The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats.

AIMS: To investigate whether glucose lowering with the selective sodium glucose transporter 2 (SGLT2) inhibitor dapagliflozin would prevent or reduce the decline of pancreatic function and disruption of normal islet morphology. METHODS: Female Zucker diabetic fatty (ZDF) rats, 7-8 weeks old, were placed on high-fat diet. Dapagliflozin (1 mg/kg/day, p.o.) was administered for ∼33 days either from initiation of high-fat diet or when rats were moderately hyperglycaemic. Insulin sensitivity and pancreatic function were evaluated using a hyperglycaemic clamp in anaesthetized animals (n = 5-6); ß-cell function was quantified using the disposition index (DI) to account for insulin resistance compensation. Pancreata from a matched subgroup (n = 7-8) were fixed and ß-cell mass and islet morphology investigated using immunohistochemical methods. RESULTS: Dapagliflozin, administered from initiation of high-fat feeding, reduced the development of hyperglycaemia; after 24 days, blood glucose was 8.6 ± 0.5 vs. 13.3 ± 1.3 mmol/l (p < 0.005 vs. vehicle) and glycated haemoglobin 3.6 ± 0.1 vs. 4.8 ± 0.26% (p < 0.003 vs. vehicle). Dapagliflozin improved insulin sensitivity index: 0.08 ± 0.01 vs. 0.02 ± 0.01 in obese controls (p < 0.03). DI was improved to the level of lean control rats (dapagliflozin 0.29 ± 0.04; obese control 0.15 ± 0.01; lean 0.28 ± 0.01). In dapagliflozin-treated rats, ß-cell mass was less variable and significant improvement in islet morphology was observed compared to vehicle-treated rats, although there was no change in mean ß-cell mass with dapagliflozin. Results were similar when dapagliflozin treatment was initiated when animals were already moderately hyperglycaemic. CONCLUSION: Sustained glucose lowering with dapagliflozin in this model of type 2 diabetes prevented the continued decline in functional adaptation of pancreatic ß-cells.

Prospective study of the incidence of ultrasound-detected intrahepatic and subcapsular hematomas in patients randomized to 6 or 24 hours of bed rest after percutaneous liver biopsy.

Percutaneous liver biopsies were performed in 40 adult patients with acute or chronic liver disease. Real-time sector scan ultrasound of the right upper quadrant was obtained just before biopsy, 1 day after biopsy, and in 10 randomly selected cases 7 days after biopsy. Twenty patients were randomized, by sealed envelope, to 6-h and 20 patients to 24-h postbiopsy bed rest. Nine patients (23%) had ultrasound-detected hematomas 1 day after liver biopsy (7 intrahepatic, 2 subcapsular). Five of these patients had been randomized to 6-h and 4 to 24-h bed rest. Follow-up ultrasound at 7 days in the 10 randomly selected patients failed to reveal any hematomas not seen on day 1 (n = 6) and showed complete or partial resolution of those that had been detected previously (n = 4). Significant drops in systolic and diastolic blood pressure and increases in pulse rate were common postbiopsy findings, and were unrelated to hematoma formation. The results of this study indicate that intrahepatic and subcapsular hematomas are common after percutaneous liver biopsy. The length of postbiopsy bed rest (6 vs. 24 h) does not appear to influence the frequency of this complication.

The WES triad -- a specific sonographic sign of gallstones in the contracted gallbladder.

The "WES" triad -- that is, the demonstration of the gallbladder Wall, the Echo of the stone, and the acoustic Shadow -- permits the specific diagnosis of stones in a contracted gallbladder. This triad positively identifies the gallbladder and helps to differentiate the contracted gallbladder with stones from a loop of bowel containing gas.