Endocrine Abstracts

Adipose inflammation is increasingly percieved to be a major factor in the pathogenesis of obesity associated insulin resistance. However, human evidence supporting this hypothesis remains largely unconvincing. An alternative model is suggested by observations made in patients with rare forms of lipodystrophy; namely that a relative inability to cope with sustained surplus energy intake underpins insulin resistaance. Recent data suggesting that subtle forms of lipodystrophy ar...

Adipose inflammation is increasingly percieved to be a major factor in the pathogenesis of obesity associated insulin resistance. However, human evidence supporting this hypothesis remains largely unconvincing. An alternative model is suggested by observations made in patients with rare forms of lipodystrophy; namely that a relative inability to cope with sustained surplus energy intake underpins insulin resistaance. Recent data suggesting that subtle forms of lipodystrophy ar...

Although abnormal glucose metabolism defines type 2 diabetes mellitus (T2DM), efforts to understand the pathogenesis of T2DM are increasingly focused on disordered lipid metabolism. Magnetic resonance spectroscopy (MRS) is a non-invasive technique which provides real time data. Its uses in metabolic studies include: 1) static measurements of energy stores e.g. intramyocellular and hepatic glycogen and triglyceride levels and, 2) dynamic measures of mitochondrial function (ATP ...

All forms of severe lipodystrophy are associated with features of the metabolic syndrome including insulin resistance, T2DM, NAFLD, dyslipidaemia and cardiovascular disease. The question I will address is if this means that what happens in patients with monogenic forms of lipodystrophy is at all relevant to common forms of insulin resistance and the metabolic syndrome....

Introduction: Lipodystrophy is a rare medical condition with a varied etiology that is characterised by a complete or partial loss of adipose tissue, which can be generalised, partial or localised. Patients have altered secretion of adipokines, such as, Leptin and Adiponectin. Ectopic lipid accumulation is common and leads to metabolic complications associated with insulin resistance (IR) such as, diabetes mellitus (DM) and hypertriglyceridemia. Levels of circulating inflammat...

Introduction: Familial Partial Lipodystrophy Type 1 (FPLD1) is characterised by loss of gluteal and limb subcutaneous fat and increased abdominal fat. The genetic basis is currently unknown. FPLD1 is frequently associated with metabolic problems including diabetes, insulin resistance, dyslipidaemia and non-alcoholic fatty liver disease. Despite central adiposity and severe metabolic abnormalities, this group of patients often do not qualify for NHS funding for bariatric surger...

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) is greatly increased in patients with lipodystrophy and some other forms of severe insulin resistance. Liver biopsy remains the definitive technique for diagnosis and staging of NAFLD. However, non-invasive techniques, such as magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are increasingly used to assess response to therapeutic interventions. The National Severe Insulin Resist...

Introduction: Immune mediated cases of severe insulin resistant diabetes are very rare. We report responses to immunosuppression with rituximab in two patients.Case 1: A 31 year old black African female, BMI 22.84 kg/m², was referred with new onset diabetes, diagnosed shortly following a miscarriage. She had weight loss, acanthosis nigricans, nocturnal hypoglycaemia and severe hyperandrogenism . She was on an insulin pump and required >1000 units in...

Objective: To evaluate the real-world experience of patients with generalized (GL) and partial (PL) lipodystrophy initiating treatment with metreleptin as part of an early access program (EAP).Methods: A retrospective data collection was conducted from four countries for patients enrolled in the EAP. A descriptive analysis was performed on selected patient characteristics, baseline organ impairments and complications, and response to metreleptin therapy,...

The study of humans carrying dominant negative mutations in PPAR gamma has contributed significantly to our understanding of its role in human physiology. To date, comparable studies of PPAR alpha have not been reported. Using a pooled approach, we undertook exon sequencing of PPARA in 11,848 adult participants of the Fenland study, a population-based cohort study with detailed metabolic phenotyping. Twenty-nine PPARA missense variants were detected (allelic ...