Decrease in Pancreatic Perfusion of Patients with Type 2 Diabetes Mellitus Detected by Perfusion Computed Tomography

Objectives: The objectives of the study was to compare pancreatic perfusion by computed tomography in type 2 diabetes and non-diabetic subjects. Material and Methods: In this case–control study, 17 patients with type 2 diabetes and 22 non-diabetic controls were examined with a dynamic 192-slices perfusion computed tomography for estimating pancreatic perfusion parameters. Results: Thirty-nine patients were included (22 with Type 2 diabetes mellitus [T2DM]), with a mean age of 64 years. There were significant differences in some pancreatic perfusion parameters in patients with and without type 2 diabetes. Blood volume (BV) was lower in pancreatic head (with T2DM: 14.0 ± 3.4 vs. without T2DM: 16.1 ± 2.4 mL/100 mL; P = 0.033), pancreatic tail (with: 14.4 ± 3.6 vs. without: 16.8 ± 2.5 mL/100 mL; P = 0.023), and in whole pancreas (with: 14.2 ± 3.2 vs. without: 16.2 ± 2.5 mL/100 mL; P = 0.042). Similar behavior was observed with mean transit time (MTT) in pancreatic head (with: 7.0 ± 1.0 vs. without: 7.9 ± 1.2 s; P = 0.018), pancreatic tail (with: 6.6 ± 1.3 vs. without: 7.7 ± 0.9 s; P = 0.005), and in whole pancreas (with: 6.8 ± 1.0 vs. without: 7.7 ± 0.9 s; P = 0.016). BV in head, tail, and whole pancreas had negative correlations with age (head r: –0.352, P = 0.032; tail r: –0.421, P = 0.031; whole pancreas r: –0.439, P = 0.007), and fasting plasma glucose (head r: –0.360, P = 0.031; tail r: –0.483, P = 0.003; whole pancreas r: –0.447, P = 0.006). In a multivariate linear regression model, HbA1c was independently associated with decrease in BV in whole pancreas (β: –0.884; CI95%: –1.750 to –0.017; P = 0.046). Conclusion: Pancreatic BV and MTT were significantly lower in patients with type 2 diabetes. BV was decreased with older age and poorer glycemic control.

Visceral Fat Accumulation Is Related to Impaired Pancreatic Blood Perfusion and Beta-Cell Dysfunction in Obese Women

<b><i>Aims/Hypothesis:</i></b> Beta-cell failure plays a fundamental role in type 2 diabetes mellitus (T2DM) development. It has been shown that the beta-cells are among the most sensitive to hypoxia. We aimed to analyze whether decrease in pancreatic perfusion relates to 1/decline in beta-cell function and 2/visceral fat accumulation in patients with T2DM. <b><i>Methods:</i></b> Fifteen women with T2DM on metformin therapy alone and fifteen women of comparable age and BMI without prediabetes/diabetes were cross-sectionally examined: clinical and anthropometric examination, fast sampled intravenous glucose tolerance test (FSIVGTT), dynamic contrast-enhanced magnetic resonance imaging to assess pancreatic perfusion (area under the curve of postcontrast saturation, AUC_TSIC), and visceral adiposity (VAT, calculated from transverse sections at the level L2–L5 vertebrae). <b><i>Results:</i></b> Pancreatic blood perfusion (AUC_TSIC) did not differ between groups (<i>p</i> = 0.273), but it negatively correlated with BMI (<i>r</i> = −0.434, <i>p</i> = 0.017), WHR (<i>r</i> = −0.411, <i>p</i> = 0.024), and VAT (<i>r</i> = −0.436, <i>p</i> = 0.016) in both groups. Moreover, AUC_TSIC in the head of the pancreas negatively correlated with the level of fasting glycemia (<i>r</i> = −0.401, <i>p</i> = 0.028) and HOMA-IR (<i>r</i> = −0.376, <i>p</i> = 0.041). <b><i>Discussion/Conclusion:</i></b> We showed that decreased pancreatic perfusion did not relate to beta-cell dysfunction in early stages of T2DM development, but it was related to VAT, insulin resistance, and higher fasting glycemia. Furthermore, lower pancreatic perfusion was related to VAT, insulin resistance, and higher fasting glycemia.

Obesity dysregulates fasting-induced changes in glucagon secretion

Hyperglucagonemia, a hallmark in obesity and insulin resistance promotes hepatic glucose output, exacerbating hyperglycemia and thus predisposing to the development type 2 diabetes. As such, glucagon signaling is a key target for new therapeutics to manage insulin resistance. We evaluated glucagon homeostasis in lean and obese mice and people. In lean mice, fasting for 24 h caused a rise in glucagon. In contrast, a decrease in serum glucagon compared to baseline was observed in diet-induced obese mice between 8 and 24 h of fasting. Fasting decreased serum insulin in both lean and obese mice. Accordingly, the glucagon:insulin ratio was unaffected by fasting in obese mice but increased in lean mice. Re-feeding (2 h) restored hyperglucagonemia in obese mice. Pancreatic perfusion studies confirm that fasting (16 h) decreases pancreatic glucagon secretion in obese mice. Consistent with our findings in the mouse, a mixed meal increased serum glucagon and insulin concentrations in obese humans, both of which decreased with time after a meal. Consequently, fasting and re-feeding less robustly affected glucagon:insulin ratios in obese compared to lean participants. The glucoregulatory disturbance in obesity may be driven by inappropriate regulation of glucagon by fasting and a static glucagon:insulin ratio.