Language：Japanese   Publisher：(一社)日本内分泌学会  

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Background: Low-triiodothyronine (T3) syndrome is a known complication in intensive care unit (ICU) patients, but the underlying mechanisms and prognostic impact are unclear. Methods and Results: This study retrospectively enrolled 2,976 patients who required care in the ICU. Of these patients, 2,425 were euthyroid and were divided into normal (n=1,666; free T3 [FT3] ≥1.88 µIU/L) and low-FT3 (n=759; FT3 <1.88 µIU/L) groups. Multivariate logistic regression analysis revealed that prognostic nutritional index >46.03 (odds ratio [OR] 2.392; 95% confidence interval [CI] 1.904-3.005), age (per 1-year increase; OR 1.022; 95% CI 1.013-1.031), creatinine (per 0.1-mg/dL increase; OR 1.019; 95% CI 1.014-1.024), and C-reactive protein (per 1-mg/dL increase; OR 1.123; 95% CI 1.095-1.151) were independently associated with low FT3. Survival rates (within 365 days) were significantly lower in the low-FT3 group. A multivariate Cox regression model showed that low FT3 was an independent predictor of 365-day mortality (hazard ratio 1.785; 95% CI 1.387-2.297). Low-T3 syndrome was significantly more frequent in patients with non-cardiovascular than cardiovascular diseases (73.5% vs. 25.8%). Prognosis was significantly poorer in the low-FT3 than normal group for patients with cardiovascular disease, particularly those with acute coronary syndrome and acute heart failure. Conclusions: Low-T3 syndrome was associated with aging, inflammatory reaction, malnutrition, and renal insufficiency and could lead to adverse outcomes in patients admitted to a non-surgical ICU.

DOI： 10.1253/circrep.CR-21-0040

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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DOI： 10.1253/circrep.CR-21-0048

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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PURPOSE: Patients with thyrotoxicosis show neuropsychological changes, and these may damage the quality of informed consent in clinical practice. Therefore, we examined patients' real-life preferences to assess whether change in risk preferences was dependent on thyroid function state. PATIENTS AND METHODS: The participants were 86 patients who were newly diagnosed with Graves' thyrotoxicosis between 1 January and 31 December 2018 (group A), and an additional 33 euthyroid patients diagnosed before 2018 (group B). In a survey conducted via a questionnaire based on the concept of behavioral economics, we sought to determine risk preferences, rationality of choices, and other relevant factors. An identical second survey was completed 6-12 months later by 36 patients in group A after their thyroid functions had been normalized by treatment, and by 11 euthyroid patients in group B. We performed paired analysis of the first and second surveys in 32 patients of group A and single regression analysis of a total of 140 surveys obtained from 119 patients by combining the first and second surveys of groups A and B with serum level of FT3 as an independent variable. RESULTS: The paired analysis indicated that there was no significant difference in any survey item. The single regression analysis revealed that willingness-to-pay (WTP) for preventive medicine and monthly average out-of-pocket (OOP) expenditure on medical care were both significantly positively associated with serum level of FT3. Patients in the hyperthyroid state tend to have high WTP for preventive medicine, which may be accelerated by the anchoring effect of OOP expenditure. CONCLUSION: Almost all risk preferences of patients with Graves' disease are constant, rational, and reproducible in the hyperthyroid and euthyroid states. However, medical professionals should be aware that the willingness of patients with thyrotoxicosis to pay for medical costs may change after the normalization of thyroid function.

DOI： 10.2147/PPA.S323472

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) including thyroid dysfunction. There are only a few reports on Graves' disease induced by ICIs. We report a case of new-onset Graves' disease after the initiation of nivolumab therapy in a patient receiving gastric cancer treatment. CASE PRESENTATION: The patient was a 66-year-old Japanese man, who was administered nivolumab (240 mg every 3 weeks) as a third-line therapy for stage IVb gastric cancer. His thyroid function was normal before the initiation of nivolumab therapy. However, he developed thyrotoxicosis before the third administration of nivolumab. Elevated, bilateral, and diffuse uptake of radioactive tracer was observed in the 99mTc-pertechnetate scintigraphy. Furthermore, the thyroid-stimulating hormone receptor antibody (TRAb) and thyroid-stimulating antibody (TSAb) test results, which were negative before the first administration of nivolumab, were positive after starting the therapy. The patient was diagnosed with Graves' disease, and the treatment with methimazole and potassium iodide restored thyroid function. CONCLUSIONS: This is the first complete report of a case of new-onset Graves' disease after starting nivolumab therapy, confirmed by diffusely increased thyroid uptake in scintigraphy and the positive conversion of antibodies against thyroid-stimulating hormone receptor. It is important to perform thyroid scintigraphy and ultrasonography to accurately diagnose and treat ICI-induced thyrotoxicosis, because there are various cases in which Graves' disease is developed with negative and positive TRAb titres.

DOI： 10.1186/s12902-020-00613-5

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BackgroundCombination therapy with an alpha-glucosidase inhibitor or glinide plus a dipeptidyl peptidase-4 inhibitor is thought to be effective for glycemic control because of its effects on postprandial hyperglycemia. However, no studies have directly compared the efficacy and safety of these two combination therapies.MethodsEighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy and an HbA1c level of ≥7.5%; none were receiving any medication for diabetes. The patients were randomized to either miglitol- or repaglinide-based combination therapy with alogliptin. Patients received miglitol or repaglinide monotherapy for 3 months (the miglitol and repaglinide groups, respectively), after which alogliptin was added to each group as combination therapy for 3 months. A meal tolerance test (MTT) was performed before the start of treatment and at the end of monotherapy and combination therapy.ResultsDuring the study period, decreases in HbA1c and glycated albumin were significantly greater in the repaglinide group than in the miglitol group; however, there was no significant difference between treatment groups at the end of the study. At the end of monotherapy, insulin secretion relative to glucose elevation (ISG0-30: area under the curve of insulin from 0 to 30 min during MTT [AUC0-30 of IRI]/AUC0-30 of plasma glucose) was significantly increased only in the repaglinide group; ISG0-30 did not significantly increase in either group after the addition of alogliptin.ConclusionsThe addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.

DOI： 10.1272/jnms.JNMS.2021_88-205

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The mechanisms of urgently presenting acute heart failure (AHF) are not clear. We evaluated the serum catecholamine values of AHF patients immediately after admission. A total of 1,475 AHF patients were screened, and 484 who were admitted from their homes and in whom serum catecholamine could be evaluated immediately after admission were analyzed. The patients were divided into three groups according to the time interval from the onset of symptoms to admission (OA): < 3 hours (early-OA group; n = 283), 3-24 hours (middle-OA group; n = 142), and ≥24 hours (late-OA group; n = 59). In the early-OA group, the systolic blood pressure (SBP) was significantly higher, orthopnea was more frequent, the pH value was significantly decreased, and the use of noninvasive positive-pressure ventilation was required significantly more often than in the other groups. The serum noradrenaline level was significantly increased in the early-OA group (1.96 [1.02-3.60] ng/mL) than in the middle-OA (1.49 [0.73-3.41] ng/mL) and late-OA (1.40 [0.91-2.42] ng/mL) groups, and the adrenaline level was significantly increased in the early-OA group (0.36 [0.13-1.17] ng/mL) than in the late-OA (0.22 [0.09-0.52] ng/mL) group. A multivariate logistic regression model indicated the early-OA group was independently associated with the SBP > 140 mmHg (odds ratio [OR]: 2.219, 95% CI: 1.375-3.581), midnight/early morning admission (OR: 3.158, 95% CI: 2.048-4.868), and high serum catecholamine value (adrenaline > 0.96 ng/mL, noradrenaline > 3.39 ng/mL, and dopamine > 0.21 ng/mL) (OR 2.091, 95% CI: 1.161-3.767). In conclusion, urgently presented AHF might be induced by an endogenous catecholamine surge, which causes an excessive rise in blood pressure leading to increased after-overload and volume-shift lung congestion.

DOI： 10.1536/ihj.19-523

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Low triiodothyronine (T3) syndrome has recently been evaluated as a prognostic marker of acute heart failure (AHF). However, in which cases low T3 syndrome typically leads to adverse outcomes remain unclear. Of 1,432 AHF patients screened, 1,190 were enrolled. Euthyroidism was present in 956 patients (80.3%), who were divided into 2 groups: the normal group (n = 445, FT3 ≥1.88 µIU/L) and low-FT3 group (n = 511, FT3 <1.88 µIU/L). The survival rates and event-free rates within 365 days were significantly lower in the low-FT3 group than in the normal group. A multivariate Cox regression model showed that the low-FT3 group was an independent predictor of 365-day mortality (hazard ratio [HR] 1.429, 95% confidence interval [CI] 1.013 to 2.015) and HF events (HR 1.349, 95% CI 1.047 to 1.739). The multivariate logistic regression analysis revealed that age (per 10-year old increase, odds ratio [OR]: 1.186, 95% CI: 1.046 to 1.345) and prognostic nutritional index (PNI; per 1-point increase, OR: 1.067, 95% CI: 1.046 to 1.089) were independently associated with the low-FT3 group. The prognosis in patients with a low PNI and over 75 years old, including all-cause death within 365 days, was significantly poorer in the low-FT3 group than in the normal group. In conclusion, adverse outcomes were predicted by the presence of low T3. AHF patients with low T3 syndrome are strongly associated with aging and malnutrition. Low T3 syndrome complicated with older age and malnutrition is likely to lead to adverse outcomes in patients with AHF.

DOI： 10.1016/j.amjcard.2019.10.051

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DOI： 10.18632/aging.101969

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that targets the low-density lipoprotein (LDL) receptor for lysosomal degradation. PCSK9 impedes the receptor-mediated clearance of LDL-cholesterol, thereby increasing serum LDL-cholesterol levels. Evolocumab, a human monoclonal antibody against PCSK9, effectively reduces serum LDL-cholesterol levels. We report the first known case of a patient who developed an atopic dermatitis (AD)-like rash during evolocumab therapy. A 43-year-old Japanese man with heterozygous familial hypercholesterolemia was treated with subcutaneous injection of 140 mg evolocumab biweekly, for 16 months. The therapy was then changed to subcutaneous injection of 420 mg evolocumab monthly. A few days after the first dose, the patient experienced pruritus and rash on his extremities. The rash worsened, while the pruritus subsided, then relapsed after the second and third doses. He had erythema and excoriation on his legs, lichenification over his popliteal fossa, xerosis on his forearms, an increased serum IgE level, and a family history of AD in his siblings. We made a provisional diagnosis of AD characterized by enhanced type 2 helper T (Th2) activity and treated him with topical corticosteroids and oral anti-histamines. His rash improved and did not relapse after the fifth dose; however, his LDL-cholesterol level increased. PCSK9 or oxidized LDL activates macrophages or dendritic cells, respectively, and enhances their activity to induce Th1 cells antagonizing Th2 cells. We hypothesized that high-dose evolocumab may suppress Th1 activity to antagonize Th2, and unmask Th2 disposition based on the patient's atopic diathesis, triggering the rash mimicking AD. Clinicians should be aware of rash development during evolocumab therapy.

DOI： 10.1272/jnms.JNMS.2019_86-309

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BACKGROUND: Resistance to thyroid hormone (RTH) usually features a syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) without suppression of the typical high thyroid hormone levels. However, some patients with RTH show thyroid-stimulating hormone (TSH) suppression due to thyrotoxicosis. We report a case of painless thyroiditis in a patient with RTH that was misdiagnosed as Graves' disease because of TSH-suppressed thyrotoxicosis. CASE PRESENTATION: A sixteen-year-old boy consulted a local general physician for fatigue. He had a goiter, and biochemical analysis showed TSH < 0.1 μIU/mL, free triiodothyronine (FT3) of 2.70 pg/mL, and free thyroxine (FT4) of 3.6 ng/dL. He was diagnosed with Graves' disease and was treated with 20 mg thiamazole. One year later, he was referred to the department of endocrinology because of SITSH. He was finally diagnosed with RTH due to the finding of a heterozygous missense mutation (methionine 334 threonine) in the thyroid hormone receptor β gene. Three years after cessation of thiamazole, his hyperthyroxinemia showed marked exacerbation with TSH suppression. We diagnosed him with painless destructive thyroiditis because of low technetium-99 m (Tc-99 m) uptake in the thyroid. Extreme hyperthyroxinemia was ameliorated, with a return to the usual SITSH levels, within 1 month without any treatment. CONCLUSION: The present case demonstrates that diagnosing RTH is difficult when patients show hyperthyroxinemia with complete suppression of TSH to undetectable levels, and the data lead to misdiagnosis of RTH as Graves' disease. The initial diagnosis is important, and Tc-99 m scintigraphy is useful for the differential diagnosis of thyrotoxicosis accompanying RTH.

DOI： 10.1186/s13044-019-0072-2

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Objective- Although postprandial hypertriglyceridemia can be a risk factor for coronary artery disease, the extent of its significance remains unknown. This study aimed to investigate the correlation between the postprandial lipid profiles rigorously estimated with the meal tolerance test and the presence of lipid-rich plaque, such as thin-cap fibroatheroma (TCFA), in the nonculprit lesion. Approach and Results- A total of 30 patients with stable coronary artery disease who underwent a multivessel examination using optical coherence tomography during catheter intervention for the culprit lesion were enrolled. Patients were divided into 2 groups: patients with TCFA (fibrous cap thickness ≤65 µm) in the nonculprit lesion and those without TCFA. Serum remnant-like particle-cholesterol and ApoB-48 (apolipoprotein B-48) levels were measured during the meal tolerance test. The value of remnant-like particle-cholesterol was significantly greater in the TCFA group than in the non-TCFA group ( P=0.045). Although the baseline ApoB-48 level was similar, the increase in the ApoB-48 level was significantly higher in the TCFA group than in the non-TCFA group ( P=0.028). In addition, the baseline apolipoprotein C-III levels was significantly greater in the TCFA group ( P=0.003). These indexes were independent predictors of the presence of TCFA (ΔApoB-48: odds ratio, 1.608; 95% confidence interval, 1.040-2.486; P=0.032; apolipoprotein C-III: odds ratio, 2.581; 95% confidence interval, 1.177-5.661; P=0.018). Conclusions- Postprandial hyperchylomicronemia correlates with the presence of TCFA in the nonculprit lesion and may be a residual risk factor for coronary artery disease.

DOI： 10.1161/ATVBAHA.118.311245

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Healthcare  

Introduction: Although reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported. Methods: Forty patients with type 2 diabetes who were admitted for glycemic control with basal–bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100–120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge. Results: In the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033). Conclusion: In type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100. Trial Registration: UMIN clinical trials registry (UMIN000023360).

DOI： 10.1007/s13300-018-0419-z

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DOI： 10.1016/j.atherosclerosissup.2018.04.121

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

The prognostic impact of a decreased blood glucose level in acute heart failure (AHF) has not been sufficiently clarified. The data from 1234 AHF patients were examined in the present study. The blood glucose (BG) levels were evaluated at admission. The patients were divided into groups based on the following: with or without diabetes mellitus (DM), and BG level ≥ 200 mg/dl (elevated BG) or &lt
200 mg/dl (decreased BG). The elevated and decreased BG patients were further divided into another three groups: 200 mg/ml ≤ BG &lt
300 mg/dl (mild-elevated), 300 mg/ml ≤ BG &lt
400 mg/dl (moderate-elevated) and BG ≥ 400 mg/ml (severe-elevated)
and 150 mg/ml ≤ BG &lt
200 mg/dl (mild-decreased), 100 mg/ml ≤ BG &lt
150 mg/dl (moderate-decreased) and BG &lt
100 mg/ml (severe-decreased), respectively. The DM patients had a significantly poorer mortality than the non-DM patients. The prognosis was different between patients with elevated or decreased BG. In DM patients with elevated BG, the severe-elevated patients had a significantly poorer prognosis than moderate- and mild-elevated patients. In the DM patients with decreased BG, the severe-decreased patients had a significantly poorer prognosis than those moderate- and mild-decreased patients. The multivariate Cox regression model showed that a severe-decreased [hazard ratio (HR) 3.245, 95% confidence interval (CI) 1.271–8.282] and severe-elevated (HR 2.300, 95% CI 1.143–4.628) status were independent predictors of 365-day mortality in AHF patients with DM. The mortality was high among AHF patients with DM. Furthermore, both severe hyperglycemia and hypoglycemia were independent predictors of the mortality in patients with AHF complicated with DM.

DOI： 10.1007/s00380-018-1151-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor or the co-administration of sodium-glucose co-transporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor to insulin therapy is not well known. A total of 58 patients with type 2 diabetes, admitted for glycemic control, were randomized to basal–bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring before discharge. Required insulin doses were not significantly different among the treatment groups. The frequency of nocturnal hypoglycemia was significantly lower in the groups treated with ipragliflozin (6.5 ± 10.6%) and ipragliflozin plus teneligliptin (6.9 ± 14.3%) than in the group treated with BBT alone (42 ± 43.6%). The administration of sodium-glucose co-transporter 2 inhibitor with or without dipeptidyl peptidase-4 inhibitor prevented nocturnal hypoglycemia in type 2 diabetes patients with BBT.

DOI： 10.1111/jdi.12588

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor or the co-administration of sodium-glucose co-transporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor to insulin therapy is not well known. A total of 58 patients with type 2 diabetes, admitted for glycemic control, were randomized to basal-bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring before discharge. Required insulin doses were not significantly different among the treatment groups. The frequency of nocturnal hypoglycemia was significantly lower in the groups treated with ipragliflozin (6.5 +/- 10.6%) and ipragliflozin plus teneligliptin (6.9 +/- 14.3%) than in the group treated with BBT alone (42 +/- 43.6%). The administration of sodium-glucose co-transporter 2 inhibitor with or without dipeptidyl peptidase-4 inhibitor prevented nocturnal hypoglycemia in type 2 diabetes patients with BBT.

DOI： 10.1111/jdi.12588

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

Aim: We studied the frequency of Achilles tendon xanthoma (ATX) in patients with acute coronary syndrome (ACS). Furthermore, we investigated the differences in clinical findings between ACS patients with and without ATX. Methods: Patients with ACS (n=335) were admitted to the coronary care unit of Nippon Medical School between July 2011 and December 2014. Informed consent for the measurement of Achilles tendon thickness (ATT) on a radiograph was obtained from 228 patients without tendon rupture. ATT of each side was measured on the radiograph in patients with ACS and in those with acromegaly (n=18), non-familial hypercholesterolemia (non-FH
n=96), and familial hypercholesterolemia (FH
n=31). Results: ATT of the right and left side in ACS patients were 6.9±1.3 and 7.0±1.6 (mm
mean± SD). In acromegaly, non-FH, and FH patients, ATT of the right/left side were 6.6±1.1/6.7±1.1, 6.2±0.9/6.6±1.0, and 9.4±3.3/10.0±3.1, respectively. ATX (ATT ≥9 mm) was found in 26 (11.4%) patients with ACS. Patients with acromegaly and non-FH had no ATX, whereas all patients with FH had ATX. No differences in age and serum lipid profiles were observed between ACS patients with and without ATX. The levels of body mass index and glycated hemoglobin of ACS patients with ATX were significantly greater than those in ACS patients without ATX (26.8±4.0 vs. 23.9±3.3, p＜0.05, and 6.9±1.4% 6.3±1.3%, p＜0.05, respectively). Conclusion: This is the first report in which the frequency of ACS patients with ATX was 11.4%. The serum lipid profiles of ACS patients with ATX were similar to those without ATX. In the future, ACS patients with ATX will be diagnosed as having FH.

DOI： 10.5551/jat.37770

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Language：Japanese   Publishing type：Research paper (other academic)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: Glucagon-like peptide-1 can reduce both postprandial plasma glucose (PG) and chylomicron (CM) levels in patients with type 2 diabetes. However, there have been no reports regarding the relationship between the postprandial metabolism of PG and CM.
Methods: Patients with type 2 diabetes who were admitted for glycemic control were randomized to insulin alone (Ins; n= 16) or insulin plus vildagliptin 100 mg (InsV; n = 16) groups. The insulin dose was adjusted to maintain normal blood glucose levels. The daily profiles of serum TG, remnant lipoprotein cholesterol (RemL-C), and apolipoprotein B48 (ApoB48) were estimated by frequent blood collection on admission and before discharge, and the daily glucose fluctuation profile was also estimated using continuous glucose monitoring (CGM) before discharge.
Results: The daily profiles of serum TG and RemL-C indicated a significant decrease before discharge compared with on admission; however, no significant changes in serum ApoB48 levels were observed in either group. At discharge, daily glucose fluctuation profile and the change in the serum ApoB48 level from fasting to the peak of the daily profile was significantly smaller in the InsV group than in the Ins group. The increment of serum ApoB48 level was significantly correlated with the mean amplitude of glycemic excursions calculated using CGM data only in the Ins group (R-2 = 0.5242, P &lt; 0.001).
Conclusions: Short-term glycemic control decreased serum TG and RemL-C levels, but not ApoB48 levels, and the postprandial metabolism of PG and CM might be regulated by the same mechanism except GLP-1 effect.

DOI： 10.5551/jat.32409

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DOVE MEDICAL PRESS LTD  

Background: We have recently reported that the attitude of patients toward risk could be a factor in the progression of diabetic complications. In general, risk preference is closely related to socioeconomic status (SES), which includes factors such as age, sex, income, and educational attainment.
Objective: We aimed to determine the effect of SES and behavioral propensity on the progress of diabetic complications in patients with type 2 diabetes mellitus (T2DM).
Methods: We conducted a survey of 238 patients with difficult-to-control T2DM treated at a hospital in Japan using a modified behavioral economics questionnaire that included questions related to SES. The patients had been referred by general practitioners or other departments in the hospital because of poor metabolic control or unstable complications.
Results: Educational attainment was significantly associated with progression of retinopathy in patients,65 years of age. Educational attainment of a high school diploma (12 years of education) or lower was a significant risk factor, but there were no differences among levels of attainment beyond high school (13-16 years or more of education). Behavioral propensities were also weakly associated with complications, but not as much as educational attainment. Personal income level and economic status did not show an association with the retinopathy levels.
Conclusion: Lower educational attainment is a strong risk factor for diabetic retinopathy, and it is independent of the economic status. The result suggests that cognitive function may play an important role in the progression of diabetic retinopathy in patients with T2DM.

DOI： 10.2147/PPA.S116198

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：DOVE MEDICAL PRESS LTD  

Background: Adherence to treatment and the metabolic control of diabetes are challenging in many patients with diabetes. The theory of neuroeconomics can provide important clues for understanding unreasonable human behavior concerning decisions between outcomes occurring at different time points.
Objective: We investigated patients with type 1 and type 2 diabetes to determine whether patients who are at a risk of developing complications are less risk averse. We also examined whether patients with type 1 and type 2 diabetes have different behavioral traits in decision making under risk.
Methods: We conducted a behavioral economics survey of 219 outpatients, 66 with type 1 diabetes and 153 with type 2 diabetes. All patients had been referred by general practitioners or other departments in the hospital. At the time of the survey, levels of hemoglobin A(1c) were not significantly different between patients with type 1 and type 2 diabetes.
Results: Patients with type 2 diabetes showed a lower response rate to the survey compared with patients with type 1 diabetes (71.9% vs 87.9%, P&lt;0.01). Logistic regression analysis indicated that diabetic retinopathy was negatively associated with risk averse in pricing of hypothetical lotteries, myopic time preference, willingness to pay for preventive medicine, and levels of satisfaction with life. Diabetic nephropathy was also negatively associated with risk averse in pricing of hypothetical lotteries. Detailed analysis revealed that a lower proportion of patients with type 2 diabetes (22.7%) were categorized as risk averse compared with patients with type 1 diabetes (43.1%, P&lt;0.05) in hypothetical lottery risk estimation.
Conclusion: This is the first report that investigated patients with diabetes in a clinical setting using a method based on behavioral economics. The results suggest that the attitude of patients toward risk plays an important role in the progress of the complications of diabetes. Different educational and psychological approaches may be necessary to assess patients with diabetes based on whether they have traits such as risk seeking or risk averse.

DOI： 10.2147/PPA.S82022

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aims/Introduction-Glucosidase inhibitors (GIs) are widely used for the primary treatment of type2 diabetes. We compared the clinical effects of three GIs (miglitol, acarbose and voglibose) in patients with obese type2 diabetes.
Materials and MethodsJapanese patients (n=81) with obese type2 diabetes (body mass index [BMI] 25kg/m(2)) were enrolled in this multicenter, open-label study. The participants were randomized into the miglitol (n=18), acarbose (n=22), voglibose (n=19) or control (n=22) groups. Glycemic control (fasting blood glucose and glycated hemoglobin [HbA1c]), bodyweight, BMI, serum insulin, serum lipids (low-density lipoprotein and high-density lipoprotein cholesterol, and triacylglycerols) and adipocytokines (leptin and adiponectin) were evaluated every 4weeks for 12weeks.
ResultsIn the miglitol group, HbA1c was improved significantly from the baseline at all points. The changes in HbA1c at 8 and 12weeks from baseline were greater in the miglitol group than the control group. The voglibose group showed significant improvements in HbA1c at 12weeks. Bodyweight and BMI were decreased significantly in the miglitol group. In addition, significant correlations were observed between the decrements in HbA1c and bodyweights over 12weeks in the miglitol (r=0.759, P&lt;0.001) and voglibose groups (r=0.667, P=0.002). Serum lipid and adipocytokine levels were not altered in any groups.
ConclusionsGIs, especially miglitol, can effectively control blood glucose and bodyweight in obese type2 diabetes. This study was registered with UMIN (no. UMIN000006465).

DOI： 10.1111/jdi.12135

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2013.12.042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: Atherosclerosis is strongly associated with an increased mortality in subjects with diabetes. The carotid intima-media thickness (IMT) is commonly measured as a surrogate marker for cardiovascular risk. Statins are well-established protective agents against atherosclerosis and reportedly suppress IMT progression in subjects with diabetes. To clarify the effects of statins on subclinical atherosclerosis, we herein investigated changes in the carotid IMT and lipid profiles in a multi-center, prospective, randomized trial.
Methods: Hypercholesterolemic subjects with type 2 diabetes were randomly assigned to open-label treatment with either pravastatin or pitavastatin. The primary endpoint of this study was the IMT change after 36 months of statin treatment.
Results: A total of 97 subjects (51 pitavastatin; 46 pravastatin) completed this 36-month study. The LDL-C decreased significantly from 163.4+/- 27.9 mg/dl at baseline to 100.4+/- 19.6 mg/dl at 36 months in the pitavastatin group and from 159.7+/- 25.6 mg/dl to 118.5+/- 22.1 mg/dl in the pravastatin group. The mean IMT showed moderate regression in both the pitavastatin (-0.070+/- 0.215 mm, P&lt;0.05) and the pravastatin (-0.067+/- 0.260 mm) group. However, there was no significant difference in the IMT change between the two groups. When the two groups were combined, the 36-month change in the mean IMT was significantly associated with HDL-C change (r=-0.24, P=0.03). Multiple linear regression analysis revealed the change in HDL-C to be an independent variable showing a positive correlation with the carotid IMT reduction.
Conclusion: The administration of statins for 3 years to subjects with type 2 diabetes resulted in a significant regression of the carotid IMT. An elevation of the plasma HDL-C with statin treatment was closely related to a regression of atherosclerosis.

DOI： 10.5551/jat.22095

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aims/IntroductionPostprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes.
Materials and MethodsPatients with type 2 diabetes (n=236) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control (aged 19-86years, 81 females and 155 males) were examined. Clinical measurements were taken on admission. The presence of carotid plaque was assessed by ultrasonography.
ResultsIn patients with carotid plaque (n=154), GA (P=0.023) was higher than those without carotid plaque (n=82). In contrast, neither fasting plasma glucose (P=0.48) nor glycated hemoglobin (P=0.41) was significantly different between the groups. The results of logistic regression analysis showed that GA (age- and sex-adjusted odds ratio [95% confidence interval], 1.05 [1.01-1.09]; P=0.017) and glycated hemoglobin (1.17 [1.01-1.37]; P=0.036) were significantly associated with the presence of carotid plaque.
ConclusionsThe positive correlation of serum GA with the presence of carotid plaque in type2 diabetes suggests that GA will serve as a useful clinical marker for predicting diabetic cardiovascular complications.

DOI： 10.1111/jdi.12085

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Other Link： http://orcid.org/0000-0002-7588-6761

Language：Japanese   Publisher：日本医師会  

糖尿病外来の医療資源配分を定量的に分析し、良好な血糖コントロールに必要な医療資源の投入量を検証することを目的に、2009年10月〜2010年9月の12ヵ月間を調査期間とし、当院内分泌専門外来担当医師1名が診療を行った糖尿病患者525名を対象に、カルテを基に後ろ向き調査を行った。その結果、調査期間の12ヵ月間で総計3423回の診療・介入があった。病型別では、1型糖尿病患者と期間中に初診の2型糖尿病患者に有意に高い診療・介入が行われていた一方、継続診療を行っている2型糖尿病患者への介入、とくにコメディカルの介入は明らかに少なく、調査期間の最後の3ヵ月間に悪化した集団をみると、コメディカルの介入は平均で0.63回であった。2型の継続治療においても、少なくとも年1回のコメディカルの介入が必要であると考えた。

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

症例は76歳男性。20年前に糖尿病と診断され経口血糖降下薬で加療されていたが、2009年7月に血糖コントロール不良のため前医へ入院しインスリンアナログ製剤による治療が開始された。退院後から低血糖が頻回となり、総インスリン値11000μU/ml、125Iインスリン結合率89.5%とインスリン抗体による低血糖が疑われた。Scatchard解析の結果はhigh-affinity siteの親和性が低く、結合能が高い、インスリン自己免疫症候群(IAS)に類似した抗体であった。持続血糖モニター(CGM)にて早朝と昼食後に再現性のある血糖低下を認めたため、その結果に基づいてインスリン調節や療養指導を行ったところ血糖変動パターンは改善した。インスリン抗体によって血糖コントロールが不安定化した糖尿病ではインスリン作用時間の予測がつきにくく治療に難渋することが多いが、CGMによる介入が血糖コントロールの安定化に有用であることを示唆する貴重な1例と考えられたため報告する。(著者抄録)

DOI： 10.11213/tonyobyo.55.874

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J00926&link_issn=&doc_id=20121210370008&doc_link_id=10.11213%2Ftonyobyo.55.874&url=https%3A%2F%2Fdoi.org%2F10.11213%2Ftonyobyo.55.874&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aims/Introduction: The development of type 2 diabetes is primarily due to lifestyle and environmental factors, as well as genetics, as shown by familial clustering. To establish mouse lines for evaluating heritable factors determining susceptibility to diet-induced diabetes, we performed selective breeding for differences in high fat diet (HFD)-induced glucose intolerance. Materials and Methods: Selective breeding was performed using hybrid mice of C57BL/6J, C3H/HeJ and AKR/N backgrounds. After 5-week HFD feeding, mice showing high and low 2-h blood glucose levels in an oral glucose tolerance test (OGTT) were selected and bred over 14 generations to produce lines prone and resistant to diet-induced glucose intolerance (designated Selectively bred Diet-induced Glucose intolerance-Prone [SDG-P] and -Resistant [SDG-R]). Results: At 5 weeks of age (pre HFD feeding), SDG-P mice showed higher blood glucose levels both in the OGTT and insulin tolerance test as compared to SDG-R mice. After receiving HFD, the glucose intolerance of SDG-P mice became more evident without hyper insulin secretion. In addition, SDG-P mice had greater body weight gain and lower HDL-cholesterol levels as compared to SDG-R mice. In comparison with C57BL/6J, a well-known strain prone to HFD-induced glucose intolerance, SDG-P mice showed significantly higher glucose levels in OGTT after the 5-week HFD feeding. Conclusions: Susceptibility to HFD-induced glucose intolerance was transmitted over generations and was intensified by selective breeding. The newly established mouse lines, SDG-P and SDG-R, may be useful in investigating the pathophysiology of type 2 diabetes through elucidating the crucial factors for determining the susceptibility to HFD-induced glucose intolerance. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00175.x, 2011)

DOI： 10.1111/j.2040-1124.2011.00175.x

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Other Link： http://orcid.org/0000-0002-7588-6761

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Language：English   Publisher：SPRINGER  

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Language：English   Publisher：ELSEVIER IRELAND LTD  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Increasing evidence indicates that phospholipid oxidation plays important roles in atherosclerosis. Here, we investigated the involvement of Rho-family GTPases inphosphatidylcholine hydroperoxide (PCOOH)induced THP-1 cell adhesion to ICAM-1. Isoprenoid depletion by fluvastatin and geranylgeranyltransferase inhibition by GGTI-286 suppressed PCOOH-induced cell adhesion to ICAM-1 and F-actin-rich membrane protrusion formation. Pull-down assays demonstrated the activation of Rac1 and Rac2 in PCOOH-treated cells. Pan-Rho-family GTPase inhibitor Clostridium difficile toxin B. Rac-specific inhibitor NSC23776, and RNA interference of the Rac isoforms suppressed the cell adhesion. These findings indicate the involvement of Rac GTPase activation in PCOOH-induced cell adhesion to ICAM-1 via actin reorganization. (C) 2011 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.bbrc.2011.02.032

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Insulin tolerance test (ITT) is the gold standard for assessing the hypothalamic-pituitary-adrenal (HPA) function. GH-releasing peptide (GHRP)-2, which has a strong GH-stimulating activity, is useful for diagnosing GH deficiency as well as ITT. Additionally, GHRP-2 is also known to activate HPA axis. There have been no comparative studies of pituitary-adrenal responsiveness between GHRP-2 test and ITT in patients with hypothalamic/pituitary disease. To assess whether GHRP-2 test could be an alternative to ITT for diagnosing HPA axis failure, both ITT and GHRP-2 test were performed in 15 patients suspected of hypopituitarism. A 100 mu g dose of GHRP-2 was administered intravenously and plasma ACTH and serum cortisol concentrations were measured. In ITT, a peak cortisol value over 18 mu g/dl is considered normal. Nine patients were diagnosed as HPA axis failure by ITT. Their median peak cortisol in GHRP-2 test was 11.4 mu g/ml. In 6 patients diagnosed as normal HPA axis status by ITT, their median peak cortisol in response to GHRP-2 test was 21.4 mu g/dl, significantly higher (p = 0.0032) than seen in patients diagnosed as HPA axis failure. There was a strong correlation between the peak cortisol in GHRP-2 test and ITT (r = 0.817; p &lt; 0.0001). When the cut-off value for the peak cortisol in GHRP-2 test was set to 13-14 mu g/dl for diagnosing HPA axis failure, the specificity and sensitivity were 100% and 88.9%, respectively. Although further studies that include normal subjects are needed, these preliminary results suggest the possibility that GHRP-2 test may be an alternative to ITT for assessing HPA axis function. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.peptides.2009.12.023

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Other Link： http://orcid.org/0000-0002-7588-6761

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Other Link： http://orcid.org/0000-0002-7588-6761

Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: We investigated how dietary management affected body weight (BW) reduction and energy expenditure in obese and normal-weight type 2 diabetic patients.
Methods: Type 2 diabetic patients who were hospitalized for diabetic control (93 men and 51 women) were checked for resting energy expenditure (REE). Subjects were divided into the two groups according to body mass index (BMI): obese (BMI &gt;= 25), and normal-weight (BMI&lt;25). Following the recommendations by JDS, JAS and JASSO, ideal body weight was calculated as [IBW = height (m) x height (m) x 22 (kg/m(2))], and dietary calorie (kcal/day) was determined as 25 kcal/kg IBW.
Results: Dietary calorie intake during hospitalization was similar in both groups. REE was greater in obese than in normal-weight patients. The difference between the calorie intake and energy expenditure (Delta calorie) was -222 +/- 26 kcal in obese patients and 69 +/- 27 kcal in normal-weight patients. Obese patients therefore had larger BW decreases than normal-weight patients (-171 +/- 12 vs. -92 +/- 11 g/day, p&lt;0.005). In the obese group, a positive correlation was found between the change of BW and Delta calorie. This correlation remained after adjusting for age, BMI, gender, and respiratory quotient. Serum lipid profiles were significantly improved in both groups.
Conclusion: These diet instructions showed the appropriate calorie restriction depending on the BMI and induced reasonable BW reduction in both obese and normal-weight subjects. The dietary program recommended by JDS, JAS and JASSO is practically useful for BW control and for improving lipid metabolism in type 2 diabetic patients.

DOI： 10.5551/jat.3806

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

The accumulation of phosphatidylcholine hydroperoxide (PCOOH), a primary oxidation product of phosphatidylcholine (PC), in blood plasma and tissues has been observed in various pathological conditions, including atherosclerosis. However, the biological roles of PCOOH in these conditions remain unknown. To estimate the athero-genicity of PCOOH, we evaluated the effect of PCOOH on THP-1 monocytic cell adherence to immobilized vascular endothelial cell adhesion molecules. THP-1 cell adhesion to intracellular adhesion molecule-1 (ICAM-1) was dose-dependently increased by addition of PCOOH. Phosphatidylcholine hydroxide (a hydroxyl analog of PCOOH) also induced THP-1 cell adhesion to ICAM-1, whereas nonoxidized PC, sn-2 truncated PCs, and other hydroperoxide compounds did not affect the adhesion. In the PCOOH-treated cells, obvious protruding F-actin-rich membrane structures were formed, and lymphocyte function-associated antigen-1 (LFA-1) was localized to the protruding structures. Cytochalasin D, an actin polymerization inhibitor, suppressed the PCOOH-induced cell adhesion to ICAM-1 and the membrane protrusions. jlr These results indicate that PCOOH evokes LFA-1-mediated cell adhesion to ICAM-1 via actin cytoskeletal organization, and the mechanism may participate in monocyte adherence to the arterial wall in the initiation of atherosclerosis.-Asai, A., F. Okajima, K. Nakagawa, D. Ibusuki, K. Tanimura, Y. Nakajima, M. Nagao, M. Sudo, T. Harada, T. Miyazawa, and S. Oikawa. Phosphatidylcholine hydroperoxide-induced THP-1 cell adhesion to intracellular adhesion molecule-1. J. Lipid Res. 2009. 50: 957-965.

DOI： 10.1194/jlr.M800582-JLR200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Aims: The atherogenicity of chylomicron remnants has been discussed. We examined whether serum apoB48 level is associated with the presence of carotid plaque in type 2 diabetic patients.
Method: Forty type 2 diabetic patients (21 males and 19 females, 52.8 +/- 11.8 years old; mean +/- S.D.) were divided into two groups by the presence or absence of carotid plaque. The diurnal change of serum apoB48 level was measured by enzyme-linked immunosorbent assay.
Results: Fasting serum apoB48 level was higher in the subjects with carotid plaque than those without (6.5 +/- 3.8 vs. 4.1 +/- 1.9 mu g/ml, p = 0.01). Age- and gender-adjusted analysis showed that the presence of carotid plaque was associated with fasting apoB48 (OR 1.43; 95% CI, 1.07-2.09, p = 0.04) and triglyceride (OR 1.14; 95% CI, 1.02-1.32, p = 0.04) levels. In normal LDL-cholesterol (&lt;140 mg/dl) subjects, the presence of carotid plaque was associated with fasting apoB48 level (OR 2.16; 95% CI, 1.22-5.32, p = 0.04), but not associated with fasting triglyceride level (OR 1.11; 95% CI, 0.99-1.30, p = 0.13).
Conclusions: Serum apoB48 level was strongly associated with the presence of carotid plaque in type 2 diabetic patients. (C) 2008 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.diabres.2008.04.028

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/S1567-5688(08)70304-0

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/S1567-5688(08)70213-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：EDITRICE KURTIS S R L  

Cases of acromegaly due to GHRH-producing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old non-acromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TRH and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS, insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.

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DOI： 10.1016/S1567-5688(06)80948-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHARMACEUTICAL SOC JAPAN  

Recent studies suggest that advanced glycation end products (AGEs) can promote the development of atherosclerotic lesions in a similar manner to oxidatively modified low density lipoproteins. As oxidative stress accelerates the formation of AGEs, antioxidant drugs may exert atheroprotective effects via suppression of AGE formation. Although amlodipine, a calcium channel blocker, and fluvastatin, a 3-hydroxy-3-methylglutaryl CoA reductase inhibitor, show antioxidant and atheroprotective effects, the relation of AGEs to their effects is unknown. We immunohistochemically investigated the inhibitory effects of chronic treatment with amlodipine (5 mg/kg per day) or fluvastatin at a dose insufficient to reduce plasma cholesterol levels (2 mg/kg per day) on the accumulation of AGEs in atherosclerotic aortas of rabbits fed 1% cholesterol diet and 10% fructose containing water. After eight weeks of treatment, AGEs, namely argpyrimidine, carboxymethyllysine and pyrraline, markedly accumulated with intimal thickening in cholesterol and fructose-fed control rabbits, while the drugs inhibited those changes other than the pyrraline deposition without plasma lipid-lowering effects. Enhanced lipid peroxidation was observed in plasma from cholesterol and fructose-fed rabbits only, and lipid peroxidation was not suppressed by the drugs. These results suggest that the atheroprotective effects of the drugs are at least partly due to the suppression of AGE accumulation although the exact mechanism of AGE suppression is ambiguous.

DOI： 10.1248/bpb.29.75

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We examined the effect of oxidized low-density lipoprotein (oxLDL) on the insulin secretion in the culture of HIT-T15 cell line, an islet beta-cell line derived from a hamster pancreatic tumor. In order to check the uptake of modified LDL by HIT-T15 cells, we prepared DiI-labeled native LDL (nLDL), acetylated LDL (AcLDL), and oxLDL. After the addition of each LDL into the cultures of HIT-T15 cells, fluorescence microscopic study was done. It was suggested that AcLDL and oxLDL were taken up by HIT-T15 cells, as well as nLDL. mRNA expression of the LDL receptor, CD36, and SR-B1 was detected in HIT-T15 by RT-PCR. The medium insulin level was measured in the culture of HIT-T15 cells with each LDL. oxLDL significantly reduced the insulin secretion stimulated by various concentrations of glucose, the intracellular content of insulin, and the expression of preproinsulin mRNA compared to the control cultures without LDL addition. In contrast, nLDL and AcLDL had no effect on the insulin secretion, the intracellular insulin level, or the expression of preproinsulin mRNA. MTT assay findings (reflecting cell numbers) were not different between cultures with and without LDLs. These results indicated that oxLDL disturbed the insulin metabolism of HIT-T15 cells.

DOI： 10.1016/j.bbalip.2004.11.018

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We examined the effect of oxidized low-density lipoprotein (oxLDL) on the insulin secretion in the culture of HIT-T 15 cell line, an islet beta-cell line derived from a hamster pancreatic minor. In order to check the uptake of modified LDL by HIT-T15 cells, we prepared DiI-labeled native LDL (nLDL), acetylated LDL (AcLDL), and oxLDL. After the addition of each LDL into the cultures of HIT-T15 cells, fluorescence microscopic study was done. It was suggested that AcLDL and oxLDL were taken up by HIT-T 15 cells, as well as nLDL. mRNA expression of the LDL receptor, CD36, and SR-B1 was detected in HIT-T15 by RT-PCR. The medium insulin level was measured in the culture of HIT-T15 cells with each LDL. oxLDL significantly reduced the insulin secretion stimulated by various concentrations of glucose, the intracellular content of insulin, and the expression of preproinsulin mRNA compared to the control cultures without LDL addition. In contrast, nLDL and AcLDL had no effect on the insulin secretion, the intracellular insulin level, or the expression of preproinsulin mRNA. MTT assay findings (reflecting cell numbers) were not different between cultures with and without LDLs. These results indicated that oxLDL disturbed the insulin metabolism of HIT-T15 cells. (C) 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.bbalip.2004.11.018

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4P-1005

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

ハムスターのインスリノーマ由来のHIT-T15細胞を用いて,膵β細胞のインスリン分泌能に対するリポ蛋白の影響について実験を行った.各々のリポ蛋白(LDL,アセチルLDL,酸化LDL)を添加し,24時間,或いは48時間インキュベートした.その上澄を100mg/dL,300mg/dL,500mg/dLのグルコースを含んだバッファーで置換し,2時間インキュベート後,そのバッファーへのインスリンの分泌量,及び細胞内のインスリン濃度に関して検討を行った.プレプロインスリンの発現に関してはリアルタイム(RT)-PCR法を用いた.実験の結果,HIT-T15細胞では酸化LDLがインスリンの合成及び遺伝子の発現,また,分泌を抑制することが示唆された

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Language：Japanese   Publisher：(一社)日本糖尿病・妊娠学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本臨床化学会  

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Language：Japanese   Publisher：日本肥満症治療学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：医学図書出版(株)  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(株)医学書院  

糖尿病と脂質異常症はともに心血管疾患の危険因子であり,両者の合併はさらに心血管疾患のリスクを増大させるため,その管理は非常に重要である.糖尿病患者における脂質異常症は臨床的に高コレステロール血症,高TG血症,低HDL-C血症としてとらえられる.脂質異常症の検査では,検診などの一般的な測定項目である総コレステロール,HDL-C,中性脂肪のほかに,リポ蛋白分析やアポ蛋白の測定などがある.これらの検査を組み合わせることで,病態を把握し,適切な治療を行うことが必要である.(著者抄録)

DOI： 10.11477/mf.1542102383

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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Language：Japanese   Publisher：ライフサイエンス出版(株)  

本研究ではマウスを用いて高脂肪食で誘発される耐糖能異常を指標として高血糖値を示す個体の選抜交配を繰り返し、高脂肪食により糖代謝異常を惹起する因子が継代によって濃縮され、病態の出現が促進される系統の樹立を目標とした。その結果、高脂肪食負荷後の血糖値を指標とした選抜交配により、次世代の糖代謝異常出現率が増加しており、高脂肪食に対する反応性が形質として濃縮され次世代に伝播したと考えられた。更に高脂肪食負荷前の5週齢で既に耐糖能異常を呈していることから、選抜交配による糖代謝異常が系統的に確立されたと考えられた。また高脂肪食負荷前の5週齢雄では体重に差がみられないことから、糖代謝異常は肥満に先行して出現していると考えられた。以上より、今後、高血糖コロニーと正常血糖コロニーの差を更に検討することにより高脂肪食が肥満・糖尿病の発症に影響する遺伝子を解明できると考えられた。

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)ライフ・サイエンス  

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Language：Japanese   Publisher：(株)医学出版  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：日本肥満症治療学会  

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Language：Japanese   Publisher：(株)北隆館  

血清脂質低下療法が冠動脈心疾患(CHD)の発症を抑制することは、多くの大規模臨床研究により明らかとされている。さまざまな薬剤の中でもHMG-CoA還元酵素阻害薬(スタチン)は、質、量ともに豊富なエビデンスに支えられ、脂質異常症治療の中心的薬剤となっている。本稿では、CHD発症リスクの低い患者に、強力なLDL-C低下作用を持つロスバスタチン(クレストール)を投与し、頸動脈内膜中膜肥厚の経時的変化が検討されたMETEOR試験を紹介し、低リスク患者に呈するスタチン治療の意義に関して考察する。(著者抄録)

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)日本臨床社  

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/2008336506

Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：日本肥満症治療学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

メタボリックシンドローム患者は、虚血性心疾患や新規糖尿病を高率に発症する。これまでにメタボリックシンドローム患者の高血糖に対し治療介入を行った臨床試験はないが、高血糖患者を対象としたさまざまな大規模臨床試験の結果からは、虚血性心疾患の発症予防には血糖コントロールだけでは不十分で、それぞれの代謝異常をトータルにコントロールすることの重要性が示唆されている。また、メタボリックシンドローム患者においては、正常空腹時血糖であっても、糖尿病新規発症のハイリスク群と考え、早期より積極的な治療介入が必要であると考えられる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

Web of Science

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Language：Japanese   Publisher：(株)メジカルビュー社  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：メデカジャパン・ラボラトリー  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(株)メディカルレビュー社  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：眼科臨床医報会  

60歳男.全身倦怠感の後に視力低下を来たし,右眼が15cm指数弁,左眼は光覚弁であった.前眼部・中間透光体の細隙灯顕微鏡所見で,右眼は前房内に細胞(1+),左眼は結膜浮腫,角膜後面沈着物,前房内細胞(3+),瞳孔領にフィブリンの析出を認め,眼底は両眼とも透見不能であった.超音波では両眼に硝子体混濁を認めた.内科でのCTで肝膿瘍,脳膿瘍を認め,血液培養でKlebsiella pneumoniaeが検出された.塩酸セフェピム,パニペネム・ベタミプロン,メロペネム・トリハイドレート,アルベカシン・サルフェート,塩酸シプロキサシン,セフトリアキソンナトリウム,セフタジジムの点滴を行うと共に,レボフロキサシン,リン酸ベタメタゾンナトリウムの点眼と,硫酸アトロピンを使用した.1週間後に右眼底透見可能となり,網膜上滲出斑を多数認めた.左眼は透見不能のままで,前房内の細胞は減少したが,角膜後面沈着物は多数残存していた.その後肝膿瘍は縮小し,全身状態も改善傾向となり,2ヵ月後右眼の網膜上滲出斑は消失し,視力も0.3まで改善したが,左眼は回復しなかった

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：間脳・下垂体・副腎系研究会  

CRH負荷試験でACTHの反応を認め,インスリン低血糖試験で無反応であったため視床下部性副腎皮質機能低下症と診断した2例を経験した.症例1(37歳女).出産5ヵ月後より易疲労感と体重増加,下肢の浮腫を自覚し,原発性甲状腺機能低下症と診断された.全身倦怠感が増強したため入院となった.負荷試験の結果より視床下部性副腎皮質機能不全と診断しサイロキシンに加えてヒドロコルチゾンの投与を開始したところ症状は改善し,消失した.症例2(67歳女).全身倦怠感,食欲低下が徐々に悪化した.進行する低ナトリウム血症を認め,下垂体機能低下症が疑われ入院となった.下垂体機能低下症,視床下部性副腎皮質機能低下症と診断し,ヒドロコルチゾンに引き続きサイロキシンの補充を開始したところ症状の改善を認めた

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)東京内科医会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

40歳女性.患者は30歳時に糖尿病性ケトアシドーシスを発症,1型糖尿病と診断され,強化インスリン療法導入となった.その後,四肢の痺れ感より糖尿病性神経障害との診断でカルバマゼピン服用を開始したが,全身に掻痒を伴う皮疹と発熱で中毒疹を疑われ緊急入院なった.所見では,顔面はじめ体幹,下肢を中心にほぼ全身に斑状の浮腫性紅斑を認め,生検と血液培養により敗血症と診断した.さらに低ガンマグロブリン症も併発しており抗生剤,ガンマグロブリン製剤の投与で発熱は軽快した.一方,パッチテストやスクラッチテストではカルバマゼピンのみ陽性で同薬によるHypersensitivity syndrome(HS)と診断し,カルバマゼピンの中止を行い,ステロイド外用薬で皮疹は改善した

DOI： 10.11213/tonyobyo1958.46.869

CiNii Books

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCI IRELAND LTD  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)文光堂  

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Language：Japanese   Publisher：(一社)日本肥満学会  

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Language：Japanese   Publisher：(一社)日本糖尿病合併症学会  

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Language：Japanese   Publisher：医歯薬出版(株)  

アポリポ蛋白E(アポE)は,カイロミクロンや超低比重リポ蛋白など中性脂肪(TG)を豊富に含んだリポ蛋白の表面に位置し,それらを構成する主要なアポリポ蛋白である.アポEには6つの表現形の異なる多型が存在し,E2が原発性III型高脂血症の原因となっていることはよく知られている.近年では,脂質代謝を介さない機能に関して様々な報告がなされており,リポ蛋白糸球体症といった特殊な腎障害がアポEの変異で発症することが明らかにされた.又,糖尿病性腎症の進展や心血管疾患,アルツハイマー病といった発症頻度の高い疾患に関してもアポEの多型が関連することが明らかにされ,その機序に関しても詳細な研究が進み,明らかになっている

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本動脈硬化学会  

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Language：Japanese   Publisher：(一社)日本老年医学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(株)南江堂  

近年,肥満,耐糖能異常,高脂血症,高血圧症等の代謝異常は,各々の異常は軽度であっても,複数合併した病態では動脈硬化性疾患が高頻度に合併することが明らかにされた.これらの代謝異常は動脈硬化の発症,進展と綿密な関係をもつ危険因子として注目されるようになった.このような危険因子の集積は,危険因子重積症候群と呼ばれる.これらは内臓脂肪症候群,Syndrome X,死の四重奏,インスリン抵抗性症候群などと呼ばれるものと,本質的には同じものである.各々の危険因子の関連性とその病態について概説した

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