Factitious hypoglycemia in insulin-treated diabetic patients.

Factitious hypoglycemia is a factitious disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), referring to intentionally covertly induced hypoglycemia, with potentially severe consequences. Knowledge of factitious hypoglycemia relies on case reports, and evidence-based information and guidelines are lacking. Diagnosing factitious hypoglycemia in insulin-treated diabetic persons is therefore challenging and often requires a long and costly process. Moreover, the typical metrics proposed to differentiate insulin-induced factitious hypoglycemia from insulinoma (i.e., high insulin and low C-peptide versus high insulin and high C-peptide, respectively) are not always applicable, depending on whether the insulin quantification method can detect the insulin analog. When factitious hypoglycemia is suspected, an emerging trend from recent publications advocates a combination of two insulin quantification methods with different cross-reactivity for insulin analogs, early on in the diagnostic process.

Total pancreatectomy with intraportal islet autotransplantation for pancreatic malignancies: a literature overview.

INTRODUCTION: 'Brittle Diabetes' (BD) is a life-threatening metabolic complication after total pancreatectomy (TP). More than 500 Intraportal islet autotransplantation (IAT) have been performed to prevent this complication, with almost 70% insulin independence after 3 years. Even when insulin independence was not achieved, IAT successfully prevented severe hypoglycemia. Currently, preliminary results for oncologic situations are promising, but their oncological outcomes are still a matter of debate. AREAS COVERED: We performed a bibliographic research of the last 25 years of data. Articles published in English in peer-reviewed journals were retained. In France, auto- and allo-islet transplantation was recently recognized as a valuable treatment for BD by the national health authority. While accepted for benign diseases, the risk of tumor spreading after IAT in oncologic situations is a source of concern. EXPERT OPINION: Preliminary results of IAT in oncological situations are very encouraging. So far, there is no evidence of tumor dissemination. In our opinion, to overcome BD TP with IAT for resectable pancreatic malignancies in patients with a higher risk of postoperative pancreatic fistula and extended pancreatic cancers can be safely performed. Diagnosis of malignancy should not be considered as an exclusion criterion for IAT.

LIPE-related lipodystrophic syndrome: clinical features and disease modeling using adipose stem cells.

OBJECTIVE: The term Multiple Symmetric Lipomatosis (MSL) describes a heterogeneous group of rare monogenic disorders and multifactorial conditions, characterized by upper-body adipose masses. Biallelic variants in LIPE encoding hormone-sensitive lipase (HSL), a key lipolytic enzyme, were implicated in three families worldwide. We aimed to further delineate LIPE-related clinical features and pathophysiological determinants. METHODS: A gene panel was used to identify pathogenic variants. The disease features were reviewed at the French lipodystrophy reference center. The immunohistological, ultrastructural, and protein expression characteristics of lipomatous tissue were determined in surgical samples from one patient. The functional impact of variants was investigated by developing a model of adipose stem cells (ASCs) isolated from lipomatous tissue. RESULTS: We identified new biallelic LIPE null variants in three unrelated patients referred for MSL and/or partial lipodystrophy. The hallmarks of the disease, appearing in adulthood, included lower-limb lipoatrophy, upper-body and abdominal pseudo-lipomatous masses, diabetes and/or insulin resistance, hypertriglyceridemia, liver steatosis, high blood pressure, and neuromuscular manifestations. Ophthalmological investigations revealed numerous auto-fluorescent drusen-like retinal deposits in all patients. Lipomatous tissue and patient ASCs showed loss of HSL and decreased expression of adipogenic and mature adipocyte markers. LIPE-mutated ASCs displayed impaired adipocyte differentiation, decreased insulin response, defective lipolysis, and mitochondrial dysfunction. CONSLUSIONS: Biallelic LIPE null variants result in a multisystemic disease requiring multidisciplinary care. Loss of HSL expression impairs adipocyte differentiation, consistent with the lipodystrophy/MSL phenotype and associated metabolic complications. Detailed ophthalmological examination could reveal retinal damage, further pointing to the nervous tissue as an important disease target.