OBJECTIVEThis study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy, including metformin.
RESEARCH DESIGN AND METHODSThirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications were randomized to receive insulin glargine or liraglutide therapy for 12 weeks. The liver proton density fat fraction (PDFF) was measured by MRS. The mean liver PDFF, the total liver volume, and the total liver fat index were measured by MRI. The Student t test, the Fisher exact test, and repeated-measures ANOVA were used for statistical analysis.
RESULTSInsulin treatment was associated with a significant improvement in glycated hemoglobin (7.9% to 7.2% [62.5 to 55.2 mmol/mol], P = 0.005), a trend toward a decrease in MRS-PDFF (12.6% to 9.9%, P = 0.06), and a significant decrease in liver mean MRI-PDFF (13.8% to 10.6%, P = 0.005), liver volume (2,010.6 to 1,858.7 mL, P = 0.01), and the total liver fat index (304.4 vs. 209.3 % · mL, P = 0.01). Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin (7.6% to 6.7% [59.8 to 50.2 mmol/mol], P < 0.001) but did not change MRS-PDFF (P = 0.80), liver mean MRI-PDFF (P = 0.15), liver volume (P = 0.30), or the total liver fat index (P = 0.39).
CONCLUSIONSThe administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes. However, the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group.To reduce the risk of long-term microvascular and macrovascular complications, diabetes therapy should aim for tight glucose control as assessed by glycated hemoglobin (HbA 1c ) below 7% (53 mmol/mol) while minimizing hypoglycemia (1,2). However, most patients still do not achieve glycemic targets and thus require
BackgroundPrimary central nervous system lymphomas (PCNSL) are rare and aggressive CNS tumors. Current management involves high-dose methotrexate (HD-MTX) typically administered intravenously (IV), despite the existence of the blood-brain barrier (BBB), which significantly decreases its bioavailability. Cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic BBB disruption (OBBBD) can theoretically circumvent this issue.MethodsWe performed a retrospective analysis of patients with newly diagnosed PCNSL treated with HD-MTX-based CIAC+OBBBD at our center between November 1999 and May 2018. OBBBD was achieved using a 25% mannitol intra-arterial infusion. Patients were followed clinically and radiologically every month until death or remission. Demographics, clinical and outcome data were collected from the medical record. All imaging studies were reviewed for evidence of complication and outcome assessment. Kaplan-Meier analyses were used to compute remission, progression-free survival (PFS) as well as overall survival times. Subgroup analyses were performed using the log rank test.ResultsForty-four patients were included in the cohort. Median follow-up was 38 months. Complete response was achieved in 34 patients (79%) at a median of 7.3 months. Actuarial median survival and PFS were 45 months and 24 months, respectively. Age, ECOG and lesion location did not impact outcome. Complications included thrombocytopenia (39%), neutropenia (20%), anemia (5%), seizures (11%), stroke (2%), and others (20%).ConclusionCIAC using HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of PCNSL. Our data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.
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