Pancreatic fat and diabetes

Noninvasive Quantification of Pancreatic Fat in Humans

The Journal of Clinical Endocrinology & Metabolism Vol. 94, No. 10 4070-4076
Ildiko Lingvay, Victoria Esser, Jaime L. Legendre, Angela L. Price, Kristen M. Wertz, Beverley Adams-Huet, Song Zhang, Roger H. Unger and Lidia S. Szczepaniak

Objective: 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.

Methods: 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.

Results: 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 <>

Conclusions: 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.



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Comments:
How is pancreatic fat related to diabetes/IFG and how is it related to fat deposition in other organs? This intriguing study examines both animal models and humans to help understand the pathophysiology of fat deposition and its relationship to diabetes.

The figure above in A. shows glucose readings along with total pancreatic Triglycerides(pTG) as assessed by magnetic resonance spectroscopy. The pancreatic triglyceride measurements were correlated with a biochemical determination of TG for the rats - Fatty and Lean Zucker rats. There is a progressive increase in pTG along with glucose levels in the Fatty Zucker rats, but no change in either levels in the lean rats. Figure B shows the correlation between the MRS technique and biochemical determination.

Humans were divided into 4 groups and were scanned by MRS as well. The results are as in the abstract. Intereting findings included that blood glucose levels 2 hours after a glucose load were most closely correlated with pTG content. HBA1c, serum Tg, # of DM risk factors, age, BMI, fasting glucose, excercise, and dietary fat intake had either no or a weak relationship to pTG content.

Also of interest was the fact that there was little relationship between pancreatic and hepatic TG content (a previous report had shown a low correlation between hepatic and myocardial TG content).

What is not known is to what degree the TG deposition is related to Beta-cell damage/loss if at all? Also can medications, diet, weight loss or more severe caloric restriction reverse the pancreatic TG deposition and if so can this lead to a new B-cell production?

Pioglitazone and changes in body fat distribution.

This topic just came up in one a paper and I thought I might dig up some details about it. We all know that the TZDs tend to change fat distribution but may not have looked into the details of it. Dr. Jensen (my mentor) in 2003 published a paper on this topic in Diabetes Care. Here are the details: (its freely available from Diabetes Care) I've added in details that I thought were interesting and put them in italics.

Shadid S, Jensen MD. Effects of Pioglitazone Versus Diet and Exercise on Metabolic Health and Fat Distribution in Upper Body Obesity. Diabetes Care. 2003;26(11):3148-3152.

METHODS:
Thirty-nine upper body obese (BMI of 28-36 and waist to hip ratio >0.85 for women and >0.95 for men), insulin-resistant, nondiabetic men and premenopausal women were randomly assigned to receive either 30 mg/day pioglitazone or a diet (500kcal/day deficit) and exercise program for 20 weeks. The exercise regimen consisted of 15 mins of aerobic exercise 3x/week and increased gradually to 45 minutes of aerobic exercise 4 times a week. Before and after the intervention, insulin sensitivity, body composition, body fat distribution (waist-to-hip ratio [WHR], computed tomography abdomen, and dual-energy X-ray absorptiometry), and abdominal and femoral fat cell size were assessed.

RESULTS:
Diet and exercise resulted in an 11.8 ± 1.1 kg weight loss. Both diet and exercise and pioglitazone improved insulin sensitivity, but only diet and exercise were associated with loss of intra-abdominal fat. Pioglitazone increased total body fat, which preferentially accumulated in the lower body depot in both men and women. WHRs decreased in both groups although in the pioglitazone group, the waist circumference did not decrease. Abdominal fat cell size decreased (P = 0.06) after diet and exercise. No statistically significant changes in fat cell size were observed in pioglitazone-treated volunteers.
Another interesting change was in terms of the cholesterol. Only the diet/exercise group had a reduction in the total cholesterol while pio group did not.
BP reductions were also more significant for the diet/exercise group than pioglitazone group.

Dr. Jensen did not find a decrease in visceral fat area. In comparison to other publications, no change has been reported in the intra-abdominal adipose tissue area by 4 reports with pio. Three have reported a decrease and most have reported a decrease in the visceral to subcutaneous fat area ratio. Just note that some of the investigators reporting decreases in visceral fat area did combine TZD with diet.
The gain in insulin sensitivity may be due to the decrease in fat cell size and an increase in their numbers instead.