Which is a better treatment for hypertensive patients with diabetes: a combination of losartan and hydrochlorothiazide or a maximum dose of losartan?

BACKGROUND: This 12-month study compared the effects of a combination of losartan 50 mg and hydrochlorothiazide 12.5 mg with a maximum dose of losartan (100 mg) in hypertensive patients with diabetes. METHODS: This was a multicenter randomized open-label study. RESULTS: A similar reduction in systolic/diastolic blood pressure from baseline to month 3 was observed in both groups. There was also a similar decrease in UACR in both groups. A significant decrease in uric acid was observed in the maximum-dose group only. eGFR decreased in the combination group after 1 year. CONCLUSIONS: The combination of losartan and a diuretic may be a useful option in such hypertensive patients with diabetes, provided that metabolic parameters are closely monitored. In patients with hyperuricemia and impaired renal function, a maximum dose of losartan may be more beneficial.

[Diabetes mellitus and atherosclerosis].

In type 2 diabetes, macroangiopathy manifests as atherosclerosis like in nondiabetic patients, characterized by formation of plaques that follows in stages but with an accelerated course due to the several risk factors. Atherosclerosis in diabetes begins earlier, is more markedly pronounced and progresses more rapidly. It is still a debated question whether antidiabetic therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with advanced type 2 diabetes. New findings result from ACCORD Study reveal that microvascular and macrovascular effects of intensive glucose lowering have to be considered separately. On the other hand, our NICE Study yielded better cardiovascular outcomes for those patients with intensive glucose-lowering therapy using rapid-acting insulin analogue reducing postprandial glucose levels with less hypoglycemia.

Central pontine and extrapontine myelinolysis associated with type 2 diabetic patient with hypokalemia.

Central pontine myelinolysis (CPM) is a demyelinating disease of the pons often associated with the demyelination of extrapontine areas of the central nervous system. Although the etiology and pathogenesis are unclear, CPM is usually associated with hyponatremia or its rapid correction, and chronic alcoholism is also a common underlying condition. We observed a 43-year-old man with diabetes mellitus who developed central pontine and extrapontine myelinolysis with no apparent evidence of hyponatremia, serum hyperosmolality or associated rapid correction, or history of alcohol abuse. On admission, the patient was lethargic with dysarthria, dysphagia, and mild tetraparesis and his face and lower extremities were severely edematous. Laboratory examination showed normoglycemia and normonatremia, although hypokalemia, elevated HbA1c, and nephrotic syndrome were also present. Magnetic resonance imaging (MRI) revealed abnormal signal intensity in the pons, the deep layers of the cerebral cortex, and the adjacent white matter consistent with central pontine and extrapontine myelinolysis. Generalized edema was reduced by the use of diuretics and extracorporeal ultrafiltration without significant changes of serum sodium or osmolality. His consciousness level and paresis gradually improved within a few weeks. Our patient is a rare case of CPM associated with diabetes without apparent evidence of sodium or glucose imbalances.

Ghrelin expression in islet cell tumors: augmented expression of ghrelin in a case of glucagonoma with multiple endocrine neoplasm type I.

Ghrelin is a 28-amino acid peptide that regulates GH release together with GHRH and somatostatin. The expression of ghrelin has been detected in the stomach, small intestine, hypothalamus, pituitary gland, kidney, placenta, and testis. Recently it was reported that ghrelin is present in pancreatic alpha-cells and that it stimulates insulin secretion. In this study, we examined the ghrelin expression in two cases of glucagonoma and two cases of insulinoma by Northern blot analysis and immunohistochemistry. Ghrelin expression was identified in a case of glucagonoma associated with multiple endocrine neoplasm type I both by Northern blot analysis using total RNA and by immunohistochemistry, although the plasma ghrelin level was not elevated. This is the first case of tumor in which ghrelin gene expression was detected by Northern blot analysis using total RNA.

Clinical usefulness of macrophage colony-stimulating factor for ovarian cancers: Long-term prognosis after five years.

We performed a randomized double blind study between 1992 and 1995 in which 214 patients with FIGO stage I to III ovarian cancers received administration of 10(6) units (low dose group) or 8x10(6) units (high dose group) of macrophage colony-stimulating factor (M-CSF) after cyclophosphamide/adriamycin/cisplatin (CAP) therapy. The period required to finish a set of intensive chemotherapy, which was the primary endpoint, was significantly shortened (p=0.0004), and the incidence of febrile neutropenia significantly decreased (p=0.04). In this study, we followed the patients for a prolonged period. The patients were divided into two groups: patients with complete tumor excision and those with incomplete excision, then the relapse rate and survival rate 5 years after initiation of the clinical study were compared. The relapse rate tended to be lower in the high dose group than in the low dose group in patients with no residual tumor (p=0.0750). However, there was no difference in the relapse rate between the two dose groups in patients with residual tumor. Although there were no significant differences in the survival rate between the high and low dose groups in patients with or without residual tumor, the survival rate in mucinous adenocarcinoma patients with no residual tumor was 64.3% in the low dose group (n=14) and 92.3% in the high dose group (n=14), showing a significantly higher rate (p=0.0436), and the survival rate tended to be higher in the high dose group in patients with serous adenocarcinoma (p=0.0786). Furthermore, in patients aged 40 years or younger with no residual tumor, the survival rates were 73.9 and 100% in the low and high dose groups, respectively, showing a significantly higher rate in the high dose group (p=0.0310). Our results suggest that administration of M-CSF can improve the long-term prognosis of ovarian cancer patients with no residual tumor, but further prospective randomized trials with a primary endpoint of relapse-preventing effect are needed.