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.

Diurnal changes in arginine vasopressin gene transcription in the rat suprachiasmatic nucleus.

The diurnal changes in arginine vasopressin (AVP) mRNA and heteronuclear (hn) RNA, an indicator for gene transcription, were examined in the hypothalamus of Sprague-Dawley rats using in situ hybridization. AVP hnRNA levels in the suprachiasmatic nucleus (SCN) varied during a 24-h cycle and showed a peak at day-time [Zeitgeber time (ZT) 5], which preceded the peak in AVP mRNA levels by 4 h. AVP hnRNA was undetectable at ZT 13 and 17, indicating that the gene transcription was almost shut down at these time points. AVP mRNA levels in the SCN continued to decrease at night (ZT 13, 17 and 21) when there were minimal changes in transcription, suggesting rapid turnover of mRNA. Similar diurnal changes in AVP hnRNA levels were observed without photic cues. On the other hand, AVP hnRNA or mRNA levels in the supraoptic nucleus, where AVP is synthesized in response to plasma osmolarity and/or volume, did not show any circadian rhythm. These data suggest that both dynamic changes in AVP gene transcription and rapid turnover of mRNA contribute to the diurnal variation in AVP mRNA levels in the SCN.

Role of ghrelin in the regulation of vasopressin release in conscious rats.

GH secretagogue (GHS) is a small, synthetic compound that has the potential to stimulate GH release via its specific receptors (GHS-R). Ghrelin is a novel 28-amino acid peptide recently isolated from human and rat stomach, and it is thought to be the endogenous ligand for GHS-R. Ghrelin has a variety of physiological functions such as the stimulation of GH release or the increase of food intake by activating NPY neurons. In the present study, we investigated the effects of ghrelin on AVP release in conscious rats. Intracerebroventricular (icv) administration of ghrelin increased the plasma AVP concentration in a dose-dependent manner (1-1000 pmol/rat), and its effect was observed as late as 60 min after the administration. Icv injection of ghrelin caused no significant change in plasma osmolality, plasma volume, or arterial blood pressure. Iv administration of ghrelin (10 nmol/rat) also increased the plasma AVP concentration, which was accompanied by a significant decrease in arterial blood pressure. Pretreatment with antiserum against NPY significantly reduced the plasma AVP increase induced by icv administration of ghrelin. These results suggest that ghrelin plays a stimulatory role in AVP release, which is possibly mediated by NPY neurons.