Efficacy of intermittent empagliflozin supplementation on dietary self-management and glycaemic control in patients with poorly controlled type 2 diabetes: A 24-week randomized controlled trial.

AIMS: To explore the effects of intermittent use of empagliflozin, a sodium-glucose co-transporter-2 inhibitor, on dietary self-management and glycaemic control in patients with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: We conducted a prospective, randomized, open-label, blinded-endpoint, parallel-group, comparative clinical trial of 50 patients with type 2 diabetes, treated with no more than three oral antidiabetic drugs (glycated haemoglobin [HbA1c] ≥52 mmol/mol but <86 mmol/mol). The participants were randomized to take 10 mg/d empagliflozin either every day (regular group, n = 25) or on the day on which they considered they had overeaten (intermittent group, n = 25) for 24 weeks. We limited empagliflozin prescription to half of the required period in the intermittent group. The primary endpoint was change in HbA1c at the end of the 24-week treatment period relative to baseline. The secondary outcomes included changes in body weight, daily energy intake and diabetes treatment-related quality of life (QoL). Energy intake was assessed using a diet-specific validated questionnaire rather than actual assessments of food intake. RESULTS: The intake rate of empagliflozin was 96.7 ± 7.2% for the regular group and 45.7 ± 7.0% for the intermittent group. Interestingly, ΔHbA1c was identical in the two groups (-0.64 ± 0.19% and - 0.65 ± 0.17%, respectively). Body weight decreased (-2.72 ± 0.52 and - 1.50 ± 0.45 kg, respectively) and diabetes treatment-related QoL increased significantly from baseline in both groups. Energy intake, however, decreased significantly only in the intermittent group (-221.0 ± 108.3 kcal/d). CONCLUSIONS: Intermittent empagliflozin supplementation is a useful therapeutic option that empowers dietary self-management, improves glycaemic control and is accompanied by body weight loss and an increase in diabetes treatment-related QoL in patients with inadequately controlled type 2 diabetes.

[Treatment strategy for elderly diabetic patient with insulin or GLP-1 receptor agonist].

It has been established that diabetes is an independent risk factor for microvascular and macrovascular complications, and many studies indicate that diabetic subjects are at greater risk of dementia, depression and fracture. Risk reductions for microvascular, macrovascular and death were observed by intensive therapy using insulin or oral diabetic agents. But a history of hypoglycemia was increased myocardial infarction, mortality, dementia and fracture. So it is important that optimum glycemic control has to be achieved without hypoglycemia. Treatment with a long-acting basal insulin analogue or glucagon-like peptide-1(GLP-1) receptor agonist, provide effective glycemic control without serious hypoglycemia in elderly patients. Self-monitoring of blood glucose might be effective in improving glycemic control in elderly patients, and it is useful for the diagnosis of hypoglycemia.

Dipeptidyl peptidase-4 inhibitor improves glycemic variability in multiple daily insulin-treated type 2 diabetes: a prospective randomized-controlled trial.

AIMS: To improve glycemic variability (GV) is crucial in the management of multiple daily insulin (MDI) treatment in diabetes. To evaluate the GV improvement in MDI treated type 2 diabetes (T2D) with low-dose metformin 750 mg/day (LMET), which was popular in the clinical practice in Japan, we compared the effect of adding vildagliptin 100 mg/day (LMET + DPP4i treatment) or increased metformin dose to 1500 mg/day (HMET treatment), in the setting of continuous glucose monitoring (CGM) analysis. MATERIALS AND METHODS: Single-center, open-label, 12 weeks-two period cross-over design. Twenty T2D with inadequately controlled (7.0% < HbA1c ≤ 9.0%) with MDI + LMET were enrolled. Primary endpoints were GV and hypoglycemia derived from CGM indices, performed after each 12 week treatment periods. RESULTS: There was no significant difference in both LMET + DPP4i treatment and HMET treatment, in terms of HbA1c, body weight changes, and total daily dose of insulin to achieve the targeted glycemia. LMET + DPP4i treatment compared to HMET treatment, significantly reduced the calculated GV value, mean (7.15 ± 1.30 vs 7.82 ± 1.60, p = 0.04), standard deviation (1.78 ± 0.55 vs 2.27 ± 1.11, p = 0.03), continuous overlapping net glycemic action (6.44 ± 1.28 vs 7.12 ± 1.69, p < 0.05), J-Index (26.7 ± 11.0 vs 34.9 ± 19.8, p < 0.05), high blood glucose index (3.01 ± 1.96 vs 6.73 ± 4.85, p = 0.02), and mean amplitude of glycemic excursions (4.53 ± 1.35 vs 5.50 ± 2.34, p = 0.03). CONCLUSION: The GV metrics regarding daily and nocturnal hypoglycemia were not significantly different between LMET + DPP4i treatment and HMET treatment. LMET + DPP4i treatment decreased GV associated with hyperglycemia. Adding DPP-4-inhibitor to the lower dose of metformin is an alternative approach to the stable GV in MDI compared to additional high-dose metformin. National Clinical Trial registration in Japan, number is JPRN-UMIN000024663. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00513-6.

Changes in subjective sleep quality in patients with type 2 diabetes who did not use Sleep agents: a cross-sectional study according to age and clinical background.

AIM: Diabetes and aging are both well-established risk factors for insomnia. Therefore, we investigated the changes in subjective sleep quality in relation to clinical backgrounds and age in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study included 380 participants with T2DM who were between 18 and 79 years of age from our outpatient clinics. Individuals with any symptoms and medical histories associated with obstructive sleep apnea (OSA) were excluded from the interview and analyses. Data were collected using self-administered questionnaires, namely the Pittsburgh Sleep Quality Index (PSQI) and the Morning-Evening Questionnaire (MEQ), as well as medical records and blood samples. We performed stratified analyses according to age decades. RESULTS: The number of patients in the age groups (in years) was as follows: < 50 (n = 69), 50-60 (n = 52), 60-70 (n = 138), and 70-80 (n = 121). PSQI score was highest in the < 50 group (4.99 ± 2.40), and significantly decreased with age (p < 0.05). Body mass index (BMI) was also highest in the < 50 group (25.5 ± 4.8 kg/m2), and markedly decreased with age (p < 0.01). Interestingly, BMI was significantly correlated with the PSQI score (rs = 0.157, p < 0.05). We also found that younger patients had shorter sleep duration, stronger daytime sleepiness, and a tendency for the evening type. CONCLUSION: Younger T2DM patients had poorer sleep quality and higher BMI. Our findings suggest that insomnia should be accounted for as a potential comorbidity when examining or treating patients with T2DM and obesity even in the younger population.

Simplification of complex insulin regimens using canagliflozin or liraglutide in patients with well-controlled type 2 diabetes: A 24-week randomized controlled trial.

AIMS/INTRODUCTION: We investigated the potential use of canagliflozin, in comparison with liraglutide, as an alternative to bolus insulin in patients with well-controlled type 2 diabetes mellitus receiving multiple daily insulin injection therapy. MATERIALS AND METHODS: In 40 patients, with glycated hemoglobin (HbA1c) levels <7.5% controlled by multiple daily insulin injection therapy, all bolus insulin was randomly switched to canagliflozin (100 mg/day) or liraglutide (0.3-0.9 mg/day) for 24 weeks. Basal insulin was continued with dose adjustment according to a predefined algorithm. The end-points were the change in the HbA1c level, glycemic variability assessed by continuous glucose monitoring, body mass index, insulin dose, quality of life (QOL) and safety assessments. Factors influencing the changes in QOL were also assessed using a simple regression analysis. RESULTS: The change in HbA1c from baseline was comparable between the treatments. Both treatments maintained the HbA1c level to the baseline levels with stable glucose variability and no severe hypoglycemia for 24 weeks, decreased total insulin dose, and significantly increased the QOL score. The change in QOL was significantly associated with injection frequency. CONCLUSIONS: For patients with well-controlled type 2 diabetes mellitus, under the support of basal insulin, complex insulin regimens can be simplified by replacing all bolus insulin with once-daily canagliflozin or liraglutide, which improves patients' QOL.

Chronotherapeutic efficacy of suvorexant on sleep quality and metabolic parameters in patients with type 2 diabetes and insomnia.

AIMS: This study aimed to assess the chronotherapeutic efficacy of suvorexant on subjective sleep parameters and metabolic parameters in patients with type 2 diabetes and insomnia. METHODS: Thirteen patients with type 2 diabetes who met the Pittsburg Sleep Quality index criteria for primary insomnia took suvorexant 20 mg/day (15 mg/day for ≥65 years) for 14 ± 2 weeks. The following parameters were assessed before and after the treatment: sleep diary for sleep duration and quality (i.e., sleep onset latency, waking after sleep onset, and sleep efficiency [sSE]), Insomnia Severity Index, clinical and biochemical data, continuous glucose monitoring (CGM), and validated self-administered questionnaire on food intake. RESULTS: Suvorexant significantly improved sSE, abdominal circumference, and sucrose intake (all p < 0.05), but did not change HbA1c, CGM parameters, or body weight. Correlation analysis revealed that changes in sSE were associated with those in HbA1c and body weight (r = -0.61 and r = -0.66, respectively; both p < 0.05). CONCLUSIONS: Suvorexant significantly improved sleep quality and obesity-associated parameters in patients with type 2 diabetes in 14 weeks. Improvements in sleep quality were associated with improvements in glycemic control. Sleep disorder treatment using suvorexant may provide metabolic benefits for patients with type 2 diabetes.

Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type 2 diabetes with sodium-glucose cotransporter 2 inhibitor: A randomized, open-label, prospective study.

AIMS/INTRODUCTION: Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium-glucose cotransporter 2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal-bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation. MATERIALS AND METHODS: This was a randomized, open-label, 7-day prospective study. Participants were type 2 diabetes patients with hyperglycemia, aged >20 years, with glycated hemoglobin >10%, daily mean preprandial blood glucose >11 mmol/L (200 mg/dL) and no previous antidiabetic medication. A total of 18 type 2 diabetes patients were randomized (1:1) to basal-bolus insulin titration algorithm (INS) alone or INS + dapagliflozin 5 mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry. RESULTS: The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal-bolus ratio (P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post-treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72 ± 0.05 vs 0.79 ± 0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group (P < 0.02). CONCLUSIONS: INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid-derived EE (failed to increase carbohydrate-derived EE) and reduced basal insulin requirement might be related to further bodyweight loss. CLINICAL TRIAL REGISTRY: National University Hospital Medical Information Network UMIN000018997.

Giant Cavernous Hemangioma of the Adrenal Gland in an Elderly Patient.

Cavernous hemangioma is a rare, non-functional, benign adrenal tumor. Adrenal cavernous hemangioma is often diagnosed after surgery with a histologic examination. A 70-year-old man complaining of appetite loss was admitted to our hospital. An incidental large left adrenal mass was found by computed tomography (CT). There were no clinical signs of adrenogenital syndrome, Cushing's syndrome or primary aldosteronism. Total resection was carried out. The pathological diagnosis was cavernous hemangioma. The differentiation of adrenal tumor is necessary in cases of large tumors, and resection is desirable given the risks of hemorrhaging and rupture.

Efficient conversion of allitol to D-psicose by Bacillus pallidus Y25.

An efficient method for conversion of allitol to D-psicose was achieved by a resting cell reaction of Bacillus pallidus Y25 for the first time. Notably, it was possible to produce D-allose and D-altrose from allitol directly via D-psicose by prolonging the reaction time. This method was applied for the preparation of D-psicose using the extract of Itea virginica as a starting material in this study. D-Psicose which is the absolutely key precursor for the production of other six carbon sugars could be obtained as the sole product at high yield.

Acute suppurative thyroiditis in infected thyroid cyst in an adult patient under hemodialysis.

Acute suppurative thyroiditis (AST) accompanied by an abscess is a rare clinical case. Hemodialysis patients are at risk for infections. Sepsis mortality was from 100 to 300 times higher for chronic dialysis patients than that for the general public. Thus, special care should be taken against infection in patients under hemodialysis.

Glycemic Variability in Type 1 Diabetes Compared with Degludec and Glargine on the Morning Injection: An Open-label Randomized Controlled Trial.

INTRODUCTION: Optimal adjustment of basal insulin to overcome hypoglycemia and glycemic variability (GV) depends on its duration of action and peak-less profile. Owing to the ability of long-acting basal insulin to avoid hypoglycemia, we titrated pre-meal glucose to normal fasting blood glucose, 80-110 mg/dL (4.5-6.1 mmol/L), and post-meal glucose to 80-140 mg/dL (4.5-7.8 mmol/L). The purpose of this study was to evaluate two basal insulin analogues degludec (IDeg) and glargine (IGlar), injected in the morning, for GV using continuous glucose monitoring (CGM) in type 1 diabetes (T1DM). METHODS: In this crossover study, 20 Japanese patients with T1DM (age 54 ± 16 years, disease duration 16 ± 8 years, BMI 24 ± 4 kg/m2, HbA1c 7.4 ± 0.8%) were randomized into one of two different starting regimens, and CGM was conducted on three consecutive days during the last week of each 12-week titration period. Treatment satisfaction was assessed at the end of each treatment period using the Diabetes Therapy-Related Quality of Life Questionnaire (DTR-QOL). RESULTS: There were no differences in HbA1c, total insulin dosage, body weight changes, and basal to bolus ratio between the IDeg and IGlar arms. The day-to-day variability in fasting interstitial GV on the CGM curves was significantly less in the IDeg than IGlar treatment period (25.9 ± 22.0 vs. 43.8 ± 30.1 mg/dl, p = 0.04). Other markers of GV, calculated by the EasyGV software, including mean amplitude of glycemic excursions (MAGE), J-index, total and nocturnal hypoglycemia were not different between the two treatment periods. The score of "satisfaction with treatment", a subdomain of the DTR-QOL system, was higher in the IDeg period. CONCLUSION: Thus, the morning injection of the two long-acting insulin analogues seemed similar with regard to the magnitude of hypoglycemia in T1DM, but treatment with IDeg was associated with lower day-to-day variation in glucose level. These results suggest that IDeg is safe with minimal morning GV in patients with T1DM. CLINICAL TRIAL REGISTRATION: Japanese Clinical Trials Registry, UMIN000012358.

Pituitary apoplexy presenting with anorexia and hyponatraemia.

Pituitary apoplexy, a syndrome caused by haemorrhage into the pituitary gland, typically manifests as sudden severe headache, visual symptoms and hypopituitarism, including adrenal insufficiency. We report a case of a 65-year-old man with adrenal insufficiency due to pituitary apoplexy presenting with anorexia following temporal headache and diagnosed through evaluation for hyponatraemia. MRI focusing on the pituitary gland helped to confirm the diagnosis. Our experience serves as a useful reminder of this atypical presentation of pituitary apoplexy, also known as 'subclinical pituitary apoplexy,' and underscores the importance of careful evaluation for hyponatraemia using serial urine osmolality, which is useful to distinguish hypovolaemic hyponatraemia from euvolaemic hyponatraemia. Clinicians should consider pituitary apoplexy as a differential diagnosis in cases of anorexia, loss of energy or hyponatraemia, following headache even when the patient is lacking classical symptoms such as severe headache or visual symptoms.

A case of juvenile acromegaly that was initially diagnosed as severe congestive heart failure from acromegaly-induced dilated cardiomyopathy.

Acromegaly is characterized by chronic hypersecretion of growth hormone (GH) and is associated with increased mortality rate because of the potential complications such as cardiovascular disease, respiratory disease, or malignancy, which are probably caused by the long-term exposure of tissues to excess GH, for at least 10 years, before diagnosis and treatment. A 22-year-old man with a 2-month history of fatigue was admitted to our hospital because of chest discomfort, dyspnea, and pitting edema of the lower limbs experienced over a 1-month period. On admission, his height and body weight were 186 cm and 138.5 kg, respectively, with a BMI of 39.8 kg/m(2). He showed acromegalic features and elevated serum GH and IGF-1 levels, which were 11.5 ng/mL and 960 ng/mL, respectively. There was no GH suppression in the 75-g oral glucose tolerance test. Pituitary magnetic resonance imaging (MRI) revealed microadenoma. Chest X-ray revealed cardiomegaly, and echocardiogram showed dilated left ventricular (LV) cavity and diffuse hypokinesis with extremely decreased ejection fraction (EF). He was diagnosed as having acromegaly with congestive heart failure from diastolic cardiomyopathy. After the successful transsphenoidal resection of the pituitary adenoma, the level of GH was normalized. However, the cardiac dysfunction did not show any improvement even after the administration of ß-blockers, angiotensin-converting enzyme inhibitor (ACE-I), or diuretics. The patient was re-hospitalized, and he died of cardiac failure at the age of 25 years. Patients with acromegaly have been reported to have about 30% higher mortality rate, and cardiovascular disease accounts for 60% of the deaths. We report a case of a patient with juvenile acromegaly who was diagnosed with severe cardiac failure at the time of diagnosis and failed to recover cardiac function even after the successful resection of the pituitary adenoma. Immediate diagnosis and treatment are required for better control of acromegalic cardiomyopathy.