Pancreatic Fat Content and  -Cell Function in Men With and Without Type 2 Diabetes: Response to Tushuizen et al.

Abstract Context Pancreatic steatosis may contribute to β-cell dysfunction in type 2 diabetes (T2D), but data are controversial. Women who had gestational diabetes mellitus (GDM) are at high risk for developing T2D. Objective To examine the association of pancreatic fat content with early/first-phase insulin secretion (as markers of β-cell function). Design Cross-sectional analysis of a subcohort of the monocentric, prospective cohort study titled Prediction, Prevention, and Subclassification of Type 2 Diabetes. Setting Ludwig Maximilians University Hospital, Munich, Germany. Participants Ninety-seven women, 3 to 16 months after pregnancy [41 normoglycemic women post-GDM, 19 women post-GDM with pathological glucose metabolism, and 37 normoglycemic women after a normoglycemic pregnancy (controls)]. Main Outcome Measures Correlation of MRI-measured pancreatic fat content with early insulin release in an oral glucose tolerance test (OGGT) [insulin increment within the first 30 minutes of the OGTT (IR30)] and first-phase insulin response (FPIR) in an intravenous glucose tolerance test (n = 65), both adjusted for insulin sensitivity index (ISI). Results Pancreatic fat content did not correlate with IR30 and FPIR adjusted for ISI. It correlated positively with body mass index, waist circumference, liver fat, and intraabdominal fat volume. Conclusion Pancreatic fat content does not correlate with β-cell function in a cohort of young women with different degrees of T2D risk.

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Computed Tomography-Estimated Pancreatic Steatosis is a Risk Factor for Carotid Plaque in Type 2 Diabetes Mellitus Patients: A Cross-Sectional Study

10.21203/rs.3.rs-127501/v1 ◽

2020 ◽

Author(s):

Pengtao Sun ◽

Chunzhi Fan ◽

Rengui Wang ◽

Tongwei Chu ◽

Xiaoli Sun ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Carotid Plaque ◽

Fat Content ◽

Cross Sectional ◽

Pancreatic Fat ◽

Pancreatic Steatosis ◽

Pancreatic Fat Content

Abstract Background Pancreatic steatosis correlates with the thickness of arterial intima. However, the correlation between pancreatic steatosis and carotid atherosclerosis plaque, which better predict the prognosis of cardiovascular disease, is unclear. We aimed to explore potential effects of pancreatic fat content measured by computer tomography (CT) on carotid plaque in patients with type 2 diabetes mellitus (T2DM).Methods Patients with T2DM who underwent CT scan of the upper abdomen and ultrasound of the carotid artery were consecutively enrolled. Based on ultrasound results, the patients were divided into non-plaque group and plaque group, and the latter was categorized into hypoechoic plaque subgroup and non-hypoechoic plaque subgroup. The CT attenuation of pancreas and spleen were measured. Pancreas-to-spleen attenuation ratio (P/S) and difference between pancreatic and splenic attenuation (P-S) were calculated. The cut-off values of P/S and P-S were obtained using receiver operating characteristic (ROC) curves. Logistic regression models were used to evaluate association of P/S or P-S with carotid plaque or hypoechoic plaque.Results A total of 337 patients with T2DM were enrolled, including 101 cases (30.0%) in the non-plaque group, 146 cases (43.3%) in the hypoechoic plaque subgroup, and 90 cases (26.7%) in the non-hypoechoic plaque subgroup. P/S and P-S in plaque group were lower than those in non-plaque group, with a cut-off value of P/S and P-S as 0.72 and -13.33, respectively. After adjusting for risk factors, P/S and P-S correlated with carotid plaque [for low P/S: OR (95% CI): 3.15 (1.47-6.73), P=0.0031; for low P-S: OR (95% CI): 2.84 (1.42-5.66), P=0.0031] as well as carotid hypoechoic plaque [for low P/S: OR (95% CI): 1.82 (1.07-3.08), P=0.0259; for low P-S: OR (95% CI): 1.82 (1.09-3.02), P=0.021].Conclusions T2DM patients with carotid plaque have higher pancreatic fat content than those without. Pancreatic steatosis correlates with carotid plaque and hypoechoic plaque in T2DM patients.

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Metabolomic Characteristics of Fatty Pancreas

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0896-8671 ◽

2019 ◽

Vol 128 (12) ◽

pp. 804-810 ◽

Cited By ~ 3

Author(s):

Benjamin Assad Jaghutriz ◽

Róbert Wagner ◽

Martin Heni ◽

Rainer Lehmann ◽

Jürgen Machann ◽

...

Keyword(s):

Insulin Secretion ◽

Beta Cell ◽

Visceral Fat ◽

Beta Cell Function ◽

Cell Function ◽

Fat Content ◽

Pancreatic Fat ◽

Total Body ◽

Pancreatic Steatosis ◽

Pancreatic Fat Content

Abstract Objective Pancreatic steatosis is associated with impaired beta cell function in patients with prediabetes. The pathomechanisms underlying this association still remain to be elucidated. Recent data show that adipocytes are situated within the pancreatic parenchyma and therefore give raise to hypothesize that pancreatic fat together with known and unknown metabolites such as hepatokines affect insulin secretion. Applying a targeted metabolomic approach we investigated possible circulating markers of pancreatic fat in order to better understand its role in the pathophysiology of impaired beta cell function. Methods We included 361 Caucasians, at increased risk of type 2 diabetes, from the Tübingen Family Study. All participants underwent a frequently sampled oral glucose tolerance test to assess insulin secretion and a magnetic resonance imaging to quantify pancreatic fat content, total body fat and visceral fat. Among the 152 subjects with prediabetes (IFG and/or IGT), two groups each with 20 individuals, having the lowest and highest pancreatic fat content were selected. The groups were matched for sex, age, BMI, total fat content, visceral fat content, liver fat content and insulin sensitivity. Metabolites were analyzed using the AbsoluteIDQ® p400 HR Kit by Biocrates. Results Pancreatic fat content of all 152 subjects with prediabetes was negatively associated with insulin secretion represented by AUCC-peptide 0–120/AUCGlucose 0–120 (p=0.04; β=− 3.24). Furthermore, pancreatic fat content was positively associated with BMI, total body and visceral fat (all p<0.005). Levels of aminoacids, biogenic amines and monosaccharides were similar between the groups with high/low pancreatic fat content (p>0.90). Also, levels of polar lipids such as lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and ceramides did not differ significantly between the groups (p>0.90). Investigating the levels of neutral lipids such as aclycarnitines, diglycerides, triglycerides and cholesteryl esters also revealed no differences between the groups (p>0.90). Conclusion The amount of pancreatic fat is not associated with the metabolomic pattern in individuals with prediabetes. This might be due to the relatively low pancreatic fat content compared to the total amount of fat stored in other depots. The impact of pancreatic steatosis on insulin secretion might be mediated by paracrine effects which cannot be detected in the circulation.

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Effect of change in pancreas and liver fat content upon beta cell function and hepatic insulin action during weight loss in type 2 diabetes

http://isrctn.org/> ◽

10.1186/isrctn57022672 ◽

2013 ◽

Author(s):

Ee Lin Lim

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Beta Cell ◽

Beta Cell Function ◽

Insulin Action ◽

Cell Function ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content

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Effect of empagliflozin on ectopic fat stores and myocardial energetics in type 2 diabetes: the EMPACEF study

Cardiovascular Diabetology ◽

10.1186/s12933-021-01237-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

B. Gaborit ◽

P. Ancel ◽

A. E. Abdullah ◽

F. Maurice ◽

I. Abdesselam ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fat Content ◽

Liver Fat ◽

Epicardial Fat ◽

Ectopic Fat ◽

Liver Fat Content ◽

Pancreatic Fat ◽

Myocardial Energetics ◽

Fat Stores

Abstract Background Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has demonstrated cardiovascular and renal protection in patients with type 2 diabetes (T2D). We hypothesized that empaglifozin (EMPA) could modulate ectopic fat stores and myocardial energetics in high-fat-high-sucrose (HFHS) diet mice and in type 2 diabetics (T2D). Methods C57BL/6 HFHS mice (n = 24) and T2D subjects (n = 56) were randomly assigned to 12 weeks of treatment with EMPA (30 mg/kg in mice, 10 mg/day in humans) or with placebo. A 4.7 T or 3 T MRI with 1H-MRS evaluation–myocardial fat (primary endpoint) and liver fat content (LFC)–were performed at baseline and at 12 weeks. In humans, standard cardiac MRI was coupled with myocardial energetics (PCr/ATP) measured with 31P-MRS. Subcutaneous (SAT) abdominal, visceral (VAT), epicardial and pancreatic fat were also evaluated. The primary efficacy endpoint was the change in epicardial fat volume between EMPA and placebo from baseline to 12 weeks. Secondary endpoints were the differences in PCr/ATP ratio, myocardial, liver and pancreatic fat content, SAT and VAT between groups at 12 weeks. Results In mice fed HFHS, EMPA significantly improved glucose tolerance and increased blood ketone bodies (KB) and β-hydroxybutyrate levels (p < 0.05) compared to placebo. Mice fed HFHS had increased myocardial and liver fat content compared to standard diet mice. EMPA significantly attenuated liver fat content by 55%, (p < 0.001) but had no effect on myocardial fat. In the human study, all the 56 patients had normal LV function with mean LVEF = 63.4 ± 7.9%. Compared to placebo, T2D patients treated with EMPA significantly lost weight (− 2.6 kg [− 1.2; − 3.7]) and improved their HbA1c by 0.88 ± 0.74%. Hematocrit and EPO levels were significantly increased in the EMPA group compared to placebo (p < 0.0001, p = 0.041). EMPA significantly increased glycosuria and plasma KB levels compared to placebo (p < 0.0001, p = 0.012, respectively), and significantly reduced liver fat content (− 27 ± 23 vs. − 2 ± 24%, p = 0.0005) and visceral fat (− 7.8% [− 15.3; − 5.6] vs. − 0.1% [− 1.1;6.5], p = 0.043), but had no effect on myocardial or epicardial fat. At 12 weeks, no significant change was observed in the myocardial PCr/ATP (p = 0.57 between groups). Conclusions EMPA effectively reduced liver fat in mice and humans without changing epicardial, myocardial fat or myocardial energetics, rebutting the thrifty substrate hypothesis for cardiovascular protection of SGLT2 inhibitors. Trial registration NCT, NCT03118336. Registered 18 April 2017, https://clinicaltrials.gov/ct2/show/NCT03118336

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