Efficacy and Patient Satisfaction of the Weekly DPP-4 Inhibitors Trelagliptin and Omarigliptin in 80 Japanese Patients with Type 2 Diabetes.

Objective We investigated the efficacy, safety, and patient satisfaction of once-weekly DPP-4 inhibitors (DPP-4Is). Methods Either of two once-weekly DPP-4Is, trelagliptin or omarigliptin, was administered alone or in combination with other antidiabetic drugs in 80 outpatients with type 2 diabetes mellitus for 3 months. The HbA1c, glycoalbumin (GA), body weight, and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores were evaluated. Results Patients switching from other daily DPP-4Is (n=29) showed no significant changes in the HbA1c or GA levels. However, the HbA1c and GA levels of patients who had been naïve to DPP-4Is (n=37) significantly improved from 9.31±2.53% to 7.02±1.20% (p<0.001) and 26.7±11.8% to 17.3±5.7% (p<0.001), respectively. Several non-serious adverse events were reported, including nausea (n=1), abdominal distension (n=1), and constipation (n=1). In the DTSQs, the total score for six questions on the primary factors representing patient treatment satisfaction was not markedly changed in patients switching from daily to weekly DPP-4Is but was significantly improved from 21.0 to 28.0 (p<0.001) in patients naïve to DPP-4Is. Conclusion These findings suggest that the use of a once-weekly DPP-4I is effective and well-tolerated in diabetes treatment and improves treatment satisfaction.

[A case of hypoglycemic coma with good outcome despite sustained unconsciousness and widespread leukoencephalopathy].

We described a 28-year-old woman with insulinoma-induced hypoglycemic coma. Her initial diffusion-weighted MRI revealed diffuse hyperintense lesions involving bilateral hemispheric white matter. She did not respond to the initial treatment with glucose. However, after surgical removal of insulinoma, she began to recover gradually, and 1 year later, returned to her previous work. In general, the outcome of hypoglycemic coma with widespread leukoencephalopathy on MRI is thought to be poor. However, we should be aware that some of such cases could recover in the long term.

Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants.

CONTEXT: Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. Although cryptic inversions leading to abnormal fusions between CYP19A1 encoding aromatase and its neighboring genes have been identified in a few patients, the molecular basis remains largely unknown. OBJECTIVE: The objective of the study was to examine the genetic causes and phenotypic determinants in AEXS. PATIENTS: Eighteen affected males from six families participated in the study. RESULTS: We identified three types of heterozygous genomic rearrangements, i.e. a 79,156-bp tandem duplication involving seven of 11 noncoding CYP19A1 exons 1, a 211,631-bp deletion involving exons 2-43 of DMXL2 and exons 5-10 of GLDN, and a 165,901-bp deletion involving exons 2-43 of DMXL2. The duplicated exon 1 functioned as transcription start sites, and the two types of deletions produced the same chimeric mRNA consisting of DMXL2 exon 1 and CYP19A1 coding exons. The DMXL2 exon 1 harbored a translation start codon, and the DMXL2/CYP19A1 chimeric mRNA was identified in only 2-5% of CYP19A1-positive transcripts. This was in contrast to the inversion-mediated chimeric mRNA that had no coding sequence on the fused exon 1 and accounted for greater than 80% of CYP19A1-positive transcripts. CYP19A1 was expressed in a limited number of tissues, whereas its neighboring genes involved in the chimeric mRNA formation were expressed widely. CONCLUSIONS: This study provides novel mechanisms leading to gain of function of CYP19A1. Furthermore, it appears that clinical severity of AEXS is primarily determined by the tissue expression pattern of relevant genes and by the structural property of promoter-associated exons of chimeric mRNA.

Diabetes mellitus after transplant: relationship to pretransplant glucose metabolism and tacrolimus or cyclosporine A-based therapy.

OBJECTIVE: The purpose of this study was to identify pretransplantation and posttransplantation indicators for the development of diabetes mellitus in the first 2 months after renal transplantation and to examine the influence of a cyclosporine A (CsA)-based versus a tacrolimus-based immunosuppressive regimen on these risk factors. METHODS: Key variables associated with the development of posttransplant diabetes mellitus (PTDM) in the first 2 months after transplantation were assessed in 48 patients who underwent living-related renal transplantation and who were treated with a CsA-based or a tacrolimus-based immunosuppressive regimen. The insulinogenic index (I Index) and glucose infusion rate (GIR) were measures of insulin secretion and insulin sensitivity, respectively. RESULTS: Eight patients developed PTDM. I Index (odds ratio, 0.000384) and GIR (odds ratio, 0.349) were significant risk factors for PTDM development. The cumulative steroid dose had a borderline association. PTDM developed in 4 of 28 CsA-treated patients and in 4 of 20 tacrolimus-treated patients. CsA therapy increased the mean I Index from 0.713+/-0.071 preoperatively to 1.130+/-0.140 postoperatively (P<0.01), whereas in tacrolimus-treated patients, I Index remained unchanged (1.09+/-0.264 preoperatively and 0.949+/-0.296 postoperatively; P=not significant). Age, duration of pretransplant dialysis, and body mass index did not predict PTDM development. All eight patients with PTDM had hypertension. CONCLUSIONS: Pre- and posttransplant abnormalities of insulin secretion and sensitivity are significant predictors of PTDM. Corticosteroid cumulative dose may affect the incidence of PTDM during the first 2 months after transplantation. CsA treatment increases insulin secretion in patients with a high pretransplant risk of PTDM.

Adrenal pseudocyst mimicking a pheochromocytoma found after a traffic accident.

We report a case of adrenal pseudocyst difficult to differentiate from pheochromocytoma. A right adrenal mass was found in a 41-year-old man after a traffic accident. Plasma level of renin was low, plasma level of aldosterone, and urine levels of aldosterone and catecholamines were high. Dynamic tests for primary aldosteronism and pheochromocytoma were negative. No abnormal uptake was shown in 131I-adosterol or 131I-MIBG scintigram. Adrenal venous sampling presented high levels of catecholamines. Laparoscopic adrenalectomy was performed. Histological examination revealed a pseudocyst with a thick fibrocollagenous wall. We discuss the mechanism of high catecholamine levels in the right adrenal vein.