Aki Ikoma

Circulating betatrophin is elevated in patients with type 1 and type 2 diabetes.

There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.

Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes

BackgroundOsteoprotegerin is a member of the tumor necrosis factor-related family and inhibits RANK stimulation of osteoclast formation as a soluble decoy receptor. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes.MethodsThe subjects were 124 patients with type 2 diabetes mellitus, including 88 males and 36 females with a mean (± SD) age of 65.6 ± 8.2 years old. Serum levels of osteoprotegerin, osteocalcin, fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D3 and adiponectin were measured by ELISA. Vascular calcification in the cervical artery was examined by ultrasound sonography. The subjects were divided into 4 quartiles depending on serum osteoprotegerin levels.ResultsVascular calcification was significantly higher in the 4th quartile and significantly lower in the 1st quartile of serum osteoprotegerin levels, compared to other quartiles. There were no differences in serum osteoprotegerin and vascular calcification among patients with different stages of diabetic nephropathy, but serum FGF23 levels were elevated in those with stage 4 diabetic nephropathy. Simple regression analysis showed that serum osteoprotegerin levels had significant positive correlations with age, systolic blood pressure and serum adiponectin levels, and significant negative correlations with BMI and serum 25-hydroxyvitamin D3.ConclusionsThese findings suggest that elevated serum osteoprotegerin may be involved in vascular calcification independently of progression of diabetic nephropathy in patients with type 2 diabetes.

Hypoadiponectinemia in patients with cerebral infarction: comparison with other atherosclerotic disorders.

The present study was undertaken to determine serum adiponectin level in patients with cerebral infarction and to further analyze any difference in serum adiponectin levels among atherosclerotic disorders. One hundred fifty-two subjects with atherosclerotic disorders were enrolled, 110 males and 42 females, with the age of 67.0 ± 9.9 years (mean ± SD). They were divided into 62 patients with cerebral infarction, 48 patients with ischemic heart disease, and 42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age, gender, and body mass index served as controls. Serum adiponectin levels were 7.2 ± 0.6 &mgr;g/mL (mean ± SE) in the patients with cerebral infarction, 7.2 ± 0.8 &mgr;g/mL in those with ischemic heart disease, and 6.9 ± 0.9 &mgr;g/mL in those with arteriosclerosis obliterans. They were significantly less than the level of 12.6 ± 1.9 &mgr;g/mL in the control group (P < 0.01). However, there was no difference in serum adiponectin level among three groups of atherosclerotic disorders. In the patients with acute cerebral infarction, serum adiponectin level was temporarily reduced from 7.3 ± 0.9 to 6.2 ± 0.8 &mgr;g/mL 14 days after the hospitalization (P < 0.01), followed by recovery to the basal value. The present findings indicate that serum adiponectin levels are equivalently reduced in patients with atherosclerotic disorders, and that serum adiponectin is changeable under acute phase of cerebral infarction.

Clinical and laboratory features of hyponatremia-induced myopathy

BackgroundThe present study was undertaken to determine the clinical and laboratory features of hyponatremia-induced myopathy.MethodsWe collected 14 hyponatremic subjects (six men and eight women) with serum creatine kinase (CK) levels of more than 500 IU/ml during the 5-year period between 2001 and 2005. The mean ± SD patients’ age was 66.5 ± 16.7 years (range, 37 to 88 years).ResultsThe causes of the hyponatremia were: syndrome of inappropriate secretion of antidiuretic hormone (SIADH; n = 4), mineralocorticoid-responsive hyponatremia of the elderly (MRHE; n = 2), hypopituitarism (n = 1), psychogenic polydipsia (n = 3), congestive heart failure (n = 3), and unknown cause (n = 1). The subjects were subgrouped into two groups: acute onset of myopathy and slowly progressive onset. The age at onset was 62.0 ± 5.7 years (mean ± SEM) in the subjects with acute onset, and 77.8 ± 1.5 years in those with slowly progressive onset (P = 0.02). At the onset, there was no difference in serum Na levels between the acute onset and the slowly progressive onset groups, but there was a significant difference in maximal serum CK levels between the groups (7072 ± 2317 vs 722 ± 104 IU/ml; P = 0.02). Maximal serum CK levels were widely distributed among the ages in the subjects with acute onset, whereas maximal serum CK levels were mildly elevated in the elderly subjects with slowly progressive onset. The elevated serum CK levels were normalized at a maximum of 14 days after the onset in all the subjects.ConclusionsThe present findings indicate that hyponatremia infrequently causes skeletal muscle disruption, and that there are two types of hyponatremia-induced myopathy, acute onset and slowly progressive onset.

Combination Therapy of Angiotensin Converting Enzyme Inhibitor and Angiotensin AT1 Receptor Antagonist in Diabetic Nephropathy

Background The present study was undertaken to determine whether combination therapy of angiotensin converting enzyme inhibitor (ACEI) and angiotensin AT1 receptor antagonist (ARA) is a useful tool for reducing albuminuria in diabetic nephropathy. Methods Thirty-four subjects with diabetic nephropathy were enrolled in the present study. All the subjects had hypertension and urinary albumin index (UAI) Results Blood pressure was significantly decreased in Group 1 subjects. Blood pressure was also reduced in Groups 2 and 3, but its reduction was not significant. Imidapril significantly reduced UAI in Group 1, from 213.1 ± 46.6 to 111.6 ± 35.6 ( p p p Conclusion These results indicate that the addition of ARA to consecutive therapy with ACEI augments a protective effect against the progression of diabetic nephropathy.

Hypothalamic Type of Hypopituitarism and Central Diabetes Insipidus Probably Linked to Rathke's Cleft Cyst

A 73-year-old woman was admitted due to weight loss and generalized malaise. The basal levels of all the anterior pituitary hormones, except for prolactin, were reduced. However, they were all elevated in response to exogenous hypothalamic hormones. After starting hydrocortisone replacement, the patient had polyuria of >5,000 mL/day. T1-weighted MRI depicted a low signal of an oval mass in the sella turcica and an iso-intense signal of another mass at the pituitary stalk. These findings indicate a hypothalamic type of hypopituitarism and masked central diabetes insipidus which possibly derived from the atypical occupation of Rathkes cleft cyst at the pituitary stalk.