Negative correlation between organ heteroplasmy, particularly hepatic heteroplasmy, and age at death revealed by post-mortem studies of m.3243A > G cases.

Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4-82] years; BMI, 16.0 ± 2.9 [13.0-22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.

Proposed carbohydrate antigen 19-9 (CA19-9) cut-off values for the detection of pancreatic cancer in patients with poorly controlled diabetes: a real-world study.

CA19-9 is a tumor marker for pancreatic cancer (PC), and the nondiabetic cut-off level is 37 U/mL. CA19-9 levels are said to rise in patients with tumors like PC and intraductal papillary mucinous neoplasm (IPMN). CA19-9 levels have also been shown to be related to HbA1c levels. We hypothesized that the CA19-9 cut-off levels would differ between patients with poorly controlled diabetes. This real-world trial was designed to test our hypotheses. This was a retrospective cohort study. All inpatients with poorly controlled diabetes had mean HbA1c levels of 10.0% and were divided into three groups: those with pancreatic cancer (PC group, N = 20), those with IPMN (IPMN group, N = 55), and those with neither (NC group, N = 985). Serum CA19-9 levels in the PC group were significantly higher than in the IPMN and NC groups (p < 0.001). CA19-9 levels did not differ statistically between the IPMN and NC groups. According to the receiver operating characteristic (ROC) analysis, serum CA19-9 levels of 98.4 U/mL had the highest sensitivity and specificity to detect PC, when comparing PC to IPMN + NC groups. Using this cut-off, the sensitivity and specificity of CA19-9 for PC were 70.0% and 96.5%, respectively, with a 0.81 area under the ROC curve. CA19-9 levels in two inpatients were >98.4 U/mL, most likely due to hepatocellular carcinoma and esophageal cancer. CA19-9 cut-off levels were thought to be 98.4 U/mL. However, we should keep in mind that the sensitivity and specificity were not 100%.

Comparison of tofogliflozin versus glimepiride as the third oral agent added to metformin plus a dipeptidyl peptidase-4 inhibitor in Japanese patients with type 2 diabetes: A randomized, 24-week, open-label, controlled trial (STOP-OB).

Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by -2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by -1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy.

Clinical factors associated with the symptoms of constipation in patients with diabetes mellitus: A multicenter study.

BACKGROUND AND AIM: Changes in treatment protocols for patients with diabetes mellitus (DM) may influence the functions of the digestive tract. This study examined possible clinical factors associated with the symptoms of constipation in patients with DM. METHODS: This was a multicenter study. Participants were consecutive Japanese patients undergoing treatment for type 1 or type 2 DM. Constipation was evaluated using the gastrointestinal symptom rating scale. Diabetic neuropathy was evaluated by the presence or absence of peripheral neuropathy of the lower limbs. RESULTS: Of 419 participants, 258 were men and 161 women (ratio: 1.6:1), with a mean age of 63.6 ± 12.5 years. In multivariate analysis, symptoms of constipation were significantly associated with age (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.01-1.04, P = 0.032), lower mental component summary (OR = 3.31, 95% CI: 1.69-6.48, P < 0.001), diabetic retinopathy (OR = 1.99, 95% CI: 1.14-3.45, P = 0.015), and diabetic neuropathy (OR = 1.86, 95% CI: 1.10-3.16, P = 0.021). In patients with peripheral neuropathy of the lower limbs, regardless of the presence of other complications (diabetic nephropathy and diabetic retinopathy), the prevalence of symptoms of constipation was twice that of patients without peripheral neuropathy (40.0-49.1% vs 22.0%). Diabetic drugs were not associated with symptoms of constipation. CONCLUSIONS: Diabetic neuropathy, defined as peripheral neuropathy of the lower limbs, was significantly associated with symptoms of constipation. Peripheral neuropathy of the lower limbs is not a direct risk factor for constipation but may be a useful criterion when assessing whether constipation is associated with DM.

Primary aldosteronism in patients with acute stroke: prevalence and diagnosis during initial hospitalization.

BACKGROUND: Hypertension is the prime risk factor for stroke, and primary aldosteronism (PA) is the most common cause of secondary hypertension. The prevalence of PA in stroke patients has never been reported. The aim of this study was to elucidate the prevalence of PA. METHODS: A total of 427 consecutive patients with acute stroke were prospectively enrolled for this study. The screening tests were performed at the initial visit and a week after admission by measuring plasma aldosterone concentration and plasma renin activity. The rapid adrenocorticotropic hormone (ACTH) test was performed as the confirmatory test when both screening tests were positive. The primary endpoint was a final diagnosis of PA. RESULTS: The sensitivity of the dual screening system for the diagnosis of PA was 88.2 %, and PA was finally diagnosed in 4.0 % of acute stroke patients and in 4.9 % of stroke patients with a history of hypertension. Patients with PA were less likely to be male and have diabetes, and they had higher blood pressure at the initial visit, lower potassium concentration, and more intracerebral hemorrhage. The rapid ACTH test was performed safely even in acute stroke patients. CONCLUSIONS: The prevalence of PA is not low among acute stroke patients. Efficient screening of PA should be performed particularly for patients with risk factors. TRIAL REGISTRATION: UMIN-CTR; UMIN000011021 . Trial registration date: June 23, 2013 (retrospectively registered).

Effects of liraglutide, a glucagon-like peptide-1 analog, on left ventricular remodeling assessed by cardiac magnetic resonance imaging in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

The clinical efficacy of glucagon-like peptide-1 (GLP-1) analogs in patients with acute myocardial infarction (AMI) is uncertain. The purpose of the present study was to evaluate the effects of the GLP-1 analog liraglutide on left ventricular (LV) remodeling in patients with AMI. We retrospectively evaluated the effects of liraglutide on LV remodeling assessed by cardiac magnetic resonance imaging (CMRI) in 15 patients with type 2 diabetes who were successfully treated with primary percutaneous coronary intervention (PCI) for AMI. Patients were divided into two groups based on their hypoglycemic medication: liraglutide use (group L; n = 6) or standard therapy (group S; n = 9). The CMRI findings in the early phase and at the 6-month follow-up were compared. At the 6-month follow-up, group S showed increases in LV end-diastolic (from 64 to 74 mL/m(2), p = 0.08) and end-systolic (from 38 to 45 mL/m(2), p = 0.13) volume indexes, whereas no such increase was observed in group L. The LV mass index (LVMI) was significantly smaller in group L than in group S at baseline (64 vs. 75 g/m(2), p = 0.05) and at follow-up (56 vs. 78 g/m(2), p = 0.009). Multivariate regression analysis showed that liraglutide use was an independent negative predictor of LVMI (ß = -0.720, p = 0.003). In conclusion, liraglutide may be able to prevent the progression of LV remodeling and is associated with a lower LV mass in diabetic patients with AMI undergoing primary PCI.

Second-line treatments for dyslipidemia in patients at risk of cardiovascular disease.

Previous studies have shown that approximately 50% patients at risk of cardiovascular disease do not achieve lipid management goals. Thus, improvements dyslipidemia management are needed. We investigated the clinical choice and efficacy of second-line treatments for dyslipidemia in the Japanese clinical setting. Using a retrospective cohort design, we collected lipid profile data from patients who had been treated with hypolipidemic agents at a stable dosage for at least 12 weeks. These patients had then been administered a second-line treatment for dyslipidemia because they had not achieved the low-density lipoprotein cholesterol (LDL-C) management goals. We included data from 641 patients in our analysis. The top three choices for second-line treatment were adding ezetimibe, switching to strong statins (statin switching), and doubling the original statin dosage (statin doubling). Adding ezetimibe, statin switching, and statin doubling decreased LDL-C levels by 28.2 ± 14.5%, 23.2 ± 24.4%, and 23.5 ± 17.2%, respectively. Among these three strategies, adding ezetimibe decreased LDL-C levels to the maximum extent. In patients with dysglycemia, baseline-adjusted change in hemoglobin A1c (HbA1c) levels decreased slightly in the adding-ezetimibe, statin-switching, and statin-doubling groups, but the differences were not statistically significant among the groups (-0.10 ± 0.62%, -0.22 ± 0.54%, and -0.12 ± 0.52%, p = 0.19). In conclusion, the most common second-line treatment options for dyslipidemia were adding ezetimibe, statin switching, or statin doubling. Adding ezetimibe resulted in the highest reduction in LDL-C levels. These strategies did not increase HbA1c levels when administered with conventional diabetes treatment.

The effect of long-term past glycemic control on executive function among patients with type 2 diabetes mellitus.

OBJECTIVE: Patients with type 2 diabetes mellitus (T2DM) show more executive dysfunction than nondiabetics. However, how long poor glycemic control affects executive function remains unclear. Thus, we aimed to investigate the relationships in a cross-sectional study. METHODS: We studied 118 T2DM outpatients (age, ≥ 60 years; excluding history of stroke, dementia and severe hypoglycemia). HbA1c values were recorded every ≤ 12 weeks for ≥ 5 years. All patients underwent verbal-fluency tests (reflecting executive function) and Mini-Mental State Examination (MMSE). The correlation between past glycemic control values and both cognitive tests scores was investigated. As markers of past glycemic control, we used average hemoglobin A1c (HbA1c) values and glycemic control variability [coefficient of variation (CV) of HbA1c values (HbA1c-CV)]. RESULTS: Verbal-fluency tests scores correlated with HbA1c-CV, but not with average HbA1c values, after adjusting for age, years of education and sex. Verbal-fluency tests scores correlated with HbA1c-CV for the past 5 years, best compared with HbA1c-CV for past < 5 years. MMSE scores were also related to only HbA1c-CV for the past 3 years in an adjustment model. CONCLUSIONS: Five-year HbA1c variability affected executive function in T2DM patients, but not average HbA1c values. Long-term longitudinal studies may be required.

Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine.

OBJECTIVE: The aim of the present study was to compare the effects on serum cytokine concentrations of paroxetine, a selective serotonin re-uptake inhibitor, and kamishoyosan, a Japanese traditional medicine, in midlife women with psychological symptoms. METHODS: Seventy-six women with psychological symptoms such as anxiety and mild depression as menopausal symptoms were enrolled in this study. Thirty-eight women received oral administration of 10mg paroxetine every day, and 38 women received oral administration of kamshoyosan every day for 6 months. Overall climacteric symptoms were assessed using Greene's climacteric scale. Serum levels of cytokines were measured using a multiplexed human cytokine assay. RESULTS: Greene's total scores in both women treated with paroxetine and in women treated with kamishoyosan decreased significantly. Percentage decreases in Greene's total, psychological and vasomotor scores during the 6-month period in the paroxetine group were significantly greater than those in the kamishoyosan group. Serum IL-6 concentration in women treated with paroxetine decreased significantly. Serum concentrations of IL-8, IL-10, macrophage inflammatory protein (MIP)-1beta and monocyte chemoattractant protein-1 in women treated with paroxetine decreased significantly. On the other hand, serum IL-6 concentration in women treated with kamishoyosan decreased significantly, but other serum concentrations did not change significantly. CONCLUSION: Decrease in IL-6 concentration may be involved in the mechanism of the actions of both paroxetine and kamishoyosan in women with psychological symptoms, and IL-6 may therefore be useful as a marker of treatment. The action of paroxetine may also be associated with decreases in IL-8, IL-10, MIP-1beta.

Associations of interleukin-6 with interleukin-1beta, interleukin-8 and macrophage inflammatory protein-1beta in midlife women.

OBJECTIVE: The aim of the present study was to determine the associations of interleukin (IL)-6 with other cytokines and chemokines and to compare these associations in peri- and postmenopausal women. METHODS: Ninety-nine perimenopausal and 92 postmenopausal women were enrolled in this study. Serum concentrations of IL-6, IL-1beta, IL-2, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor (TNF)-alpha, interferon gamma, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, macrophage inflammatory protein (MIP)-1beta and monocyte chemotactic protein (MCP)-1 were measured simultaneously using a multiplexed cytokine assay. RESULTS: Among the 17 cytokines, IL-6, IL-1beta, IL-5, IL-7, IL-8, IL-10, MCP-1 and MIP-1beta were detected in serum in more than 50% of the women. Serum levels of IL-4 and MCP-1 in postmenopausal women were significantly higher than those in perimenopausal women. Serum IL-6 concentrations showed significant and positive correlations with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, and these correlations were still significant after adjustment for age and body mass index. CONCLUSION: Serum IL-6 concentration was found to be closely associated with serum concentrations of IL-1beta, IL-8, MIP-1beta, IL-7 and MCP-1 in women regardless of menopausal status, suggesting that these cytokines act in concert with the progression of several symptoms and various diseases.

Circulating osteoprotegerin is associated with age and systolic blood pressure, but not with lipid profile or fasting glucose, in postmenopausal women.

OBJECTIVE: Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis and osteoclast activation, has been reported to be linked to vascular biology. The aim of this study was to clarify the relationships between circulating OPG and the risk factors for vascular disorders in postmenopausal women. DESIGN: Eighty Japanese postmenopausal women were enrolled in this cross-sectional study. Clinical parameters (age, number of years since menopause, body mass index, systolic and diastolic blood pressure); serum concentrations of OPG, creatinine, calcium, and phosphorus; serum lipid profile; plasma glucose; and bone mineral density of the L2-4 vertebral bodies were determined for each woman. RESULTS: In rank-order correlation analysis, serum OPG concentrations had significant positive correlations with age (r = 0.29, P = 0.03), systolic blood pressure (r = 0.45, P < 0.01), diastolic blood pressure (r = 0.34, P < 0.01), and serum creatinine (r = 0.29, P = 0.04). Serum OPG concentration also had a marginally significant negative correlation with bone mineral density of the L2-4 vertebral bodies (r = -0.25, P = 0.06). However, serum OPG did not correlate with body mass index, serum lipid profile, or plasma glucose. The correlation of serum OPG with systolic blood pressure persisted after adjustment for both age and serum creatinine. CONCLUSIONS: These results suggest that increased circulating OPG in postmenopausal women is closely related to higher systolic blood pressure, which could cause atherosclerosis.

Associations of circulating adiponectin with estradiol and monocyte chemotactic protein-1 in postmenopausal women.

OBJECTIVE: The aim of the present study was to clarify the association of serum adiponectin concentrations with serum 17beta-estradiol concentrations in pre-, peri-, and postmenopausal women. In addition, the associations of serum adiponectin with serum concentrations of proinflammatory and anti-inflammatory cytokines were examined in women during the menopausal transition. DESIGN: A total of 197 women were enrolled in this study: 33 premenopausal women, 80 perimenopausal women, and 84 postmenopausal women. Serum adiponectin concentration was measured by an enzyme-linked immunosorbent assay. Serum concentrations of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha, anti-inflammatory cytokine IL-10, and the chemokines IL-8, macrophage inflammatory protein-1beta and monocyte chemotactic protein-1 were measured by using a multiplexed human cytokine assay. RESULTS: Serum adiponectin concentration showed a significant negative correlation with serum estradiol concentration (r= -0.400, P=0.001) in postmenopausal women but not in pre- and perimenopausal women, and this correlation was significant after adjustment for age and body mass index. Serum adiponectin concentration also showed a significant negative correlation with serum monocyte chemotactic protein-1 concentration (r= -0.244, P=0.05) in postmenopausal women. CONCLUSION: An increase in adiponectin level due to a decrease in estradiol results in a reduction in monocyte chemotactic protein-1 level in postmenopausal women, suggesting that adiponectin may be associated with a protective role against insulin resistance and atherosclerosis, which occur in the postmenopausal stage.

Rationale and Design of the STOP-OB Study for Evaluating the Effects of Tofogliflozin and Glimepiride on Fat Deposition in Type 2 Diabetes Patients Treated with Metformin/DPP-4 Inhibitor Dual Therapy.

BACKGROUND: The global pandemic of type 2 diabetes mellitus (T2DM) is an enormous clinical and socioeconomic burden. Biguanides and DPP-4 inhibitors (DPP-4i) are the most commonly used therapies in Japanese T2DM patients. When glycemic control is not adequate despite combination of these drugs, there is no consensus on the next step drug. Systematic reviews and meta-analyses of previous trials have indicated that glycemic control with triple combination therapies yields similar results. Thus, beneficial effects on cardiovascular risk factors may be important. The present study was designed to evaluate body fat percentage and several insulin resistance parameters after addition of tofogliflozin or glimepiride to the regimens of patients being treated with metformin and a DPP-4 inhibitor but failing to attain adequate blood glucose control. METHODS: Sodium glucose cotransporter-2 inhibitor, tofogliflozin versus glimepiride, comparative trial in patients with type 2 diabetes on body composition is an ongoing, multicenter, prospective, randomized, open-label, parallel-group trial. T2DM patients treated with metformin/DPP-4 inhibitor dual therapy have been recruited and randomly assigned to 20 mg/day tofogliflozin (n = 32) or 0.5 mg/day glimepiride (n = 32) groups, with either of these drugs being added to pre-existing regimens for 24 weeks. PLANNED OUTCOMES: The primary endpoint is the change in body fat percentage from baseline to 24 weeks. The secondary outcomes are changes in body composition other than fat percentage, body weight, parameters related to glycemic control and ß-cell function, parameters related to lipids and arteriosclerosis, parameters related to liver function, parameters related to diabetic nephropathy, and uric acid levels. Safety parameters will also be analyzed. This is the first trial comparing the effects and safety of adding an SGLT2i and a sulfonylurea as the third-line oral agent to metformin/DPP-4i dual therapy. The results will provide valuable information for choosing third-line oral agents. TRIAL REGISTRATION: UMIN000026161. FUNDING: Kowa Co. Ltd. and Kowa Pharmaceutical Co. Ltd., Tokyo, Japan.

Association of serum cytokine concentrations with psychological symptoms in midlife women.

OBJECTIVE: The purpose of the present study was to clarify the association of serum cytokine concentrations, determined using a multiplexed cytokine assay, with psychological symptoms in midlife women. METHODS: Fifty-three peri- and post-menopausal women with and without psychological symptoms in Greene's climacteric scale were enrolled in this study. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. RESULTS: Serum interleukin (IL)-6 concentration in women with psychological symptoms (2.71+/-047 pg/ml) was significantly (p=0.009) higher than that in women without psychological symptoms (0.98+/-0.18 pg/ml). Serum IL-8 concentration in women with psychological symptoms (33.4+/-8.17 pg/ml) was also significantly (p=0.022) higher than that in women without psychological symptoms (7.87+/-1.64 pg/ml). In addition, serum IL-10 concentration in women with psychological symptoms (0.74+/-0.26 pg/ml) was significantly (p=0.048) higher than that in women without psychological symptoms (0.07+/-0.04 pg/ml). Tumor necrosis factor (TNF)-alpha in serum was detected only in women with psychological symptoms. Serum IL-2 concentration in women with psychological symptoms tended (p=0.066) to be higher than that in women without psychological symptoms. No significant differences were found between levels of other cytokines in women with and without psychological symptoms. CONCLUSION: Psychological stress manifested as climacteric symptoms in midlife women may be associated with increases in serum concentrations of IL-6, IL-8, IL-10, and TNF-alpha.

Associations of adiponectin with sex hormone-binding globulin levels in aging male and female populations.

BACKGROUND: Changes with aging in serum gonadal hormones, sex hormone-binding globulin (SHBG) and adiponectin, which are involved in insulin resistance and metabolic syndrome, are different in men and women. We examined the relationships of serum adiponectin concentrations with serum concentrations of hormones and SHBG in men and women. METHODS: One hundred fifty-four men and 180 women aged from 50 to 85 years were included in the cross-sectional study. Serum concentrations of testosterone, estradiol, dehydroepiandrosterone-sulfate, SHBG and adiponectin were measured in men and women. RESULTS: Serum adiponectin concentration showed a significant positive correlation with serum SHBG concentration in men and women (r=0.404, p<0.0001 and r=0.348, p<0.0001, respectively). Multiple regression analysis also showed that SHBG was the significant predictor for adiponectin in men and women. Serum adiponectin concentration in men showed a significant positive correlation with total testosterone concentration, but that in women was not significantly correlated with total testosterone concentration. Both adiponectin and SHBG concentrations in men (r=-0.222, p=0.0051 and r=-0.334, p<0.0001, respectively) and women (r=-0.281, p=0.0014 and r=-0.251, p=0.0048, respectively) showed significant negative correlations with the homeostasis model assessment (HOMA) index. CONCLUSION: Correlations between adiponectin and SHBG were significantly positive in both men and women, and both adiponectin and SHBG might be involved in insulin resistance in both sexes.

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women.

OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period. METHODS: The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured. RESULTS: Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p<0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p<0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different. CONCLUSION: The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.

Changes in serum cytokine concentrations during the menopausal transition.

OBJECTIVE: The purpose of the present study was to clarify the changes in serum concentrations of 17 cytokines in healthy women during the menopausal transition by using a multiplexed cytokine assay and to clarify the associations of these cytokines with serum estradiol concentration. METHODS: Sixteen premenopausal, 54 perimenopausal and 52 postmenopausal women were enrolled in this study. Seventeen cytokines in serum samples were measured simultaneously using a Bio-Plex human cytokine 17-Plex assay. RESULTS: Serum IL-6 concentration showed a weak positive correlation with age (r=0.196, p<0.05). Postmenopausal women for whom less than 5 years had passed since menopause showed significant (p<0.05) increase in serum concentrations of IL-2, GM-CSF and G-CSF, while serum IL-4 concentration was significantly (p<0.05) increased in postmenopausal women for whom more than 5 years had passed since menopause. Serum estradiol concentration showed a significant negative correlation with serum IL-6 concentration and weak negative correlations with serum concentrations of IL-2, IL-8 and GM-CSF. CONCLUSION: We were able to simultaneously measure the levels of 17 cytokines using a highly sensitive cytokine assay, and we found that the changes in serum cytokine concentrations during the menopausal transition differed. We also found that serum IL-6 concentration during the menopausal transition was negatively correlated with serum estradiol concentration.

[Clinical application of undercarboxylated osteocalcin].

Undercarboxylated osteocalcin (ucOC) is a sensitive marker of vitamin K (VK) status. Serum ucOC concentration in perimenopausal women is significantly higher than that in premenopausal women. In addition, serum ucOC concentration is closely associated with not only FSH concentration but also estradiol concentration. Serum ucOC concentration rapidly increases in women after bilateral oophorectomy. The effect of hormone therapy (HT) on alternate days on ucOC concentration is weaker than the effect of HT daily and ucOC concentration after 12 months of HT daily may be decreased due to the conversion of ucOC to carboxylated OC by the effect of VK through increased TG induced by oral conjugated equine estrogen (CEE) . Additionally, the effect of HT with transdermal estradiol on ucOC concentration in women is weaker than the effect of HT with oral CEE.

Predicting the ability of elderly diabetes patients to acquire the insulin self-injection technique based on the number of animal names recalled.

AIMS/INTRODUCTION: To our knowledge, no studies have reported that cognitive tests can be used to evaluate whether or not patients can acquire the insulin self-injection technique. We investigated whether or not the number of animal names recalled in 1 min by elderly diabetes patients could be used as a predictor of the patients' ability to acquire the insulin self-injection technique within 1 week. MATERIALS AND METHODS: We enrolled 57 inpatients with type 2 diabetes aged >60 years who were starting insulin therapy. We carried out the Mini-Mental State Examination and verbal fluency tests, which included recalling animal names and common nouns starting with the letters 'a,' 'ka' and 'shi' (Japanese letters). We used 12 checkpoints for insulin self-injection to judge the patients' levels of acquisition of the technique. The most predictive cognitive test was determined by multivariate logistic regression analysis. RESULTS: In the present study, multivariate logistic analysis showed that the number of animal names recalled was the most reliable predictor of the ability to acquire the insulin self-injection technique within 1 week. A figure of 11 animal names predicted a successful acquisition, with a sensitivity of 73% and a specificity of 91% being observed (area under the curve 0.87, 95% confidence interval 0.76-0.97, P < 0.01). CONCLUSIONS: The number of animal names recalled in 1 min was the most useful indicator of the ability of elderly diabetes patients to learn to manage insulin self-injection therapy within 1 week. The cut-off value was 11 animal names.

Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women.

OBJECTIVE: The purpose of this study was to identify serum cytokine concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes. METHODS: Serum concentrations of 17 cytokines were simultaneously measured using a multiplexed human cytokine assay in 129 premenopausal, perimenopausal, and postmenopausal women and 50 bilateral oophorectomized women. RESULTS: Serum IL-8 concentrations in midlife women and bilateral oophorectomized women with severe hot flashes were significantly higher than the concentrations in women without hot flashes and women with mild and moderate hot flashes. Serum macrophage inflammatory protein-1beta concentration in women with severe hot flashes was significantly higher than those in women without hot flashes and women with mild and moderate hot flashes. CONCLUSION: Serum IL-8 concentrations in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women with hot flashes were significantly higher than those in women without hot flashes. IL-8 may be associated with peripheral vasodilation in women with hot flashes.