Effects of pitavastatin on serum lipids and high sensitivity C-reactive protein in type 2 diabetic patients.

AIM: Previous studies have been inconsistent results about the effects of statins on serum triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and high sensitivity C-reactive protein (hsCRP) levels. We therefore investigated the effects of pitavastatin on serum lipid profiles and hsCRP levels in patients with type 2 diabetes mellitus. METHODS: The study population was 65 Japanese type 2 diabetic patients who had been administered 2 mg daily of pitavastatin and completed a 6-month follow-up. Serum lipids and hsCRP were measured before and after treatment for 1, 3, and 6 months. RESULTS: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and TG had significantly reduced after 1 month and remained reduced for 6 months, while HDL-C levels had significantly increased after 1 month and remained at the higher level for 6 months. Baseline median levels of hsCRP were 0.49 mg/L and showed a significant reduction to 0.37 mg/L at 6 months' treatment (p<0.001). Six-month changes in hsCRP levels were not associated with those in TC, LDL-C, HDL-C or TG. CONCLUSION: Pitavastatin improved serum lipid profiles and reduced serum hsCRP levels in type 2 diabetic patients with relatively low inflammation. The effect on hsCRP was not related to the effects on serum lipid profiles.

Masked early symptoms of pneumonia in patients with rheumatoid arthritis during tocilizumab treatment: a report of two cases.

Although reports of serious infections in clinical trials for rheumatoid arthritis (RA) with tocilizumab, anti-interleukin6 (IL-6) receptor antibody, have been relatively few, there is still some concern about infections. We report here two cases of patients who developed severe pneumonia during tocilizumab treatment for RA. Both patients initially presented with only minimal clinical symptoms and modest elevations in serum C-reactive protein. Tocilizumab might suppress the early inflammatory symptoms of pneumonia.

Reduced epinephrine reserve in response to insulin-induced hypoglycemia in patients with pituitary adenoma.

OBJECTIVE: Hypoglycemia induces rapid secretion of counterregulatory hormones such as catecholamine, glucagon, cortisol, and GH. Insulin-induced hypoglycemia is used for evaluating GH-IGF-I and ACTH-adrenal axes in patients with pituitary disorders. The aim of this study was to determine whether the response of catecholamine secretion to hypoglycemia is disrupted in patients with pituitary adenoma. METHODS: The study population comprised 23 patients with pituitary adenoma (non-functioning adenoma or prolactinoma). An insulin tolerance test was performed and serum catecholamines as well as plasma GH and serum cortisol were measured. RESULTS: The study patients showed diminished response of plasma epinephrine to insulin-induced hypoglycemia. With the cutoff level of peak epinephrine for defining severe impairment set at 400 pg/ml, more patients with secondary adrenal insufficiency showed severe impairment of the epinephrine response than did those without it. Peak epinephrine levels to insulin-induced hypoglycemia were significantly correlated with peak cortisol levels. In patients with secondary hypothyroidism, secondary hypogonadism, GH deficiency, or diabetes insipidus, the prevalence of severe impairment of the epinephrine response was similar to that in patients without these deficiencies. CONCLUSIONS: Impaired epinephrine secretion in response to insulin-induced hypoglycemia was frequently observed in patients with pituitary adenoma. This disorder was especially severe in patients with secondary adrenal insufficiency.

Independent association between insulin-like growth factor-I and dehydroepiandrosterone sulphate in women in middle adulthood.

OBJECTIVE: The age-related decrease in circulating dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth factor (IGF)-I levels is suggested to be involved in various age-related changes. As both hormones are regulated differently, by ACTH and GH, respectively, reasons for the almost parallel changes of their circulating levels during ageing remain unknown. The objectives of this study were to verify variables that influence serum IGF-I as well as DHEAS levels in subjects in middle adulthood. SUBJECTS AND METHODS: We determined serum DHEAS and IGF-I levels in 362 Japanese subjects aged 30-65 years (225 men and 137 women) undergoing health examinations, who had no hepatic disease, renal disease, malignant disease, diabetes mellitus, or asthma. Variables influencing DHEAS and IGF-I were analysed. RESULTS: DHEAS as well as IGF-I levels were higher in men than in women. DHEAS was positively associated with IGF-I and negatively with age, in both men and women. By multivariate regression analysis, age was negatively associated with DHEAS in both men and women. IGF-I was found to be independently associated with DHEAS in women. Age was the only negative independent factor for IGF-I in both men and women, while DHEAS was the only positive independent factor in women. CONCLUSIONS: The present study demonstrates that DHEAS and IGF-I levels are associated with each other, independent of age, in women in middle adulthood.

Menopause, but not age, is an independent risk factor for fasting plasma glucose levels in nondiabetic women.

OBJECTIVE: Glucose metabolism is influenced by various genetic and environmental factors. In women the prevalence of abnormal glucose metabolism is known to increase around and after age 50. The aim of this study was to determine whether menopause augments fasting plasma glucose (FPG) levels in women. DESIGN: Of 672 Japanese women who underwent health examinations, we studied 505 nondiabetic participants who had no history of hysterectomy and had never used estrogens or progestins. All participants were administered an oral glucose tolerance test, and their blood measurements and information about their menopause status were obtained. RESULTS: Of these 505 women, 208 were premenopausal and 297 were postmenopausal. Age, body mass index, triglycerides level, total cholesterol level, low-density lipoprotein cholesterol level, blood pressure, and homeostasis model assessment insulin sensitivity index rose across quintiles of FPG levels, whereas high-density lipoprotein cholesterol level and homeostasis model assessment pancreatic beta-cell function index did not. The number of premenopausal women declined and the number of postmenopausal women increased across quintiles of FPG levels. Univariate regression analysis demonstrated that age, body mass index, triglycerides level, low-density lipoprotein cholesterol level, and menopause status were associated with FPG level, whereas high-density lipoprotein cholesterol level was not. Stepwise multivariate regression analysis showed that the independent risk factors for elevated FPG levels were body mass index, menopause, and triglycerides level, whereas age and low-density lipoprotein cholesterol level did not contribute to FPG levels. CONCLUSIONS: Menopause, but not age, is directly involved in augmented FPG levels in nondiabetic women.

Reduction of a pancreatic tumor after total removal of an ACTH secreting pituitary tumor: differential diagnosis of Cushing's syndrome.

Endocrinologic tests sometimes fail to distinguish adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma from ectopic ACTH-secreting tumor. The authors experienced a case of Cushing's disease associated with a pancreatic tumor. Venous sampling contributed to the final diagnosis of Cushing's disease in this complex case, while endocrinologic tests showed paradoxical results. A 54-year-old woman presented with Cushing's syndrome and pancreatic tumor. Magnetic resonance imaging (MRI) failed to reveal a pituitary tumor, but a gadolinium-enhanced tumor with cystic components was seen in the pancreatic tail. Results of conventional endocrinologic tests suggested ectopic ACTH syndrome, but venous sampling including cavernous sinus sampling indicated an ACTH-secreting pituitary adenoma. Transsphenoidal surgery revealed a pituitary microadenoma, and total removal of the tumor was achieved. Postoperative abdominal MRI revealed that the pancreatic tumor diminished gradually without treatment. Selective cavernous sinus sampling was useful for distinguishing ACTH-secreting pituitary adenoma from ectopic ACTH syndrome in this complex case. This was a rare case in which the pancreatic tumor diminished after total removal of the ACTH-secreting pituitary adenoma.

Regeneration of tubular complex is promoted by a free space.

OBJECTIVES: Regeneration of the pancreas is initiated by the tubular complexes that consist of a cluster of epithelia surrounded by the mesenchymal cells. They have the potential to become pancreatic lobes, but their growth stops before the complete regeneration of the organ. To elucidate the possibility that we could promote the regeneration of the pancreas, the potential for growth or differentiation of tubular complex was analyzed. METHODS: The intact lobes were growing around the silk knot after ligation of the pancreas in adult mice. To develop this reaction to a quantitative assay, tubular complexes were induced on the silk strings in the pancreas and were growing into a free space under the silicon cover. The proliferation and differentiation of new lobes with or without the space were analyzed. RESULTS: The number of tubular complexes, which express PDX-1, was increased 5.4 times by the space effect. The proliferating cell nuclear antigen labeling index of acinar cells was 1.7 times stimulated, but that of tubular complex was not changed. The amputated pancreas recovered 49.5% of the resected part under the silicon cover; however, it remained the same weight without the cover. CONCLUSION: The proliferation and differentiation of tubular complex are promoted by a free space.

New analytical method for pancreas and liver regeneration: normalization of streptozotocin-induced hyperglycemia by retrograde injection of insulin producing cells.

We established a new analytical system in which functioning cells were transplanted directly into the pancreas and liver. The retrograde transplantation of beta cell line, Min6 cells, into the streptozotocin-diabetic mice normalized plasma glucose and insulin levels. The injected cells were protected from pancreatic enzymes with enzyme inhibitor. Blood glucose decreased gradually over 10 days and the diabetic mice recovered weight at the same time. Intraperitoneal glucose tolerance test showed that the peak of plasma glucose of the transplanted mice was less than half that of the control. The insulin secretion of the transplanted mice was recovered and stimulated 4.6 times from the basal secretion. Histological analyses showed that the pancreas and liver were characterized by Min6 cell clusters dispersed throughout the organs. Min6 cells were detected near the pancreatic or bile ducts. It is suggested that the injected cells obstructed the peripheral ducts where they settled. The weight of pancreas and liver did not differ significantly in either Min6 transplanted or the control mice. The metabolic effects on the weights of these organs appeared the same in both groups. This is the first report that cells transplanted via ducts into the pancreas and liver performed their biological function. Our transplantation model makes possible the in vivo analysis of the regeneration machinery of the pancreas and liver.

PTHrP-producing tumor: squamous cell carcinoma of the liver accompanied by humoral hypercalcemia of malignancy, increased IL-6 and leukocytosis.

A 77-year-old man was admitted to our hospital showing symptoms of general fatigue and appetite loss. He had leukocytosis, thrombocytosis and hypercalcemia with elevated serum levels of parathyroid hormone related peptide (PTHrP) and interleukin-6 (IL-6). An increase in tumor markers SCC and CYFURA21-1 was observed. The liver contained a huge tumor, which was proved to be PTHrP producing squamous cell carcinoma by immuno-histochemical analysis. Since the tumor did not express IL-6, it was assumed to be induced by PTHrP in osteoblasts. This is the first report of PTHrP producing squamous cell carcinoma of the liver.