Circulating osteocalcin is increased in early-stage diabetes

We aimed to examine whether circulating levels of osteocalcin, bone formation marker secreted from osteoblast, are changed in glucose-intolerant subjects without taking glucose lowering agent, because bone metabolism is reportedly related to glucose metabolism in animal and human studies. According to 75 g oral glucose tolerance test (75 g-OGTT), all subjects (47.6 ± 10.2 years of age; 45 men and 10 women) were divided into three categories: normal glucose tolerance (NGT, n = 39), prediabetes (PDM, n = 11) that included impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and diabetes (T2DM, n = 5). Serum osteocalcin levels were increased in T2DM as compared to NGT. In all the participants, simple regression analysis model revealed positive correlation of osteocalcin with plasma glucose at 120 min, G(120), on 75 g-OGTT, negative with both creatinine and Ln(CRP), but not significantly with fasting plasma glucose. Osteocalcin and leptin were independent variables for G(120) (P = 0.026 and 0.035, respectively). In multinomial logistic analysis leptin (PDM vs. NGT: P = 0.02 Odds ratio (OR) of 1.05, 95% confidence intervals, 1.007-1.084) and osteocalcin (T2DM vs. NGT: P = 0.038, OR 10.8, 1.13-102.4) were independently associated. We conclude that circulating osteocalcin and leptin are related to glucose intolerant state.     

Possible relationship between adiponectin and renal tubular injury in diabetic nephropathy

Adiponectin is an adipose-derived protein which has anti-inflammatory and anti-atherogenic properties in addition to insulin-sensitizing effects. To date, the role of adiponectin in the pathogenesis of diabetic nephropathy remains unclear. The aim of the present study was to explore the relationship between adiponectin and renal tubular injury in diabetic nephropathy. We determined serum and urinary adiponectin levels in type 2 diabetic patients with normoalbuminuria (n = 19), microalbuminuria (n = 18), and overt diabetic nephropathy (n = 16), and then analyzed the correlations between serum and urinary adiponectin, urinary N-acetylglucosaminidase (NAG) as a clinical marker of renal tubular injury, urinary monocyte chemoattractant protein-1 (MCP-1) as an inflammatory marker in renal tubulointerstitium, and clinical markers of renal disease. Notably, serum and urinary adiponectin levels were significantly increased in patients with overt diabetic nephropathy compared to those with normoalbuminuria and microalbuminuria. In univariate linear regression analysis, serum adiponectin levels were positively correlated with serum creatinine (r = 0.648, P<0.0001), urinary albumin (r = 0.583, P<0.0001), urinary NAG (r = 0.406, P<0.01), urinary MCP-1 (r = 0.514, P<0.0001), and urinary adiponectin (r = 0.691, P<0.0001) levels in all diabetic patients. Urinary adiponectin levels were also positively correlated with serum creatinine (r = 0.729, P<0.0001), urinary albumin (r = 0.799, P<0.0001), urinary NAG (r = 0.701, P<0.0001), and urinary MCP-1 (r = 0.801, P<0.0001) levels in all diabetic patients. Multiple linear regression analysis showed that serum creatinine and urinary adiponectin levels were independently associated with serum adiponectin levels (r(2) = 0.522), and that serum creatinine, urinary NAG, urinary MCP-1, and serum adiponectin levels were independent determinants of urinary adiponectin levels (r(2) = 0.851). These results collectively indicate that renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in overt diabetic nephropathy. We presume that an increase in circulating adiponectin in overt diabetic nephropathy might be a physiological response to mitigate renal tubular injury and to prevent the further progression of diabetic nephropathy through its anti-inflammatory and anti-atherogenic effects.     

Assessment of compliance for oral medicines with MMSE, Mini-Mental State Examination, in hospitalized elderly patients

The minimental state examination (MMSE) is a widely used, standardized method to assess cognitive function including movement-related disorders with high reliability. We studied the relationship between MMSE scores and the ability to take oral medications correctly (ingestion compliance) in 70 elderly inpatients (mean age 71.3+/-7.0 years). Patients with abnormal glucose tolerance as determined by an HbA(1c) level of 5.8% or greater including diabetes showed a trend of lower MMSE scores compared with patients with normal glucose tolerance, and the scores were negatively correlated with HbA1c, age, and systolic blood pressure (P<0.05). Self-management in taking oral medications was very difficult in 4 patients whose MMSE scores were 21 points or less. Thus ingestion supervisions by nurses were required in these patients. Furthermore, 9 of 12 noncompliant patients had MMSE scores ranging from 22 to 26 points. We instructed these patients to take medications in a one-dose package as a useful tool to improve compliance. The MMSE score was 27 or higher in 44 of 54 compliant patients, and 10 patients had scores ranging from 21 to 26. The sensitivity and specificity for noncompliance at an MMSE score cut-off point of 26 were 75.0% and 81.5%, respectively. In conclusion, it is necessary to coordinate ingestion methods matched to each patient according to their abilities to comply with medication schedules. They should be preevaluated with the MMSE to improve ingestion compliance. The MMSE is a recommended test in hospitalized elderly patients for the assessment of the ability to take medications safely.     

Unilateral pulmonary artery banding to promote contralateral pulmonary artery growth

A full-term baby with double-outlet right ventricle and total anomalous pulmonary venous connection (TAPVC) complicated with left main pulmonary artery (PA) stenosis, presented with heart failure caused by increased pulmonary blood flow. Based on significant discrepancies in size and development between the left and right PAs, we performed right PA banding concomitant with TAPVC repair to promote left PA growth and restrict overall PA flow. PA-graphy performed 3?months after surgery showed marked increase in the left PA size with appropriately low pressure, which enabled us to successfully complete Glenn anastomosis. Under appropriate patient selection, unilateral PA banding for patients with unbalanced peripheral PA size could serve as an effective and less invasive strategy to simultaneously promote PA growth and control PA flow.     

Studies on genetic differentiation of Salmonella enteritidis isolates by plasmid profile]

Since 1989, the number of salmonellosis cases caused by S. Enteritidis has increased considerably in Japan. Genetic differentiation of 385 strains isolated from January 1982 to December 1988 and January 1989 to April 1991 were used for plasmid profiles. Plasmids were found in 377 out of 385 strains; therefore, only 8 strains carried no plasmid. Among 377 strains, 15 different plasmid profile types (OP-1 to OP-15) were classified. The most common plasmid profile types from 1982 to 1988 were OP-7 (70 kbp) and OP-8 (70 kbp and 2 kbp). On the other hand, the most common plasmid profile types from 1989 to 1991 were OP-1 (60 kbp) and OP-2 (60 kbp and 54 kbp). Serovar-specific virulence 60 kbp plasmids of S. Enteritidis were identified in 7 plasmid profile types (A total of 200 strains). In the other plasmid profile types, 70 kbp plasmids were found in 5 plasmid profile types (A total of 173 strains). In restriction enzyme analysis of 70 kbp plasmid DNAs obtained from 5 plasmid profile types of S. Enteritidis, we found that these plasmid DNAs shared both 60 kbp and 10 kbp fragments. These results indicate that these plasmid profile types also carried serovar-specific virulence plasmids of S. Enteritidis. The strains of plasmid profile type OP-2 were SA (sulfisoxazole) and SM (streptomycin) resistance, and the 54 kbp plasmids in the strains of OP-2 were transferred by bacterial conjugation into the E. coli strains. All transconjugants acquired SM resistance.     

Free radical-mediated tolbutamide desensitization of K+ATP channels in rat pancreatic beta-cells

To study the effects of hydroxyl radicals on the sensitivity of the ATP-sensitive K+ (K+ ATP) channel to tolbutamide, we used patch clamp and microfluorometric techniques in pancreatic beta-cells isolated from rats. cell-attached membrane patches, exposure of the cells to 0.3 mM H2O2 increased the probability of opening of K+ATP channels in the presence of 2.8 mM glucose. Tolbutamide dose-dependently inhibited the K+ATP channel with half-maximal inhibition (IC50) at 0.8 microM before and immediately after exposure to H2O2. After prolonged exposure (>20 min) to H2O2, the IC50 was increased to 15 microM. The presence of both ATP and ADP at concentrations ranging from 0.01 to 0.1 mM in the inside-out bath solution significantly enhanced the inhibition of the channels by 10 microM tolbutamide. Addition of 0.3 mM H2O2 induced a transient minute increase in the cytoplasmic Ca2+ concentration ([Ca2+]i) within 10 min, followed by a sustained pronounced increase in [Ca2]i. After more than 20 min of exposure of cells to 0.3mM H2O2, [Ca2]i was increased to above 2 microM. Treatment of the cytoplasmic face of inside-out membrane patches with 1 microM Ca2+ attenuated the tolbutamide-sensitivity of the K+ATP channel, but not the ATP-sensitivity of the channel. These findings indicate that H2O2 reduces tolbutamide sensitivity by inducing a sustained increase in [Ca2+]i.     

Lower 1,5-anhydroglucitol is associated with adverse clinical events after percutaneous coronary intervention

Diabetes mellitus and impaired glucose tolerance are well-known risk factors for coronary artery disease (CAD) and adverse clinical events after percutaneous coronary intervention (PCI). Postprandial hyperglycemia is an important risk factor for CAD and serum 1,5-anhydroglucitol (1,5-AG) reflects postprandial hyperglycemia more robustly than hemoglobin (Hb)A1c. We aimed to clarify the relationship between serum 1,5-AG level and adverse clinical events after PCI. We enrolled 141 patients after PCI with follow-up coronary angiography. We evaluated associations between glycemic biomarkers including HbA1c and 1,5-AG and cardiovascular events during follow-up. Median serum 1,5-AG level was significantly lower in patients with any coronary revascularization and target lesion revascularization (TLR) [13.4 µg/ml (first quartile, third quartile 9.80, 18.3) vs. 18.7 (12.8, 24.2), p = 0.005; 13.4 µg/ml (10.2, 16.4) vs. 18.7 (12.9, 24.2), p = 0.001, respectively]. Multivariate logistic analysis showed lower 1,5-AG was independently associated with any coronary revascularization and TLR (odds ratio 0.93, 95 % confidence interval 0.86–0.99, p = 0.04; 0.90, 0.81–0.99, p = 0.044, respectively), whereas higher HbA1c was not. Postprandial hyperglycemia and lower 1,5-AG are important risk factors for adverse clinical events after PCI.