Super paramagnetic iron oxide contrast-enhanced magnetic resonance imaging was useful in differentiating an insulinoma from an accessory spleen: a case report with review of literature.

When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors.

Younger patients and low c-peptide immunoreactivity index but not nutritional states affect fasting blood ketone levels in Japanese with type 1 diabetes after sodium-glucose cotransporter 2 inhibitor administration.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. MATERIALS AND METHODS: In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. RESULTS: All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (ß = -0.504, p = .003) and a low ratio of basal to bolus insulin (ß = -0.420, p = .005). CONCLUSIONS: When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.

Home-measured pulse pressure is a predictor of cardiovascular disease in type 2 diabetes: The KAMOGAWA-HBP study.

BACKGROUND AND AIMS: Pulse pressure (PP) is a prognostic predictor of cardiovascular mortality. This retrospective cohort study aimed to investigate the association between home PP measurements and cardiovascular disease in patients with type 2 diabetes. METHODS AND RESULTS: Home blood pressure was measured for 14 consecutive days in 1082 patients with type 2 diabetes, and pulse pressure was calculated. A 10 mmHg increase in morning PP was associated with a 1.30-fold increase in the risk of cardiovascular disease. The risk of cardiovascular disease was 1.88 times higher in the morning in the higher PP group than in the lower PP group. In the receiver operating characteristic analysis, the areas under the curve (95% confidence interval) corresponding to the PP (morning, evening, and clinic) for new-onset cardiovascular disease were 0.63 (0.58-0.69), 0.62 (0.57-0.67), and 0.59 (0.54-0.64), respectively. The area under the curve for PP measured in the morning was significantly greater than that for PP measured in the clinic (P = 0.032). CONCLUSION: Home-measured PP is a better predictor of new-onset cardiovascular disease than clinic-measured PP, in patients with type 2 diabetes.

Insulin dose reduction in dapagliflozin combination therapy for type 1 diabetes mellitus: the RISING-STAR study.

To clarify the frequency of hypoglycemia in patients with type 1 diabetes mellitus receiving dapagliflozin combination therapy to reduce their basal insulin dose. Sixty subjects were assigned to two groups according to their basal insulin-to-total daily dose (TDD) ratio: group A (basal insulin/TDD <40%) and group B (≥40%). Reduction of the basal insulin dose was instituted in group B, but not in group A. The number of hypoglycemic events per day and ketosis frequency were the primary and secondary endpoints, respectively. The hypoglycemia frequency before and after the intervention was 0.23 and 0.26 times/day in group A and 0.19 and 0.23 times/day in group B, respectively, with no significant difference between the groups. The total insulin dose reduction was approximately 10% in both groups. Ketosis frequency increased significantly after the intervention (from 0.013 to 0.086 times/day in group A and 0.013 to 0.059 times/day in group B). Time-in-range, mean amplitude of glycemic excursion, and glycated hemoglobin A1c improved in both groups. No significant difference in hypoglycemia frequency was observed between patients with and without reduction of the basal insulin dose. The combination therapy improved glycemic control and patient satisfaction regarding hyperglycemia. Nevertheless, adequate attention to ketosis is crucial.

Association between Body Weight Gain from 20 Years of Age and Diabetic Nephropathy in Japanese Patients with Type 2 Diabetes.

BACKGROUND/AIMS: It has been reported that the body mass index shows a U-shaped association with death from cardiovascular disease (CVD) in the Asian population. The relationship between body weight (BW) gain from early adulthood and diabetic nephropathy remains to be elucidated in Japanese patients with type 2 diabetes. Our aim was to investigate the association between BW gain from early adulthood and diabetic nephropathy in Japanese patients with type 2 diabetes. METHODS: We assessed the BW of 471 consecutive patients with type 2 diabetes and calculated the change in BW from the age of 20 years to the lifetime maximum (ΔBWmax-20y). We then evaluated the relationship of ΔBWmax-20y with the degree of urinary albumin excretion (UAE), which is a useful marker for CVD. RESULTS: ΔBWmax-20y negatively correlated with the logarithm of UAE (r = -0.160, p = 0.002). Multiple regression analysis demonstrated that ΔBWmax-20y was independently correlated with the logarithm of UAE (ß =-0.112, p =0.034). CONCLUSIONS: BW gain from the age of 20 years is correlated with diabetic nephropathy in Japanese patients with type 2 diabetes.

Various patterns of disrupted daily rest-activity rhythmicity associated with diabetes.

Disruptions to sleep and circadian rhythms have now been recognized as common comorbidities in patients with medical illnesses. We aimed to determine if the diurnal rhythms for rest and activity were disrupted in parallel with the development of diabetic complications. Ninety outpatients in our diabetes clinic who had a body mass index <25 kg m(2) wore an actigraph for 7 consecutive days (42 men; mean age 68.7 ± 8.2 years). Patients with neuropsychiatric diseases, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or blindness, or those who performed shiftwork were excluded. We grouped the actigraph recordings into 1-h periods and counted the number of minutes that showed activity. Stepwise regression analysis showed an association between a diabetic clinical background and measurements of circadian rhythms such as daytime activity, night-time activity, phase, interdaily stability, intradaily variability and relative amplitude. Higher age, body mass index, total cholesterol levels and insulin usage were associated with lower daytime activity and higher intradaily variability, whereas higher haemoglobin A1c levels and the presence of neuropathy were associated with greater daytime activity. The presence of proliferative retinopathy and increased levels of microalbuminuria were associated with higher intradaily variability and lower interdaily stability and amplitude. The presence of cardiovascular disease was associated with advanced phase, whereas painful neuropathy was associated with delayed phase. Our study demonstrated that different diabetic complications were associated independently with a variety of alterations in the circadian rest and activity rhythms. Our findings have provided novel insights that may be helpful in developing interventions for sleep-wake disorders associated with diabetes.

The novel association between red complex of oral microbe and body mass index in healthy Japanese: a population based cross-sectional study.

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.

[Insomnia disorder comorbid with diabetes].

Insomnia disorder is one of the most prevalent conditions comorbid with diabetes and has been shown to have a possible role in the development of diabetes. Insomnia is characterized by a state of excessive physiological and cognitive arousal with alterations in autonomic and hypothalamic-pituitary-adrenal function. The chronic neuroendocrine activation in insomnia may predispose insomniacs to the development of metabolic disorders including glucose intolerance. In contrast, diabetic complications, in combination with the disruption of a sleep-wake homeostatic and circadian process, can be key factors precipitating insomnia symptoms and involve several subtypes of insomnia. Furthermore, inappropriate lifestyles are also likely responsible for the exacerbation of insomnia and diabetes. Thus, the pathogenesis of insomnia disorder and diabetes could mutually interact to develop each disease with a vicious cycle, accounting for the high comorbidity between the diseases.

N-terminal pro-brain natriuretic peptide could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

N-terminal pro-brain natriuretic peptide (NT-proBNP), which is a useful biomarker of chronic heart failure, has been shown to be a strong predictor of cardiovascular mortality. The aim of this study was to evaluate the relationships between NT-proBNP and markers of subclinical atherosclerosis in patients with type 2 diabetes. Relationships of NT-proBNP to pulse wave velocity (PWV) or ankle-brachial index (ABI) as well as to various parameters, including body mass index, blood pressure, serum lipid concentration, serum uric acid concentration, and glycemic control (hemoglobin A1c), age, hemoglobin, serum creatinine concentration, severity of diabetic nephropathy or retinopathy, current treatment of diabetes, cardiothoracic ratio on chest radiograph, presence of left ventricular hypertrophy and/or ST-T changes evaluated by electrocardiograph, smoking status and presence of cardiovascular disease were investigated in 323 consecutive patients with type 2 diabetes. Log (NT-proBNP) correlated positively with PWV (r = 0.283, p < 0.0001) and correlated negatively with ABI (r = -0.144, p = 0.0094). Multiple regression analysis demonstrated that age (ß = 0.200, p = 0.0033), systolic blood pressure (ß = 0.246, p < 0.0001), total cholesterol (ß = -0.135, p = 0.0326), uric acid (ß = 0.133, p = 0.0462), creatinine (ß = -0.184, p = 0.0122), smoking status (ß = -0.129, p = 0.0499) and log (NT-proBNP) (ß = 0.177, p = 0.0149) were independently correlated with PWV and that systolic blood pressure (ß = -0.145, p = 0.0310), log triglyceride (ß = -0.151, p = 0.0397) and log (NT-proBNP) (ß = -0.207, p = 0.0094) were independently correlated with ABI. In conclusion, NT-proBNP could be a marker of subclinical atherosclerosis in patients with type 2 diabetes.

Serum pepsinogen I/II ratio is correlated with albuminuria in patients with type 2 diabetes.

Helicobacter pylori infection, which is a common cause of atrophic gastritis, has been reported to represent a causal factor increasing the vascular damage and consequent albuminuria. On the other hand, decreased serum pepsinogen (PG) I/II ratio can be used to assess gastric mucosal atrophy. To the best of our knowledge, there are no studies investigating the correlation between PG I/II ratio and diabetic nephropathy. Therefore, we investigated a relationship between PG I/II ratio and degree of urinary albumin excretion (UAE) in patients with type 2 diabetes. We evaluated relationships between PG I/II ratio and degree of UAE or estimated glomerular filtration rate as well as various factors, including age, body mass index, blood pressure, hemoglobin A1c, serum lipid concentrations, uric acid or C-reactive protein in 333 consecutive patients with type 2 diabetes. PG I/II ratio correlated positively with logarithm of UAE in all patients (r = 0.174, P = 0.0016) and in patients without Helicobacter pylori infection (r = 0.352, P < 0.0001). Multiple regression analysis identified that PG I/II ratio correlated independently with logarithm of UAE in all patients (ß = 0.264, P = 0.0005) and in patients without Helicobacter pylori infection (ß = 0.295, P = 0.0022). These data suggest that serum PG I/II ratio is correlated with diabetic nephropathy.

Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes.

This study assessed the endocrine pancreatic responses to liraglutide (0.9 mg once a day) during normal living conditions in Japanese patients with type 2 diabetes. The study included 14 hospitalized patients with type 2 diabetes. Meal tests were performed after improvement of glycemic control achieved by two weeks of multiple insulin injection therapy and after approximately two weeks of liraglutide treatment. Continuous glucose monitoring was performed to compare daily variation in glycemic control between multiple insulin injection therapy and liraglutide treatment. Liraglutide reduced plasma glucose levels after the test meals (60-180 min; p<0.05), as a result of significant increases in insulin secretion (0-180 min; p<0.05) and decreases in the incremental ratio of plasma glucagon (15-60 min; p<0.05). Continuous glucose monitoring showed that liraglutide treatment was also associated with a decrease in glucose variability. We also demonstrated that optimal glycemic control seen as a reduction in 24-h mean glucose levels and variability was obtained only with liraglutide monotherapy. In conclusion, liraglutide treatment increases insulin secretion and suppresses glucagon secretion in Japanese patients with type 2 diabetes under normal living conditions. The main therapeutic advantages of liraglutide are its use as monotherapy and its ability to decrease glucose variability.

Impact of continued high blood pressure on the progression of diabetic nephropathy after 10 years: KAMOGAWA-HBP study.

Albuminuria is a prognostic marker of worsening renal outcomes in people with hypertension and type 2 diabetes. High home systolic blood pressure is associated with the development of diabetic nephropathy. We assessed the impact of chronic high home blood pressure on diabetic nephropathy progression 10 years after study entry. The participants measured their blood pressure three times in the morning for 14 days at study entry and 10 years after study entry. A retrospective cohort of 165 people with type 2 diabetes at a single hospital was classified into four groups (good control maintenance, improvement, deterioration, and continuous high blood pressure groups) according to a morning home systolic blood pressure ≥125 mmHg at study entry and 10 years after study entry. Logistic regression analysis was performed to determine the association between home blood pressure control and the progression of diabetic nephropathy. After 10 years of entry, the status of nephropathy improved for 5.5% of the participants, remained unchanged for 72.1%, and progressed for 22.4%. The odds ratio of the continuous high blood pressure group versus that of the good control maintenance group for the progression of diabetic nephropathy was 10.41 (95% CI, 1.26-86.15). After adjusting for the introduction of renin-angiotensin-aldosterone system inhibitors during the follow-up period, there was no significant difference in the odds ratio of worsening nephropathy between these groups. The deterioration and improvement groups did not have significant diabetic nephropathy progression compared to the good control maintenance group. Chronic high home blood pressure was associated with the progression of diabetic nephropathy, and RAAS inhibitors could attenuate the negative effect. We demonstrated that chronic home blood pressure was associated with the progression of diabetic nephropathy.

Effects of dapagliflozin on renal function in type 1 diabetes patients in the real world: A retrospective multicenter study of the KAMOGAWA-A cohort.

AIMS: This study aimed to investigate the effects of dapagliflozin on renal function of type 1 diabetes patients. METHODS: This retrospective multicenter cohort study enrolled 295 type 1 diabetes patients. The primary outcome was defined as the change in the estimated glomerular filtration rate (eGFR) after 24 months of dapagliflozin treatment. The secondary outcomes were defined as the changes in HbA1c, daily insulin dosage, and urinary albumin-to-creatinine ratio (UACR) after 24 months. RESULTS: Finally, 255 patients were included in the final analysis (dapagliflozin group; 76 patients, non-use group; 179 patients), with a median eGFR of 74.0 mL/min/1.73 m2. A 1:1 propensity score matching was performed, and 142 patients were analyzed in a linear mixed model. The least squares mean change in eGFR in the dapagliflozin group was -3.14 mL/min/1.73 m2 (95% CI: -5.62 to -0.66), a significantly smaller decrease than in the non-use group (-6.94 mL/min/1.73 m2 (95% CI: -9.39 to -4.50)) (p = 0.032). HbA1c level, total insulin dose, and UACR change were significantly lower in the dapagliflozin group than in the non-use group. CONCLUSIONS: At 24 months, the decline in eGFR was significantly lower in the dapagliflozin group than in the non-use group without increasing diabetic ketoacidosis and hypoglycemia.

Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study.

AIMS/INTRODUCTION: Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. RESULTS: With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02-2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74-2.13) in males and 2.28 (1.01-5.15) in females. CONCLUSIONS: In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.

Low urine pH Is a predictor of chronic kidney disease.

BACKGROUND/AIMS: A variety of risk factors for chronic kidney disease (CKD), including the metabolic syndrome, were recently reported. It has been suggested that a low urine pH is another characteristic of the metabolic syndrome. However, the relationship between urine pH and CKD remains to be elucidated. METHODS: A cohort study was performed on 1,811 subjects who underwent a health check-up, and we examined whether low urine pH could be a predictor of CKD. The following risk factors for CKD were evaluated: age, gender, history of alcohol intake and smoking, BMI, systolic blood pressure, fasting plasma glucose, total cholesterol, uric acid, total leukocyte count, CKD stage, fasting urine pH, and protein at baseline. RESULTS: We followed 1,811 subjects for a median period of 7.7 years. Three hundred and thirty-nine subjects developed stage 3 CKD defined as progression to estimated glomerular filtration rate < 60 ml/min/1.73 m(2). Multiple Cox regression analysis revealed that the adjusted HR (95% CI) for stage 3 CKD was 1.32 (1.06-1.65; p = 0.0129) in subjects with fasting urine pH 5.0-5.5 compared to subjects with pH 6.5-7.0. CONCLUSION: Our study suggests that low urine pH is an independent predictor of stage 3 CKD.

Second measurement of morning systolic blood pressure is more closely associated with albuminuria.

BACKGROUND/AIMS: It is important to control blood pressure as well as to control blood glucose for the prevention of diabetic nephropathy. However, to our knowledge, there are no reports investigating which blood pressure, including morning, evening and clinic, is more closely associated with albuminuria and whether one measurement is sufficient or not in patients with Type 2 diabetes. METHODS: We measured morning, evening and clinic blood pressure and compared the area under the curve (AUC) of blood pressure for urinary albumin excretion equal to or more than 30 mg/g creatinine using receiver-operating characteristic curve analyses and odds ratio for albuminuria defined as urinary albumin excretion equal to or more than 30 mg/g creatinine in 858 patients with Type 2 diabetes. RESULTS: Odds ratio (95% confidence interval (CI)) of morning, evening and clinic systolic blood pressure for albuminuria was 1.034 (1.024 - 1.044), 1.033 (1.023 - 1.043) and 1.013 (1.055 - 1.021), respectively (p < 0.001 in all), and AUC of morning, evening and clinic systolic blood pressure was 0.644 (0.628 - 0.700) (p < 0.001 vs. clinic), 0.660 (0.623 - 0.696) (p < 0.001 vs. clinic) and 0.597 (0.559 - 0.636), respectively. AUC of the second morning systolic blood pressure was greater than the first (p = 0.033). CONCLUSION: The second measurement of morning systolic blood pressure is more closely associated with albuminuria than the first measurement of the morning in addition to clinic systolic blood pressure.

Relationship between cardio-ankle vascular index (CAVI) and coronary artery calcification (CAC) in patients with type 2 diabetes mellitus.

Early detection of atherosclerosis is important for patients with type 2 diabetes mellitus because cardiovascular disease (CVD) is a main cause of death in these people. In this study, we investigated the relationship between an arterial stiffness parameter called cardio-ankle vascular index (CAVI) and coronary artery calcification (CAC). We performed a cross-sectional study in 371 type 2 diabetic patients with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAVI and CAC score determined by multislice computed tomography as well as major cardiovascular risk factors, including age, body mass index, hemoglobinA1c and the Framingham CHD risk score. CAVI was correlated with age (r = 0.301, p < 0.0001), uric acid (r = 0.236, p < 0.0001), estimated glomerular filtration rate (r = -0.145, p = 0.0166), CHD risk score (r = 0.327, p < 0.0001) and log (CAC + 1) (r = 0.303, p < 0.0001). The area under the receiver operating characteristic curve for CAVI was higher than that of CHD risk score in predicting CAC >0, CAC >100, CAC >400, or CAC >1000. CAVI is positively correlated with CAC, and is considered to be a useful method to detect CAC.

Impact of sustained hypertension on new cardiovascular events in patients with type 2 diabetes: KAMOGAWA-HBP study.

We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow-up of 7.0 (interquartile range, 4.0-9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02-2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes.

Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

OBJECTIVE: The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events. METHODS: This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event. RESULTS: The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01-1.24) and 1.19 (1.07-1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07-2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46-3.61), using the Youden's index. CONCLUSION: Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.

17ß-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30.

Senescence marker protein-30 (SMP30) plays an important role in intracellular Ca(2+) homeostasis. The aim of the present study was to investigate the effects of estrogens on liver apoptotic damage and changes in SMP30 expression induced by a high saturated fatty acid diet (HSFD). Ovariectomized mice (OVX) and sham-operated mice (SHAM) were randomly divided into five groups: SHAM fed a normal diet (SHAM/ND), SHAM fed HSFD (SHAM/HSFD), OVX fed ND (OVX/ND), OVX fed HSFD (OVX/HSFD) and OVX fed HSFD with 17ß-estradiol (E2) supplementation using an implanted slow-release pellet (OVX/HSFD+E2). After 8 weeks, markers of endoplasmic reticulum (ER) stress and apoptosis, and levels of tumor necrosis factor-α (TNFα and SMP30 expression were investigated. Compared with SHAM/ND, OVX/HSFD mice showed significantly increased spliced X-box protein-1 (s-XBP1), phosphorylated eukaryotic initiation factor-2α (p-eIF2α), glucose-regulated protein 78 (GPR78), C/EBP homologous protein (CHOP), cytosolic cytochrome c, caspase-3 activity, and TNFα, and significantly decreased SMP30. These differences in OVX/HSFD mice were restored to the levels of SHAM/ND mice by E2 supplementation. These results suggest that E2 supplementation attenuates HSFD-induced liver apoptotic death in ovariectomized mice by up-regulating SMP30.