Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy

Abstract

BackgroundTo study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients.MethodsIn a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated.ResultsThe FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = − 0.53, p = 0.027) and HDL-cholesterol (r = − 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group.ConclusionsThis study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

Non-Alcoholic Fatty Liver in Patients with Chylomicronemia

“…FCS is by nature a genetically determined model of partial lipodystrophy, covering a wide range of phenotypes including underweight patients presenting abnormally low skin folds an almost complete absence of subcutaneous adipose tissue [ 36 ]. Partial or complete lipodystrophy has also been associated with an increased pancreatic fat content [ 37 ], thus conferring a pro-inflammatory environment at the pancreas immediate vicinity. Accordingly, intrapancreatic fat (non-alcoholic fatty pancreas disease, NAFPD) has been identified as an independent correlate of acute pancreatitis [ 38 ].…”

NAFLD as a continuum: from obesity to metabolic syndrome and diabetes

“…It explains, for example, the metabolic pattern usually observed in patients with lipodystrophies. These genetic diseases are characterized by different degrees of incapacity to expand subcutaneous adipose tissue (SAT) and increased ectopic fat in muscle [28], liver [29] and pancreas [30]. Consequently, patients with lipodystrophies have severe IR, which can lead to MetS, NAFLD and diabetes.…”

Clinical and imaging features of women with polygenic partial lipodystrophy: a case series

“…Approximately 85% of total adipose tissue mass in healthy individuals is in the subcutaneous compartment, reflecting its importance as a major site of energy storage [ 24 ]. In lipodystrophies, the loss of subcutaneous white adipose tissue is associated with free fatty acid metabolism dysregulated in visceral adipose tissue and increased deposition in liver, pancreas and muscle, and endothelial dysfunction [ 4 , 25 – 27 ]. Independent of VAT or upper body fat depot, studies have shown that increased lower body fat particularly gluteofemoral fat, is independently associated with reduced cardiovascular risk, and conversely, reduced lower body fat is associated with increased cardiovascular risk [ 4 , 21 , 26 , 28 ].…”