Atypical Clinical Courses of Graves' Disease Confound Differential Diagnosis of Hyperthyroidism.

BACKGROUND: This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. METHODS: We retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. RESULTS: Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 [49%]; subacute thyroiditis, 29/67 [43%]), and some were positive for anti-TSH receptor antibodies. CONCLUSION: Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.

Use of the Japanese Version of the Montreal Cognitive Assessment to Estimate Cognitive Decline in Patients Aged 75 Years or Older with and without Type 2 Diabetes Mellitus.

BACKGROUND: The number of people diagnosed with dementia worldwide is set to increase significantly. Patients with dementia often have comorbidities, particularly diabetes, and patients with type 2 diabetes mellitus (T2DM) have a high risk of cognitive decline. This study investigated whether older people with T2DM have disease-specific cognitive deficits. METHODS: The Montreal Cognitive Assessment is a well-known tool for examining mild cognitive impairment, and the modified Japanese version (MoCA-J) has been confirmed as effective. Using the MoCA-J, we assessed the cognitive function of Japanese adults aged ≥75 years with and without T2DM and analyzed the results. RESULTS: Thirty-three patients with T2DM and 23 non-DM patients completed the examination, and MoCA-J total scores differed between these groups (T2DM mean, 21.4 ± 3.5; non-DM mean, 23.5 ± 3.6). Only 9% of patients with T2DM and 39% of those with non-DM had scores ≥26, which is the cutoff point for mild cognitive impairment, although all patients were capable of self-care. Additionally, delayed recall scores were significantly lower for the older patients with T2DM had for the non-DM group. CONCLUSIONS: Patients aged ≥75 years with T2DM might have worse cognition than those without T2DM; the inability to perform delayed recall in T2DM patients suggests a decline in cognitive function. Therefore, patients aged ≥75 years with T2DM should receive explanations of their care that are individualized in relation to their cognitive status.

Clinical Significance of Low-Triiodothyronine Syndrome in Patients Requiring Non-Surgical Intensive Care　- Triiodothyronine Is a Comprehensive Prognostic Marker for Critical Patients With Cardiovascular Disease.

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.

Risk Preferences, Rationality of Choices, and Willingness to Pay for Preventive Medicine in Patients with Graves' Thyrotoxicosis.

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.

Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Type 1 Diabetes Mellitus on Body Composition and Glucose Variabilities: Single-Arm, Exploratory Trial.

INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors are widely used in the management of type 2 diabetes mellitus; they prevent cardiovascular events and reduce fat mass. However, little is known about the effects of SGLT2 inhibitors on type 1 diabetes mellitus as an adjuvant to insulin therapy. Therefore, we aimed to elucidate the effects of SGLT2 inhibitors on body composition of patients with type 1 diabetes mellitus and assess blood glucose variability. METHODS: A single-center, single-arm, prospective, interventional study was performed on Japanese patients with type 1 diabetes mellitus who were not administered SGLT2 inhibitors prior to this study. These patients were equipped with flash glucose monitoring (FGM) and administered ipragliflozin 50 mg daily. Body composition was evaluated using bioelectrical impedance analysis, and glycemic variabilities were assessed using FGM before and after SGLT2 inhibitor treatment. RESULTS: After 52 weeks of treatment, the total fat mass tended to be reduced (- 9.10% from baseline, P = 0.098). In addition, skeletal muscle mass also decreased (- 2.98% from baseline, P = 0.023). Although the basal insulin dose was reduced, SGLT2 inhibitors decreased HbA1c levels. FGM revealed that glycemic variabilities were also reduced, and time within the target glucose range increased (51.7% vs. 62.5%, P = 0.004). CONCLUSION: SGLT2 inhibitors have beneficial effects on glycemic variabilities and fat mass reductions in patients with type 1 diabetes mellitus. However, loss of skeletal muscle is a major concern; therefore, caution is required when using SGLT2 inhibitors in lean patients with type 1 diabetes mellitus. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000042407).

Efficacy and Safety of Miglitol- or Repaglinide-Based Combination Therapy with Alogliptin for Drug-Naïve Patients with Type 2 Diabetes: An Open-Label, Single-Center, Parallel, Randomized Controlled Pilot Study.

BACKGROUND: Combination 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 these two combination therapies in relation to efficacy and safety. METHODS: Eighteen patients with type 2 diabetes were studied. All had diabetes not adequately controlled with diet and exercise therapy, an HbA1c level of ≥7.5%, and were not 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. RESULTS: During 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 higher only in the repaglinide group; ISG0-30 did not significantly increase in either group after the addition of alogliptin. CONCLUSIONS: The addition of alogliptin to repaglinide monotherapy did not cause glucose-independent inappropriate insulin secretion and did not appear to increase the incidence of hypoglycemia.

Assessing Patient Satisfaction Following Sodium Glucose Co-Transporter 2 Inhibitor Treatment for Type 1 Diabetes Mellitus: A Prospective Study in Japan.

INTRODUCTION: In Japan, several sodium glucose co-transporter 2 (SGLT2) inhibitors have been used for type 1 diabetes mellitus as an adjuvant therapy to insulin therapy; however, there are no clinical reports regarding the satisfaction of its use. Therefore, we conducted a survey among patients with type 1 diabetes undergoing treatment using an SGLT2 inhibitor. METHODS: This is a single-arm open-label prospective study including 24 patients with type 1 diabetes who were to be initiated on ipragliflozin treatment between March and August 2019. All participants provided written informed consent. They completed the Diabetes Treatment Satisfaction Questionnaire (DTSQ) for the survey and 3 months of observation after the administration of an SGLT2 inhibitor (50 mg of ipragliflozin), and changes from baseline diabetes treatment satisfaction were evaluated using modified DTSQ scores (five-step evaluation) and were analyzed. RESULTS: The average score for each question on DTSQ significantly increased [mean (standard deviation); 0.25 (0.25) vs 0.83 (0.77), P = 0.004]. Approximately 75% of the patients perceived an improvement in glycemic control over short periods of time. Finally, 54.2% of patients were highly satisfied and would recommend the SGLT2 inhibitor treatment [0.0 (0.0) vs. 0.92 (1.32), P < 0.001]. After the administration of ipragliflozin, reductions in body weight [24.0 (2.9) vs. 23.4 (2.9) kg/m2, P = 0.002], total insulin [39.1 (12.9) vs. 34.3 (12.5) units, P = 0.013], and glycated hemoglobin [7.77 (0.97) vs. 7.40 (0.86) %, P = 0.013] were observed, without any severe side effects. Improvements in glycemic variability indexes were observed through flash glucose monitoring. CONCLUSIONS: SGLT2 inhibitors may improve clinical treatment satisfaction by improving glycemic variability in patients with type 1 diabetes mellitus, while not inducing severe side effects with careful use. TRIAL REGISTRATION: This study is registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000040487).

New-onset graves' disease after the initiation of nivolumab therapy for gastric cancer: a case report.

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.

Mechanisms of Urgently Presenting Acute Heart Failure.

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.

Empagliflozin Administration Can Decrease the Dose of Loop Diuretics and Prevent the Exacerbation of Renal Tubular Injury in Patients With Compensated Heart Failure Complicated by Diabetes.

Background: Whether the dose of loop diuretics can be decreased by administration of a sodium-glucose cotransporter 2 (SGLT2) inhibitor in diabetic outpatients with compensated heart failure (HF) is unclear. Methods and Results: This study prospectively enrolled 60 diabetic outpatients with compensated HF. Patients were randomly divided into 2 groups: those administered the SGLT2 inhibitor empagliflozin (n=28) and those not (n=30). Changes in the daily dose of loop diuretics, blood sampling data, and urinary renal tubular biomarkers were evaluated 6 months after the intervention. The median (interquartile range) furosemide dose decreased significantly over the 6-month follow-up period in the empagliflozin group (from 40 [20-40] to 20 [10-20] mg), but not in the non-empagliflozin group (from 23 [20-40] to 40 [20-40] mg). Hemoglobin levels increased significantly in the empagliflozin group (from 13.2 [11.9-14.6] to 14.0 [12.7-15.0] g/dL). In addition, excretion of acetyl-ß-D-glucosaminidase decreased significantly over the 6-month follow-up in the empagliflozin group (from 4.8 [2.6-11.7] to 3.3 [2.1-5.4] IU/L), especially in the group in which the dose of loop diuretics decreased (from 4.7 [2.5-14.8] to 3.3 [2.1-4.5] IU/L). Conclusions: Empagliflozin administration decreased the dose of loop diuretics and increased the production of erythropoietin, which may help prevent renal tubular injury in diabetic outpatients with HF.

Plasma Xanthine Oxidoreductase (XOR) Activity in Cardiovascular Disease Outpatients.

Background: The mechanisms of the increased plasma xanthine oxidoreductase (XOR) activity in outpatients with cardiovascular disease were unclear. Methods and Results: A total of 372 outpatients were screened, and 301 outpatients with cardiovascular disease were prospectively analyzed. Blood samples were collected from patients who visited a daily cardiovascular outpatient clinic. Patients with diabetes mellitus (DM) were significantly more likely to be classified into the high-XOR group (≥100 pg/h/mL; 50%) than the low-XOR group (<100 pmol/h/mL; 28.7%). On multivariate logistic regression analysis, DM (OR, 2.683; 95% CI: 1.441-4.996) was independently associated with high plasma XOR activity in all cohorts. In the diabetic cardiovascular disease patients (n=100), median body mass index (BMI) in the high-XOR group (28.0 kg/m2; IQR, 25.2-29.4 kg/m2, n=32) was significantly higher than in the low-XOR group (23.6 kg/m2; IQR, 21.2-25.7 kg/m2, n=68), and BMI was independently associated with high plasma XOR activity (OR, 1.340; 95% CI: 1.149-1.540). Plasma hydrogen peroxide was significantly higher in DM patients with high plasma XOR activity and obesity (>22 kg/m2) than in other patients. Conclusions: DM with obesity is one of the mechanisms of XOR enhancement in cardiovascular disease. The increase of XOR is a possible pathway for the production of reactive oxygen species in obese cardiovascular disease patients with DM.

Relation of Low Triiodothyronine Syndrome Associated With Aging and Malnutrition to Adverse Outcome in Patients With Acute Heart Failure.

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.

Painless destructive thyroiditis in a patient with resistance to thyroid hormone: a case report.

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 ß 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.

Atopic Dermatitis-Like Rash During Evolocumab Treatment of Familial Hypercholesterolemia.

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.

Postprandial Hyperchylomicronemia and Thin-Cap Fibroatheroma in Nonculprit Lesions.

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.

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

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).

Decreased blood glucose at admission has a prognostic impact in patients with severely decompensated acute heart failure complicated with diabetes mellitus.

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 < 200 mg/dl (decreased BG). The elevated and decreased BG patients were further divided into another three groups: 200 mg/ml ≤ BG < 300 mg/dl (mild-elevated), 300 mg/ml ≤ BG < 400 mg/dl (moderate-elevated) and BG ≥ 400 mg/ml (severe-elevated); and 150 mg/ml ≤ BG < 200 mg/dl (mild-decreased), 100 mg/ml ≤ BG < 150 mg/dl (moderate-decreased) and BG < 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.

Frequency of Achilles Tendon Xanthoma in Patients with Acute Coronary Syndrome.

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.