The effect of alogliptin and pioglitazone combination therapy on various aspects of ß-cell function in patients with recent-onset type 2 diabetes.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) management requires continuous treatment intensification due to progressive decline in ß-cell function in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), vs ALO monotherapy or placebo (PBO), on ß-cell function and glycemic control in T2DM. MATERIAL AND METHODS: A 16-week, two-center, randomized, double-blind, PBO-controlled, parallel-arm intervention study in 71 patients with well-controlled T2DM (age 59.1±6.3 years; A1C 6.7±0.1%) treated with metformin, sulfonylurea, or glinide monotherapy was conducted. Patients were treated with combined ALO 25 mg and PIO 30 mg daily or ALO 25 mg daily monotherapy or PBO. Main outcome measures included change in A1C and fasting plasma glucose (FPG) from baseline to week 16. In addition, change in ß-cell function parameters obtained from standardized meal tests at baseline and at week 16 was measured. RESULTS: ALO/PIO and ALO decreased A1C from baseline by 0.9±0.1 and 0.4±0.2% respectively (both P<0.001 vs PBO). FPG was decreased to a greater extent by ALO/PIO compared with ALO monotherapy (P<0.01). ALO/PIO treatment improved ß-cell glucose sensitivity (vs PBO; P<0.001) and fasting secretory tone (vs PBO; P=0.001), while ALO monotherapy did not change ß-cell function parameters. All treatments were well tolerated. CONCLUSION: Short-term treatment with ALO/PIO or ALO improved glycemic control in well-controlled T2DM patients, but only combined ALO/PIO improved ß-cell function. These data support that initial combination therapy with a DPP4 inhibitor and TZD to address multiple core defects in T2DM may be a sensible approach.

Ruptured Rathke cleft cyst mimicking pituitary apoplexy.

Rathke cleft cysts (RCCs) are benign cystic lesions of the sellar and suprasellar region that are asymptomatic in most cases. Occasionally, compression of the optic pathway and hypothalamo-pituitary structures may cause clinical symptoms, such as headaches, visual deficits and endocrinopathies. Acute presentation caused by hemorrhage into an RCC have been described in the literature, and the term "Rathke cleft cyst apoplexy" has been coined. We present the case of a 32-year-old man with acute onset of meningitis-type symptoms and imaging findings resembling hemorrhagic pituitary tumor apoplexy. In retrospect, clinical symptoms, intraoperative appearance, and histologic examination were compatible with the diagnosis of nonhemorrhagic rupture of an RCC. Thus, the clinical presentation of "Rathke cleft cyst apoplexy" is not necessarily caused by hemorrhage.

Pituitary apoplexy: re-evaluation of risk factors for bleeding into pituitary adenomas and impact on outcome.

OBJECTIVE: To assess frequency, symptoms and outcome of pituitary apoplexy (PA) among pituitary adenoma patients, to gain better insight into risk factors for bleeding into pituitary adenoma and to estimate the sequelae of PA by means of a matched control group. METHOD: By reviewing charts of 574 patients with pituitary adenoma, we analysed incidence, symptoms and outcome of PA and potential risk factors for developing PA by means of a control group (patients with pituitary adenoma without PA). RESULTS: In total, 42 suffered from PA, all had macroadenomas; 30/217 male (14%) and 12/179 female (7%) macroadenoma patients, 32/194 patients with clinically non-functioning (16.5%) and 10/202 with clinically active (5.0%) macroadenoma were affected. Antithrombotic therapy predisposed patients to PA (P=0.026), diabetes mellitus and hypertension did not (P=1.00). Patients with PA and pituitary adenoma patients without PA had similar frequencies of hypopituitarism (45 vs 48%, P>0.05) and visual field defects (38 vs 55%, P>0.05), but ophthalmoplegia was significantly more common (76 vs 5%, P<0.001) in patients with PA. Nearly all patients were treated by surgery; most recovered from ophthalmoplegia, whereas visual function improved only moderately. Endocrine outcome was worse in patients with PA than in patients without PA. CONCLUSIONS: Male sex and characteristics of the adenoma itself (especially tumour size and tumour type) rather than patient's cardiovascular risk factors such as diabetes and hypertension seem to predispose to PA; antithrombotic therapy may also be important.