Severe Metabolic Complications Research Articles

Preclinical evaluation of tissue-selective gene therapies for congenital generalised lipodystrophy.

Lipodystrophy is a rare disorder which can be life-threatening. Here individuals fail to develop or maintain appropriate adipose tissue stores. This typically causes severe metabolic complications, including hepatic steatosis and lipoatrophic diabetes. There is no cure for lipodystrophy, and treatment options remain very limited. Here we evaluate whether tissue-selective adeno-associated virus (AAV) vectors can provide a targeted form of gene therapy for lipodystrophy, using a preclinical lipodystrophic mouse model of Bscl2 deficiency. We designed AAV vectors containing the mini/aP2 or thyroxine-binding globulin promoter to selectively target adipose or liver respectively. The AAV-aP2 vectors also contained the liver-specific microRNA-122 target sequence, restricting hepatic transgene expression. Systemic delivery of AAV-aP2 vectors overexpressing human BSCL2 restored adipose tissue development and metabolic health in lipodystrophic mice without detectable expression in the liver. High doses (1 × 1012 GCs) of liver-selective vectors led to off target expression and adipose tissue development, whilst low doses (1 × 1010 GCs) expressed selectively and robustly in the liver but did not improve metabolic health. This reveals that adipose tissue-selective, but not liver directed, AAV-mediated gene therapy is sufficient to substantially recover metabolic health in generalised lipodystrophy. This provides an exciting potential new avenue for an effective, targeted, and thereby safer therapeutic intervention.

Diagnosis, treatment and management of lipodystrophy: the physician perspective on the patient journey

BackgroundLipodystrophy syndromes are a heterogeneous group of rare, life-limiting diseases characterized by a selective loss of adipose tissue and severe metabolic complications. There is a paucity of information describing the experiences and challenges faced by physicians who have seen and treated patients with lipodystrophy. This study aimed to provide a better understanding of the physician’s perspective regarding the patient journey in lipodystrophy, including diagnosis, the burden of disease, and treatment approaches.MethodsThirty-three physicians from six countries who had seen or treated patients with lipodystrophy were interviewed using a semi-structured questionnaire. Interviews were transcribed, anonymized, and analyzed for themes and trends. Four main themes were developed: (1) the diagnostic journey in lipodystrophy including the disease features or ‘triggers’ that result in the onward referral of patients to specialist medical centers with experience in managing lipodystrophy; (2) the impact of lipodystrophy on patient quality of life (QoL); (3) the use of standard therapies and leptin replacement therapy (metreleptin) in lipodystrophy, and (4) barriers to metreleptin use.ResultsParticipants reported that, due to their rarity and phenotypic heterogeneity, lipodystrophy cases are frequently unrecognized, leading to delays in diagnosis and medical intervention. Early consultation with multidisciplinary specialist medical teams was recommended for suspected lipodystrophy cases. The development and progression of metabolic complications were identified as key triggers for the referral of patients to specialist centers for follow-up care. Participants emphasized the impact of lipodystrophy on patient QoL, including effects on mental health and self-image. Although participants routinely used standard medical therapies to treat specific metabolic complications associated with lipodystrophy, it was acknowledged that metreleptin was typically required in patients with congenital generalized lipodystrophy and in some acquired generalized and partial lipodystrophy cases. A lack of experience among some participants and restrictions to access remained as barriers to metreleptin use.ConclusionsTo our knowledge, this is one of the first studies describing the qualitative experiences of physicians regarding the diagnosis and management of lipodystrophy. Other physician-centered studies may help increase the awareness of lipodystrophy among the wider medical community and support clinical approaches to this rare disease.

A rapid action plan to improve diagnosis and management of lipodystrophy syndromes.

Lipodystrophy syndromes are rare diseases that can present with a broad range of symptoms. Delays in diagnosis are common, which in turn, may predispose to the development of severe metabolic complications and end-organ damage. Many patients with lipodystrophy syndromes are only diagnosed after significant metabolic abnormalities arise. Prompt action by clinical teams may improve disease outcomes in lipodystrophy syndromes. The aim of the Rapid Action Plan is to serve as a set of recommendations from experts that can support clinicians with limited experience in lipodystrophy syndromes. The Rapid Action Plan was developed using insights gathered through a series of advisory meetings with clinical experts in lipodystrophy syndromes. A skeleton template was used to facilitate interviews. A consensus document was developed, reviewed, and approved by all experts. Lipodystrophy is a clinical diagnosis. The Rapid Action Plan discusses tools that can help diagnose lipodystrophy syndromes. The roles of clinical and family history, physical exam, patient and family member photos, routine blood tests, leptin levels, skinfold measurements, imaging studies, and genetic testing are explored. Additional topics such as communicating the diagnosis to the patients/families and patient referrals are covered. A set of recommendations regarding screening and monitoring for metabolic diseases and end-organ abnormalities is presented. Finally, the treatment of lipodystrophy syndromes is reviewed. The Rapid Action Plan may assist clinical teams with the prompt diagnosis and holistic work-up and management of patients with lipodystrophy syndromes, which may improve outcomes for patients with this rare disease.

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.

The significance of precise diabetes diagnosis: a case of euglycemic diabetic ketoacidosis induced by the introduction of empagliflozin with simultaneous reduction of insulin dosage

Euglycemic diabetic ketoacidosis (euDKA) is a rare but severe metabolic complication of diabetes mellitus characterised by elevated anion gap metabolic acidosis despite normal or mildly elevated blood glucose levels. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as effective antidiabetic medications, yet their use is associated with an increased risk of euDKA, especially when coupled with insulin dose reduction. We present the case of a 50-year-old male with a 20-year history of diabetes mellitus, initially managed with insulin and metformin, who developed euDKA following the introduction of empagliflozin and sitagliptin alongside a reduction in insulin therapy. Despite normoglycaemia the patient exhibited symptoms of ketoacidosis, including chronic fatigue, polydipsia, and polyuria. Diagnostic workup revealed metabolic acidosis, elevated inflammatory markers, acute kidney injury and ketonuria. Subsequent specialised laboratory tests confirmed type 1 diabetes mellitus (T1DM) with the presence of anti-glutamic acid decarboxylase (anti-GAD) antibodies and the absence of C-peptide secretion. Management involved fluid therapy, intravenous insulin and glucose administration. This case underscores the diagnostic challenges of euDKA and emphasises the importance of differentiating between T1DM and T2DM, as management strategies vary significantly. Patient education on insulin therapy and injection techniques is crucial to prevent complications such as improper insulin delivery and dose reduction, which can precipitate euDKA. In conclusion, clinicians should be vigilant for euDKA in patients on SGLT2 inhibitors, particularly when insulin dose reduction is involved. Comprehensive patient education and accurate differentiation between diabetes types are essential for timely diagnosis and optimal management, thereby reducing the risk of severe complications.

The Use of Milk Bovine Extracellular Vesicles to Mitigate Gut-Liver Axis Dysfunction Under Pediatric Parenteral Nutrition

Parenteral Nutrition (PN) is a lifesaving strategy that provides intravenous nutrition in patients when enteral feeding is contraindicated, or access is insuffcient to prevent malnutrition. PN is used in low-birth-weight neonates whereprolonged use is associated with severe metabolic complications, including parenteral nutrition-associated liver disease (PNALD). PNALD is characterized by hepatitis, cholestasis, fibrosis, steatosis, and eventual organ failure. Elevated rates of PNALD in pediatric patients may be driven by liver immaturity, aberrant metabolic adaptation, and leaky gut barrier.To characterize the etiology of PNALD, we recently established a pediatric mouse model of PN. Using this model, we explored the intravenous use of bioactive milk components to augment hepatic immune response in pediatric mice without enteral milk intake. Extracellular vesicles (EVs) are involved in cell-to-cell communication, contain immune-augmenting microRNA, and are enriched in bovine milk. After isolating EVs from bovine milk and characterizing them, we explored EV use in vitro via M1 macrophage responses, showing TNF-alpha inhibition in the presence of LPS. Wethen hypothesized that EVs would protect the pediatric liver from hepatitis under PN feeding in vivo. Mouse pups were randomized to intravenous PN, PN + EV (1.39x109 particles/uL), or sham surgery control for 6 days. Flow cytometry showed PN elevated hepatic macrophages (CD11b+F4/80+), myeloid-derived suppressor cells (CD11b+GR1+) andreduced relative T cell populations compared with sham controls. PN+EV treatment restored hepatic immune profiles to patterns observed in sham controls. Spleen and liver cytokines also mirrored changes in hepatic flow results, where elevated proinflammatory IL-1 beta was induced with PN alone, but similar levels were found in sham and PN+EVanimals. MicroRNA sequencing showed the EV isolates contain 48% Let-7, a described myeloid suppressor microRNA. This data demonstrates that intravenous EV administration - or future synthetic microRNA - may provide a noveltherapeutic approach for patients requiring PN nutrition support, especially those with elevated risk of PNALD induced inflammation and organ dysfunction. Dairy Innovation Hub, UW-Madison. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations. Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations. Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R2 = 0.466, and mean bias of 23 kcal/day. This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth.

Pancreatitis in pregnancy: The complex interplay with triglycerides and diabetes

Pancreatitis in pregnancy: The complex interplay with triglycerides and diabetes

Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa

BackgroundCongenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment.MethodsCGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records.ResultsData from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth–37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age.ConclusionsThis analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Genetic variants in DBC1, SIRT1, UCP2 and ADRB2 as potential biomarkers for severe obesity and metabolic complications.

Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications. This study enrolled 305 individuals with severe obesity (cases, BMI≥35kg/m2) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9kg/m2). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays. Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms. This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits.

From scarcity to solutions: Therapeutic strategies to restore adipose tissue functionality in rare disorders of lipodystrophy.

Lipodystrophy is a rare disorder characterised by abnormal or deficient adipose tissue formation and distribution. It poses significant challenges to affected individuals, including the development of severe metabolic complications like diabetes and fatty liver disease. These conditions are often chronic, debilitating and life-threatening, with limited treatment options and a lack of specialised expertise. This review aims to raise awareness of lipodystrophy disorders and highlights therapeutic strategies to restore adipose tissue functionality. Extensive research has been conducted, including both historical and recent advances. We have examined and summarised the literature to provide an overview of potential strategies to restore adipose tissue functionality and treat/reverse metabolic complications in lipodystrophy disorders. A wealth of basic and clinical research has investigated various therapeutic approaches for lipodystrophy. These include ground-breaking methods such as adipose tissue transplantation, innovative leptin replacement therapy, targeted inhibition of lipolysis and cutting-edge gene and cell therapies. Each approach shows great potential in addressing the complex challenges posed by lipodystrophy. Lipodystrophy disorders require urgent attention and innovative treatments. Through rigorous basic and clinical research, several promising therapeutic strategies have emerged that could restore adipose tissue functionality and reverse the severe metabolic complications associated with this condition. However, further research and collaboration between academics, clinicians, patient advocacy groups and pharmaceutical companies will be crucial in transforming these scientific breakthroughs into effective and viable treatment options for individuals and families affected by lipodystrophy. Fostering such interdisciplinary partnerships could pave the way for a brighter future for those battling this debilitating disorder.

Anti-Diabetic Agents in Covid-19, Their Possible Role Beyond Diabetes

Recent reports from various observational investigations revealed and published the outcomes of Non-insulin Anti-diabetic agents. Patients additionally with Type-II Diabetes Mellitus and coronavirus disease, caused by severe acute respiratory syndrome [SARS] has become widespread disease in the world since last 3 years. Age, sex, ethnicity, obesity and co-morbidities all apparently enhance the risk of worst consequences. Glucose lowering drugs and anti-viral drug treatment could limit the risk but impose restrictions on their usage which needs to be carefully assessed. This severe acute respiratory syndrome [coronavirus] might be a potentially triggering and worsen the aspect for the diabetic patients that can bring about severe metabolic complications effecting β-cell function leading to hyperglycaemia and diabetic ketoacidosis.

The impact of sarcopenia and obesity on mortality of older adults: five years results.

Sarcopeniaandobesity can cause severe physical and metabolic complications. We aimed to investigate the risk of mortality associated with sarcopenia andobesity in older adults. We designed a retrospective, observational cohort study showing the 5-year mortality of older patients in a tertiary geriatric outpatient clinic.Sociodemographic characteristics, medical history, anthropometric measurements, medications, and comorbidities were recorded. Sarcopenia was evaluated with skeletal muscle mass, handgrip strength, and gait speed. We defined sarcopenic obesity as sarcopenia plus obesity(as a body mass index ≥ 30kg/m2).We classified the participants into four groups according to whether they were sarcopenic and/or obese: non-sarcopenic non-obese, non-sarcopenic obese, sarcopenic non-obese, and sarcopenic obese. The final overall survival of the patients was obtained from the hospital data system. Of the 175 patients, the mean age was 76.1 ± 6.4, and the majority were female (n = 120). Sixty-eight had sarcopenia (39%). The prevalence of obesity was 27%. Thirty-eight patients had died within five years (22%). The mortality rate was significantly higher in the oldest (age 85 and above) and sarcopenic groups (p < 0.001, 0.004, respectively). The mortality rate was highest in the sarcopenic obese group (40.9%). Age (HR: 1.13, 95% CI: 1.07-1.19, p: < 0.001), sarcopenic obesity (HR: 4.85, 95% CI: 1.91-12.31, p: 0.001), sarcopenia (HR: 2.26, 95% CI: 1.15-4.43, p: 0.018) and obesity (HR: 2.15, 95% CI: 1.11-4.17, p: 0.023) were independently associated with mortality at 5years. The Kaplan-Meier analysis and Log-Rank test showed that sarcopenic obese patients had the highest cumulative mortality incidence rates. Sarcopenic-obese participants had the highest mortality incidence compared to those without obesity or sarcopenia. In addition, the presence of sarcopenia or obesity alone also had a significant role in mortality risk. So, we should especially focus on maintaining or increasing muscle mass and preventing obesity.

Clinical and Paraclinical Profiles of Patients with Viral Hepatitis C in Cotonou

Background: Chronic hepatitis C virus (HCV) infection induces the occurence of severe chronic liver disease and metabolic complications. Our goal was to study the clinical and paraclinical profile of patients with hepatitis C virus at the Natioanl Teaching Hospital Hubert Koutoukou Maga of Cotonou. Methods: This was a cross-sectional and descriptive study conducted at the Teaching Clinic of Hepato-Gastroenterology of the Natioanl Teaching Hospital Hubert Koutoukou Maga of Cotonou with the treated patients, from January 1, 2012, to October 31, 2018. Results: A total of 80 patients with hepatitis C were included in the study. The mean age was 60.2 ± 10.8 years old with extremes of 34 and 84 years. Most of the subjects surveyed were women (62.5%) with a sex ratio of 0.6. Arterial hypertension was the prevalent history in these patients (61.2%). HCV carriage was known for less than 5 years in 70% of cases. The most represented genotype was viral genotype 2 (57.2%). Complications were noted in 47.5% of respondents, dominated by cirrhosis (40%). FibroTest was the main method of non-invasive evaluation of fibrosis. Conclusion: In our study, hepatitis C affects mostly women. It is often diagnosed late. Hence, there is a real need to reinforce awareness.

Chylothorax due to thrombosis of the jugular and subclavian veins in a patient with gastric cancer: a case report

BackgroundChylothorax is a rare condition due to leakage of chyle in the thoracic cavity. When large amounts of chyle leak into the thoracic cavity, it can lead to severe respiratory, immune, and metabolic complications. Chylothorax has many potential underlying etiologies, and the most common causes are traumatic chylothorax and lymphoma. Venous thrombosis of the upper extremities is a rare cause of a chylothorax.Case presentationA 62-year-old Dutch man with a medical history of gastric cancer, treated with neoadjuvant chemotherapy and surgery 13 months prior, presented with dyspnea and a swollen left arm. Computed tomography thorax showed bilateral pleural effusion that was more prominent on the left side. The computed tomography scan further revealed thrombosis of the left jugular and subclavian veins and osseal masses suggesting cancer metastasis. Thoracentesis was performed to confirm the suspicion of gastric cancer metastasis. The obtained fluid was milky with a high level of triglycerides, but contained no malignant cells; hence, the diagnosis of the pleural effusion was chylothorax. Treatment with anticoagulation and a medium-chain-triglycerides diet was started. Furthermore, bone metastasis was confirmed with a bone biopsy.ConclusionOur case report demonstrates chylothorax as a rare cause of dyspnea in a patient with pleural effusion and a history of cancer. Therefore, this diagnosis should be considered in all patients with a history of cancer with new-onset pleural effusion and thrombosis of the upper extremities or clavicular/mediastinal lymphadenopathy.

Assessing the impact of usage of steroids among newly detected diabetes patients in a study among covid-19 patients across India

Background: There is a bidirectional relationship between COVID-19 and diabetes. New-onset diabetes and severe metabolic complications of pre-existing diabetes in patients with COVID-19 have been observed. Steroids are medications used for treatment of several diseases, including COVID-19. Its pharmacological action increases blood glucose and poses additional challenges in the management. Aim: To study the impact of steroids on newly detected diabetes patients with a history of COVID-19 in a cohort group. Method: 2263 patients from 15 different sites across India were analysed following a specific eligibility criterion. The patients were segregated into three groups - No steroids, Low steroids [less than or equal to the median dose (50mg)], and High steroids [greater than the median dose (50mg)]. Two-way Analysis of Variance (ANOVA) test was used to test the relationship between Diabetes status and Steroid usage. Results: The steroid dosage for the management of COVID-19 in the Newly-Detected Diabetes (NDD) group received higher doses of steroids. All steroid doses were adjusted and standardized to prednisolone 5mg. The average maximum doses of steroids used in the management of COVID-19 for NDD was 86.6 mg/day. Within the NDD group, those who received a lower steroid dose had a higher HRCT score as compared to the No steroid and High steroid groups. Also, amongst all patients who did not receive steroids for management of COVID-19, NDD had a statistically higher HRCT score. Conclusion: The prevailing hypothesis that increased application of steroids causes diabetes-like disease spectrums in patients recovering from COVID-19. The findings however require reconsidering steroid usage as the leading cause of COVID-induced diabetes.

The Effect of BSCL2 Gene on Fat Deposition Traits in Pigs.

BSCL2 encodes seipin, a transmembrane endoplasmic reticulum protein associated with lipodystrophy and severe metabolic complications, including diabetes and hepatic steatosis. In pigs, BSCL2 expression increases during adipocyte differentiation. In the present study, we identified significant gene variants associated with fat deposition (FD)-related processes based on subcutaneous fat tissue RNA-seq data. In the association study, to prove our hypothesis, three Polish pig breeds were included: Złotnicka White (ZW, n = 72), Polish Landrace (PL, n = 201), and Polish Large White (PLW, n = 169). Based on variant calling analysis and χ2 tests, BSCL2 mutations showing significantly different genotype/allele distribution between high- and low-fat pigs were selected for a comprehensive association study. Four interesting BSCL2 variants (rs346079334, rs341493267, rs330154033, and rs81333153) belonging to downstream and missense mutations were investigated. Our study showed a significant decrease in minor allele frequency for two BSCL2 variants (rs346079334 and rs341493267) in PL pigs in 2020-2021. In ZW, BSCL2 mutations significantly affected loin and ham fats, meat redness, and growth performance traits, such as feed conversion and daily feed intake. Similar observations were noted for PLW and PL, where BSCL2 mutations influenced fat depositions and meat traits, such as loin eye area, loin mass and fat, carcass yield, and growth performance traits. Based on the observation in pigs, our study supports the theory that BSCL2 expressed in subcutaneous fat is involved in the FD process.

Efficacy of low carbohydrate diet (LCD) on obesity and alcohol intake from bio-psycho-social points of view

Background: There is a bidirectional relationship between COVID-19 and diabetes. New-onset diabetes and severe metabolic complications of pre-existing diabetes in patients with COVID-19 have been observed. Steroids are medications used for treatment of several diseases, including COVID-19. Its pharmacological action increases blood glucose and poses additional challenges in the management. Aim: To study the impact of steroids on newly detected diabetes patients with a history of COVID-19 in a cohort group. Method: 2263 patients from 15 different sites across India were analysed following a specific eligibility criterion. The patients were segregated into three groups - No steroids, Low steroids [less than or equal to the median dose (50mg)], and High steroids [greater than the median dose (50mg)]. Two-way Analysis of Variance (ANOVA) test was used to test the relationship between Diabetes status and Steroid usage. Results: The steroid dosage for the management of COVID-19 in the Newly-Detected Diabetes (NDD) group received higher doses of steroids. All steroid doses were adjusted and standardized to prednisolone 5mg. The average maximum doses of steroids used in the management of COVID-19 for NDD was 86.6 mg/day. Within the NDD group, those who received a lower steroid dose had a higher HRCT score as compared to the No steroid and High steroid groups. Also, amongst all patients who did not receive steroids for management of COVID-19, NDD had a statistically higher HRCT score. Conclusion: The prevailing hypothesis that increased application of steroids causes diabetes-like disease spectrums in patients recovering from COVID-19. The findings however require reconsidering steroid usage as the leading cause of COVID-induced diabetes.

Phenotypic Differences Among Familial Partial Lipodystrophy Due to LMNA or PPARG Variants.

Despite several reports of familial partial lipodystrophy (FPLD) type 2 (FPLD2) due to heterozygous LMNA variants and FPLD3 due to PPARG variants, the phenotypic differences among them remain unclear. To compare the body fat distribution, metabolic parameters, and prevalence of metabolic complications between FPLD3 and FPLD2. A retrospective, cross-sectional comparison of patients from 2 tertiary referral centers-UT Southwestern Medical Center and the National Institute of Diabetes and Digestive and Kidney Diseases. A total of 196 females and 59 males with FPLD2 (age 2-86 years) and 28 females and 4 males with FPLD3 (age 9-72 years) were included. The main outcome measures were skinfold thickness, regional body fat by dual-energy X-ray absorptiometry (DXA), metabolic variables, and prevalence of diabetes mellitus and hypertriglyceridemia. Compared with subjects with FPLD2, subjects with FPLD3 had significantly increased prevalence of hypertriglyceridemia (66% vs 84%) and diabetes (44% vs 72%); and had higher median fasting serum triglycerides (208 vs 255 mg/dL), and mean hemoglobin A1c (6.4% vs 7.5%). Compared with subjects with FPLD2, subjects with FPLD3 also had significantly higher mean upper limb fat (21% vs 27%) and lower limb fat (16% vs 21%) on DXA and increased median skinfold thickness at the anterior thigh (5.8 vs 11.3 mm), calf (4 vs 6 mm), triceps (5.5 vs 7.5 mm), and biceps (4.3 vs 6.8 mm). Compared with subjects with FPLD2, subjects with FPLD3 have milder lipodystrophy but develop more severe metabolic complications, suggesting that the remaining adipose tissue in subjects with FPLD3 may be dysfunctional or those with mild metabolic disease are underrecognized.

Bladder paraganglioma: basic characteristics and new perspectives on perioperative management.

Paraganglioma and pheochromocytoma are rare neuroendocrine tumors with severe metabolic and cardiovascular complications. Bladder PGLs are rare, and their clinical management is not precise. Here, we discuss the basic characteristics and perioperative management of bladder PGLs. We retrospectively reviewed 20 bladder PGL cases diagnosed at Sun Yat-sen University Cancer Center. Case notes were reviewed, clinical presentations, therapies, and outcomes were collected, and data analysis was performed. Ten male and ten female patients with a median age of 47.5years (range 14-69years) were included. Most patients (65%) had no symptoms, and PGL was detected incidentally during medical checkups. All patients were treated surgically; 4 (20%) underwent transurethral resection of bladder tumor (TURBT), and 16 (80%) underwent partial cystectomy. Strong intraoperative blood pressure fluctuations were observed in 13 patients (65%). Two patients who were treated preoperatively with α-receptor blockers also experienced severe intraoperative blood pressure fluctuations. Postoperative measurements of troponin I were available for 3 patients, and all were significantly elevated. All patients were diagnosed with bladder PGL on postoperative pathological examination. The median follow-up time was 51months (range 2-147months), and 2 patients were lost to follow-up at 1 and 3months; 16 (88.9%) survived without recurrence, 2 patients (11.1%) experienced recurrence, and 1 patient died. Most bladder paragangliomas are easily mistaken for bladder urothelial carcinoma, and robust hemodynamic instability during surgery might be a challenge for urologists. Postoperative monitoring of troponin I, regardless of the presence of clinical symptoms, is recommended for patients with bladder PGL.