Taro Harada

Association of serum apolipoprotein B48 level with the presence of carotid plaque in type 2 diabetes mellitus

AIMS The atherogenicity of chylomicron remnants has been discussed. We examined whether serum apoB48 level is associated with the presence of carotid plaque in type 2 diabetic patients. METHOD Forty type 2 diabetic patients (21 males and 19 females, 52.8+/-11.8 years old; mean+/-S.D.) were divided into two groups by the presence or absence of carotid plaque. The diurnal change of serum apoB48 level was measured by enzyme-linked immunosorbent assay. RESULTS Fasting serum apoB48 level was higher in the subjects with carotid plaque than those without (6.5+/-3.8vs. 4.1+/-1.9 microg/ml, p=0.01). Age- and gender-adjusted analysis showed that the presence of carotid plaque was associated with fasting apoB48 (OR 1.43; 95% CI, 1.07-2.09, p=0.04) and triglyceride (OR 1.14; 95% CI, 1.02-1.32, p=0.04) levels. In normal LDL-cholesterol (<140 mg/dl) subjects, the presence of carotid plaque was associated with fasting apoB48 level (OR 2.16; 95% CI, 1.22-5.32, p=0.04), but not associated with fasting triglyceride level (OR 1.11; 95% CI, 0.99-1.30, p=0.13). CONCLUSIONS Serum apoB48 level was strongly associated with the presence of carotid plaque in type 2 diabetic patients.

Comparison of three α‐glucosidase inhibitors for glycemic control and bodyweight reduction in Japanese patients with obese type 2 diabetes

α‐Glucosidase inhibitors (αGIs) are widely used for the primary treatment of type 2 diabetes. We compared the clinical effects of three αGIs (miglitol, acarbose and voglibose) in patients with obese type 2 diabetes.

Selective breeding of mice for different susceptibilities to high fat diet-induced glucose intolerance : Development of two novel mouse lines, Selectively bred Diet-induced Glucose intolerance-Prone and -Resistant

Aims/Introduction:  The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet‐induced diabetes, we performed selective breeding for differences in high fat diet (HFD)‐induced glucose intolerance.

Comparison of pituitary-adrenal responsiveness between insulin tolerance test and growth hormone-releasing peptide-2 test: a pilot study.

Insulin tolerance test (ITT) is the gold standard for assessing the hypothalamic-pituitary-adrenal (HPA) function. GH-releasing peptide (GHRP)-2, which has a strong GH-stimulating activity, is useful for diagnosing GH deficiency as well as ITT. Additionally, GHRP-2 is also known to activate HPA axis. There have been no comparative studies of pituitary-adrenal responsiveness between GHRP-2 test and ITT in patients with hypothalamic/pituitary disease. To assess whether GHRP-2 test could be an alternative to ITT for diagnosing HPA axis failure, both ITT and GHRP-2 test were performed in 15 patients suspected of hypopituitarism. A 100mug dose of GHRP-2 was administered intravenously and plasma ACTH and serum cortisol concentrations were measured. In ITT, a peak cortisol value over 18mug/dl is considered normal. Nine patients were diagnosed as HPA axis failure by ITT. Their median peak cortisol in GHRP-2 test was 11.4mug/ml. In 6 patients diagnosed as normal HPA axis status by ITT, their median peak cortisol in response to GHRP-2 test was 21.4mug/dl, significantly higher (p=0.0032) than seen in patients diagnosed as HPA axis failure. There was a strong correlation between the peak cortisol in GHRP-2 test and ITT (r=0.817; p<0.0001). When the cut-off value for the peak cortisol in GHRP-2 test was set to 13-14mug/dl for diagnosing HPA axis failure, the specificity and sensitivity were 100% and 88.9%, respectively. Although further studies that include normal subjects are needed, these preliminary results suggest the possibility that GHRP-2 test may be an alternative to ITT for assessing HPA axis function.

Association of glycated albumin with the presence of carotid plaque in patients with type 2 diabetes.

Postprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes.

Frequency of Achilles Tendon Xanthoma in Patients with Acute Coronary Syndrome

Aim: We studied the frequency of Achilles tendon xanthoma (ATX) in patients with acute coronary syndrome (ACS). Furthermore, we investigated the differences in clinical findings between ACS patients with and without ATX. Methods: Patients with ACS (n = 335) were admitted to the coronary care unit of Nippon Medical School between July 2011 and December 2014. Informed consent for the measurement of Achilles tendon thickness (ATT) on a radiograph was obtained from 228 patients without tendon rupture. ATT of each side was measured on the radiograph in patients with ACS and in those with acromegaly (n = 18), non-familial hypercholesterolemia (non-FH; n = 96), and familial hypercholesterolemia (FH; n = 31). Results: ATT of the right and left side in ACS patients were 6.9 ± 1.3 and 7.0 ± 1.6 (mm; mean ± SD). In acromegaly, non-FH, and FH patients, ATT of the right/left side were 6.6 ± 1.1/6.7 ± 1.1, 6.2 ± 0.9/6.6 ± 1.0, and 9.4 ± 3.3/10.0 ± 3.1, respectively. ATX (ATT ≥ 9 mm) was found in 26 (11.4%) patients with ACS. Patients with acromegaly and non-FH had no ATX, whereas all patients with FH had ATX. No differences in age and serum lipid profiles were observed between ACS patients with and without ATX. The levels of body mass index and glycated hemoglobin of ACS patients with ATX were significantly greater than those in ACS patients without ATX (26.8 ± 4.0 vs. 23.9 ± 3.3, p < 0.05, and 6.9 ± 1.4% 6.3 ± 1.3%, p < 0.05, respectively). Conclusion: This is the first report in which the frequency of ACS patients with ATX was 11.4%. The serum lipid profiles of ACS patients with ATX were similar to those without ATX. In the future, ACS patients with ATX will be diagnosed as having FH.

ACTH stimulation test and computed tomography are useful for differentiating the subtype of primary aldosteronism

The diagnostic steps for primary aldosteronism (PA) include case screening tests, confirmatory tests, and localization. The aim of this study was to identify useful confirmatory tests and their cut-off values for differentiating the subtype of primary aldosteronism, especially in unilateral PA, such as aldosterone-producing adenoma, and bilateral PA, such as idiopathic hyperaldosteronism. Seventy-six patients who underwent all four confirmatory tests, the captopril-challenge test (CCT), furosemide upright test (FUT), saline infusion test (SIT), and ACTH stimulation test (AST), and who were confirmed to have an aldosterone excess by adrenal venous sampling (AVS) were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n=17) or bilateral aldosterone excess (n=59) by AVS. The SIT-positive rate was significantly higher in the unilateral group (94.1%) than in the bilateral group (57.6%). Multivariable logistic regression analysis showed that tumor on computed tomography (CT) and plasma aldosterone concentration (PAC)max/cortisol on the AST were useful for differentiating the subtype of PA. Receiver operating characteristic (ROC) curve analysis for distinguishing the subtype of PA showed that a cut-off value of 18.3 PACmax/cortisol on the AST had a sensitivity of 83% and a specificity of 88%. The area under the ROC curve was 0.918 (95% confidence interval 0.7916-0.9708). These data suggest that abdominal CT and AST are useful for differentiating the subtype of PA and the indication for AVS.

Levels of glucose-regulatory hormones in patients with non-islet cell tumor hypoglycemia: including a review of the literature

Non-islet cell tumor hypoglycemia (NICTH) is one of the causes of spontaneous hypoglycemia. The pathogenesis of NICTH is thought to be an excessive production by tumors of big insulin-like growth factor (IGF)-II. This study investigated the levels of glucose-regulatory hormones in patients with NICTH with high serum levels of big IGF-II (big IGF-II group) and compared these with profiles of patients with spontaneous hypoglycemia with normal IGF-II (normal IGF-II group). Circulating IRI, CPR, ACTH, cortisol, GH, and IGF-I levels measured during hypoglycemic episodes were examined retrospectively in 37 patients with big IGF-II producing NICTH and 6 hypoglycemic patients with normal IGF-II. The hormone profile data of 15 patients with NICTH from published case reports were reviewed and included in the analyses. Mean plasma glucose levels (36 vs. 29 mg/dL), serum IRI (0.53 vs. 0.37 μIU/mL), CPR (0.15 vs. 0.20 ng/mL), IGF-I SDS (-3.55 vs. -3.18 SD) and ACTH levels (27.3 vs. 33.8 pg/mL) were not significantly different between the big and normal IGF-II groups. However, mean serum GH (0.85 vs. 9.62 ng/mL) and plasma cortisol levels (16.2 vs. 34.5 μg/dL) were significantly lower in the big IGF-II group than in the normal IGF-II group (both p<0.05). In conclusion, although the magnitude of the decrease in insulin and IGF-I levels did not differ between spontaneous hypoglycemic patients caused by other etiologies, patients with NICTH tended to have low basal GH levels during hypoglycemic episodes. These differences in hormone profile may be helpful for selecting patients who require analysis of IGF-II.