bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why Should We Measure Low-Density Lipoprotein Cholesterol Directly? Comparison of Low-Density Lipoprotein Cholesterol Assessment by Friedewald Estimation, and Direct Measurement
Authors: Cohen Hofit 
Published: May 2021

Abstract
Intorduction: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are an important biomarker for coronary artery disease. In clinical and research settings worldwide, levels LDL-C are often not measured and are estimated using the Friedewald equation (total cholesterol - HDL cholesterol - triglycerides)/5). Bias of either over or underestimation of LDL-C can be corrected by direct measurement of LDL-C. We assessed the precision of the Friedewald equation in a heterogonous patients population within a wide range of lipid levels. Methods: A sample of consecutive fasting lipid profiles was obtained from ambulatory and hospitalized patients at the Chaim Sheba Medical Center, Tel-Hashomer. LDL-C concentrations were directly measured (dir LDL-C) (Olympus, Ireland) and correspondingly calculated at by the Friedewald equation (calc LDL-C). Results: 32,245 samples were analyzed. In 93% of the samples, underestimation of plasma levels of LDL-C was observed using the Friedewald equation. In 11,054 patients (34.3%), the difference between dir LDL and calc LDL were over 10mg/dl. In 7,693 patients (23.8%), the difference between dir LDL and calc LDL were over 20mg/dl. The difference between dir LDL and calc LDL correlated with plasma TG levels, including TG levels within the normal range. The difference between cal LDL and dir LDL levels is inversely correlated to cholesterol plasma levels. Conclusions: Direct measurement of LDL-C is more precise than Friedewald’s formula and overcomes the inaccurateness, due to elevated TG levels or relatively low LDL-C levels, in the setting of a heterogeneous Israeli population. In the era of extremely low LDL-C treatment goals, our findings require consideration due to their clinical importance and direct measurement of plasma LDL-C should be implemented as underestimation of LDL levels may lead to inappropriate therapeutic decisions.
Bone Breaking Triglycerides
Authors: Dauterive Ellen , Wright Virginia 
Published: May 2021

Abstract
A 40 yo African American female with pmhx of T2DM, DLD was admitted for worsening leg and arm pain that started a year prior but had worsened in the last 6 months. Pain started in the right arm and progressed to include the right leg and left leg. She had presented to the ER 3 times in the last 3 weeks with no diagnosis and prescribed anti-inflammatories. On ROS she had unintended weight loss of 50 lbs. Pain was not relieved with anti-inflammatories or narcotics. She was diagnosed with diabetes in the previous 5 years and had not been compliant with her medications. Plain x-rays showed OA of the hip. An osseus survey showed multiple expansile, bubbly, and lucent intramedullary lesions consistent with polyostotic fibrous dysplasia versus multiple myeloma. CT showed a radiolucent lesion of the left femur with absence of normal bone trabeculae. Her labs showed normal calcium, phosphorous, renal function, PTH and no evidence of monoclonal gammopathy. Vitamin D was low at 8.2 ng/ml (6.6–49 ng/ml). CT CAP showed no concern for malignancy in other organs. A lipid profile was done and showed elevated fasting triglycerides of 2617 mg/dL (&lt;150 mg/dl) and LDL direct 54 mg/dl (&lt;100 mg/dl). A1c was 11.2% on admission. She denied any use of alcohol, estrogens, SSRI’s. No history of pancreatitis. On physical exam she did not have tendinous xanthomas, eruptive xanthomas, palmar xanthomas, or lipemia retinalis. Family history not significant for lipid disorders. Patient was fasted for 24 hours and then started on intensive insulin regimen as well as fenofibrate for hypertriglyceridemia. Triglycerides came down to less than 500 over 7 days. She was evaluated by ortho for her bone lesions and underwent bone lesion biopsy as well as prophylactic IMN of her bilateral femurs for prevention of impending fragility fractures. Bone biopsy was significant for xanthoma of the bone. Following discharge, she remained on fenofibrate and fish oil as well as a basal/bolus insulin regimen. Triglycerides remained controlled. She has not followed up outpatient for further workup. This case highlights an atypical presentation of triglyceride deposition in the setting of hypertriglyceridemia. It shows that hypertriglyceridemia should be included in the differential for lytic lesions when preliminary workup is negative. It also highlights that complications other than pancreatitis and cardiovascular disease can significantly alter a patient’s life if triglycerides go untreated.
Challenges in Managing Metabolic Complications in a Patient With Familial Partial Lipodystrophy Type 3
Authors: Shah Kajal , Charitou Marina 
Published: May 2021

Abstract
Familial partial lipodystrophy (FPL) is a rare group of autosomal dominant genetic disorders which causes variable loss of subcutaneous fat from abdomen, thorax or extremities in addition to the numerous metabolic complications like insulin resistance, diabetes mellitus and dyslipidemia1. FPL type 3 was first characterized by Agarwal et al. in 20021, in which peroxisome proliferator-activated receptor-γ (PPARγ) gene was the molecular basis of this disorder. It is extremely rare and so far only 30 patients or so have been recognized with this mutation2. FPL3 is unique because it generally spares the loss of fat from trunk, face and neck region and also presents with more severe metabolic derangements. We report a case of a young female with PPARγ mutation leading to numerous metabolic complications. A 19 year old female with FPL3 was seen by adult endocrinology as a transition from pediatric endocrinology. She was found to have hypertriglyceridemia on routine labs done at the age of 11. Patient reported loss of subcutaneous fat from her extremities and eruptive xanthoma on flexor surfaces at the time of diagnosis along with a positive family history of hypertriglyceridemia induced pancreatitis and Myocardial infarction at the age of 40 in her father. Her triglyceride level has varied between 600 and 3000 (normal 20–149 mg/dl) over the years. FPL3 was diagnosed based on genetic testing. She was prescribed fenofibrate and fish oil, and statin was added thereafter. She developed type 2 diabetes and was started on metformin and pioglitazone. She was noted to have hypertension and was treated with amlodipine and lisinopril. She also was found to have Polycystic Ovarian Syndrome (PCOS) based on menstrual irregularities, hirsutism and ultrasound showing multiple ovarian cysts, and was treated with spironolactone. Her most recent labs show triglyceride level of 2400 mg/dl and HbA1c of 8.3. PPARγ gene mutation in FPL3 leads to insulin resistance and hence patients often develop hypertriglyceridemia, type 2 diabetes, PCOS and hypertension. In terms of treatment options, we are still limited to pioglitazone, metformin, statins and fish oil. Often these are not sufficient in addressing the complexity of metabolic derangements in these patients who have an increased risk of cardiovascular events at a young age. Further research about agents targeting this gene in particular would be beneficial. 1. Agarwal et al. A novel heterozygous mutation in peroxisome proliferator-activated receptor-gamma gene in a patient with familial partial lipodystrophy. J Clin Endocrinol Metab. 2002 Jan; 87(1):408–411. 2. Garg A. Lipodystrophies: Genetic and Acquired Body Fat Disorders. J Clin Endocrinol Metab. 2011;96(11): 3313–3325.
Familial Partial Lipodystrophy: A Case Study and Review of Recent Literature
Authors: Tipu Ali , Hasan Farhad , Grimes Michael 
Published: May 2021

Abstract
Introduction: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by loss of subcutaneous adipose tissue, mainly from the extremities and gluteal region. FPLD is associated with a variety of metabolic abnormalities including severe hypertriglyceridemia (HTG), insulin resistance (IR), and hepatic steatosis. We present a case of FPLD and summarize recent literature on the metabolic features and their management in patients with this rare disease. Case: A 44 year old female with medical history of Type 2 DM, hypertension, hypothyroidism and recurrent pancreatitis from severe HTG was referred to our clinic. She was diagnosed with Type 2 DM in her 30s. Over the ensuing years she had significant IR requiring increasing doses of concentrated insulin (up to 250 units/day). She reported progressive loss of subcutaneous fat from extremities in the preceding 2–3 years. She had recurrent pancreatitis, including a recent hospitalization with TG&gt;8000 mg/dL. On examination, she had typical features of FPLD including loss of subcutaneous adipose tissue from upper and lower extremities including gluteal region, visible skeletal muscles and veins in the extremities, and neck and truncal obesity (Fig. 1). Family history was significant for similar physical and metabolic manifestations in her father and brother. For HTG, she is treated with fibrates and high intensity statin. We avoided the use of fish oil in the patient, because she did not feel well when she was previously on this. Results of the genetic testing are pending. Discussion: FPLD is rare, predominantly autosomal dominant, disorder characterized phenotypically by variable loss of subcutaneous fat and metabolically by severe HTG and insulin resistance. The severity of metabolic derangements is proportional to the degree of the lipodystrophy. The proposed mechanism is limited capacity of adipose tissue to store fat leading to ectopic fat deposition, lipotoxicity and vascular inflammation. Diagnosis is often clinical, especially the loss of subcutaneous fat in the extremities and signs of IR, and is confirmed by genetic testing. Dunnigan syndrome is the most common type of FPLD, which occurs from an autosomal dominant missense mutation in lamin A/C (LMNA). Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much less common. Treatment of FPLD is challenging, and mostly focuses on managing the metabolic abnormalities. Recent evidence suggests that fish oil may in fact worsen HTG when the main defect driving increased TG is impaired chylomicron clearance, which our patient had on lipid NMR profile. Metreleptin, a human leptin analog, has recently been approved for the management of FPLD with evidence of improved metabolic abnormalities. Recent data also suggests that GLP1 agonists and SGLT2 inhibitors improved glycemic control and reduced daily insulin requirements.
Severe Hypercholesterolemia in Very-Low-Carbohydrate Diet
Authors: Modarressi Taher 
Published: May 2021

Abstract
There is growing popularity and interest in very-low-carbohydrate (VLC) diets for a variety of established and perceived health benefits. While some impacts have been seen in cardiometabolic diseases such as diabetes, hypertension and short-term weight loss (particularly when paired with caloric restriction), other effects such as in energy levels, mood and sense of well-being are variable. In the extreme, these diets suggest restriction of dietary carbohydrates (CHO) to less than 20 grams daily and often encourage a compensatory increase in dietary fat to promote ketogenesis. There has been concern about the long-term effects of these changes, as well as unintended consequences of increased saturated fat intake. A minority of patients, such as in the case below, may experience exaggerated lipid changes, thought to be influenced by underlying metabolic and genetic factors. Meta-analyses have shown conflicting results of the effects of VLC diets on low density lipoprotein cholesterol (LDL-C) levels.
A 63-year-old woman presented for outpatient consultation for markedly elevated LDL-C 524 mg/dL. The rest of her lipid panel was as follows: total cholesterol 637 mg/dL, triglycerides 152 mg/dL, HDL-C 83 mg/dL. She was asymptomatic. Record review of annual laboratory testing from her primary care physician revealed baseline LDL-C 114–134 mg/dL between 2012 and 2017. Her lipid panel in 2017 was as follows: total cholesterol 216 mg/dL, triglycerides 82 mg/dL, HDL-C 68 mg/dL, LDL-C 132 mg/dL. She described that in late 2017 she began a VLC diet for perceived metabolic benefits, and in the past year intensified CHO restriction to less than 15 grams daily. In 2018–2019, her LDL-C level increased to 303–316 mg/dL, and in 2020 to 524 mg/dL.
She had no history of diabetes, liver or kidney disease, nephrotic syndrome, hypothyroidism or alcohol use. She took no prescribed medications. She reported over-the-counter use of magnesium and potassium. She denied use of any other supplements or herbal remedies. Her past medical history included osteoarthritis. Her family history included hyperlipidemia in her mother, and coronary artery disease in both parents with age of onset in their 70s. She was a lifelong non-smoker and did not drink alcohol. Her BMI was 21.5. On examination, she was normotensive, euthyroid-appearing, and had no stigmata of familial hypercholesterolemia. Other labs were grossly normal, including blood counts, comprehensive metabolic panel, thyroid function tests, hemoglobin A1c and urinalysis. She was counseled extensively regarding her laboratory results and concerns about her cardiovascular safety.
This case demonstrates an exaggerated lipid response to a VLC diet, and supports the National Lipid Association scientific statement Class IIa recommendation to obtain baseline and follow-up lipid profiles in patients who follow such diets due to variation in lipid response.
Antidiabetic Effects of NRDT50, the Enzyme Composition for Regulating Sugar Metabolism, in Db/db Mice
Authors: Kim Daham , Ku Cheol Ryong , Kim Jung Seung , Hwang Jihwan , Cho Yoon Hee , Lee Eun Jig 
Published: May 2021

Abstract
Objective: The enzyme composition (NRDT50) which includes glucosyl transferase, fructosyl transferase, amylase, glucose oxidase, and catalase can regulate the absorption of glucose into the body by converting the carbohydrates in food to a form of sugar that is not absorbed in the stomach before being decomposed in the small intestine into glucose. The aim of this study was to evaluate the antidiabetic effects of repeated oral administration of NRDT50 in db/db mice. Methods: The 7-week-old db/db mice were divided into 3 groups; control, NRDT50 (300mg/kg/day), and voglibose (0.3mg/kg/day). Mice received a standard diet containing drugs for 1 month. Fasting and postprandial glucose level was measured every week. Mixed meal test, biochemical assays, and fecal microbiota analysis were performed. Results: There were no significant differences in body weight or food intake between the three groups. However, NRDT50 treatment led to a significant reduction in fasting and postprandial blood glucose levels compared to control after 3, 4 weeks. The blood glucose levels during the mixed meal test were significantly lower in NRDT50 group compared to control group. NRDT50 treatment reduced triglyceride level, tend to reduce LDL level, and increased relative Bacteroidetes-Firmicutes ratio. NRDT50 treatment did not demonstrate any negative side effects on biochemical and histopathological examination. Conclusion: NRDT50 is expected to be useful for people who are at risk of hyperglycemia or diabetes and thus need to regulate blood sugar with safe. It may also improve the gut microbiota profile by inducing the production of oligosaccharides in the alimentary tract.
Comparison Between Linagliptin and Canagliflozin Effect on Inflammatory Markers, CD34+ Cell Gene Expression and Urine Exosomes in Type 2 Diabetes Subjects
Authors: Nandula Seshagiri R , Janapala Rajesh , Sen Sabyasachi 
Published: May 2021

Abstract
Introduction: Peripheral blood derived CD34 +ve Endothelial progenitor cells (EPCs) has been shown to help vascular regeneration and are dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). We conducted two separate clinical trials using Canagliflozin, an SGLT2 inhibitor and Linagliptin, a DPP4 inhibitor where these medications or matched placebo was added to other oral antidiabetic medication such Metformin and Insulin. Our goal was to do a comparative analysis based on the effect of the medications on CD34+ve hematopoetic progenitor cell function such as migration, colony formation and podocyte specific urine exosome analysis. Methods: Approximately 30 subjects were enrolled in the two studies 29 subjects were enrolled in this 12–16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo AND Linagliptin (Lina 5mg), compared to placebo. T2DM (30–70 years old), HbA1c of 7–10%, were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0 (baseline), 6 or 8 (mid-point), and 12 or 16 (final). A mixed model regression analysis was done with a p-value &lt;0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure in cana group. There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin on endothelium, not seen in Lina group. There was an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA, PECAM-1, a mature endothelial marker and NOS3 (or eNOS) with both Cana and Lina. There was improvement in CD34+ numbers by direct counting (not statistically significant) with both medications. Data on urine podocyte specific exosomal protein indicates an advantage with Cana compared to Lina, though it did not reach stat significance. Conclusions: Our study indicates that Canagliflozin improves several components of vascular function by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes in CD34+ progenitor cells compared to Linagliptin.
Medicsen Smartpatch: A New Approach to Diabetes Management
Authors: Ruiz Alejandro , García Rafael Danilo , Jorgensen Carlos , Jorgensen Eduardo 
Published: May 2021

Abstract
Introduction: Diabetes is a metabolic disorder characterized by a dysregulation of the glucose levels. With insulin being the main drug to be administrated for glucose levels modulation, it needs to be injected subcutaneously with daily injections, which can lead to poor patient compliance, apart from several side-effects. Although other administration methodologies have been investigated (oral or inhaled insulin), they show enough drawbacks to not to be consider as feasible alternatives for diabetes therapy. That′s why Medicsen has developed a Smartpatch that integrates a wide range of technologies, with the purpose of ensuring the correct insulin delivery from the skin′s surface to the bloodstream using a non-invasive and painless drug delivery method through a phenomenon induced by sonophoresis. Materials and Methods: Several in vitro and in vivo tests have been performed to prove the efficacy and safety of the technology, allowing us to collect experimental evidence through different methodologies that demonstrate the therapeutic potential of the device. Among these methodologies, permeability studies using Franz diffusion Cell and swine models (that prove efficacy of the technology) as well as safety studies, for both the insulin and the skin are highlighted. Results: In voltage experiments, the mean time for the disappearance of the membrane potential between the compartments separated by skin was: 334.7 (SD+/-103.6) seconds. Regarding the slope of the voltage line, as an approximation to the transfer speed, an arithmetic mean of (μ)= 0.0164 Mvolts/sec (+/- SD(σ): 0.006) was obtained. No significant differences were found between the circular dichroism spectra of samples (minimum peak at 219nm (sd+/-8.31) and that of the standard, which suggests that the molecular structure of insulin maintains stability. In the same way, HPLC studies shows no variability between the standard and all groups tested. Regardin skin safety, SEM images shows no significant damage to the skin, and ELISA test for TNF α and IL-2, as well as other biochemical tests, show no differences between control and samples. On In vivo experiments with our technology, glucose changes are comparable to those evoked through direct drug injection using conventional syringes. Lastly, the technology proved to be effective in the delivery of insulin through the skin in a non-invasive way, as observed in a Franz Diffusion Cell system and in the in vivo model of blood glucose reduction. Conclusions: Results observed during in vitro and in vivo studies indicate that the technology developed by Medicsen is effective and safe for the patient and the insulin. Following steps, including human trials, will be critical to fully demonstrate its potential in the treatment of diabetes.