model Assessment ◽

Rapid Improvement ◽

Double Blind

We evaluated the effect of glimepiride plus metformin and rosiglitazone plus metformin on glucose, and on cardiovascular risk parameters such as lipoprotein(a) (Lp[a]) and homocysteine (HCT) in patients with type 2 diabetes and metabolic syndrome. Ninety-nine patients in the multicentre, randomized, double-blind study took metformin (1500 mg/day) plus glimepiride (2 mg/day) or rosiglitazone (4 mg/day) for 12 months. Changes in body mass index, glycosylated haemoglobin (HbA1c), Lp(a) and HCT were primary efficacy variables. Fasting plasma glucose (FPG), post-prandial plasma glucose (PPG) and homeostasis model assessment index were also used to assess efficacy. On average, HbA1c decreased by 9.1% and 8.1%, FPG decreased by 7.3% and 10.9%, and PPG decreased by 7.6% and 10.5%, respectively, in the glimepiride and rosiglitazone groups after 12 months. Patients receiving rosiglitazone experienced more rapid improvement in glycaemic control than those on glimepiride, and showed a significant improvement in insulin resistance-related parameters. There was a statistically significant decrease in basal homocysteinaemia in glimepiride-treated patients (−27.3%), but not in rosiglitazone-treated patients. Rosiglitazone plus metformin significantly improved long-term control of insulin resistance-related parameters compared with glimepiride plus metformin, although glimepiride treatment was associated with a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients, and with significant improvements in non-traditional risk factors for cardiovascular disease, such as basal homocysteinaemia and plasma Lp(a) levels.

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A16 FIBER SUPPLEMENTATION DIFFERENTIALLY MODULATES RESPONSES TO FECAL MICROBIAL TRANSPLANTATION IN PATIENTS WITH METABOLIC SYNDROME AND SEVERE OBESITY: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT TRIAL

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.015 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 20-21

Author(s):

V Mocanu ◽

Z Zhang ◽

E Deehan ◽

K Samarasinghe ◽

N Hotte ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Insulin Sensitivity ◽

Dietary Intake ◽

Primary Outcome ◽

Linear Mixed Model ◽

Severe Obesity ◽

Pilot Trial ◽

Model Assessment ◽

Double Blind

Abstract Background Fecal microbial transplantation (FMT) from lean donors to obese patients with metabolic syndrome (MS) has been associated with promising yet short-term metabolic improvements. The concept of using dietary or fiber supplementation to enhance effects induced by FMT has been much discussed in the literature, but to date no human trials have examined this concept. Aims The aim of this study was to determine if fiber supplementation following FMT was able to enhance or sustain FMT-mediated metabolic benefits. Methods We performed a 12-wk double-blind randomized placebo-controlled trial in patients with severe obesity and MS recruited from Edmonton’s Bariatric Clinic from 2018 to 2019. Patients were stratified by sex and block randomized 1:1:1:1 amongst one of four groups: (1) Placebo FMT and a non-fermentable fiber (NF) (2) Placebo FMT and fermentable fiber (FF); (3) FMT and non-fermentable fiber (FMT-NF); and (4) FMT and fermentable fiber (FMT-FF). Patients received a single dose of FMT (50g donor stool) with 20 oral capsules followed by a 6-wk period of daily fiber. The primary outcome was evaluating mean differences (MD) in insulin sensitivity from baseline to 6-wks using the homeostatic model assessment of insulin resistance (HOMA2-IR). Results Sixty-eight patients were randomized with 61 completing the primary outcome (NF = 17; FF = 15; FMT-NF = 14; FMT-FF = 15) and evaluated using a modified intent-to-treat analysis. Baseline characteristics were similar with a mean BMI 45 ± 7 kg/m2, a female predominance (83.6%), and a HOMA2-IR of 3.43 ± 2.2. There were no baseline differences in clinical characteristics, metabolic parameters, medications, or dietary intake. FMT-NF had improvements in HOMA2-IR (MD -24.0% ± 12.0%; p=0.02), insulin sensitivity (MD 27.6% ± 12.3%; p=0.02), and insulinemia (MD -25.4% ± 12.3%; p=0.02) from baseline to 6-wks (Figure 1). These benefits were associated with increased microbial richness and improvements in GLP-1 metabolism. Linear mixed model regression revealed that select bacterial taxa including Phascolarctobacterium, Ruminococcaeceae, and B. stercoris correlated with increased insulin sensitivity. Findings occurred in the absence of changes in anthropometric parameters, dietary intake, medication regimen and were not observed in groups receiving fermentable fiber or in any group following cessation of fiber. Conclusions This proof-of-concept trial provides evidence that a single FMT dose combined with daily non-fermentable fiber supplementation can successfully improve insulin resistance in patients with metabolic syndrome and severe obesity on optimized medical therapy. Funding Agencies W. Garfield Weston Foundation

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Effect of Hedan tablets on body weight and insulin resistance in patients with metabolic syndrome

Obesity Facts ◽

10.1159/000520711 ◽

2021 ◽

Author(s):

Lian-Yong Liu ◽

Lin Zhou ◽

Xing-Zhen Liu ◽

Da-Jin Zou

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Weight ◽

Treatment Group ◽

Lipid Level ◽

Lipid Lowering ◽

Controlled Study ◽

Control Group ◽

Model Assessment ◽

Double Blind

Introduction: Apart from their recognized lipid-lowering effect, Hedan tablets, a mixture of Chinese herbal medicines, have demonstrated a certain weight-loss effect in clinical practice. The aim of this randomized, double-blind, placebo-controlled study is to verify the effect of Hedan tablets on body weight (BW) and insulin resistance (IR) in patients with metabolic syndrome (MetS). Methods: A total of 62 eligible patients with MetS were divided into two groups: the treatment group (Hedan tablets at 4.38 g/day tid) and the control group (placebo treatment). Both groups attended follow-ups at 8, 16, and 24 weeks during the process. The parameters of the assessment include lipid level, BW, triglyceride (TG) to high-density lipoprotein cholesterol (HDLc) ratio (TG/HDLc), homeostasis model assessment for IR (HOMA-IR) index, and adiponectin. Results: Patients in the treatment group showed a significant decrease in BW compared with the control group (−4.47 vs. 0.06 kg) after 8 weeks of treatment. A significant decrease in body mass index was also observed in the treatment group after 16 weeks of treatment (−1.79 vs. −0.03 kg/m2). In the treatment group, 20 out of 31 (64.5%) patients lost 5–10% BW and 4 out of 31 (12.9%) patients lost over 10% BW after 24 weeks of treatment. Although there were no significant changes in the patients’ HOMA-IR, the treatment group showed a significant reduction in TG/HDLc (−0.98 vs. −0.19) after 8 weeks of treatment and a significant increase in adiponectin (6.87 vs. −0.43) after 16 weeks of treatment. Discussion/Conclusion: The Hedan tablets significantly improve BW, BMI, TG/HDLc, and adiponectin in patients with MetS. Thus, Hedan tablets may be used as an adjunct to existing MetS management methods.

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Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome

Nutrients ◽

10.3390/nu13020548 ◽

2021 ◽

Vol 13 (2) ◽

pp. 548

Author(s):

Chia-Wen Lu ◽

Yi-Chen Lee ◽

Chia-Sheng Kuo ◽

Chien-Hsieh Chiang ◽

Hao-Hsiang Chang ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Linear Models ◽

Serum Zinc ◽

Serum Levels ◽

Least Square ◽

Model Assessment ◽

Serum Concentrations ◽

Metabolic Factors ◽

Homeostatic Model Assessment

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 μg/L, 1043.45 ± 306.36 μg/L, and 1246.83 ± 538.13 μg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35–10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25–3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24–3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

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Homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic syndrome at baseline of a multicentric Brazilian cohort: ELSA-Brasil study

Cadernos de Saúde Pública ◽

10.1590/0102-311x00072120 ◽

2020 ◽

Vol 36 (8) ◽

Author(s):

Maria de Fátima Haueisen Sander Diniz ◽

Alline Maria Rezende Beleigoli ◽

Maria Inês Schmidt ◽

Bruce B. Duncan ◽

Antônio Luiz P. Ribeiro ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Normal Weight ◽

Overweight And Obesity ◽

Model Assessment ◽

Adult Health ◽

Homeostasis Model Assessment ◽

The Metabolic Syndrome ◽

Brazilian Cohort ◽

Overweight Or Obesity

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.

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Metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis

European Journal of Pediatrics ◽

10.1007/s00431-020-03924-w ◽

2021 ◽

Author(s):

Francesca Caroppo ◽

Alfonso Galderisi ◽

Laura Ventura ◽

Anna Belloni Fortina

Keyword(s):

Metabolic Disease ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Model Assessment ◽

Limited Data ◽

Single Center ◽

Increased Risk ◽

High Prevalence ◽

Homeostatic Model Assessment ◽

Homeostatic Model

AbstractPsoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3–10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known:• Psoriasis in adults is strongly associated with metabolic disease and insulin resistance.• Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New:• This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance.• In children with psoriasis metabolic syndrome risk factors should be assessed.

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Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity

European Respiratory Journal ◽

10.1183/13993003.00918-2015 ◽

2016 ◽

Vol 47 (6) ◽

pp. 1718-1726 ◽

Cited By ~ 1

Author(s):

Oscar L. Llanos ◽

Panagis Galiatsatos ◽

Edmarie Guzmán-Vélez ◽

Susheel P. Patil ◽

Philip L. Smith ◽

...

Keyword(s):

Insulin Resistance ◽

Fasting Glucose ◽

Sleep Apnoea ◽

Model Assessment ◽

Rapid Eye Movement Sleep ◽

Homeostasis Model Assessment ◽

Tonsillar Hypertrophy ◽

Insulin Resistant ◽

Bariatric Patients ◽

Respiratory Disturbance

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h−1, diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp.Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104–0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196–0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.

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Insulin Resistance in Association with Thyroid Function, Psychoemotional State, and Cardiovascular Risk Factors

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18073388 ◽

2021 ◽

Vol 18 (7) ◽

pp. 3388

Author(s):

Nijole Kazukauskiene ◽

Aurelija Podlipskyte ◽

Giedrius Varoneckas ◽

Narseta Mickuviene

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Thyroid Function ◽

Study Groups ◽

Model Assessment ◽

Psychoemotional State ◽

Study Participants

Background: Individuals with insulin resistance (IR) have a high risk of diabetes or metabolic syndrome, and they are more likely to have depression. Furthermore, IR by itself is a major cardiovascular risk factor in healthy persons. Thus, we aimed to investigate IR in association with thyroid function, psychoemotional state, and cardiovascular risk factors among 45–84-year-old citizens of Palanga. Methods: A randomized epidemiological study was performed with 850 subjects. All participants were evaluated for sociodemographic, clinical, and cardiovascular risk factors and biochemical analysis. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Results: All study participants were stratified into groups without IR (HOMA-IR ≤ 2.7) and with IR (HOMA-IR > 2.7). The analysis of parameters between the two study groups showed some statistically significant relationships between IR and cardiovascular risk factors. The predictable accuracy was presented using receiver performance characteristic curves for HOMA-IR scores in women and men separately. If the HOMA-IR score is higher than 3.45, individuals are significantly more likely to have type 2 diabetes mellitus (T2DM). Conclusions: An increase of fasting glucose and more frequent incidence of metabolic syndrome, diabetes, and cardiovascular diseases in subjects with IR are associated with the prevalence of cardiovascular risk factors. There was no significant association between thyroid function and HOMA-IR. HOMA-IR cut-offs could predict the presence of T2DM.

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Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-2373 ◽

2013 ◽

Vol 98 (12) ◽

pp. 4899-4907 ◽

Cited By ~ 235

Author(s):

Kyung Hee Park ◽

Lesya Zaichenko ◽

Mary Brinkoetter ◽

Bindiya Thakkar ◽

Ayse Sahin-Efe ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Body Mass Index ◽

Body Mass ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Cvd Risk ◽

Baseline Serum ◽

The Metabolic Syndrome ◽

Increased Risk

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P < .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P < .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

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Female offspring born to obese and insulin-resistant dams are not at increased risk for obesity and metabolic dysfunction during early development

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0371 ◽

2018 ◽

Vol 96 (1) ◽

pp. 97-102 ◽

Cited By ~ 1

Author(s):

Hanin Aburasayn ◽

Rami Al Batran ◽

Keshav Gopal ◽

Malak Almutairi ◽

Amina Eshreif ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Female Offspring ◽

Metabolic Dysfunction ◽

Insulin Resistant ◽

The Metabolic Syndrome ◽

Rate Versus ◽

Increased Risk ◽

Study Completion ◽

Reduced Rate

The percentage of women who are obese at the time of conception or during pregnancy is increasing, with animal and human studies demonstrating that offspring born to obese dams or mothers are at increased risk for obesity and the metabolic syndrome. Our goal was to confirm in an experimental model of metabolic syndrome in the dam, whether the offspring would be at increased risk of obesity. Conversely, we observed that male offspring born to dams with metabolic syndrome had no alterations in their body mass profiles, whereas female offspring born to dams with metabolic syndrome were heavier at weaning, but exhibited no perturbations in energy metabolism. Moreover, they gained weight at a reduced rate versus female offspring born to healthy dams, and thus weighed less at study completion. Hence, our findings suggest that factors other than increased adiposity and insulin resistance during pregnancy are responsible for the increased risk of obesity in children born to obese mothers.

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