Improvement In Metabolic Profile Research Articles

8443 Incretin-Mimetic Therapy In Hypertriglyceridemia-Induced Pancreatitis - A Case Report

Abstract Disclosure: A. Iqbal: None. U. Alwahab: None. Introduction The use of incretin-mimetic therapy (IMT), which includes human glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonists, in patients with a history of pancreatitis is controversial. While clinical trials have demonstrated a slightly increased incidence of acute pancreatitis (AP) in patients on IMT, it is unclear if patients with hypertriglyceridemia (HTG)-induced pancreatitis areat similar risk. In patients with type 2 diabetes (T2D) and HTG, control of diabetes and improvement of metabolic profile using IMT could decrease the risk of HTG-induced pancreatitis. Case Description We report a case of a patient with diabetes and a history of HTG-induced pancreatitis where IMT was successfully used without precipitation of AP. Patient A is a 44-year-old male with obesity (BMI 38.25 kg/m2 ), T2D, and severe HTG associated with recurrent episodes of AP. His triglyceride (TG) level has ranged from 983 to >4,000 mg/dL. He is on fenofibrate, icosapent ethyl, and rosuvastatin. His last hospitalization for acute pancreatitis was 3months prior. His most recent hemoglobin A1c is 7.4%, TG is 302mg/dL, and he is being treated with glipizide, metformin, empagliflozin, and multiple daily injections of insulin. For management of his obesity and T2D, he is then started on tirzepatide, in conjunction with diet and lifestyle modification, which is slowly up-titrated to 7.5 mg weekly. After 12 months of tirzepatide treatment, he has lost 10 lbs, his A1C is now 5.9%, triglycerides have improved to 172 mg/dL, and he has had no precipitation of AP. Discussion While a history of pancreatitis is a relative contraindication to the use of IMT, attention should be paid to the cause of pancreatitis. Obesity and uncontrolled diabetes are frequent triggers of AP. IMT helps improve metabolic profile in patients with obesity, uncontrolled diabetes, and hypertriglyceridemia, thus decreasing triglyceride levels and preventing further episodes of AP as seen in our patient. The use of IMT in patients with a history of AP should be done on an individualized basis. Controlling the trigger for the AP (such as hypertriglyceridemia) should be prioritized and shared medical decision-making with the patient should be done regarding the benefits and risks of IMT. Presentation: 6/3/2024

THU142 One-year Change In Bile Acids And Its Association With Changes In Metabolic Profile After Sleeve Gastrectomy In Youth

Abstract Disclosure: S. Tuli: None. S. Kaur: None. M. Bredella: None. M. Misra: None. V. Singhal: None. Introduction: Bile acids (BAs) are hydroxylated steroid acids. Primary (10) BAs (cholic acid (CA) and chenodeoxycholic acid (CDCA) are synthesized by the liver. Secondary (20) BAs (deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) are formed from 10 BAs by the action of intestinal flora. Preclinical studies indicate a role of BAs in weight loss and metabolic improvements after metabolic and bariatric surgery (MBS). Data are inconsistent regarding changes in BAs after sleeve gastrectomy (SG), the most common MBS. Further, how BA changes contribute to metabolic improvements after SG is unclear. Objective: Evaluate changes in serum BAs 1 year after SG in youth with obesity and associations with changes in metabolic parameters. Methods: 16 adolescents (75% females) 13-22 years old with severe obesity were followed for one-year post-SG with assessments at baseline and during a mixed meal tolerance test (MMTT). We measured fasting BAs, glucose, insulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipids. Blood was drawn at 15, 30, 60, 90, and 120 minutes for glucose and insulin and at 0, 15, 60, and 120 minutes for BAs. Data are reported as changes over 15 minutes [t15–t0 of MMTT (Δ15)], area under the curve (AUC), and % change. Results: BMI decreased by 25.7% (p<0.0001). For 10 BAs: fasting CA levels decreased (33.3%, p=0.005), while Δ15 CA, CDCA and, total 10 BAs (113.3%, 188.9%, 152.9%, p<0.005), and AUC for CDCA and total 10 BAs (34.2%, p=0.004; 30.3%, p=0.015) increased one-year post-SG. For 20 BA: Δ15 DCA and total 20 BAs (212.5%, p≤0.011; 195.2%, p=0.004), and AUC DCA and total 20 BAs (95.0%, p=0.031; 59.4%, p=0.035) increased. Δ15 and AUC total BA also increased (100%, p=0.002; 1060.9%, p≤0.0001). Insulin resistance (HOMA-IR) (58.6%), low-density lipoprotein (LDL) (11.2%), triglyceride (14.6%), and ALT (26.9%) decreased (p<0.05), while high-density lipoprotein (HDL) levels (10.2%, p=0.04) increased. Decreases in AUC insulin were associated with increases in AUC 20/10 BA (ρ=-0.687, p=0.009). HBA1C decreases were associated with increases in AUC total BAs (ρ=-0.531, p=0.034). Increases in the insulinogenic index (Δ30 Insulin/ Δ30 glucose) correlated positively with fasting DCA (ρ=0.567, p=0.028). Increases in HDL were associated with increases in fasting CA (ρ=0.580, p=0.018) and UDCA (ρ=0.592, p=0.016). Conclusion: Total, 10, and 20 bile acids increase after SG in youth associated with improvements in metabolic profile. Presentation: Thursday, June 15, 2023

Bariatric endoscopic-surgical therapies for NAFLD. Should they be considered viable options among current treatments?

Nowadays, non-alcoholic fatty liver disease is one of the first causes of liver transplant worldwide; many efforts have been done to find the perfect drug for this multifactorial disease. Presently we just have a few drugs that could be used in specific and limited clinical scenarios. Current evidence suggests that bariatric endoscopic and surgical therapies could be strategies with optimal outcomes, with high impact in quality of life, decrease of cardiovascular risk, and improvement in metabolic profile, despite being considered expensive procedures. This review proposes to consider these therapies early together with liver fibrosis evaluation, with long term cost-effectiveness benefits in the absence of response to lifestyle modifications and pharmacological treatments.

OR25-6 In Men on Testosterone Therapy, Baseline Testosterone Level of <264 ng/dL is Associated with Greater Improvement in Body Composition, While Level of ≥264 ng/dL Favors Improvement in Metabolic Profile

Abstract Context Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dL is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study investigating whether baseline T levels also influences body composition and metabolic response to T therapy. Objective To determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with baseline T level of < 264 ng/dL compared to those with levels ≥264ng/dL Methods: Secondary analysis of single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dL, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of < 264 ng/dL (N=43) and those with ≥264 ng/dL (N=57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, sclerostin), adiponectin, and leptin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD, and body composition by dual-energy x-ray absorptiometry (DXA). Results Men with T < 264 ng/dL showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dL (4.2±4.1 vs 2.7±3.8%; p=0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7±11.5 vs 4.4±4.3%, 7.3±11.6 vs 2.4±6.8%; p=0.033 and p=0.043, respectively). Men with T ≥ 264 ng/dL showed significant decreases in HbA1c at 12 months (-3.1±9.2 vs 3.2±13.9%; p=0.005), fasting glucose at 18 months (-4.2±31.9 vs 13.0±57.3%; p=0.040), LDL at 6 months (-6.4±27.5 vs 12.8±44.1%; p=0.034), leptin at 18 months (-40.2±35.1 vs -27.6±31.0%; p=0.034) compared to those with T < 264 ng/dL. No significant differences in BMD and bone turnover markers were observed. Conclusion T therapy results in improvement in body composition irrespective of baseline T levels but T <264 ng/dL is associated with greater improvement in FFM, whereas T level of ≥264 ng/dL favors improvement in metabolic profile. Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.

Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy.

ContextMale hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy.ObjectiveThe aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl.MethodsThis is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40–74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA).ResultsMen with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (−3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (−4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (−6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (−40.2 ± 35.1 vs. −27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed.ConclusionT therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Metabolic Changes across Tertiles of Delta Changes in Height SDS during Growth Hormone Therapy in Children with Growth Hormone Deficiency

Introduction: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy. Methods: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 ± 2.3 years; h-SDS: −2.25 ± −1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment. Results: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern. Discussion/Conclusions: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children.

The effects of CPAP therapy on metabolic profile and subjective sleep parameters in patients with OSA: a prospective trial study.

ObjectiveSeveral studies confirmed a positive association between obstructive sleep apnea (OSA) and metabolic syndrome. Continuous positive airway pressure (CPAP) is the main treatment for patients with moderate and severe OSA. CPAP therapy in adults with OSA results in reduction in sleepiness, blood pressure and improvement of metabolic profile. In this study, we aimed to evaluate the effects of CPAP therapy on various components of metabolic syndrome and subjective sleep parameters in patients with OSA.Material and MethodsIn this prospective trial study, 28 patients with moderate and severe OSA enrolled. Patients were asked to fill out the validated Persian version of questionnaires including Epworth sleepiness scale, insomnia severity index, STOP-BANG and Beck depression inventory - II, before and after treatment with CPAP. Weight and blood pressure were recorded before and after treatment. Only 14 patients agreed to blood sampling before and after CPAP therapy (at least 3 months of treatment). Fasting blood samples were analyzed for measuring the levels of FBS (fasting blood sugar), TG (triglyceride), total cholesterol, HDL, LDL, AST, and ALT.ResultsDiastolic blood pressure, ISI and STOP-BANG score significantly decreased after treatment (p-value: 0.008, 0.022 and 0.004, respectively). FBS and TG levels decreased after treatment, but only TG levels had significant difference (p-value: 0.46 and 0.016, respectively).DiscussionCPAP therapy had positive effects on diastolic blood pressure, TG levels and ISI score. More studies with larger sample size and longer follow-up periods are warranted to investigate the effects of CPAP therapy on blood pressure, and metabolic parameters.

Metabolic Profile Correction in Patients with Obstructive Sleep Apnea Depends on the Duration of CPAP Therapy Sessions

Obstructive sleep apnea (OSA) is a common, heterogeneous chronic disease with sleep fragmentation, metabolic and cardiovascular disorders. Continuous Positive Air Pressure (CPAP) therapy is the primary treatment for patients with OSA. However, the effects of long-term CPAP therapy with night sessions &gt; 6 hours remain poorly understood. The aim of the study was to study the effects of different durations of night sessions of CPAP therapy on the “metabolic profile” of patients with severe OSA. Materials and methods. In a retrospective case-control study comparing two CPAP-therapy regimens by matching pairs from among patients with verified severe OSA (apnea-hypopnea index&gt; 30/h), arterial hypertension, obesity of I-II degrees according to the WHO classification (1997), signed informed consent, 2 groups of 18 people each were formed, comparable in age, anthropometric and somnographic indicators, using CPAP therapy 4-6 hours / night and more than 6 hours / night, respectively. Patients received CPAP therapy for a year, visits were carried out at 3, 6 and 12 months. The severity of sleep apnea was verified during nighttime computed somnography (CSG) on WatchPAT-200 hardware (ItamarMedical, Israel) with original software zzzPATTMSW ver. 5.1.77.7 (ItamarMedical, Israel) by registering the main respiratory polygraphic characteristics from 11.00 PM to 7:30 AM. The optimal therapeutic level of CPAP therapy was titrated at home using devices for automatic selection of therapeutic pressure (PR System One REMstar Auto CPAP Machine with A-Flex (Philips Respironics, USA)) within 7 days after the diagnostic study. To assess the compliance of OSA patients at 3-6-12 months of CPAP-therapy, we used the original compliance analysis program Encore Pro v.2.14 (Philips Respironics, USA). Results. With the initial comparability of the groups, by the 3rd month of therapy, patients with CPAP &gt; 6 h/night showed a statistically significant advantage over the patients with 4-6 h CPAP-therapy in ESS, neck circumference and testosterone. By the 6th month, statistically significant differences of BMI, VAI, leptin, oral glucose tolerance test, fasting insulin, HOMA-IR, lipid metabolism (HDL, LDL, triglycerides, Apo-B) appeared. By the 12th month of therapy, the CPAP group &gt; 6 h/night had a statistically significant advantage in waist circumference, fasting blood glucose and uric acid. Differences between groups at control points persisted throughout the observation period. Conclusions. Long-term home-based CPAP therapy with sessions &gt; 6 h/night has an advantage over therapy with sessions 4-6 h/night in achieving a rapid and pronounced improvement in metabolic profile and hormonal levels in patients with severe OSA.

Moderate to Intense Physical Activity Is Associated With Improved Clinical, CD4/CD8 Ratio, and Immune Activation Status in HIV-Infected Patients on ART.

BackgroundPhysical activity has anti-inflammatory effects and reduces morbidity and mortality in the general population, but its role in the clinical, CD4/CD8 ratio, and immune activation status of HIV-infected patients has been poorly studied.MethodsA cross-sectional study was carried out in a cohort of 155 HIV-infected patients on stable antiretroviral therapy (ART) to compare clinical, biochemical, CD4/CD8 ratio, and immune activation status according to their physical activity in the last 2 years (sedentary/low vs moderate/intense) assessed by the iPAQ. A binary logistic regression and mixed analysis of variance were performed to evaluate the impact of levels of physical activity on CD4/CD8 ratio.ResultsIn our series, 77 (49.7%) out of 155 patients were sedentary, and 78 (50.3%) practiced moderate/intense physical activity. Moderate/intense physical activity was associated with better metabolic control (lower body mass index, P = .024; glucose, P = .024; and triglyceride, P = .002) and CDC HIV stage (P = .046), lower CD8+ (P = .018), CD4+CD8+ (P = .026), CD4+CD86+ (P = .045), CD4+HLA-DR+ (P = .011), CD8+HLA-DR+ (P = .048) T lymphocytes and CD16+HLA-DR+ natural killer cells (P = .026), and higher CD3+CD4+ T lymphocytes (P = .016) and CD4/CD8 ratio (P = .001). Sedentary lifestyle (odds ratio [OR], 2.12; P = .042), CD4 nadir (OR, 1.005; P < .001), and CD8+CD38+ T cells (OR, 1.27; P = .006) were independently associated with low CD4/CD8 ratio (<0.8). Earlier and more intense CD4/CD8 ratio recovery was observed in patients with higher physical activity in the 2-year follow-up with a significant interaction between these variables: F(2, 124) = 3.31; P = .049; partial η2 = 0.042.ConclusionsModerate to high physical activity is associated with beneficial health effects, improvement in metabolic profile, and reduction of chronic inflammation in patients with HIV. Although more studies and clinical trials are needed to confirm these findings, a healthy lifestyle including at least moderate physical activity should be recommended to HIV patients on stable ART.

Potential Therapeutic Effects of Ursodeoxycholic Acid in Comparison to Ramipril in a Rat model of Diabetic Nephropathy

Abstract Background &amp; Aim Diabetic nephrectomy (DN) is a chronic progressive disorder that complicates long standing diabetes. Albuminuria is a prominent clinical feature of DN. Ursodeoxycholic acid (UDCA) is a physiologic hydrodrophillic bile acid that is therapeutically used in the treatment of primary biliary cirrhosis. It is known to alleviate endoplasmic reticulum (ER) stress in podocytes. In comparison to Ramipril as a standard ACEI therapy of DN, the present study was designed to investigate the effect of UDCA treatment on DN in association with renal biomarkers changes. Method Four groups of male Wister rats (6 per group) were designed; Normal control group, DN untreated group (High fat diet + STZ injection of 45 mg/kg + uninephrectomy), DN/Ramipril group; (1 mg/kg/d orally for 12 weeks) and DN/UDCA group (40 mg/kg/d orally for 12 weeks). Results DN rats treated with UDCA for 12 weeks exhibited significant decrease in ER stress marker, ATF6 with mean percentage value of 73.8% and improvement of podocyte structural deformities that is accompanied by a significant reduction in albuminuria by mean percentage value of 43.8% comparatively to Ramipril that caused reduction in ATF6 level with mean percentage value of 65.5% and reduction in albuminuria by mean percentage value of 50.2%. The remarkable improvement in metabolic profile and the neutral effect on blood pressure in UDCA treated group could explain the renoprotection at histopathological basis rather than the proved hemodynamic effect of ramipril. Conclusion Participation of ER stressmediated apoptosis in the pathophysiology of diabetic nephropathy make the UDCA a potential therapeutic option or add-on therapy due to its anti-apoptotic property apart from classic metabolic and hemodynamic aspects.

Remote versus early corticosteroid wean outcomes in heart transplant recipients in the contemporary era.

The risks and benefits of remote corticosteroid weaning in heart transplant recipients more than 2years post-transplant are unknown. We compared outcomes in patients undergoing early and remote steroid weaning after heart transplantation. We performed a retrospective study (range 09, 1991-04, 2017). Primary outcomes included short-term and long-term mortality, allograft dysfunction, and burden of rejection. Secondary outcomes included impact on hemoglobin A1c, lipid panel, bone scan T-score, and body mass index. 63 patients underwent corticosteroid weaning between 2012 and 2017. Outcomes of patients weaned early (n=34; median time from transplant=1.1years) were compared with those weaned late (n=29; median time from transplant=4.4years). 52 (82.5%) patients were successfully weaned off corticosteroids. No statistically significant difference in outcomes was found between the early and late weaning groups (p=.20). There were no differences in allograft function (p-value=.16), incidence of rejection (p=.46), or mortality (p=.15). Improvement in metabolic profile was seen in both groups but was not statistically significant. In heart transplant recipients, remote vs early weaning of corticosteroids is not associated with significant differences in graft function or the incidence of rejection after 1-year follow-up. Moreover, there were no significant differences in survival up to 3years between the two groups.

Efficacy of testosterone replacement therapy for treating metabolic disturbances in late-onset hypogonadism: a systematic review and meta-analysis.

Late onset hypogonadism (LOH) is an age-dependent reduction of testosterone associated with alterations of metabolic profile, including glucose control, insulin sensitivity, and lipid profile. The purpose of this study was to investigate the efficacy of testosterone replacement therapy (TRT) for treating metabolic disturbances through a meta-analysis of randomized clinical trials (RCTs). A systematic review of literature published from 1964 to November, 2019 was performed using the PubMed/Medline, Embase, and Cochrane databases. Among the 1562 articles screened, 17 articles were selected for qualitative analysis and 16 articles (n = 1373) were included for data synthesis following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Criteria for final inclusion were RCTs. Sixteen studies were finally included (TRT group, n = 709; placebo group, n = 664). Among the metabolic markers, HbA1C [Mean difference (MD) = - 0.172, 95% CI - 0.329, - 0.015], HOMA IR (MD = - 0.514, 95% CI - 0.863, - 0.165), serum insulin (MD = - 12.622, 95% CI - 19.660, - 5.585), and leptin (MD = - 2.381, 95% CI - 2.952, - 1.810) showed significant improvement after TRT versus placebo. Among the lipid profiles, total cholesterol showed significant improvement (MD = - 0.433, 95% CI - 0.761, - 0.105) after TRT. However, HDL showed a decrease (MD = - 0.069, 95% CI - 0.121, - 0.018) after TRT. Among anthropometric markers, waist circumference showed significant improvement (MD = - 0.1640, 95% CI - 2.857, - 0.423). This study demonstrated greater improvement in metabolic profiles for patients given TRT versus placebo. Further well-designed trials are needed to verify our findings and further elucidate effects of TRT on lipid profiles. This systematic review demonstrates that TRT can exert a net beneficial effect on metabolic profiles.

Metabolic profiles differences of overweight patients on olanzapine, clozapine and risperidone

AimsWe set out to examine the differences in metabolic profiles of at risk (overweight) patients across commonly used atypical antipsychotics (Olanzapine, Risperidone, Clozapine). We hypothesized that Olanzapine and Clozapine group will have more metabolic abnormalities compared to Risperidone.BackgroundCardiovascular diseases remain the leading cause of morbidity and mortality among people with schizophrenia. Since the introduction of atypical antipsychotics, there is cumulative evidence of their association with metabolic abnormalities. Clozapine and Olanzapine are known to constitute the highest metabolic risks amongst atypical antipsychotics.MethodThis study is based on the data of 67 subjects recruited into a 12-week open-labelled trial looking at the effects of adjunctive Aripiprazole in atypical antipsychotics for weight reduction and improvement in metabolic profile. Metabolic profiles including weight, waist circumference, fasting blood glucose, HbA1c, serum total, HDL and LDL cholesterol levels and triglycerides were measured at baseline. The measurements were then compared across the different subgroups of atypical antipsychotics. The definition of metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel (Adults Treatment Panel III) was used.ResultThe atypical antipsychotics were grouped into Olanzapine (n = 27), Risperidone (n = 24) and Clozapine (n = 16). More than 50% of clozapine-treated and Olanzapine-treated overweight patients were demonstrated to have metabolic syndrome at baseline. There was a statistically significant difference in serum triglycerides (p = 0.012), LDL (p = 0.046) and HbA1c (p = 0.045) across the three groups as demonstrated by one-way ANOVA. A Tukey post hoc test showed that both the Olanzapine (p = 0.032) and Risperidone (p = 0.013) groups demonstrated statistically significant lower serum triglycerides when compared to Clozapine. Interestingly, the mean serum HbA1c was significantly lower in Clozapine when compared to Olanzapine group (p = 0.045), perhaps reflecting the closer monitoring of fasting blood sugar in clozapine patients. When controlled for age and BMI, the significant differences in serum triglycerides remain between Clozapine and Risperidone groups [but not for serum HbA1c]. There were no statistically significant differences across the groups with respect to other metabolic parameters.ConclusionAt baseline, metabolic dysregulation was demonstrated in all subgroups of overweight patients. As hypothesized, patients on Olanzapine and Clozapine groups fared worse than Risperidone. Further studies examining long term effects of atypical antipsychotics in a larger sample of patients are warranted to confirm these findings. These findings have clinical significance in terms of choosing the first antipsychotic for drug naïve patients or where there is no clinically significant difference in efficacy.

Metabolic profiles differences of overweight patients on olanzapine, clozapine and risperidone

AimsWe set out to examine the differences in metabolic profiles of at risk (overweight) patients across commonly used atypical antipsychotics (Olanzapine, Risperidone, Clozapine). We hypothesized that Olanzapine and Clozapine group will have more metabolic abnormalities compared to Risperidone.BackgroundCardiovascular diseases remain the leading cause of morbidity and mortality among people with schizophrenia. Since the introduction of atypical antipsychotics, there is cumulative evidence of their association with metabolic abnormalities. Clozapine and Olanzapine are known to constitute the highest metabolic risks amongst atypical antipsychotics.MethodThis study is based on the data of 67 subjects recruited into a 12-week open-labelled trial looking at the effects of adjunctive Aripiprazole in atypical antipsychotics for weight reduction and improvement in metabolic profile. Metabolic profiles including weight, waist circumference, fasting blood glucose, HbA1c, serum total, HDL and LDL cholesterol levels and triglycerides were measured at baseline. The measurements were then compared across the different subgroups of atypical antipsychotics. The definition of metabolic syndrome proposed by the Third Report of the National Cholesterol Education Program Expert Panel (Adults Treatment Panel III) was used.ResultThe atypical antipsychotics were grouped into Olanzapine (n = 27), Risperidone (n = 24) and Clozapine (n = 16). More than 50% of clozapine-treated and Olanzapine-treated overweight patients were demonstrated to have metabolic syndrome at baseline. There was a statistically significant difference in serum triglycerides (p = 0.012), LDL (p = 0.046) and HbA1c (p = 0.045) across the three groups as demonstrated by one-way ANOVA. A Tukey post hoc test showed that both the Olanzapine (p = 0.032) and Risperidone (p = 0.013) groups demonstrated statistically significant lower serum triglycerides when compared to Clozapine. Interestingly, the mean serum HbA1c was significantly lower in Clozapine when compared to Olanzapine group (p = 0.045), perhaps reflecting the closer monitoring of fasting blood sugar in clozapine patients. When controlled for age and BMI, the significant differences in serum triglycerides remain between Clozapine and Risperidone groups [but not for serum HbA1c]. There were no statistically significant differences across the groups with respect to other metabolic parameters.ConclusionAt baseline, metabolic dysregulation was demonstrated in all subgroups of overweight patients. As hypothesized, patients on Olanzapine and Clozapine groups fared worse than Risperidone. Further studies examining long term effects of atypical antipsychotics in a larger sample of patients are warranted to confirm these findings. These findings have clinical significance in terms of choosing the first antipsychotic for drug naïve patients or where there is no clinically significant difference in efficacy.

Effect of aripiprazole as an adjunct to atypical antipsychotics on weight and metabolic profile: a 12-week open-label trial.

Background:Atypical antipsychotics are widely prescribed, yet have been associated with weight gain and metabolic syndrome.Aim:To study the effect of adjunct low-dose aripiprazole on weight and metabolic parameters of subjects on atypical antipsychotics (olanzapine, clozapine or risperidone).Methods:The study was carried out as an open-label trial with a fixed dose of 5 mg aripiprazole added to the patient’s current antipsychotic for 12 weeks. The primary outcome measure was mean change in weight, while secondary outcome measures included change in waist circumference; fasting blood glucose; HbA1c; triglycerides; total, HDL and LDL cholesterol levels; functioning; and neurocognition.Results:For the overall study (n = 55), there was no significant effect of adjunct aripiprazole on the weight of the subjects. However, the clozapine group achieved significant weight loss (p = 0.002) and also had significant improvements in total cholesterol (p < 0.001), HDL (p = 0.016), LDL (p = 0.044) and triglyceride levels (p = 0.038). The olanzapine group had significant improvement in triglycerides (p = 0.001), and other metabolic parameters for this group showed improvement trends, but did not reach statistical significance. The risperidone group did not show any significant improvement in weight or metabolic parameters.Conclusions:The study adds support to the adjunctive use of aripiprazole to clozapine for weight loss and improvement in metabolic profile, and for reduction in cardiometabolic risk for patients on olanzapine.Trial Registration:Clinicaltrials.gov identifier: NCT02949752

Spexin as an indicator of beneficial effects of exercise in human obesity and diabetes

Spexin is a novel neuropeptide playing an emerging role in metabolic diseases such as obesity and diabetes via involvement in energy homeostasis and food intake. The present study investigated the effects of obesity and type 2 diabetes (T2D) on circulating levels of spexin and its modulation by physical exercise. Normal-weight (n = 50) and obese adults with and without T2D (n = 69 and n = 66, respectively) were enrolled in the study. A subgroup of obese participants (n = 47) underwent a supervised 3-month exercise programme. Plasma spexin levels were measured by ELISA and correlated with various markers. Plasma spexin levels decreased in obese participants with or without T2D compared with those of normal-weight participants (0.43 ± 0.11, 0.44 ± 0.12 and 0.61 ± 0.23 ng/ml, respectively; P < 0.001). Spexin levels negatively correlated with adiposity markers and blood pressure in the whole study population (P < 0.05). Multiple regression analysis revealed blood pressure was the greatest predictive determinant of plasma spexin levels, which significantly increased in response to physical exercise in obese participants without and with T2D (P < 0.05). Spexin levels significantly increased only in responders to exercise (those with increased oxygen consumption, VO2 max) with a concomitant improvement in metabolic profile. In conclusion, plasma spexin levels may be an indicator of response to physical exercise.

Lessons Learned from the POUNDS Lost Study: Genetic, Metabolic, and Behavioral Factors Affecting Changes in Body Weight, Body Composition, and Cardiometabolic Risk.

This paper reviews the genetic and non-genetic factors that provided predictions of, or were associated with, weight loss and other metabolic changes in the POUNDS Lost clinical trial of weight loss. This trial randomized 811 individuals who were overweight or obese to one of four diets that contained either 15% or 25% protein and 20% or 40% fat in a 2× 2 factorial design. A standard behavioral weight loss program was available for all participants who were followed for 2years with an 80% completion rate. Nineteen genes and five genetic risk scores were used along with demographic, behavioral, endocrine, and metabolic measurements. Genetic variations in most of the genes were associated with weight loss, but this association often varied with the dietary assignment. A number of demographic and behavioral factors, including attendance at behavioral sessions and food cravings were predictive of weight changes. A high baseline level of free triiodothyronine or free thyroxine predicted the magnitude of weight loss. Several perfluoroakyl compounds predicted more rapid weight regain. Genetic evidence from POUNDS Lost provides guidance toward selection of a personalized weight loss diet and improvement in metabolic profile. There is still room for additional research into the predictors of weight loss.

Evaluation of voglibose on body weight in rats

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.

Role of microRNA in CB1 antagonist–mediated regulation of adipose tissue macrophage polarization and chemotaxis during diet-induced obesity

Although cannabinoid receptor 1 (CB1) antagonists have been shown to attenuate diet-induced obesity (DIO) and associated inflammation, the precise molecular mechanisms involved are not clear. In the current study, we investigated the role of microRNA (miR) in the regulation of adipose tissue macrophage (ATM) phenotype following treatment of DIO mice with the CB1 antagonist SR141716A. DIO mice were fed high-fat diet (HFD) for 12 weeks and then treated daily with SR141716A (10 mg/kg) for 4 weeks while continuing HFD. Treated mice experienced weight loss, persistent reduction in fat mass, improvements in metabolic profile, and decreased adipose inflammation. CB1 blockade resulted in down-regulation of several miRs in ATMs, including the miR-466 family and miR-762. Reduced expression of the miR-466 family led to induction of anti-inflammatory M2 transcription factors KLF4 and STAT6, whereas down-regulation of miR-762 promoted induction of AGAP-2, a negative regulator of the neuroimmune retention cues, Netrin-1 and its coreceptor UNC5B. Furthermore, treatment of primary macrophages with SR141716A up-regulated KLF4 and STAT6, reduced secretion of Netrin-1, and increased migration toward the lymph node chemoattractant CCL19. These studies demonstrate for the first time that CB1 receptor blockade attenuates DIO-associated inflammation through alterations in ATM miR expression that promote M2 ATM polarization and macrophage egress from adipose tissue. The current study also identifies additional novel therapeutic targets for diet-induced obesity and metabolic disorder.

High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration

Background and objectiveOnline haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyze the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. Material and methodsProspective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated hemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analyzed. ResultsAge at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m2, with 48 (35.5–76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=−0.531, p=0.005), 2 years (r=−0.463, p=0.046), and at the end of follow-up (r=−0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1–2.22]mg/dL vs. 1.01 [0.15–6.96]mg/dL, p=0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=−0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=−0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (−0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. ConclusionThere is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.