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.

Comparison of the Efficacy of Repaglinide Versus the Combination of Mitiglinide and Voglibose on Glycemic Variability in Japanese Patients with Type 2 Diabetes.

BACKGROUND: Glycemic variability is a risk factor for total death and cardiovascular events. There are no obvious guidelines for the direct treatment of glycemic variability, but it can be improved with the treatment of postprandial hyperglycemia. OBJECTIVE: We compared the effect of repaglinide versus the combination of mitiglinide and voglibose, used to improve postprandial hyperglycemia, on glycemic variability in Japanese patients with type 2 diabetes. METHODS: We performed an open-label randomized cross-over trial between April 2016 and April 2018. Patients with type 2 diabetes who were admitted to our hospital were enrolled in our study (n = 12). Glycemic variability. was assessed using a continuous glucose monitoring system. RESULTS: The average glucose level of the repaglinide phase (146.1 ± 20.7 mg/dl) and the combination of mitiglinide and voglibose phase (132.3 ± 19.8 mg/dl) were similar (P = 0.10). The standard division (P = 0.0005), coefficient of variation (P = 0.006), and mean amplitude of glycemic excursion (P = 0.002) of glucose were lower in the combination of mitiglinide and voglibose phase than in the repaglinide phase. CONCLUSION: Treatment with the combination of mitiglinide and voglibose might be more effective than repaglinide for the improvement of glycemic variability.

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.

Cerebral Salt-wasting Syndrome and Inappropriate Antidiuretic Hormone Syndrome after Subarachnoid Hemorrhaging.

Hyponatremia is a common finding after subarachnoid hemorrhaging (SAH) and can be caused by either cerebral salt-wasting syndrome (CSWS) or syndrome of inappropriate antidiuretic hormone (SIADH). Distinguishing between these two entities can be difficult because they have similar manifestations, including hyponatremia, serum hypo-osmolality, and high urine osmolality. We herein report the case of a 60-year-old man who suffered from SAH complicated by hyponatremia. During his initial hospitalization, he was diagnosed with CSWS. He was readmitted one week later with hyponatremia and was diagnosed with SIADH. This is the first report of SAH causing CSWS followed by SIADH. These two different sources of hyponatremia require different treatments.

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.

[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.

Effect of repaglinide versus glimepiride on daily blood glucose variability and changes in blood inflammatory and oxidative stress markers.

BACKGROUND: Hemoglobin A1c is the main treatment target for patients with type 2 diabetes. It has also been shown recently that postprandial glucose and daily glucose fluctuations affect the progression of diabetic complications and atherosclerotic damages. METHODS: Continuous glucose monitoring was performed in patients with type 2 diabetes to evaluate the efficacy of repaglinide vs. glimepiride on postprandial glucose spikes and fluctuations. A total of 10 Japanese patients with type 2 diabetes treated with glimepiride monotherapy were enrolled. After observation period for 8 weeks, glimepiride was changed to repaglinide. Continuous glucose monitoring was performed whilst consuming calorie-restricted diets for two days at baseline and at the end of the 12-week trial. Blood and urine samples were collected for measurement of glucose control parameters and inflammatory and oxidative stress markers on the last day of taking either glimepiride or repaglinide. RESULTS: Nine patients completed the trial. Although the glucose control parameters were not significantly different between glimepiride and repaglinide, the mean amplitude of glycemic excursions measured by continuous glucose monitoring was significantly reduced by changing treatment from glimepiride to repaglinide. The levels of plasminogen activator inhibitor-1, high sensitivity C-reactive protein, and urinary 8-hydoroxydeoxyguanosine were reduced significantly by repaglinide treatment. CONCLUSION: These results suggest that repaglinide may decrease the risk of cardiovascular disease in type 2 diabetes by minimizing glucose fluctuations thereby reducing inflammation and oxidative stress.

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.

Assessment of daily food and nutrient intake in Japanese type 2 diabetes mellitus patients using dietary reference intakes.

Medical nutrition therapy for the management of diabetes plays an important role in preventing diabetes complications and managing metabolic control. However, little is known about actual eating habits of individuals with type 2 diabetic mellitus (T2DM), especially in Japan. Therefore, we sought to (1) assess the dietary intake of individuals with T2DM, and (2) characterize their intake relative to national recommendations. This cross-sectional study involved 149 patients (77 males and 72 females) aged 40-79 years with T2DM recruited at a Kyoto hospital. Dietary intake was assessed using a validated self-administered diet history questionnaire. Under-consumption, adequacy, and over-consumption, of nutrients were compared to the age- and sex-based standards of the Japanese Dietary Reference Intakes. Among the results, most notable are (1) the inadequacy of diets in men with respect to intake of vitamins and minerals, likely owing to low intake of vegetables and fruits; (2) excess contributions of fat intake to total energy in both sexes; and (3) excess consumption of sweets and beverages relative to the national average. The prevalence of diabetes complications may be increasing because of a major gap between the typical dietary intake of individuals with T2DM and dietary recommendation.

Serum albumin levels predict vascular dysfunction with paradoxical pathogenesis in healthy individuals.

BACKGROUND: Serum albumin is affected by both nutritional status and inflammation. It is, therefore, thought to be highly linked with pathogenesis of vascular dysfunction. METHODS: Cross-sectional data from 2091 individuals aged 23-87, who underwent a general health examination, were analyzed. First, we investigated the association between serum albumin level and vascular functions, as assessed by brachial-ankle pulse-wave velocity (PWV). Then, we evaluated the prevalence of hyperglycemia (fasting blood sugar >or=100mg/dl), metabolic syndrome as determined by NCEP criteria, and inflammation (CRP >or=0.4mg/dl), across tertiles of albumin levels. RESULTS: In a multivariate regression model, a U-shaped relationship between serum albumin and PWV was statistically significant when albumin level was treated as a continuous variable in g/dl and centered at 4.4g/dl (quadratic term P-value=0.006). The highest tertile of albumin level (4.6-5.4g/dl) was associated with increased odds ratios for hyperglycemia of 1.35 (1.07-1.70) compared to the middle tertile (4.4-4.5g/dl), whereas the lowest tertile (3.3-4.3g/dl) was associated with reduced odds ratios for hyperglycemia of 0.80 (0.65-0.99). The highest tertile was also associated with increased odds ratios for metabolic syndrome of 1.30 (0.96-1.76) compared to the middle tertile, whereas the lowest tertile was associated with reduced odds ratios of 0.70 (0.51-0.95). Furthermore, the lowest tertile was associated with increased prevalence of inflammation with an adjusted odds ratio of 1.85 (1.15-2.97). CONCLUSIONS: The current results demonstrate that extremes of serum albumin levels are linked to vascular dysfunction among healthy individuals. Furthermore, serum albumin is paradoxically linked to vascular disease under conditions both of overnutrition and of malnutrition and inflammation complex.

Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion.

Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

Evaluation of characteristics and degree of remodeling in coronary atherosclerotic lesions by 64-detector multislice computed tomography (MSCT).

BACKGROUND: Multislice computed tomography (MSCT) permits reliable imaging of not only the coronary artery lumen but also vessel wall. It is assumed that both lipid-rich plaques and those that display positive remodeling are more prone to rupture and erosion with subsequent coronary events. The purpose of this study was to assess the correlation between the characteristics of coronary arteries by MSCT and several measures of coronary heart disease (CHD) risk. METHODS: This study consisted of 424 consecutive participants who received MSCT and coronary angiography (CAG). We assessed coronary artery findings including coronary artery calcification (CAC), degree of remodeling and narrowing of lumen and characteristics including uric acid (UA) and high-sensitivity C-reactive protein (hs-CRP). Statistical analyses were conducted for four subgroups classified by the presence of significant stenosis and positive remodeling. RESULTS: Hs-CRP was 2.10+/-2.70mg/L in positive remodeling (+) and stenosis (+) group (PS), 1.05+/-0.97mg/L in positive remodeling (-) and stenosis (+) group (nPS), 0.94+/-0.88mg/L in positive remodeling (+) and stenosis (-) group (PnS) and 0.44+/-0.49mg/L in positive remodeling (-) and stenosis (-) group (nPnS). The results of logistic regression analysis showed that hs-CRP was higher in PS compared with the other groups (p<0.001) and higher in nPS and PnS compared with nPnS (p<0.05). CONCLUSIONS: Regardless of significant stenosis, positive remodeling by MSCT correlates to the increase of hs-CRP.

Bone stiffness in men with type 2 diabetes mellitus.

Osteoporosis in elderly men as well as women is increasingly recognized, and patients with type 2 diabetes mellitus have higher risk of fracture than nondiabetic subjects. The aim of the present study was to investigate the relationship between bone stiffness and serum testosterone concentration as well as other variables in men with type 2 diabetes mellitus. The relationships between bone stiffness and serum bioavailable testosterone concentrations as well as other variables including age, duration of diabetes, glycemic control (hemoglobin A(1c)), or body mass index were evaluated in 294 men with type 2 diabetes mellitus. An inverse correlation was found between stiffness index and age. A positive correlation was found between stiffness index and serum bioavailable testosterone concentration (r = 0.231, P = .0005). Stiffness index was significantly less in current smokers (81.6 +/- 17.7) than in past smokers (86.6 +/- 17.8, P = .0396) or nonsmokers (87.7 +/- 15.2, P = .0426). Multiple regression analysis demonstrated that serum bioavailable testosterone concentration (beta = .271, P = .0006) and smoking status (beta = -0.147, P = .0408) were independent determinants of stiffness index. In conclusion, bone stiffness was associated with serum bioavailable testosterone concentration but not associated with hemoglobin A(1c) or duration of diabetes in men with type 2 diabetes mellitus.

Bone mass and bone resorption in postmenopausal women with type 2 diabetes mellitus.

The aim of the present study was to examine the relationships between bone mass or bone resorption evaluated by urinary cross-linked N-telopeptides of type I collagen (NTx) concentration and known and potential contributors to bone mass or bone resorption such as sex hormones, age, duration of diabetes, glycemic control (hemoglobin A(1c) [HbA(1c)]), body mass index (BMI), severity of diabetic complications, smoking status, and current treatment of diabetes in postmenopausal women with type 2 diabetes mellitus (n = 196). In addition, the relationship of bone mass to pulse wave velocity, which is an earlier indicator of cardiovascular disease, was investigated in a subgroup of patients (n = 120). Bone mass was evaluated by the quantitative ultrasound method. A higher stiffness index indicates higher bone mass. Inverse correlations were found between the stiffness index and age (r = -0.374, P < .0001) and between the stiffness index and log (urinary albumin excretion) (r = -0.170, P = .0398), and a positive correlation was found between the stiffness index and serum dehydroepiandrosterone sulfate (DHEA-S) concentration (r = 0.201, P = .0136). No significant correlations were found between the stiffness index and duration of diabetes, HbA(1c), BMI, or serum estradiol concentration. No significant correlations were found between urinary NTx concentration and age, duration of diabetes, HbA(1c), BMI, serum estradiol concentration, or serum DHEA-S concentration. The stiffness index correlated inversely with urinary NTx concentration (r = -0.262, P = .0002). No significant correlation was found between the stiffness index and pulse wave velocity (r = -0.165, P = .0714). Multiple regression analysis demonstrated that serum DHEA-S concentration was an independent determinant of the stiffness index (beta = .207, P = .0428). In conclusion, serum DHEA-S concentration correlated positively with bone mass, whereas glycemic control, BMI, or duration of diabetes did not correlate with bone mass or urinary NTx concentration in postmenopausal women with type 2 diabetes mellitus.

Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.

Hyperuricemia has been reported to be associated with increased risk of renal insufficiency as well as cardiovascular events. The aim of this study was to evaluate the relationships between serum uric acid concentration and degree of urinary albumin excretion as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Serum uric acid concentrations were measured in 343 men with type 2 diabetes mellitus. We then evaluated relationships of serum uric acid concentrations to degree of urinary albumin excretion as well as to major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, and glycemic control (hemoglobin A1c). The relationships between serum uric acid concentration and pulse wave velocity or ankle-brachial index (n=236) and between serum uric acid concentration and carotid intima-media thickness or plaque score (n=125) were investigated additionally in a subgroup of patients. Serum uric acid concentration correlated positively with logarithm of urinary albumin excretion (r=0.302, P<.0001). Positive correlation was found between serum uric acid concentration and intima-media thickness (r=0.233, P=.0087), whereas inverse correlation was found between serum uric acid concentration and ankle-brachial index (r=-0.150, P=.0207). Multiple regression analysis demonstrated that serum uric acid concentration (beta=.281, P<.0001), duration of diabetes (beta=.253, P<.0001), hemoglobin A1c (beta=.166, P=.0034), serum triglyceride concentration (beta=.125, P=.0472), and systolic blood pressure (beta=.275, P=.0013) were independent determinants of logarithm of urinary albumin excretion. In conclusion, serum uric acid concentration is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.

Serum prostate-specific antigen levels in men with type 2 diabetes.

OBJECTIVE: The aims of this study were to examine if serum prostate-specific antigen (PSA) levels are lower in men with type 2 diabetes compared with those in healthy men and to investigate what factors may be associated with serum PSA levels in men with type 2 diabetes. RESEARCH DESIGN AND METHODS: We compared the serum PSA levels in 224 diabetic men with those in 1,293 healthy men and investigated the relationships between serum PSA levels and various variables. RESULTS: Except for men aged 40-49 years, serum PSA levels were lower in diabetic men than in healthy men. Multiple regression analysis demonstrated that age, BMI, and presence of diabetes were independent determinants of serum PSA level. CONCLUSIONS: Serum PSA levels were lower in diabetic men compared with those in healthy men, which is in line with previous reports that patients with type 2 diabetes are at a decreased risk of prostate cancer.

Joint effect of alcohol and usual sleep duration on the risk of dysglycemia.

STUDY OBJECTIVES: Sleep duration and alcohol use influence metabolic function. However, limited information exists regarding a combined effect of alcohol and sleep duration on glucose metabolism. The aim of this study was to assess the potential interaction effect of alcohol and inappropriate sleep duration on dysglycemia epidemiologically. DESIGN: Cross-sectional and observational retrospective study. SETTING: A medical health checkup program in a general hospital. PARTICIPANTS: 2933 apparently healthy Japanese individuals, aged 46 to 60 years. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: We examined the relationships between usual sleep duration and dysglycemia, and furthermore assessed the combined effects of alcohol consumption and sleep time on glucose dysmetabolism. A U-shaped relationship between sleep duration and the prevalence of hyperglycemia (fasting plasma glucose level > or =110 mg/dL) was observed when sleep duration was treated as a continuous variables and centered at 7.0 h (quadratic term P = 0.024). In a multivariate quadratic regression model, there was a significant interaction effect between sleep duration and alcohol consumption category (nondrinkers, light-moderate drinkers [ethanol comsumption < or =210 g/wk], and heavy drinkers [ethanol consumption of >210 g/wk]) on fasting plasma glucose levels, with shorter or longer sleep duration being more diabetogenic in individuals who consumed more alcohol (P interaction = 0.018). Furthermore, we found a similar interaction effect of sleep duration and alcohol consumption on the incidence of hyperglycemia during the past 5 years (P interaction = 0.039). CONCLUSION: Alcohol interacts with reduced sleep duration to increase the risk of dysglycemia.

Association between serum testosterone concentration and collagen degradation fragments in men with type 2 diabetes mellitus.

The aim of the present study was to evaluate relationships between serum endogenous androgens and urinary concentration of cross-linked N-telopeptides of type I collagen (NTx), a bone resorption marker, in men with type 2 diabetes mellitus because low androgen concentrations are associated with both osteoporosis and cardiovascular disease. Relationships between serum free testosterone and urinary NTx concentrations were investigated in 246 consecutive men with type 2 diabetes mellitus. In addition, relationships between urinary NTx concentration and other variables including age, duration of diabetes, blood pressure, serum lipid concentration, hemoglobin A(1c), and body mass index were evaluated. Urinary NTx concentrations were 27.8 (26.4-29.3) nmol of bone collagen equivalent per millimole of creatinine, correlating inversely with serum free testosterone (r = -0.263, P < .0001). Multiple regression analysis identified serum free testosterone (beta = -.292, P < .0001), hemoglobin A(1c) (beta = .144, P = .0404), and smoking status (beta = .143, P = .0402) as independent determinants of urinary NTx. In conclusion, serum free testosterone concentration correlated inversely with urinary NTx concentration, which may partly account for an observed link between osteoporosis and cardiovascular disease in men with type 2 diabetes mellitus.