Noninvasive Quantification of Pancreatic Fat in Humans
ABSTRACT To validate magnetic resonance spectroscopy (MRS) as a tool for non-invasive quantification of pancreatic triglyceride (TG) content and to measure the pancreatic TG content in a diverse human population with a wide range of body mass index (BMI) and glucose control.
To validate the MRS method, we measured TG content in the pancreatic tissue of 12 lean and 12 fatty ZDF rats (ages 5-14 weeks) both by MRS and the gold standard biochemical assay. We used MRS to measure pancreatic TG content in vivo in 79 human volunteers. Additionally, to assess the reproducibility of the method, in 33 volunteers we obtained duplicate MRS measurements 1-2 weeks apart.
MRS quantifies pancreatic TG content with high reproducibility and concordance to the biochemical measurement (Spearman's rank correlation coefficient = 0.91). In humans, median pancreatic TG content was as follows: (1) normal weight and normoglycemic group 0.46 f/w%, (2) overweight or obese but normoglycemic group 3.16 f/w%, (3) impaired fasting glucose or impaired glucose tolerance group (BMI matched with group 2) 5.64 f/w%, and (4) untreated type 2 diabetes group (BMI matched with group 2) 5.54 f/w% (Jonckheere-Terpstra trend test across groups p < 0.001).
Human pancreatic steatosis, as measured by MRS, increases with BMI and with impaired glycemia. MRS is a quantitative and reproducible non-invasive clinical research tool which will enable systematic studies of the relationship between ectopic fat accumulation in the pancreas and development of type 2 diabetes.
SourceAvailable from: László Czakó[Show abstract] [Hide abstract]
ABSTRACT: Objectives To evaluate the relationship of exocrine pancreatic insufficiency with the level of glycemic control in diabetes (DM). Methods Patients with type 2 DM treated in our clinic were prospectively recruited into the study. Pancreatic diabetes was excluded. Cases with HbA1c ≥7% formed Group A (n=59), and with HbA1c <7% Group B (n=42). The fecal level of pancreatic elastase (PE-1) was measured and morphological examinations of the pancreas were performed. Results The PE-1 level was significantly lower in Group A than in Group B (385.9±171.1 μg/g, vs. 454.6±147.3 μg/g, p=0.038). The PE-1 level was not correlated with HbA1c (r= -0.132, p=0.187), the duration of DM (r= -0.046, p=0.65), age (r=0.010, p=0.921), BMI (r=0.203, p=0.059), or pancreatic steatosis (r=0.117, p=0.244). The size of the pancreas did not differ significantly between Groups A and B. Conclusions An exocrine pancreatic insufficiency demonstrated by fecal PE-1 determination is more frequent in type 2 DM patients with poor glycemic control. The impaired exocrine pancreatic function cannot be explained by an alteration in the size of the pancreas or by pancreatic steatosis.Pancreatology 09/2014; 14(5). DOI:10.1016/j.pan.2014.07.004 · 2.50 Impact Factor
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ABSTRACT: Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.PLoS ONE 08/2014; 9(8):e101285. DOI:10.1371/journal.pone.0101285 · 3.53 Impact Factor
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ABSTRACT: In past decades, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease developed into a global public health disease with an endemic scale. Although up to now the pathogenesis of T2DM is still poorly understood, ectopic lipid accumulation is one of the strongest predictors for T2DM and is closely associated with insulin resistance.This review aims (i) to overview recent literature on the impact of intracellular lipid deposition, (ii) to point out changes in ectopic fat accumulation during diabetes progression or shortly after initializing individual therapy, and finally (iii) to expose unsolved questions and future perspectives in the role of ectopic lipids for the development of insulin resistance and T2DM.Wiener Medizinische Wochenschrift 07/2014; DOI:10.1007/s10354-014-0292-y