Metabolic Abnormalities In Patients Research Articles

Associations of Insulin Resistance and High-Sensitivity C-Reactive Protein with Metabolic Abnormalities in Korean Patients with Type 2 Diabetes Mellitus: A Preliminary Study.

We conducted this single-center, retrospective, cohort study to examine whether insulin resistance (IR) and high-sensitivity C-reactive protein (hsCRP) have a relationship with metabolic abnormalities in patients with type 2 diabetes mellitus (T2DM). In a total of 3758 patients (n = 3758) with T2DM, we analyzed medical records and thereby evaluated their baseline characteristics such as age, sex, duration of T2DM, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference, body mass index (BMI), visceral fat thickness (VFT), fasting plasma insulin levels, C-peptide levels, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of β-cell function (HOMA-β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), albuminuria, intima-media thickness (IMT) and hsCRP. The patients were stratified according to the tertile of the K index of the insulin tolerance test (KITT) or hsCRP. Thus, they were divided into the lowest (≥2.37), middle (1.54-2.36) and highest tertile (0-1.53) of KITT and the lowest (0.00-0.49), middle (0.50-1.21) and highest tertile (≥1.22) of hsCRP. Moreover, associations of KITT and hsCRP with metabolic abnormalities, such as steatotic liver disease (SLD), metabolic syndrome (MetS), albuminuria, diabetic retinopathy and carotid atherosclerosis, were also analyzed. There was a significant positive correlation between the prevalence of SLD, MetS, albuminuria and diabetic retinopathy and KITT (p < 0.001). Moreover, there was a significant positive association between the prevalence of SLD, MetS and albuminuria and hsCRP (p < 0.001). In conclusion, our results indicate that clinicians should consider the relationships of IR and hsCRP with metabolic abnormalities in the management of patients with T2DM. However, further large-scale, prospective, multi-center studies are warranted to confirm our results.

Effects of Metreleptin in Patients with Generalized Lipodystrophy Before vs After the Onset of Severe Metabolic Disease.

Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD). Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health. Retrospective analysis of patients ≥ 6 months old with congenital (n=47) or acquired (n=16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means (LSM) for HbA1c, insulin area under the curve (AUC) from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index (APRI) for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24, 108) months follow-up. Compared to late groups, early groups based on metabolic status had higher mean±SEM insulin AUC (20831±1 vs 11948±1), lower HbA1c (5.3±0.3 vs 6.8±0.3%), triglycerides (101±1 vs 193±1 mg/dL), urine protein excretion (85±1.5 vs 404±1.4 mg/24 hr), ALT (30±1 vs 53±1 U/L), AST (23±1 vs 40±1 U/L), and APRI (0.22±1.3 vs 0.78±1.3), and higher platelets (257±24 vs 152±28 K/µL) during follow-up (P<0.05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5±0.5 vs 6.4±0.2%) and higher AST (40±1vs 23±1 U/L) during follow (P<0.05). Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.

Metabolic abnormalities in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2

Background. It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect hepatocytes. At the same time, overweight and obesity are surrogate markers of the adverse effects of coronavirus disease 2019 (COVID-19). The purpose of the study: to evaluate changes in lipid and carbohydrate metabolism and their indices in the serum of patients with non-alcoholic fatty liver disease (NAFLD) with an immune response to SARS-CoV-2. Materials and methods. We studied 37 patients with NAFLD who had IgG to SARS-CoV-2. All patients were divided into two groups: group I consisted of 19 participants who were PCR-negative for SARS-CoV-2, group II included 18 patients who had COVID-19, as confirmed by PCR testing. The content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient, insulin resistance indices (HOMA-IR), TG to glucose (TG/Gly) and TG to HDL-C (TG/HDL-C) ratio were assessed in all patients. Results. Among patients with NAFLD with an immune response to SARS-CoV-2, dyslipidemia manifested by a probable increase in the median TG content in groups I and II by 2.5 and 3.4 times (р = 0.0001), respectively; TC — by 1.2 times (р = 0.0425) in both groups, with a tendency to increase; VLDL-C — by 1.8 (р = 0.010) and 2.5 times (р = 0.0022), respectively, and a decrease in the median content of HDL-C by 1.7 (р = 0.0016) and 1.9 times (р = 0.0008), respectively, in blood serum. The identified changes led to a statistically significant increase in the median atherogenicity coefficient in groups I and II — by 2.2 (р = 0.0036) and 2.5 times (р = 0.007). An increase in the HOMA-IR did not have a statistically significant difference between the groups: in group I, this index increased by 3.1 times (p &lt; 0.05) compared with the controls, in group II — by 3 times (p &lt; 0.05). In addition, patients in both groups had a statistically significant increase in TG/Gly and TG/HDL-C ratio compared to controls. However, the detected changes were more pronounced in group II, where TG/Gly and TG/HDL-C levels were 1.5 (р = 0.038) and 1.9 times (р = 0.035), respectively, higher than in group I. Conclusions. Patients with an immune response to SARS-CoV-2 with NAFLD have disorders of lipid and carbohydrate metabolism. At the same time, the signs of dyslipidemia were more pronounced in participants with a history of SARS-CoV-2. TG/Gly and TG/HDL-C ratio should be included in the diagnostic algorithm for assessing insulin resistance in patients with COVID-19 who are overweight or obese.

Lipid parameters and depression in patients with chronic tinnitus: A cross-sectional observation

BackgroundPathophysiological theories assume importance of metabolic abnormalities in patients with major depression - and possibly chronic tinnitus. Although chronic tinnitus frequently correlates with depression, links between high-density lipoprotein (HDL) and depression are uninvestigated. MethodsTwo-hundred patients with chronic tinnitus (Mage = 55; 51% female) were examined. Serum levels of total cholesterol (TC), triglycerides (TGs), HDL, low-density lipoprotein cholesterol (LDL), non-HDL, as well as LDL/HDL and TC/HDL ratios were analysed. Questionnaires included depression subscales of the ICD-10 Symptom Rating, the Hospital Anxiety and Depression Scale (HADS_D), and the Berlin Mood Questionnaire (BSF). Multivariate analyses of covariance and linear regression models - which controlled age, tinnitus-related distress and perceived stress - investigated between-subgroup differences (p < 0.05) and linear associations between HDL indices and depression (p < 0.01). ResultsHDL levels did not differ for tinnitus-symptom durations, smoking and alcohol use levels, statin or antihypertensive drug use, and body-mass indices. Relative to non-to-mildly depressed patients with chronic tinnitus, patients with moderate-to-severe depression (n = 45; 23%) had significantly lower HDL levels (d = −0.35) and higher LDL/HDL (d = 0.39) and TC/HDL ratios (d = 0.40). Across participants, HDL-levels were negatively associated with depression as measured by the HADS_D and BSF_indifference scales. ConclusionsIn keeping with general depression research, low serum HDL levels correlate with depressive symptomatology in patients with chronic tinnitus. This association may be influenced by proximal (e.g. modulations of HPA-axis activity) or distal factors (e.g. maladaptive coping behaviours) – both of which should be conceptualized within psychological stimulus-processing frameworks.

Prognostic Significance of Serum Interleukin-6 Levels in Oral Squamous Cell Carcinoma.

Introduction The prognosis of oral squamous cell carcinoma (OSCC) is often poor despite standard treatments. Additionally, no useful prognostic markers are available. Therefore, we aimed to investigate the relationship between serum Interleukin-6 (IL-6) levels and prognosis and explore its local and systemic effects in patients with OSCC. Methods Ninety-five new cases of OSCC were included, and the prognosis was compared between high and low serum IL-6 groups. The localization of IL-6 in OSCC tissues was examined. Furthermore, a comprehensive gene expression analysis was performed in OSCC tissues and compared between the two groups. Results A significant difference in overall survival and disease-free survival was observed. Furthermore, a substantial expression of IL-6 was localized in the stroma. Comprehensive gene expression analysis of tumor localization showed increased expression of genes related to oxidoreductase and lipid metabolism in the primary tissues of the group with high serum IL-6 levels. Regarding the correlation between blood tests and serum IL-6 levels, a strong positive correlation was observed between inflammatory responses and nutritional factors. Conclusion These results suggest that serum IL-6 may be a prognostic factor for metabolic abnormalities in patients with OSCC and that aggressive nutritional interventions may contribute to prognosis.

Metabolic Abnormalities Following Tirzepatide Monotherapy in Japanese Patients with Type 2 Diabetes: A Phase 3 SURPASS J-mono Post Hoc Analysis.

The presence of metabolic abnormalities in patients with type 2 diabetes (T2D) increases the risk of cardiovascular disease and other comorbidities. This analysis compared the effects of tirzepatide (5, 10, and 15mg) and dulaglutide 0.75mg on the prevalence of metabolic abnormalities in Japanese patients with T2D. This was a post hoc analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled, parallel-group, phase 3 trial that compared the efficacy and safety of tirzepatide monotherapy (5, 10, and 15mg) to dulaglutide 0.75mg in Japanese patients with T2D. Thresholds for abnormalities were based on the Japanese criteria for metabolic syndrome. Proportions of participants meeting a composite endpoint (visceral fat accumulation measured by waist circumference plus two or more of dyslipidemia, hypertension, or hyperglycemia) or individual component thresholds were calculated at baseline and week 52 for the overall population and for baseline body mass index (BMI) subgroups (< 25, 25 to < 30, and ≥ 30kg/m2). Of 636 randomized participants, 431 (67.8%) met the composite endpoint at baseline, with similar findings observed across treatment arms. At week 52, the proportion of participants on treatment that met the composite endpoint was 31.7%, 23.0%, and 14.2% in the tirzepatide 5-, 10-, and 15-mg arms, respectively, and 56.5% in the dulaglutide arm (p < 0.001). A higher proportion met the composite endpoint at baseline in the BMI 25 to < 30 and ≥ 30kg/m2 subgroups (73.2-79.3%) compared with the < 25kg/m2 subgroup (45.3%), with reductions observed across all BMI subgroups treated with tirzepatide. The proportion of participants with individual metabolic abnormalities showed similar trends to those observed for the composite endpoint. Tirzepatide was consistently superior to dulaglutide across all assessments. Tirzepatide reduced the prevalence of multiple metabolic abnormalities, indicating tirzepatide may have metabolic benefit in Japanese patients with T2D. ClinicalTrials.gov, NCT03861052.

Cardiovascular risk assessments in patients with cortisol-producing adenoma: impact of clinical features and genetic characteristics.

The causes of adrenal Cushing's syndrome (CS) encompass a wide spectrum of adrenal cortisol proliferations that exhibit clinical and molecular heterogeneity. The aims of our study were to investigate whether clinical and molecular heterogeneity influences endothelial function and metabolic abnormalities in patients with cortisol-producing adenoma (CPA). We retrospectively enrolled 25 patients with CPA and 45 patients with essential hypertension (EH). All CPAs were studied by direct sequencing of PRKACA. Flow-mediated vasodilation (FMD), an index of vascular endothelial function, was significantly lower in CS and subclinical CS (SCS) groups than in the EH group. FMD impairment did not differ significantly between CS and SCS groups. No differences in FMD were seen between PRKACA mutant and wild-type groups. FMD correlated negatively with hemoglobin A1c (HbA1c) in both PRKACA mutant and wild-type groups, as well as in CS and SCS groups. After adrenalectomy, systolic blood pressure (SBP) and HbA1c decreased significantly from baseline in the CS group, and SBP and low-density lipoprotein cholesterol (LDL-C) decreased significantly from baseline in the SCS group. While SBP and LDL-C decreased significantly from baseline in patients with wild-type PRKACA, only HbA1c decreased from baseline in patients harboring PRKACA mutations. Our data showed that patients with CPA have impaired endothelial function compared with EH patients and suggest the need for strict monitoring of atherosclerosis, even in patients with SCS or without PRKACA mutation.

Dissecting Relations between Depression Severity, Antidepressant Use, and Metabolic Syndrome Components in the NHANES 2005-2020.

We aimed to dissect the complex relations between depressive symptoms, antidepressant use, and constituent metabolic syndrome (MetS) components in a representative U.S. population sample. A total of 15,315 eligible participants were included from 2005 to March 2020. MetS components were defined as hypertension, elevated triglycerides, reduced high-density lipoprotein cholesterol, central obesity, and elevated blood glucose. Depressive symptoms were classified as mild, moderate, or severe. Logistic regression was used to evaluate the relationship between depression severity, antidepressant use, individual MetS components and their degree of clustering. Severe depression was associated with the number of MetS components in a graded fashion. ORs for severe depression ranged from 2.08 [95%CI, 1.29-3.37] to 3.35 [95%CI, 1.57-7.14] for one to five clustered components. Moderate depression was associated with hypertension, central obesity, raised triglyceride, and elevated blood glucose (OR = 1.37 [95%CI, 1.09-1.72], 1.82 [95%CI, 1.21-2.74], 1.63 [95%CI, 1.25-2.14], and 1.37 [95%CI, 1.05-1.79], respectively). Antidepressant use was associated with hypertension (OR = 1.40, 95%CI [1.14-1.72]), raised triglyceride (OR = 1.43, 95%CI [1.17-1.74]), and the presence of five MetS components (OR = 1.74, 95%CI [1.13-2.68]) after adjusting for depressive symptoms. The depression severity and antidepressant use were associated with individual MetS components and their graded clustering. Metabolic abnormalities in patients with depression need to be recognized and treated.

Comparison of olanzapine-induced weight gain and metabolism abnormalities between topiramate and vitamin C in patients with schizophrenia: a preliminary study.

Topiramate (TPM) may reduce olanzapine (OLZ)-related weight gain and metabolism abnormalities in patients with schizophrenia. However, differences in the efficacy of OLZ-related weight gain and metabolism abnormalities between TPM and vitamin C (VC) are not clear. This study aimed to investigate whether TPM is more effective than VC in reducing OLZ-induced weight gain and metabolic abnormalities in patients with schizophrenia and explore their patterns. This was a 12-week longitudinal comparison study in OLZ-treated patients with schizophrenia. Twenty-two patients who received OLZ monotherapy plus VC treatment (OLZ + VC group) was matched to 22 patients who received OLZ monotherapy plus TPM treatment (OLZ + TPM group). Body mass index (BMI) and metabolism indicators were measured at baseline and 12-weeks follow-up. A significant difference in triglyceride (TG) levels at different time points (pre-treatment: F = 7.89, p = 0.008; 4-weeks treatment: F = 13.19, p = 0.001; 12-weeks treatment: F = 54.48, p < 0.001) was found. Latent profile analysis demonstrated that a 2-class model for OLZ + TPM group (high vs. low BMI in the first 4 weeks) and OLZ + VC group (high vs. low), respectively. Our findings suggested that TPM could better mitigates OLZ-induced increase in TG levels. The trajectories of change also differed in all metabolic indexes over time between the two groups.

Contribution of skeletal muscle-specific microRNA-133b to insulin resistance in heart failure.

Insulin resistance (IR) is one of the hallmarks of heart failure (HF). Abnormalities in skeletal muscle (SM) metabolism have been identified in patients with HF. However, the underlying mechanisms of IR development in SM in HF are poorly understood. Herein, we hypothesize that HF upregulates miR-133b in SM and in turn alters glucose metabolism and the propensity toward IR. Mitochondria isolated from SM of mice with HF induced by transverse aortic constriction (TAC) showed lower respiration and downregulation of muscle-specific components of the tricarboxylic acid (TCA) cycle, AMP deaminase 1 (AMPD1), and fumarate compared with those from control animals. RNA-Seq and subsequent qPCR validation confirmed upregulation of SM-specific microRNA (miRNA), miR-133b, in TAC versus sham animals. miR-133b overexpression alone resulted in significantly lower mitochondrial respiration, cellular glucose uptake, and glycolysis along with lower ATP production and cellular energy reserve compared with the scramble (Scr) in C2C12 cells. miR-133b binds to the 3'-untranslated region (UTR) of KLF15, the transcription factor for the insulin-sensitive glucose transporter, GLUT4. Overexpression of miR-133b lowers GLUT4 and lowers pAkt in presence of insulin in C2C12 cells. Finally, lowering miR-133b in primary skeletal myocytes isolated from TAC mice using antagomir-133b reversed the changes in KLF15, GLUT4, and AMPD1 compared with the scramble-transfected myocytes. Taken together, these data demonstrate a role for SM miR-133b in altered glucose metabolism in HF and suggest the therapeutic potential in HF to improve glucose uptake and glycolysis by restoring GLUT4 abundance. The data uncover a novel mechanism for IR and ultimately SM metabolic abnormalities in patients with HF.NEW & NOTEWORTHY Heart failure is associated with systemic insulin resistance and abnormalities in glucose metabolism but the underlying mechanisms are poorly understood. In the skeletal muscle, the major peripheral site of glucose utilization, we observe an increase in miR-133b in heart failure mice, which reduces the insulin-sensitive glucose transporter (GLUT4), glucose uptake, and metabolism in C2C12 and in myocytes. The antagomir for miR-133b restores GLUT4 protein and markers of metabolism in skeletal myocytes from heart failure mice demonstrating that miR-133b is an exciting target for systemic insulin resistance in heart failure and an important player in the cross talk between the heart and the periphery in the heart failure syndrome.

Prevalence of metabolic abnormalities in patients having the risk of recurrent renal stones

Prevalence of metabolic abnormalities in patients having the risk of recurrent renal stones

Metabolic Abnormalities, Cardiovascular Disease, and Metabolic Syndrome in Adult Rheumatoid Arthritis Patients: Current Perspectives and Clinical Implications.

Rheumatoid arthritis is a prevalent worldwide disease, associated with an increased risk of multiple metabolic abnormalities that generate a higher disease burden. To gather the available evidence on the epidemiology, pathophysiology, current perspectives, clinical implications and prognosis of metabolic abnormalities in patients with rheumatoid arthritis. This is a narrative literature review. Search was conducted in PubMed, OVID, and Taylor & Francis databases, using the following MeSH terms: "Arthritis Rheumatoid", "Metabolic Diseases", and "Metabolic Syndrome". This study describes the main metabolic manifestations of rheumatoid arthritis. Research has recognized that rheumatoid arthritis and metabolic abnormalities share pathophysiological mechanisms with an additive effect that increases cardiovascular risk. In that context, appropriate antirheumatic treatment can also impact on cardiovascular risk. There are metabolic abnormalities in rheumatoid arthritis patients that increase cardiovascular risk. Therefore, it is crucial to evaluate cardiovascular risk to provide appropriate comprehensive management to reduce morbidity and mortality in patients with this disease.

The Beneficial Effect of a Healthy Dietary Pattern on Androgen Deprivation Therapy-Related Metabolic Abnormalities in Patients with Prostate Cancer: A Meta-Analysis Based on Randomized Controlled Trials and Systematic Review.

Metabolic abnormalities as side effects of androgen-deprivation therapy (ADT) can accelerate progression of prostate cancer (PCa) and increase risks of cardiovascular diseases. A healthy dietary pattern (DP) plays an important role in regulating glycolipid metabolism, while evidence about DP on ADT-related metabolic abnormalities is still controversial. To explore the effect of DP on metabolic outcomes in PCa patients with ADT, PubMed, Embase, Cochrane, and CINAHL were searched from inception to 10 September 2022. Risk of biases was evaluated through Cochrane Collaboration’s Tool. If heterogeneity was low, the fixed-effects model was carried out; otherwise, the random-effects model was used. Data were determined by calculating mean difference (MD) or standardized MD (SMD) with 95% confidence intervals (CIs). Nine studies involving 421 patients were included. The results showed that healthy DP significantly improved glycated hemoglobin (MD: −0.13; 95% CI: −0.24, −0.02; p = 0.020), body mass index (MD: −1.02; 95% CI: −1.29, −0.75; p < 0.001), body fat mass (MD: −1.78; 95% CI: −2.58, −0.97; p < 0.001), triglyceride (MD: −0.28; 95% CI: −0.51, −0.04; p = 0.020), systolic blood pressure (MD: −6.30; 95% CI: −11.15, −1.44; p = 0.010), and diastolic blood pressure (MD: −2.94; 95% CI: −5.63, −0.25; p = 0.030), although its beneficial effects on other glycolipid metabolic indicators were not found. Additionally, a healthy DP also lowered the level of PSA (MD: −1.79; 95% CI: −2.25, −1.33; p < 0.001). The meta-analysis demonstrated that a healthy DP could improve ADT-related metabolic abnormalities and be worthy of being recommended for PCa patients with ADT.

Twenty-four hour urine parameters in nephrolithiasis patients with obstructive sleep apnea syndrome

Objective: To study 24-hour urine metabolic abnormalities in patients with obstructive sleep apnea syndrome (OSAS), diagnosed by polysomnography. The purpose was to identify whether OSAS is independently associated with a distinctive set of 24-hour urine studies in a cohort of stone formers. Patients and Methods: Using our institutional stone database (2013–2017), 1132 consecutive patients with 24-hour urine collections were identified. After applying our exclusion criteria, the final cohort consisted of 376 patients of which 45 patients had OSAS. Descriptive statistics were used to compare 24-hour urine parameters between patients with and without OSAS. Logistic regression models were used to assess the association between OSAS and 24-hour urine parameters. Results: On univariate analysis, patients with OSAS were older (57.7 versus 48.2, p &lt; 0.001) with a higher body mass index (BMI) (35 versus 27.8, p &lt; 0.001), and higher likelihood of diabetes mellitus (DM) (57.8 versus 10.6%, p &lt; 0.001) and hypertension (HTN) (60% versus 23.9%, p &lt; 0.001). Patients with OSAS had higher 24-hour total amount of urine volume (2018 versus 1818 ml, p = 0.03), calcium (279.7 versus 208 mg, p = 0.02), oxalate (41.6 versus 31.3 mg, p &lt; 0.001), yet lower 24-hour urine pH (5.75 versus 6.03, p = 0.001). On multivariable linear regression analysis, OSAS did not affect any of the 24-hour urinary parameters. Conclusion: OSAS is a prevalent comorbidity among nephrolithiasis patients. We found no major differences in 24-hour urine parameters between nephrolithiasis patients with OSAS and those without OSAS. Further study is needed to determine whether the severity of OSAS and compliance with treatment play a role in the pathogenesis of stone formation. Level of evidence: 2b

The relationship of antipsychotic treatment with reduced brown adipose tissue activity in patients with schizophrenia

BackgroundAntipsychotic drug (APD) treatment has been associated with metabolic abnormalities. Brown adipose tissue (BAT) is the main site of adaptive thermogenesis and secretes various metabolism-improving factors known as batokines. We explored the association of BAT activity with APD treatment and metabolic abnormalities in patients with schizophrenia by measuring the blood levels of bone morphogenetic protein 8b (BMP8b), a batokine secreted by mature BAT. MethodsBMP8b levels were compared among 50 drug-free, 32 aripiprazole-treated, and 91 clozapine-treated patients with schizophrenia. Regression analysis was used to explore factors, including APD types, that might be associated with BMP8b levels and the potential effect of BMP8b on metabolic syndrome (MS). ResultsAPD-treated patients had decreased BMP8b levels relative to drug-free patients. The difference still existed after adjustment for body mass index and Brief Psychiatric Rating Scale scores. Among APD-treated group, clozapine was associated with even lower BMP8b levels than the less obesogenic APD, aripiprazole. Furthermore, higher BMP8b levels were associated with lower risks of MS after adjustment for BMI and APD treatment. ConclusionUsing drug-free patients as the comparison group to understand the effect of APDs, this is the first study to show APD treatment is associated with reduced BAT activity that is measured by BMP8b levels, with clozapine associated a more significant reduction than aripiprazole treatment. BMP8b might have a beneficial effect against metabolic abnormalities and this effect is independent of APD treatment. Future studies exploring the causal relationship between APD treatment and BMP8b levels and the underlying mechanisms are warranted.

A pilot study to determine association of parental metabolic syndrome with development of metabolic risk in Indian children, adolescents and youth with Type-1 diabetes

Background and aimsPrevalence of metabolic syndrome (MS) is increasing in children with type-1 diabetes (T1D). Genetic and environmental factors shared among family members are considered significant risk factors. We conducted this study to assess the association of parental MS with development of metabolic risk (MR) in patients with T1D. MethodThis cross-sectional study included 29 patients with T1D along with their parents (29 triads). Demographic data, anthropometry, blood pressure, biochemical measurements and body composition measurements were performed using standard protocols. Insulin resistance was calculated using estimated glucose disposal rate (eGDR) in patients and using HOMA-IR in their parents. MS was diagnosed using International Diabetes Federation Consensus Definition, 2017. ResultsOf total study participants, 44.8% patients with T1D had MR while 25.3% of parents had MS. Low HDL was identified as the most common component of MS. 64.3% patients with T1D, who had parents with MS, had MR. The odds ratio (OR) for development of MR in patients with T1D with parents affected by MS was 4.9 (95% confidence interval 1.0–24.1) while relative risk (RR) was 2.4 (95% confidence interval 0.9–6.1). MR in patients with T1D was found to have a strong correlation with parental MS and also with development of double diabetes (DD). ConclusionIn conclusion, parental MS increases the risk of development of metabolic abnormalities in patients with T1D. Thus, positive family history may serve as a useful indicator for targeted screening to detect DD.

Selective targeting of angiopoietin-like 3 (ANGPTL3) with vupanorsen for the treatment of patients with familial partial lipodystrophy (FPLD): results of a proof-of-concept study

BackgroundFamilial partial lipodystrophy (FPLD) is a rare disease characterized by selective loss of peripheral subcutaneous fat, associated with dyslipidemia and diabetes mellitus. Reductions in circulating levels of ANGPTL3 are associated with lower triglyceride and other atherogenic lipids, making it an attractive target for treatment of FPLD patients. This proof-of-concept study was conducted to assess the efficacy and safety of targeting ANGPTL3 with vupanorsen in patients with FPLD.MethodsThis was an open-label study. Four patients with FPLD (two with pathogenic variants in LMNA gene, and two with no causative genetic variant), diabetes (HbA1c ≥ 7.0 % and ≤ 12 %), hypertriglyceridemia (≥ 500 mg/dL), and hepatic steatosis (hepatic fat fraction, HFF ≥ 6.4 %) were included. Patients received vupanorsen subcutaneously at a dose of 20 mg weekly for 26 weeks. The primary endpoint was the percent change from baseline in fasting triglycerides at Week 27. Other endpoints analyzed at the same time point included changes in ANGPTL3, fasting lipids and lipoproteins, insulin secretion/sensitivity, postprandial lipids, and glycemic changes in response to a mixed meal test, HFF measured by MRI, and body composition measured by dual-energy absorptiometry (DEXA).ResultsBaseline mean ± SD fasting triglyceride level was 9.24 ± 4.9 mmol/L (817.8 ± 431.9 mg/dL). Treatment resulted in reduction in fasting levels of triglycerides by 59.9 %, ANGPTL3 by 54.7 %, and in several other lipoproteins/lipids, including very low-density lipoprotein cholesterol by 53.5 %, non-high-density lipoprotein cholesterol by 20.9 %, and free fatty acids (FFA) by 41.7 %. The area under the curve for postprandial triglycerides, FFA, and glucose was reduced by 60 %, 32 %, and 14 %, respectively. Treatment with vupanorsen also resulted in 55 % reduction in adipose tissue insulin resistance index, while other insulin sensitivity indices and HbA1c levels were not changed. Additional investigations into HFF and DEXA parameters suggested dynamic changes in fat partitioning during treatment. Adverse events observed were related to common serious complications associated with diabetes and FPLD. Vupanorsen was well tolerated, and there was no effect on platelet count.ConclusionsAlthough limited, these results suggest that targeting ANGPTL3 with vupanorsen could address several metabolic abnormalities in patients with FPLD.

Drug metabolism-related eight-gene signature can predict the prognosis of gastric adenocarcinoma.

BackgroundMetabolic abnormalities in patients with gastric adenocarcinoma lead to drug resistance and poor prognosis. Therefore, this study aimed to explore biomarkers that can predict the prognostic risk of gastric adenocarcinoma by analyzing drug metabolism‐related genes.MethodsThe RNA‐seq and clinical information on gastric adenocarcinoma were downloaded from the UCSC and gene expression omnibus databases. Univariate and least absolute shrinkage and selection operator regression analyses were used to identify the prognostic gene signature of gastric adenocarcinoma. The relationships between gastric adenocarcinoma prognostic risk and tumor microenvironment were assessed using CIBERSORT, EPIC, QUANTISEQ, MCPCounter, xCell, and TIMER algorithms. The potential drugs that could target the gene signatures were predicted in WebGestalt, and molecular docking analysis verified their binding stabilities.ResultsCombined with clinical information, an eight‐gene signature, including GPX3, ABCA1, NNMT, NOS3, SLCO4A1, ADH4, DHRS7, and TAP1, was identified from the drug metabolism‐related gene set. Based on their expressions, risk scores were calculated, and patients were divided into high‐ and low‐risk groups, which had significant differences in survival status and immune infiltrations. Risk group was also identified as an independent prognostic factor of gastric adenocarcinoma, and the established prognostic and nomogram models exhibited excellent capacities for predicting prognosis. Finally, miconazole and niacin were predicted as potential therapeutic drugs for gastric adenocarcinoma that bond stably with NOS3 and NNMT through hydrogen interactions.ConclusionsThis study proposed a drug metabolism‐related eight‐gene signature as a potential biomarker to predict the gastric adenocarcinoma prognosis risks.

Associations of Genetic Variants of Methylenetetrahydrofolate Reductase and Serum Folate Levels with Metabolic Parameters in Patients with Schizophrenia.

The one-carbon metabolism pathway is a suitable candidate for studying the genetic and epigenetic factors contributing to metabolic abnormalities in patients with schizophrenia. We recruited 232 patients with schizophrenia and analyzed their serum folate, vitamin B12, and homocysteine levels and metabolic parameters to investigate the associations of genetic variants of methylenetetrahydrofolate reductase (MTHFR) and folate levels with metabolic parameters. MTHFR C677T and MTHFR A1298C were genotyped. Results showed that MTHFR 677T allele carriers had lower levels of total cholesterol and low-density lipoprotein cholesterol than those with the 677CC genotype. Metabolic parameters did not differ between MTHFR 1298C and 1298AA carriers. Patients with a low folate level had a lower high-density lipoprotein cholesterol level than those with a normal folate level, but the effect disappeared after adjustment for age, sex, and types of antipsychotics used. We found significant interactions between MTHFR A1298C and the folate level status (low vs. normal) in terms of body mass index and waist circumference. In conclusion, genetic variants in one-carbon metabolism might play a role in antipsychotic-induced metabolic abnormalities. Prospective studies on drug-naïve, first-episode patients with schizophrenia are warranted to identify key regions of DNA methylation changes accounting for antipsychotic-induced metabolic abnormalities.

Advanced glycation end products and oxidative stress as a basis for metabolic abnormalities in patients with type 1 diabetes after successful simultaneous pancreas-kidney transplantation

To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism. The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels. All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51). The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.