Effects of Valsartan on Inflammatory and Oxidative Stress Markers in Hypertensive, Hyperglycemic Patients: An Open-Label, Prospective Study

AbstractBackground: Diabetes mellitus and hypertension are aggravated by activation of the renin-angiotensin system caused by increased oxygen stress and local inflammatory responses. Several studies have suggested that angiotensin II type 1 receptors can reduce inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, IL-18, soluble vascular cell adhesion molecule [VCAM]-I, and l-selectin) and oxidative stress markers (urinary 8-hydroxy-7,8-dihydro-2'-deoxyguanosine [8-OHdG] and 8-epi-prostaglandin F2α [8-isoprostane]) in hypertensive patients.Objective: The aim of this study was to assess the effects of valsartan, an angiotensin II receptor blocker, on inflammatory and oxidative stress markers in hypertensive patients with mild diabetes or impaired glucose tolerance.Methods: In this open-label, prospective study, hypertensive patients aged >20 years with mild diabetes (requiring treatment by diet alone or an oral hypoglycemic), seen on an outpatient basis at the Division of Diabetes, Metabolism, and Endocrinology, Omori Hospital, Toyko, Japan, who were receiving a therapeutic dietary regimen for ≥1 month in the treatment of diabetes or hypertension, were eligible for enrollment. Blood pressure, inflammatory markers (hs-CRP, IL-6, IL-18, VCAM-1, and L-selectin), and oxidative stress markers (urinary 8-OHdG and 8-isoprostane) were monitored before treatment commencement with valsartan (40-80 mg/d) and after 3 months of treatment.Results: A total of 26 patients (18 men, 8 women; mean [SD] age, 57.7 [11.3] years; mean [SD] weight, 65.3 [13.1] kg) were enrolled in the study. After 3 months of treatment, patients' mean (SD) blood pressure had significantly decreased from 153.1 (11.2)/88.3 (11.4) to 143.7 (13.7)/85.2 (9.0) mm Hg (P < 0.05). Among the inflammatory and oxidative stress markers, hs-CRP, VCAM-1, and urinary 8-OHdG concentrations decreased significantly from 0.231 (0.199) to 0.134 (0.111) mg/dL (P = 0.043), 471.1 (193.9) to 403.2 (135.2) ng/mL (P = 0.012), and 12.12 (5.99) to 8.07 (3.36) ng/mg · creatinine (P = 0.001), respectively. The reductions in these markers were observed in patients regardless of whether or not their glycosylated hemoglobin (HbA1c) concentration improved (defined as a decrease of ≥1% in HbA1c).Conclusion: This small, open-label, prospective study found that a 3-month treatment with valsartan was associated with a significant reduction of hs-CRP, VCAM-1, and urinary 8-OHdG concentrations independent of improvement in HbA1c concentration in these hypertensive patients with hyperglycemia

Urinary Myoinositol Index: A New and Better Marker for Postmeal Hyperglycemia

We investigated the usefulness of the urinary myoinositol index (UMI) for identifying postmeal hyperglycemia in type 2 diabetics undergoing a meal tolerance test. Fifty-eight patients (18 males, 40 females) were enrolled, fasted overnight and blood collected prior to and 1 and 2 hours following the test meal. Urine was collected 2 hours after the test meal. Plasma 1,5-anhydroglucitol (1,5-AG) was measured enzymatically, and UMI with an improved enzymatic cycling method. Simple and multiple regression analyses were employed to determine correlations between plasma glucose (PG) and three PG markers; HbA1C (Japan Diabetes Society), 1,5-AG and UMI. Study population characteristics were age 67.6±7.9 years, body mass index 24.9±3.8kg/m2 and waist circumference 90.2±10.4cm. Mean concentrations for PG were 130±23mg/dL (fasting), 179±46mg/dL (1h postmeal) and 150±49mg/dL (2h postmeal), HbA1C (6.3±0.6%), 1,5-AG (11.9±5.7μg/mL) and 2h UMI (52.0±35.9mg/gCr). Correlation coefficients were calculated between 1h postmeal PG and HbA1C (r=0.558), 1,5-AG (r=0.256), and 2h UMI (r=0.496), and 2h postmeal PG HbA1C (r=0.605), 1,5-AG (r=0.306), and 2h UMI (r=0.606). Two hour UMI and HbA1C (Japan Diabetes Society) were significant determinants of 2h postmeal PG. As HbA1C reflects PG excursion during the previous 1-3 months, UMI may be a useful marker for monitoring and management of postmeal hyperglycemia in type 2 diabetics

Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report

<p>Abstract</p> <p>Background</p> <p>Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare.</p> <p>Case presentation</p> <p>A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia.</p> <p>Discussion</p> <p>We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases.</p

Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM

Chromosomal Aberrations Caused by Cu K-shell Ionization in Hypoxic Cells Containing Cu-ATSM

The enhancement effect on chromosomal aberrations via selective X-ray energy absorption by Cu atoms in GM05389 normal fibroblast cells containing non-labeled copper(II)-diacetyl-bis(N4-methyl- thiosemicarbazone)(Cu-ATSM) was examined. The amounts of Cu-ATSM taken into cells were detected by PIXE analysis, and it was clarified that the amount of Cu atoms taken into hypoxic cells was about 2 or 3-times higher compared to that into normoxic cells. Radioisotope analysis with 64Cu-ATSM showed that 8.7% of all Cu atoms taken into a whole cell was distributed to the nucleus, and the remaining atoms to the cytoplasm in the cells. Irradiation with monochromatic X rays (CuK-H X rays) having an energy just above the Cu K-shell absorption edge on the hypoxic cells induced high yield of chromosomal aberrations, compared to that with X rays (CuK-L X rays) having an energy just below the Cu K-shell absorption edge. Enhanced chromosomal aberrations caused by Cu K-shell ionization or excitation was clearly observed in this study

Associations between fatty acid intake and diabetic retinopathy in a Japanese population

Abstract Residents of Chikusei City, aged 40–74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07–6.39), p for trend = 0.025, and 2.40 (1.12–5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners