Dietary Survey of Japanese Individuals with Type 2 Diabetes Mellitus on a Low-Carbohydrate Diet: An Observational Study.

The nutrient intake of persons with diabetes placed on a low-carbohydrate diet remains unclear. This study aimed to assess nutrient intake in persons with type 2 diabetes mellitus treated with a low-carbohydrate diet. The brief-type self-administered diet history questionnaire was used to collect the dietary information of 335 outpatients at Kitasato Institute Hospital, while their clinical characteristics were collected from their electronic medical records. The median age, HbA1c level, and body mass index of the participants were 68 (60-74) years, 49 (45-55) mmol/mol [6.7 (6.3-7.2)%], and 24.0 (21.8-26.7) kg/m2, respectively; median energy intake was 1457 (1153-1786) kcal/day; and protein-energy, fat-energy, and available carbohydrate-energy ratios were 18.6 (15.7-21.4)%E, 36.8 (31.6-43.2)%E, and 34.6 (26.0-42.4)%E, respectively. As the available carbohydrate-energy ratio decreased, the fat-energy ratio increased significantly. The total dietary fibre and salt intake were 7.1 (5.6-8.4) g/1000 kcal and 6.5 (5.6-7.5) g/1000 kcal, respectively. Japanese individuals with type 2 diabetes mellitus placed on a low-carbohydrate diet had a fat-to-energy ratio exceeding 30%, while the fat-energy ratio increased as the carbohydrate-energy ratio decreased.

Hemifacial spasm associated with posterior inferior cerebellar artery aneurysm: illustrative case.

BACKGROUND: Hemifacial spasms (HFSs) complicated by intracranial aneurysms are rare. Recently, endovascular treatment has been widely used for this disease entity and can allow the cessation of intracranial aneurysm arterial pulsation, leading to recovery from the HFS. Here, the authors present a case of HFS associated with an ipsilateral posterior inferior cerebellar artery (PICA) aneurysm successfully treated with open surgery. OBSERVATIONS: A 68-year-old woman was annually followed-up for an incidentally found right PICA aneurysm. Over 3 years, the PICA aneurysm gradually increased in size, which eventually led to right HFS. An axial fast spoiled gradient-recalled echo sequence with gadolinium enhancement showed the PICA aneurysm compressing the root exit zone (REZ), which was attributed as the cause of the HFS. However, a fusion image of the three-dimensional T1-weighted fast spin-echo sequence and magnetic resonance angiogram clearly showed a direct contact between the REZ and the anterior inferior cerebellar artery (AICA), which was located at the apex of the PICA aneurysm. Intraoperatively, the AICA was found compressing the REZ; hence, microvascular decompression with aneurysmal clipping was performed. The HFS resolved immediately after surgery. LESSONS: In cases of HFS associated with an ipsilateral intracranial aneurysm, a detailed neuroradiological assessment to identify the responsible lesion is important to use the most optimal treatment of choice.

A major flood caused by a typhoon did not affect the population genetic structure of a river mayfly metapopulation.

Floods affect the population structure of organisms that inhabit streams. In recent decades, the scale of floods has become larger due to climate change. Under these circumstances, on 12 October 2019, the largest typhoon in the history of observation in Japan struck the Japanese Archipelago. This typhoon caused heavy rainfall in various places, and the Chikuma-Shinano River System (Japan's largest) suffered great damage. Eight years before the large-scale disturbance in the river system, the population structure of the mayfly Isonychia japonica was studied in detail using quantitative sampling (population numbers and biomass) and by sequencing the mtDNA cytochrome c oxidase subunit I. To understand the impact of the flood on the population and genetic structures, we repeated the same research approximately 1 year after the flood. Direct comparison of sites before and after the flood revealed no significant changes between pre- and post-flood population genetic structure. This indicates high in situ resistance and/or resilience recovery of the populations to the disturbance. We hypothesize that this high resistance/resilience to flood disturbance is a result of strong selection for such traits in the rivers of the Japanese Archipelago, which are short, steep, flow rapidly and violently, and are strongly affected by floods.

Development and validation of an equation to predict the incidence of coronary heart disease in patients with type 2 diabetes in Japan.

OBJECTIVE: In the diabetes treatment policy after the Kumamoto Declaration 2013, it is difficult to accurately predict the incidence of complications in patients using the JJ risk engine. This study was conducted to develop a prediction equation suitable for the current diabetes treatment policy using patient data from Kitasato University Kitasato Institute Hospital (Hospital A) and to externally validate the developed equation using patient data from Kitasato University Hospital (Hospital B). Outlier tests were performed on the patient data from Hospital A to exclude the outliers. Prediction equation was developed using the patient data excluding the outliers and was subjected to external validation. RESULTS: By excluding outlier data, we could develop a new prediction equation for the incidence of coronary heart disease (CHD) as a complication of type 2 diabetes, incorporating the use of antidiabetic drugs with a high risk of hypoglycemia. This is the first prediction equation in Japan that incorporates the use of antidiabetic drugs. We believe that it will be useful in preventive medicine for treatment for people at high risk of CHD as a complication of diabetes or other diseases. In the future, we would like to confirm the accuracy of this equation at other facilities.

Changes in Body Weight, Dysglycemia, and Dyslipidemia After Moderately Low-Carbohydrate Diet Education (LOCABO Challenge Program) Among Workers in Japan.

PURPOSE: It is theorized that the prevalence of obesity has not decreased owing to poor adherence to implemented programs addressing metabolic syndrome, obesity, and diabetes in Japan. Therefore, we intended to evaluate the influence of a moderately low-carbohydrate diet on improving markers of metabolic syndrome among workers in Japan. PATIENTS AND METHODS: Participants with metabolic syndrome or obesity were recruited based on the eligibility criteria for the Specific Health Guidance program and educated on a moderately low-carbohydrate diet between spring 2016 and fall 2018. The participants were then made to report their food intake and body weight once a week for the next 12 weeks and were counselled on maintaining a moderately low-carbohydrate diet. HbA1c levels, lipid profile, body weight, and sleep quality were evaluated. The normality of the data was evaluated using the Skewness/Kurtosis test. Each variable was compared before and after the intervention using the Wilcoxon signed-rank test. Further, a subgroup analysis of the data from the participants whose variables were abnormal at baseline was performed. RESULTS: Among the 101 enrolled participants, a decrease in the median weight (from 82.5 to 79.7 kg, p<0.001, n=46), body mass index (from 27.3 to 26.9 kg/m2, p<0.001, n=46), and apnea-hypopnea index (from 24.1 to 17.1, p<0.01, n=39) was observed. Subgroup analysis of participants with abnormal baseline values revealed changes in HbA1c (from 6.7% to 5.8%, p<0.001, n=34), total cholesterol (from 220 to 209 mg/dL, p<0.01, n=54), low-density lipoprotein cholesterol (from 133 to 120 mg/dL, p<0.001, n=31), high-density lipoprotein cholesterol (from 35 to 40 mg/dL, p<0.01, n=31), triglycerides (from 242 to 190 mg/dL, p<0.01, n=57), and deep sleep percentage (from 10.4% to 18.2%, p<0.05, n=7). CONCLUSION: A moderately low-carbohydrate diet may be considered a potential intervention for improving the markers of metabolic syndrome, obesity, and diabetes.

A retrospective study on the usefulness of the JJ risk engine for predicting the incidence rate of coronary heart disease in type 2 diabetes patients.

OBJECTIVE: In 2018, we conducted a retrospective survey using the medical records of 484 patients with type 2 diabetes. The observed value of coronary heart disease (CHD) incidence after 5 years and the predicted value by the JJ risk engine as of 2013 were compared and verified using the discrimination and calibration values. RESULTS: Among the total cases analyzed, the C-statistic was 0.588, and the calibration was p < 0.05; thus, the JJ risk engine could not correctly predict the risk of CHD. However, in the group expected to have a low frequency of hypoglycemia, the C-statistic was 0.646; the predictability of the JJ risk engine was relatively accurate. Therefore, it is difficult to accurately predict the complication rate of patients using the JJ risk engine based on the diabetes treatment policy after the Kumamoto Declaration 2013. The JJ risk engine has several input items (variables), and it is difficult to satisfy them all unless the environment is well-equipped with testing facilities, such as a university hospital. Therefore, it is necessary to create a new risk engine that requires fewer input items than the JJ risk engine and is applicable to several patients.

Efficacy of a Moderately Low Carbohydrate Diet in a 36-Month Observational Study of Japanese Patients with Type 2 Diabetes.

We previously showed that a non-calorie-restricted, moderately low-carbohydrate diet (mLCD) is more effective than caloric restriction for glycemic and lipid profile control in patients with type 2 diabetes. To determine whether mLCD intervention is sustainable, effective, and safe over a long period, we performed a 36-month observational study. We sequentially enrolled 200 patients with type 2 diabetes and taught them how to follow the mLCD. We compared the following parameters pre- and post-dietary intervention in an outpatient setting: glycated hemoglobin (HbA1c), body weight, lipid profile (total cholesterol, low and high-density lipoprotein cholesterol, triglycerides), systolic and diastolic blood pressure, liver enzymes (aspartate aminotransferase, alanine aminotransferase), and renal function (urea nitrogen, creatinine, estimated glomerular filtration rate). Data from 157 participants were analyzed (43 were lost to follow-up). The following parameters decreased over the period of study: HbA1c (from 8.0 ± 1.5% to 7.5 ± 1.3%, p < 0.0001) and alanine aminotransferase (from 29.9 ± 23.6 to 26.2 ± 18.4 IL/L, p = 0.009). Parameters that increased were high-density lipoprotein cholesterol (from 58.9 ± 15.9 to 61.2 ± 17.4 mg/dL, p = 0.001) and urea nitrogen (from 15.9 ± 5.2 to 17.0 ± 5.4 mg/dL, p = 0.003). Over 36 months, the mLCD intervention showed sustained effectiveness (without safety concerns) in improving HbA1c, lipid profile, and liver enzymes in Japanese patients with type 2 diabetes.

Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

BACKGROUND: We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding. RESULTS: All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite. CONCLUSIONS: Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

[Japanese Model of Asheville Project. Its Overview and Initiative].

The Asheville Project® began in 1996 in Asheville, North Carolina, where community pharmacists, in collaboration with physicians, provide health coaching to patients with lifestyle diseases to accomplish their improved self-management of the disease. The project has now widely expanded across the United States. With periodical coaching by pharmacists, according to the reports of these programs, patients have been reported to show improvements in self-management and laboratory data, including the number of doctor visits, medication adherence and the number of foot examinations. Economically, the total medical costs for this disease have decreased 34% over a 5-year period by complying with the Asheville Project. In implementing this model in Japan, various questions, such as the feasibility for busy pharmacists to expend 30-60 min for meeting individually with patients, effective collaboration between pharmacy and physician, patients' acceptance of support by pharmacists to modify their behavior, etc. had to be answered. Thus, we developed a program entitled, "A Health Coaching Program by Community Pharmacists in a Collaborative Practice," aimed at preventing the aggravation of lifestyle diseases; we evaluated its feasibility for the above mentioned concerns. The content of this coaching program has been prepared with reference to the Asheville Project® and with the support of Kitasato University School of Pharmacy and the Iowa Pharmacy Association, USA. We herein introduce this coaching program, as well as what the pharmacists have learned through this program.

[Pilot Study of "Japanese Model of Asheville Project"～How Did It Work?].

For prevention of the aggravation of diabetic nephropathy, a treatment method that combines self-care with medical guidance is becoming increasingly important, leading to the development of programs for lifestyle modification for the patients. To assess the effectiveness of such programs, we have conducted a feasibility study of a patient self-care support program with medical collaboration by registered pharmacists in community pharmacies involving patients with diabetic nephropathy who are under treatment at medical institutions, including our hospital. This study evaluated the two primary measurements, which are A) the actual execution rate versus planned programs, and B) the patient satisfaction rate. In addition, the achievement rate of behavioral objectives, satisfaction rate of diabetes treatment, degree of concerns (Diabetes Treatment Satisfaction Questionnaire; DTSQ, Problem Areas in Diabetes; PAID) and other physiological indicators have been evaluated. With the approval of the IRB at Kitasato University, sixteen out of 18 patients have continued to participate in the support program, and the study has shown high patient satisfaction with pharmacist coaching support. Patients have gained interest in managing their lifestyles, thereby increasing self-efficacy. Also, information shared between the pharmacists and the physicians has clarified patients' issues and concerns pertaining to their lifestyles, which were effectively utilized in the coaching program. Through meetings with pharmacists, patients have been reassured of the expertise of the pharmacist and thus gained mutual trust, which leads to the patient's behavioral change. We believe that the collaboration of patients, pharmacists and physicians has resulted in effective team-based patient care.

Insulin degludec requires lower bolus insulin doses than does insulin glargine in Japanese diabetic patients with insulin-dependent state.

BACKGROUND: The study presents a comparison of the glucose-lowering effects, glycemic variability, and insulin doses during treatment with insulin degludec or insulin glargine. METHODS: In this open-label, single-center, 2-way crossover study, 13 Japanese diabetic outpatients in the insulin-dependent state on basal-bolus therapy were assigned to receive either insulin glargine followed by insulin degludec, or insulin degludec followed by insulin glargine. Basal insulin doses were fixed in principle, and patients self-adjusted their bolus insulin doses. Seventy-two-hour continuous glucose monitoring was performed 2 weeks after switching the basal insulin. RESULTS: Mean blood glucose (mg/dL) was not significantly different between insulin degludec and insulin glargine over 48 hours (141.8 ± 35.2 vs 151.8 ± 43.3), at nighttime (125.6 ± 40.0 vs 124.7 ± 50.4), or at daytime (149.3 ± 37.1 vs 163.3 ± 44.5). The standard deviation (mg/dL) was also similar (for 48 hours: 48.9 ± 19.4 vs 50.3 ± 17.3; nighttime: 18.7 ± 14.3 vs 13.7 ± 6.7; daytime: 49.3 ± 20.0 vs 44.3 ± 17.7). Other indices of glycemic control, glycemic variability, and hypoglycemia were similar for both insulin analogs. Total daily insulin dose (TDD) and total daily bolus insulin dose (TDBD) were significantly lower with insulin degludec than with insulin glargine (TDD: 0.42 ± 0.20 vs 0.46 ± 0.22 U/kg/day, P = .028; TDBD: 0.27 ± 0.13 vs 0.30 ± 0.14 U/kg/day, P = .036). CONCLUSIONS: Insulin degludec and insulin glargine provided effective and stable glycemic control. Insulin degludec required lower TDD and TDBD in this population of patients.

A non-calorie-restricted low-carbohydrate diet is effective as an alternative therapy for patients with type 2 diabetes.

OBJECTIVE: Although caloric restriction is a widely used intervention to reduce body weight and insulin resistance, many patients are unable to comply with such dietary therapy for long periods. The clinical effectiveness of low-carbohydrate diets was recently described in a position statement of Diabetes UK and a scientific review conducted by the American Diabetes Association. However, randomised trials of dietary interventions in Japanese patients with type 2 diabetes are scarce. Therefore, the aim of this study was to examine the effects of a non-calorie-restricted, low-carbohydrate diet in Japanese patients unable to adhere to a calorie-restricted diet. METHODS: The enrolled patients were randomly allocated to receive a conventional calorie-restricted diet or low-carbohydrate diet. The patients received consultations every two months from a registered dietician for six months. We compared the effects of the two dietary interventions on glycaemic control and metabolic profiles. RESULTS: The HbA1c levels decreased significantly from baseline to six months in the low-carbohydrate diet group (baseline 7.6±0.4%, six months 7.0±0.7%, p=0.03) but not in the calorie-restricted group (baseline 7.7±0.6%, six months 7.5±1.0%, n.s.), (between-group comparison, p=0.03). The patients in the former group also experienced improvements in their triglyceride levels, without experiencing any major adverse effects or a decline in the quality of life. CONCLUSION: Our findings suggest that a low-carbohydrate diet is effective in lowering the HbA1c and triglyceride levels in patients with type 2 diabetes who are unable to adhere to a calorie-restricted diet.

Two-way crossover comparison of insulin glargine and insulin detemir in basal-bolus therapy using continuous glucose monitoring.

OBJECTIVE: This study aimed to compare the glucose-lowering effect and glycemic variability of insulin glargine with those of insulin detemir. MATERIAL AND METHODS: This was an open-label, single-center, randomized, two-way crossover study in patients with diabetes on basal-bolus insulin therapy, with neutral protamine Hagedorn (NPH) insulin as basal insulin. Patients switched from NPH insulin to a course either of insulin glargine followed by insulin detemir, or insulin detemir followed by insulin glargine, continuing the same dose of the prior bolus of insulin. To evaluate the glucose-lowering effect, daily glycemic profiles were recorded for 72 hours by continuous glucose monitoring (CGM) in an outpatient setting. The mean amplitude of glycemic excursions, standard deviation (SD), and the mean of daily difference (MODD) were used to assess intraday and day-to-day glycemic variability. RESULTS: Eleven patients were enrolled and nine completed the study. Mean blood glucose calculated from CGM values was significantly lower with insulin glargine compared with insulin detemir (9.6 ± 2.4 mmol/L versus 10.4 ± 2.8 mmol/L, P = 0.038). The SD was significantly lower with insulin glargine versus insulin detemir (2.5 ± 0.9 mmol/L vs 3.5 ± 1.6 mmol/L, P = 0.011). The MODD value was significantly lower with insulin glargine than with insulin detemir (2.2 ± 1.1 mmol/L vs 3.6 ± 1.7 mmol/L, P = 0.011). There was no significant difference between the two insulin analogs in terms of hypoglycemia. CONCLUSION: This study suggests that insulin glargine leads to more effective and more stable glycemic control than the same dose of insulin detemir.

Comparison of oxidative stress markers in type 2 diabetes: basal bolus therapy versus twice daily premixed insulin analogs.

AIMS: Several studies have shown that twice-daily injection of premixed insulin analog (MIX) therapy achieves glycemic control equivalent to that with basal-bolus (BB) therapy. However, glycemic fluctuations that lead to oxidative stress may be associated with the risk of diabetic complications. Therefore, in this study, we compared oxidative stress markers between MIX therapy and BB therapy. METHODS: In this cross-sectional study, we recruited a total of 37 patients (17 patients in the BB group and 20 patients in the MIX group) and compared urinary 8-isoprostane and urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. RESULTS: There were no significant differences in urinary 8-isoprostane (BB vs MIX: 199+/-92 pg/mg Cr vs 266+/-107 pg/mg Cr) or urinary 8-OHdG (4.7+/-1.6 ng/mg Cr vs 5.4+/-1.9 ng/mg Cr, respectively). Conclusion These results suggest that MIX is equivalent to BB in terms of glycemic fluctuations and oxidative stress.

Experimental study of combination therapy with S-1 against pancreatic cancer.

PURPOSE: To determine the most effective combination chemotherapy with S-1 against pancreatic cancer and to clarify the mechanism of synergy between S-1 and the partner drug. METHODS: We tested a combination of S-1 with the following antitumor drugs in an in vitro MTT assay against pancreatic cancer cell line MIA PaCa-2: gemcitabine (GEM), cisplatin (CDDP), irinotecan (CPT-11), mitomycin C, adriamycin, and paclitaxel. The efficacy of S-1, GEM, and a combination of S-1 and GEM was also tested in vivo by administering S-1 (10 mg/kg) orally to nude mice five times a week for 3 weeks, and GEM (100 mg/kg) intravenously every 2-3 days for a total of six times. A treated-to-control ratio (T/C) of relative mean tumor weight values less than 50% was determined to be effective. Furthermore, we investigated the mechanism of the synergistic effect of S-1 and GEM on the cell cycle by flow cytometry, because both S-1 and GEM are known as antimetabolic drugs. To verify cell death induced by a change in the distribution of the cell cycle phases, we investigated apoptosis by sub-G1 analysis and a TUNEL assay. RESULTS: From classical isobolography analysis of the in vitro MTT assay, the combination of S-1 plus GEM was found to be the most effective of the combinations tested. In vivo, T/C (percentage) with the combination of S-1 plus GEM was 48.2%, which was lower than that of S-1 or GEM alone, and the combination enhanced antitumor activity. Cell cycle analysis showed greater cell cycle delay with the combination treatment (S-1 plus GEM) than for each single drug treatment, and apoptotic cells were detected only in treatments including GEM. CONCLUSION: The combination chemotherapy of S-1 and GEM appears to be useful for pancreatic cancer. Both cycle delay by S-1 plus GEM and apoptosis induced by GEM are involved in this synergistic mechanism.

Telmisartan but not candesartan affects adiponectin expression in vivo and in vitro.

To examine the effects of telmisartan on peroxisome proliferator-activated receptor gamma activation, we compared the effects of telmisartan with those of candesartan on adipocytokines and glucose and lipid metabolism in vivo and in vitro. In vivo, 56 patients with both type 2 diabetes and hypertension were enrolled and randomized to receive either telmisartan (40 mg) or candesartan (8 mg) for 3 months. Serum adiponectin, HbA1c levels, lipid profiles and blood pressure were recorded at the beginning and 3 months later. In vitro, differentiated 3T3-L1 adipocytes were treated with telmisartan, candesartan, pioglitazone or vehicle for 24 h, and then adiponectin mRNA and protein levels were measured. The results showed that most of the metabolic parameters, including the lipid profiles, did not change significantly during the study in either group. However, the changes in serum adiponectin and plasma glucose over 3 months were significantly greater in the telmisartan group than in the candesartan group. In vitro, although the protein level of adiponectin was not significantly elevated, the mRNA expression of adiponectin was elevated 1.5-fold by telmisartan in 3T3-L1 adipocytes. Our findings suggest that telmisartan may have beneficial effects in type 2 diabetes beyond its antihypertensive effect.

Prevalence of hepatitis E virus among wild boar in the Ehime area of western Japan.

AIMS: Transmission of hepatitis E virus (HEV) from wild boar to humans has been reported, particularly from Japan. We attempted to clarify this issue. METHODS: We assessed the IgG class antibodies against HEV (anti-HEV) in serum samples taken from 406 boar living in the Ehime area of western Japan from 2001 to 2004, of which 392 were captured in the wild (wild-caught boar) and 14 had been kept in a breeding farm (bred boar). RESULTS: Anti-HEV positive rate in the bred boar (10/14, 71.4%) was significantly higher than in the wild-caught boar (100/392, 25.5%) (P < 0.001). Of the 392 wild-caught boar, 12 (3.1%) were positive for HEV-RNA, 10 of which were then subjected to phylogenetic analyses by sequencing an 821-nt fragment within ORF1. All the 10 isolates segregated to genotype 3, and eight of them were mutually related to form a cluster. All the eight HEV isolates in this cluster were from the wild-caught boar living in one and the same habitat within the studied area, while the other two independent isolates were from different regions. CONCLUSION: HEV infection is endemic in wild boar in the Ehime area, and we should regard the wild boar as an important reservoir of HEV.