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Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias., (© 2024 Wiley Periodicals LLC.)

Monitoring glycemic control status is the cornerstone of diabetes management. This study aimed to reveal whether moderate-carbohydrate (CHO) diets increase the risk of free fatty acid (FFA) levels, and it presents the short-term effects of four different diet models on blood sugar, glycemic variability (GV), and FFA levels. This crossover study included 17 patients with type 1 diabetes mellitus to identify the effects of four diets with different CHO contents and glycemic index (GI) on GV and plasma FFA levels. Diet 1 (D1) contained 40% CHO with a low GI, diet 2 (D2) contained 40% CHO with a high GI, diet 3 (D3) contained 60% CHO with a low GI, and diet 4 (D4) contained 60% CHO with a high GI. Interventions were performed with sensor monitoring in four-day periods and completed in four weeks. No statistical difference was observed among the groups in terms of blood glucose area under the curve ( p = 0.78), mean blood glucose levels ( p = 0.28), GV ( p = 0.59), and time in range ( p = 0.567). FFA and total triglyceride levels were higher in the D1 group ( p < 0.014 and p = 0.002, respectively). Different diets may increase the risk of cardiovascular diseases by affecting GI, FFA, and blood glucose levels.

Background: This study aims to show the clinical and biochemical features in patients with severe hypertriglyceridemia (HTG) associated with rare variants in the apolipoprotein A-V (APOA5) gene., Materials and Methods: Demographics, blood lipid levels, body mass index (BMI) and APOA5 mutation subtypes were collected from the endocrinology clinic registry and analyzed for a retrospective cohort study of ten patients with severe HTG and APOA5 gene variants., Results: Of the 10 cases, four were female, and six were male. The median age was 45.0 years (min-max: 21-60 years), the median triglyceride was 2429.5 mg/dL (27.5 mmol/L) (min-max: 1351-4087 mg/dL, 15.3-46.2 mmol/L), and the mean BMI was calculated as 30.4 ± 4.4 kg/m 2 (min-max: 24.9-41.0 kg/m 2 ). Four cases had diabetes mellitus (DM); two were on intensive insulin therapy, and two were on basal insulin therapy. The mean hemoglobin A1c was 9.2 ± 1.2 % (min-max: 8.3-11.0 %). Among the study group, eight different APOA5 gene mutations were detected. These variants were heterozygous in 2 patients and homozygous (bi-allelic) in 8 patients. One patient was homozygous for APOA5 p.Ser19Trp, a relatively common polymorphism that is a risk variant for HTG., Conclusion: We report a cohort of patients with biallelic and single copy APOA5 variants, who were diagnosed later in life. Most had secondary factors, such as DM or obesity with increased BMI. Most rare APOA5 variants found in our patients were of uncertain significance. Our results add to the growing evidence that rare variants in certain candidate genes may predispose to developing HTG, together with secondary factors such as obesity. The genetic basis of HTG in many other patients is still unknown and remains the subject of further investigation., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The OPG/RANKL (osteoprotegerin/receptor activator of nuclear factor kappa-B) system, which plays a crucial role in bone metabolism, is also associated with vascular calcification. Acromegaly is characterized by excessive secretion of growth hormone and insulin-like growth factor, and studies have demonstrated an elevated risk of cardiovascular disease in individuals with acromegaly. In this study, our objective was to investigate the relationship between OPG/RANKL and various cardiovascular risk scoring systems., Methods: We recruited 44 consecutive acromegaly patients and 41 healthy controls with a similar age and gender distribution for this study., Results: While RANKL levels were significantly higher in the acromegaly group compared to the controls, OPG levels were not found to be significantly different between the two groups. Furthermore, within the acromegaly group, RANKL levels were significantly higher in patients with active acromegaly compared to those with controlled acromegaly. Osteoprotegerin levels showed a positive correlation with the Framingham risk score (FRS) in the acromegaly group. Linear regression analysis revealed an association of OPG with FRS (adjusted R 2 value of 21.7%)., Conclusion: OPG and RANKL may serve as potential markers for assessment of cardiovascular calcification and prediction of the cardiovascular risk status in acromegalic patients., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Background: Lipodystrophy is a rare disease characterized by loss of adipose tissue. Natural history studies have demonstrated significant burden of disease; however, there is limited data on the impact of lipodystrophy on quality of life (QoL) and psychoemotional well-being. The QuaLip study is a prospective observational real-world study that aims to determine the impact of lipodystrophy on QoL and psychoemotional well-being and explore subjective burden of the disease. Sixty-seven adult patients and eight pediatric patients with lipodystrophy were included. Patients were followed up for 24 months and assessments were repeated every three months. Patients were examined by licensed psychiatrists at baseline, and at year 1 and year 2 visits., Results: Eighteen (27.69%) of 65 adult patients (two subjects refused psychiatric assessment) were diagnosed with a psychiatric disorder (e.g., depressive episodes, mixed anxiety and depressive disorder, anxiety disorder, adjustment disorder, recurrent depression, panic disorder, generalized anxiety disorder, unspecified mood disorder, nonorganic sleep disorder, post-traumatic stress disorder, depressive episode comorbidity, social phobia and obsessive-compulsive disorder comorbidity). Lipodystrophy disease and QoL questionnaires revealed a significant disease burden over the study period. More than one-third of patients reported depression symptoms on the Beck Depression Inventory and more than one-fourth of the patients reported significant hunger throughout the study period. Physical appearance, fatigue, and pain contributed to the disease burden. QoL scores were lower in patients with psychiatric disease and in those with poor metabolic control. Attention deficit hyperactivity disorder, depressive disorder, sub-threshold depressive symptoms, obsessive-compulsive disorder, appetite problems, and issues with physical appearance were identified in selected pediatric subjects., Conclusions: Lipodystrophy has a significant impact on QoL and psychoemotional well-being. Psychiatric disorders seem to be underdiagnosed among patients with lipodystrophy., (© 2024. The Author(s).)

Context: The diagnosis of familial partial lipodystrophy (FPLD) is currently made based on clinical judgment., Objective: There is a need for objective diagnostic tools that can diagnose FPLD accurately., Methods: We have developed a new method that uses measurements from pelvic magnetic resonance imaging (MRI) at the pubis level. We evaluated measurements from a lipodystrophy cohort (n = 59; median age [25th-75th percentiles]: 32 [24-44]; 48 females and 11 males) and age- and sex-matched controls (n = 29). Another dataset included MRIs from 289 consecutive patients., Results: Receiver operating characteristic curve analysis revealed a potential cut-point of ≤13 mm gluteal fat thickness for the diagnosis of FPLD. A combination of gluteal fat thickness ≤13 mm and pubic/gluteal fat ratio ≥2.5 (based on a receiver operating characteristic curve) provided 96.67% (95% CI, 82.78-99.92) sensitivity and 91.38% (95% CI, 81.02-97.14) specificity in the overall cohort and 100.00% (95% CI, 87.23-100.00) sensitivity and 90.00% (95% CI, 76.34-97.21) specificity in females for the diagnosis of FPLD. When this approach was tested in a larger dataset of random patients, FPLD was differentiated from subjects without lipodystrophy with 96.67% (95% CI, 82.78-99.92) sensitivity and 100.00% (95% CI, 98.73-100.00) specificity. When only women were analyzed, the sensitivity and the specificity was 100.00% (95% CI, 87.23-100.00 and 97.95-100.00, respectively). The performance of gluteal fat thickness and pubic/gluteal fat thickness ratio was comparable to readouts performed by radiologists with expertise in lipodystrophy., Conclusion: The combined use of gluteal fat thickness and pubic/gluteal fat ratio from pelvic MRI is a promising method to diagnose FPLD that can reliably identify FPLD in women. Our findings need to be tested in larger populations and prospectively., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective. Besides the early detection and treatment of diabetic foot ulcers, being aware of the risk factors for major amputation plays a crucial role in preventing the major lower limb amputations. Major lower limb amputations are not just mentally and physically hard for patients, but also have an effect on patient's survival and are a financial burden on both patients and healthcare systems. Subjects and Methods. We defined 37 potential risk factors for major amputation and these risk factors were investigated among 507 patients who had ulcers in their feet and were seen by the diabetic foot ulcer council at Ege University Faculty of Medicine. In our study, 106 (20.9%) patients ended up undergoing major lower limb amputation. Results. The univariate analysis showed that 24 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, 6 risk factors remained statistically significant. Multivariate-adjusted hazard ratios were 4.172 for hyperlipidemia, 3.747 for albumin <3.365 g/dL, 3.368 for C-reactive protein (CRP) >2.185 mg/L, 2.067 for presence of gangrenous Wagner stage, 1.931 for smoking tobacco >30 pack/year, and 1.790 for hematocrit (HCT) <31.5%. Most patients with major amputation presented with a neuroischemic foot (58%). Gender and age were not found to be risk factors for major amputation. Having less than 7% of hemoglobin A1c (HbA1c) levels had a direct proportion with major amputation numbers. The mortality rates in one year, two and three years after the major amputation operations were 24.6%, 30%, and 35.9%, respectively. Conclusion. Being familiar with these risk factors for major amputation is crucial for multi-disciplinary teams to take good care of patients with diabetic foot ulcers and to lower the need for major amputations., (© 2023 Bugra Zengin et al., published by Sciendo.)

Introduction: Not only are early detection and treatment of diabetic foot ulcers important, but also acknowledging potential risk factors for amputation gives clinicians a considerable advantage in preventing amputations. Amputations impact both healthcare services and the physical and mental health of patients. This study aimed to investigate the risk factors for amputation in patients with diabetic foot ulcers., Methods: The sample for this study was patients with diabetic foot ulcers who were treated by the diabetic foot council at our hospital between 2005 and 2020. A total of 32 risk factors for amputation were identified and investigated among 518 patients., Results: Our univariate analysis showed that 24 of 32 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, seven risk factors remained statistically significant. The risk factors most significantly associated with amputation were Wagner grading, abnormal peripheral arteries, hypertension, high thrombocyte levels, low haematocrit levels, hypercholesterolaemia and male sex, respectively. The most common cause of death in patients with diabetes who have undergone amputation is cardiovascular disease, followed by sepsis., Conclusion: To enable optimum treatment of patients with diabetic foot ulcers it is important for physicians to be aware of the amputation risk factors, and thus avoid amputations. Correcting risk factors, using suitable footwear and routinely inspecting feet are crucial factors for preventing amputations in patients with diabetic foot ulcers., Competing Interests: Disclosures: Burak Yuzuguldu, Bugra Zengin, Ilgin Yildirim Simsir and Sevki Cetinkalp have no financial or non-financial relationships or activities to declare in relation to this article., (© Touch Medical Media 2023.)

Purpose: Acromegaly is associated with oxidative stress and inflammation parameters. Chitotriosidase (CHITO) is a marker of macrophage activation and plays a pivotal role in the activation of inflammatory and immunological responses. Our study aimed to determine CHITO,YKL-40, advanced glycation end product (AGE), and high-sensitivity C-reactive protein (hsCRP) levels to investigate malondialdehyde (MDA), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and to evaluate any association of these parameters with carotid intima media thickness (cIMT) in patients with controlled acromegaly., Methods: Thirty controlled acromegaly patients and 41 age- and sex-matched control cases were studied. We obtained demographic data, hormonal and metabolic parameters, and cIMT. CHITO activity was measured with the fluorometric method of Chamoles et al. YKL-40 and hsCRP levels were measured using ELISA. AGEs were measured based on spectrofluorimetric detection. GSH-Px activity was determined by a colorimetric assay. MDA, SOD, and catalase activities were determined in hemolysis., Results: Higher CHITO, AGE, and hsCRP concentrations were observed in patients with acromegaly compared to controls. SOD levels were non-significantly higher in the acromegaly group, while catalase activities were lower in patients with acromegaly. Correlation analyses of CHITO, AGEs, YKL-40, hsCRP, MDA, catalase, GSH-Px, and SOD with metabolic, anthropometric, and laboratory parameters did not demonstrate any significant correlation (p > 0.05). There was no significant difference between groups with regard to cIMT levels., Conclusion: This is the first study investigating CHITO and AGE levels in patients with acromegaly. Serum CHITO, AGE, and hsCRP levels in acromegalic patients were significantly increased. It may be important to evaluate CHITO, AGE, and hsCRP levels in acromegalic patients who are already under cardiometabolic surveillance due to risk of developing cardiovascular disease., (© 2022. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Reduced life expectancy has resulted from an increased incidence of chronic complications in patients with diabetes. The diabetic foot is one of these complications and generally presents together with diabetic neuropathy and vascular insufficiency. Hypoxia-inducible factor-1α (HIF-1α) is important in developing the adaptation response to hypoxia and facilitates healing through regulation of keratinocyte migration and epithelium restoration in wounds. Fetuin-A is a transporter protein that is synthesized in the liver and inhibits vascular and ectopic calcifications. It has been observed that altered fetuin-A is associated with peripheral artery disease through vascular calcification and is associated with inflammation and metabolic syndrome occurrence in diabetic patients. Fibrinogen is an acute-phase reactant and has a major role in homeostasis, tissue repair, and wound healing. Increased fibrinogen blood level is one of the factors that facilitates the hypercoagulability in diabetics. Homocysteine has atherogenic features and causes vascular toxicity by enhancing low-density lipoprotein oxidation. We evaluated the association of serum HIF-1α, fetuin-A, fibrinogen, and homocysteine levels with amputation in 31 patients diagnosed with diabetes mellitus. According to our evaluation, a negative correlation was determined between fetuin-A and amputation level ( P = .012, r = -0.450), which was statistically significant. Unfortunately, there was no significant correlation between HIF-1α, fibrinogen, homocysteine, and amputation level ( P > .05). As a result, it was suggested that vascular calcification due to fetuin-A deficiency may be important in the diabetic foot pathogenesis and that fetuin-A levels may be a predictor for amputation level.