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Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training.
Jerobin, J, Ramanjaneya, M, Bettahi, I, Parammal, R, Siveen, KS, Alkasem, M, Aye, M, Sathyapalan, T, Skarulis, M, Atkin, SL, et al
Lipids in health and disease. 2021;(1):34
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined. METHODS Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h. RESULTS Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels. CONCLUSION This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.
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Family History of Diabetes and the Effectiveness of Lifestyle Intervention on Insulin Secretion and Insulin Resistance in Chinese Individuals with Metabolic Syndrome.
Zhu, H, Chen, X, Zhang, B, Yang, W, Xing, X
Journal of diabetes research. 2021;:8822702
Abstract
AIMS: The current study aims to explore if a family history of diabetes can influence the efficiency of lifestyle intervention on insulin secretion and study the insulin resistance in Chinese men and women with metabolic syndrome in a cohort with a 2-year follow-up. METHODS 151 individuals (90 individuals did not have a family history of diabetes (DMFH (-)) and 61 with a family history of diabetes (DMFH (+)) with metabolic syndrome participated in the lifestyle intervention program at baseline and finished with 1-year follow-up. 124 individuals have two-year follow-up data. A family history of diabetes was ascertained by self-report. Lifestyle interventions were individual sessions on lifestyle changes. RESULTS During the 1-year follow-up, Ln Insulinogenic index (Δbaseline-1year = 0.29 ± 0.65, P = 0.001) and 30-min glucose (Δbaseline-1year = -0.41 ± 1.71, P = 0.024) changed significantly in the DMFH(-) group; in the DMFH(+) group, Ln ISIm (Δbaseline-1year = -0.22 ± 0.60, P = 0.022) and 30-min glucose (Δbaseline-1year = 0.53 ± 1.89, P = 0.032) changed significantly, and there was no significant change of other parameters. The change of 30 min glucose during a 1-year intervention has shown a significant difference between the two groups (P = 0.002). During the 2 years intervention, Ln Insulinogenic index changed significantly in the DMFH(-) group (Δbaseline-1year = 0.33 ± 0.66, P < 0.001 and Δbaseline-2year = 0.43 ± 1.17, P = 0.034). Fasting insulin (Δbaseline-2year = 2.95 ± 8.69, P = 0.034), 2 h insulin (Δbaseline-2year = 23.75 ± 44.89, P = 0.002), Ln HOMA-B (Δbaseline-2year = 0.43 ± 1.02, P = 0.009), Ln HOMA-IR (Δbaseline-2year = 0.53 ± 1.04, P = 0.002), Ln ISIm (Δbaseline-2year = 0.52 ± 0.95, P = 0.004), and Ln Insulinogenic index (Δbaseline-2year = 0.66 ± 1.18, P = 0.047) changed significantly after 2 years of intervention, compared to the baseline in the DMFH(+) group. The change of Ln ISIm (P = 0.023), fasting (P = 0.030), and 2 h insulin (P = 0.007) during the 2-year intervention has shown a significant difference between the two groups. Family history of diabetes was related with a 0.500 unit increase in 2-year ISIm (P = 0.020) modified by lifestyle intervention adjusted for age, baseline BMI, sex, and baseline waist circumference and a 0.476 unit increase in 2-year ISIm (P = 0.027) with extra adjustment for weight change. CONCLUSIONS Patients with a family history of diabetes benefit more from lifestyle intervention in regard to insulin resistance than those without a family history of diabetes adjusting for age, baseline BMI, sex, baseline waist circumference, and weight change.
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Berberine Phospholipid Is an Effective Insulin Sensitizer and Improves Metabolic and Hormonal Disorders in Women with Polycystic Ovary Syndrome: A One-Group Pretest-Post-Test Explanatory Study.
Rondanelli, M, Riva, A, Petrangolini, G, Allegrini, P, Giacosa, A, Fazia, T, Bernardinelli, L, Gasparri, C, Peroni, G, Perna, S
Nutrients. 2021;(10)
Abstract
Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disease in females of reproductive age and is characterized by multifactorial unhealthy conditions related to hormonal unbalance and also to dysmetabolism and inflammation. Recently, increasing evidence has shown that natural plant-based products may play a role in PCOS management. The aim of this one-group pretest-post-test explanatory study was to evaluate, in normal-overweight PCOS women with normal menses, the effectiveness of berberine on: Insulin resistance (IR) by Homeostasis Model Assessment (HOMA); Inflammation by C-Reactive Protein (CRP), Tumor Necrosis Factor α (TNF-α); Lipid metabolism; Sex hormone profile and symptoms correlated to hyperandrogenism, such as acne, by Global Acne Grading System (GAGS) and Cardiff Acne Disability Index (CADI); Body composition by DXA. Finally, adverse effects were assessed by liver and kidney functions and creatine phosphokinase (CPK). All these parameters were collected at baseline and 60 days after supplementation with a new bioavailable and safe berberine formulation. Twelve females (aged 26.6 ± 4.9, BMI 25.3 ± 3.6) were supplied for 60 days with two tablets/day (550 mg/table) of the bioavailable berberine. Results showed a statistically significant decrease in HOMA, CRP, TNF-α, Triglycerides, testosterone, Body Mass Index (BMI), Visceral Adipose Tissue (VAT), fat mass, GAGS and CADI scores, and a statistically significant increase in sex hormone-binding globulin (SHBG). Liver and kidney functions and CPK are not statistically significantly different. Therefore, berberine can represent a safe novel dietary supplement, helpful in treatment strategy for PCOS.
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Use of flash glucose monitoring system in assessing safety of the SGLT2 inhibitors during Ramadan fasting in high risk insulin treated patients with type 2 diabetes.
Abdelgadir, E, Rashid, F, Bashier, A, Al Saeed, M, Khalifa, A, Alawadi, F, Hassanein, M
Diabetes & metabolic syndrome. 2019;(5):2927-2932
Abstract
BACKGROUND The risks of hypoglycemia, dehydration and kidney injury may theoretically be aggravated by people with type 2 diabetes treated with Insulin and SGLT2 inhibitors during Ramadan. Data on safety and efficacy of SGLT2-I in people with type 2 diabetes treated with insulin is scanty. We aimed to assess the impact of SGLT2 inhibitors during Ramadan in high-risk patients with type 2 diabetes treated with insulin, on hypoglycemia, glycemic control and kidney function. METHODS This is a prospective interventional study on high-risk diabetes patients who insisted on fasting. All patients were treated with insulin ± SGLT2I. All patients received a FGMS and Ramadan focused education. All patients attended clinic before and post Ramadan where they were advised on treatment modification as well as biometric and biochemical measurements. RESULTS 95 patients enrolled in the study and 49 of them were on SGLT2i. There was a no significant change in creatinine in both groups. FGMS showed an improvement in the sensor-calculated HbA1c from 7.3 ± 1.5 to 6.8 ± 1.1 and from 8 ± 1.6 to 7.7 ± 1.5 in the SGLT2 group and the non-SGT2i groups, respectively. The hypoglycemia was predominantly reported during Ramadan between 12:00 to 18:00 h, while in pre-Ramadan readings was during 2400-0600 and 1200-1800 slots. CONCLUSIONS This is the first study that assesses the use of SGLT2i along with insulin during Ramadan, using FGMS in high-risk patients with type 2 diabetes under optimal care. There was minimal interruption of fasting, significant improvement in glycemic control, and no significant change in the kidney function after Ramadan.
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The resting metabolic rate in women with polycystic ovary syndrome and its relation to the hormonal milieu, insulin metabolism, and body fat distribution: a cohort study.
Romualdi, D, Versace, V, Tagliaferri, V, De Cicco, S, Immediata, V, Apa, R, Guido, M, Lanzone, A
Journal of endocrinological investigation. 2019;(9):1089-1097
Abstract
PURPOSE To evaluate possible alterations of a major determinant of energy expenditure, the resting metabolic rate (RMR), in women with polycystic ovary syndrome (PCOS) compared with age-BMI similar controls. To assess whether the hormonal milieu, the body fat distribution and the insulin metabolism may affect energy consumption in these patients. METHODS This is a monocentric observational prospective cohort study, including 109 Caucasian PCOS subjects and 31 healthy control women. (Median age PCOS 26.0 ± 9.2 years, controls 25.5 ± 8.5 years; median BMI-body mass index PCOS 26.4 ± 9.4 kg/m2, controls 27.2 ± 12.8 kg/m2). RMR was evaluated by the SenseWear Armband (SWA), a reliable and validated metabolic holter, never previously used in the PCOS population to this purpose. Hormonal assessment, insulin metabolism evaluated by HOMA-IR and OGTT, anthropometric features (BMI and WHR) were also assessed. RESULTS Median RMR resulted similar in PCOS and control women: 1520.0 ± 248.00 kcal/day vs 1464.0 ± 332.70 kcal/day (p = 0.472), even after adjusting for BMI, fat distribution, insulin metabolism parameters. RMR resulted significantly correlated with BMI, WHR, estradiol levels, SHBG, total cholesterol, triglycerides, basal glycaemia, basal insulinemia, AUC insulin 240', and HOMA. In the subgroup of patients with WHR > 0.85, PCOS women showed a significantly lower RMR compared with controls. CONCLUSIONS The higher prevalence of obesity, which negatively influences the reproductive and general health of PCOS women, could be related to factors other than an intrinsic alteration of the RMR. Further studies are needed to clarify the possible role of the visceral fat in modulating the energy balance in PCOS. TRIAL REGISTRATION NUMBER clinicaltrials.gov Identifier NCT03132545.
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Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men.
Matikainen, N, Söderlund, S, Björnson, E, Bogl, LH, Pietiläinen, KH, Hakkarainen, A, Lundbom, N, Eliasson, B, Räsänen, SM, Rivellese, A, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2017;(6):534-542
Abstract
BACKGROUND AND AIMS Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. METHODS AND RESULTS As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). CONCLUSION In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge.
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Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
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Rubin, DA, Clark, SJ, Haqq, AM, Castner, DM, Ng, J, Judelson, DA
Hormone research in paediatrics. 2017;(3):153-161
Abstract
BACKGROUND Prader-Willi syndrome (PWS) is characterized by excessive adiposity. Excess adiposity negatively affects hormonal and metabolic responses to aerobic exercise. This study determined whether PWS and/or adiposity affected hormonal and metabolic responses to resistance exercise. METHODS Eleven children with PWS (11.4 ± 3.1 years, 43.9 ± 7.5% body fat), 12 lean children (9.3 ± 1.4 years, 18.3 ± 4.9% body fat), and 13 obese children (9.6 ± 1.3 years, 40.3 ± 5.2% body fat) participated. The children stepped onto an elevated platform while wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). For the children with PWS, the platform height was 23.0 cm and vest load was computed as (20% of stature × 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and vest load 50% of the lean body mass. Blood samples were obtained before, immediately after, and during recovery from exercise (+15, +30, and +60 min). RESULTS All groups had similar catecholamine, insulin, and glucagon responses. The groups showed no major differences in glucose and lactate levels. The PWS children demonstrated earlier increases in fatty acids during recovery and higher glycerol and ketone levels than the controls. CONCLUSION The PWS children demonstrated largely intact hormonal, glycolytic, and lipolytic responses to lower-body resistance exercise. In PWS, elevated ketone levels suggest an incomplete fat oxidation.
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Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial.
Ellis, KL, Zhou, Y, Beshansky, JR, Ainehsazan, E, Selker, HP, Cupples, LA, Huggins, GS, Peter, I
The pharmacogenomics journal. 2015;(6):488-95
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Abstract
Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect clinical outcomes in acute coronary syndromes (ACS). In an Immediate Myocardial Metabolic Enhancement During Initial Assessment And Treatment In Emergency Care (IMMEDIATE) trial's sub-study (n = 318), we explored effects of 132,634 genetic variants on plasma glucose and potassium response to 12-h GIK infusion. Associations between metabolite-associated variants and infarct size (n = 84) were assessed. The 'G' allele of rs12641551, near ACSL1, as well as the 'A' allele of XPO4 rs2585897 were associated with a differential glucose response (P for 2 degrees of freedom test, P2df ⩽ 4.75 × 10(-7)) and infarct size with GIK (P2df < 0.05). Variants within or near TAS1R3, LCA5, DNAH5, PTPRG, MAGI1, PTCSC3, STRADA, AKAP12, ARFGEF2, ADCYAP1, SETX, NDRG4 and ABCB11 modified glucose response, and near CSF1/AHCYL1 potassium response (P2df ⩽ 4.26 × 10(-7)), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.
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Roles of circulating WNT-signaling proteins and WNT-inhibitors in human adiposity, insulin resistance, insulin secretion, and inflammation.
Almario, RU, Karakas, SE
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;(2):152-7
Abstract
Wingless-type MMTV integration site family member (WNT) signaling and WNT-inhibitors have been implicated in regulation of adipogenesis, insulin resistance, pancreatic function, and inflammation. Our goal was to determine serum proteins involved in WNT signaling (WNT5 and WISP2) and WNT inhibition (SFRP4 and SFRP5) as they relate to obesity, serum adipokines, insulin resistance, insulin secretion, and inflammation in humans. Study population comprised 57 insulin resistant women with polycystic ovary syndrome (PCOS) and 27 reference women. In a cross-sectional study, blood samples were obtained at fasting, during oral, and frequently sampled intravenous glucose tolerance tests. Serum WNT5, WISP2, and SFRP4 concentrations did not differ between PCOS vs. reference women. Serum WNT5 correlated inversely with weight both in PCOS and reference women, and correlated directly with insulin response during oral glucose tolerance test in PCOS women. Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5×10(-6) as compared to both PCOS groups). Serum SFRP5 correlated inversely with IL-1β, TNF-α, cholesterol, and apoprotein B. These findings demonstrated that WNT5 correlated inversely with adiposity and directly with insulin response, and the WNT-inhibitor SFRP5 may be anti-inflammatory. Better understanding of the role of WNT signaling in obesity, insulin resistance, insulin secretion, lipoprotein metabolism, and inflammation is important for prevention and treatment of metabolic syndrome, diabetes and cardiovascular disease.
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Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome.
Straznicky, NE, Grima, MT, Lambert, EA, Sari, CI, Eikelis, N, Nestel, PJ, Phillips, SE, Hering, D, Karapanagiotidis, S, Dixon, JB, et al
The Journal of clinical endocrinology and metabolism. 2015;(4):1544-50
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CONTEXT Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations. OBJECTIVE To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome. PARTICIPANTS AND METHODS Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.7 ± 0.6 kg/m(2)) underwent euglycemic hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry, Doppler echocardiography, and oral glucose tolerance test. RESULTS Univariate correlation analyses showed inverse associations between insulin clearance and arterial norepinephrine concentration (r = -0.44, P = .0006), calculated norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r = -0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P = .04). Insulin clearance and sensitivity did not differ between genders, however females had higher AI compared to males (35 ± 3% versus 14 ± 2%, P < .001). In age and gender adjusted stepwise regression analyses, arterial norepinephrine concentration alone explained 19% of the variance in insulin clearance. When all significant variables were entered into the regression model, arterial norepinephrine, AI, gender, and M were independent predictors of insulin clearance, together explaining 41% of the variance. CONCLUSIONS Arterial norepinephrine concentration is inversely and independently associated with whole-body insulin clearance rate in obese individuals with metabolic syndrome. Prospective studies are needed to determine the direction of causality and the chronology of interactions between insulin clearance and sympathetic neural activity.