Partial lipodystrophy of the limbs in a diabetes clinic setting

WOS: 000380079700009PubMed ID: 26776282Objective: Partial lipodystrophy of the limbs (PLL) is a newly described form of lipodystrophy that is characterized by symmetrical distal lipoatrophy of the limbs and insulin resistant diabetes. Research design and methods: In this study, we prospectively screened our patients with type 2 diabetes for the presence of PLL phenotype. Metabolic parameters of PLL patients were compared to those with type 2 diabetes who applied to our diabetes clinic during the same period of time. Results: Between Sep 2013 and Mar 2015, 2020 patients with type 2 diabetes were evaluated for the presence of PLL. PLL was confirmed in 16 patients. The prevalence of PLL was calculated as 0.79% in our diabetes clinic. The most common phenotypic presentations were loss of subcutaneous fat in the forearms, calves and thighs, and loss of fat in forearms and calves. Patients with PLL had poor metabolic control and marked insulin resistance compared to subjects with type 2 diabetes. Diabetes had been diagnosed at a younger age in patients with PLL. Patients with PLL also had more atherogenic lipid profiles. Conclusions: Our data suggests that PLL is a relatively common form of lipodystrophy in diabetes clinics, which is associated with poor metabolic control and marked insulin resistance. The recognition of PLL in patients with type 2 diabetes can help better clinical management by alerting the physician to these associated co-morbidities. (C) 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved

A subset of patients with acquired partial lipodystrophy developing severe metabolic abnormalities

###EgeUn###Purpose/Aim of the study: Acquired partial lipodystrophy (APL) is a rare disease characterized by selective loss of adipose tissue. In this study, we aimed to present a subset of patients with APL, who developed severe metabolic abnormalities, from our national lipodystrophy registry. Materials and Methods: Severe metabolic abnormalities were defined as: poorly controlled diabetes (HbA1c above 7% despite treatment with insulin more than 1 unit/kg/day combined with oral antidiabetics), severe hypertriglyceridemia (triglycerides above 500 mg/dL despite treatment with lipid-lowering drugs), episodes of acute pancreatitis, or severe hepatic involvement (biopsy-proven non-alcoholic steatohepatitis (NASH)). Results: Among 140 patients with all forms of lipodystrophy (28 with APL), we identified 6 APL patients with severe metabolic abnormalities. The geometric mean for age was 37 years (range: 27-50 years; 4 females and 2 males). Five patients had poorly controlled diabetes despite treatment with high-dose insulin combined with oral antidiabetics. Severe hypertriglyceridemia developed in five patients, of those three experienced episodes of acute pancreatitis. Although all six patients had hepatic steatosis at various levels on imaging studies, NASH was proven in two patients on liver biopsy. Our data suggested that APL patients with severe metabolic abnormalities had a more advanced fat loss and longer disease duration. Conclusions: We suggest that these patients represent a potential subgroup of APL who may benefit from metreleptin or investigational therapies as standard treatment strategies fail to achieve a good metabolic control

Natural History Of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey

Context: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat. Objective: We aimed to study natural history and disease burden of various subtypes of CGL. Design: We attempted to ascertain nearly all patients with CGL in Turkey. Setting: This was a nationwide study. Patients or Other Participants: Participants included 33 patients (22 families) with CGL and 30 healthy controls. Main Outcome Measure(s): We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up. Results: Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316 + 1G > T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C > T, c. 631delG, c. 62A > T, and c. 465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c. 259C > T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events. Conclusions: CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.WoSScopu