Efficacy and Safety of 5-Aminolevulinic Acid Combined with Iron on Skeletal Muscle Mass Index and Physical Performance of Patients with Sarcopenia: A Multicenter, Double-Blinded, Randomized-Controlled Trial (ALADDIN Study).

Sarcopenia is a geriatric syndrome characterized by decreased physical performance, muscle mass, and strength. Since the intake of 5-aminolevulinic acid (ALA) with iron can increase muscle mass and mitochondria in mice and elevate physical exercise performance in humans, the beneficial effects of ALA in patients with sarcopenia are expected, but this remains unexplored in the literature. This study aimed to assess the efficacy and dose dependency of ALA combined with iron in sarcopenia by measuring skeletal muscle mass index (SMI). Subjects with sarcopenia were enrolled and randomized into the ALA and sodium ferrous citrate (SFC) intake groups (ALA50/SFC29, ALA100/SFC29, ALA150/SFC29, ALA 100/SFC57, and ALA0/SFC29 placebo) and ingested the assigned study food for 12 weeks. The primary endpoint, the change in SMI from baseline to week 12, did not differ significantly between the groups. Hand grip significantly increased or tended to increase from baseline after 12 weeks with all doses of ALA or SFC compared with the placebo group. No consistent changes were observed in the other endpoints, including calf circumference, physical function, or quality of life (QOL). Although this study suggests safe administration and the possibility of ALA improving hand grip strength in patients with sarcopenia, further investigation is required.

Quality-of-Life Comparison of Dapagliflozin Versus Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial (J-BOND Study).

INTRODUCTION: No study has compared the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) on patients' quality-of-life (QOL). METHODS: We enrolled 253 drug-naïve Japanese patients with type 2 diabetes mellitus (T2DM), randomly assigned them into a dapagliflozin (SGLT2i) group or DPP4i group in approximately 1:1 ratio, and monitored them for 24 weeks. The primary endpoint was the proportion of subjects indicating improvement in the "overall quality of life" domain of SHIELD-WQ-9 at week 24. Secondary endpoints included other domains of SHIELD-WQ-9, DTR-QOL, EQ-5D-5L, medication preference, medication adherence, diet therapy adherence, body weight, body mass index (BMI), abdominal circumference, HbA1c, and frequency of adverse events. RESULTS: The proportion of subjects indicating improvement in the "overall quality of life" domain of SHIELD-WQ-9 at week 24 was higher in the dapagliflozin group (28.4%) than in the DPP4i group (18.6%) (p = 0.08). The proportion of subjects indicating improvement in the "physical health" domain of SHIELD-WQ-9 at week 24 was significantly higher in the dapagliflozin group (42.2%) than in the DPP4i group (23.7%) (p = 0.004). Total scores and domain 1 scores of DTR-QOL showed greater improvement in the dapagliflozin group (14.3 ± 15.6 and 15.5 ± 20.8, respectively) than in the DPP4i group (10.2 ± 15.6 and 10.3 ± 19.5, respectively) (both p = 0.05). EQ-5D-5L scores had significantly improved in the DPP4i group (0.023 ± 0.088) (p = 0.005); the intergroup difference was not significant (p = 0.14). Body weight (p < 0.001), BMI (p < 0.001), and abdominal circumference (p = 0.019) had significantly decreased in the dapagliflozin group compared with the corresponding values in the DPP4i group. CONCLUSION: Dapagliflozin showed a comparable or more favorable benefit on Japanese patients' QOL compared with DPP4is. Dapagliflozin was well tolerated. It significantly reduced body weight, which was significantly correlated with improvement in the patients' QOL. This study demonstrates that dapagliflozin can be used as a first-line drug for T2DM in Japan with a beneficial impact on patients' QOL. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN000030514); Japan Registry of Clinical Trials (jRCTs051180165).

Efficacy of dapagliflozin versus sitagliptin on cardiometabolic risk factors in Japanese patients with type 2 diabetes: a prospective, randomized study (DIVERSITY-CVR).

BACKGROUND: Few prospective studies have compared the cardiovascular benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors. We aimed to clarify the efficacy of dapagliflozin versus sitagliptin for modulating cardiometabolic risk factors including high glycated hemoglobin (HbA1c) levels, hypoglycemia, and body weight. METHODS: This prospective, randomized, open-label, blinded-endpoint, parallel-group trial enrolled 340 Japanese patients with early-stage type 2 diabetes receiving metformin alone or no glucose-lowering agents, who were randomized to receive dapagliflozin or sitagliptin for 24 weeks. The primary endpoint was the proportion of patients who achieved the composite endpoint of HbA1c level maintenance < 7.0% (53 mmol/mol), avoidance of hypoglycemia (maintenance of sensor glucose ≥ 3.0 mmol/L or ≥ 54 mg/dL), and ≥ 3.0% body weight loss from baseline. Secondary endpoints included components of the primary endpoint, other metabolic indices, and glucose variability indices measured using flash glucose monitoring. RESULTS: Clinical characteristics of patients were age, 58.1 ± 12.2 years; known duration of diabetes, 5.8 ± 6.1 years; body weight, 74.7 ± 14.2 kg; body mass index, 27.9 ± 4.1 kg/m2; and HbA1c level, 7.8 ± 0.8% at baseline. The achievement ratio of primary endpoint was significantly higher in the dapagliflozin group than in the sitagliptin group (24.4% vs. 13.8%, P < 0.05). While the rates of HbA1c level maintenance < 7.0% (53 mmol/mol) and avoidance of hypoglycemia were comparable between the groups (49.4 vs. 50.0% and 88.7 vs. 92.3% for dapagliflozin vs. sitagliptin, respectively), body weight loss of ≥ 3.0% was significantly achieved in the dapagliflozin group (54.4 vs. 19.6%, P < 0.001). Moreover, dapagliflozin was superior to sitagliptin regarding several secondary endpoints that modulate cardiometabolic risk, namely reducing fasting plasma glucose, insulin, uric acid, increasing high-density lipoprotein cholesterol, and suppressing the increase in serum creatinine and the decrease in estimated glomerular filtration rate. On the other hand, sitagliptin was superior to dapagliflozin in suppressing glucose variability. CONCLUSIONS: Compared to sitagliptin, dapagliflozin was significantly more effective at improving cardiometabolic risk factors, suggesting that SGLT2 inhibitors might be more suitable than DPP-4 inhibitors for preventing cardiovascular events in patients with early-stage but inadequately controlled type 2 diabetes. Trial registration Trial number, UMIN000028014; registered on June 30, 2017.

The Effect of Linagliptin versus Metformin Treatment-Related Quality of Life in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: There have been no studies directly comparing the effect of dipeptidyl peptidase-4 inhibitors with that of metformin on treatment-related quality of life (QOL) when used as first-line therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Forty-four participants who failed to achieve target glycemic control with diet and exercise therapy were randomly allocated to receive linagliptin or metformin therapy. We compared treatment-related QOL among the two groups using the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q version 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire. RESULTS: After randomization, 21 patients in the linagliptin group and 22 patients in the metformin treatment group were included in the full analysis set. Biochemical parameters, incidence of adverse effects, and rate of adherence to medication were comparable between the two groups. Over the 24-week treatment period, no significant differences in overall OHA-Q scores between the groups were observed, although the subscale 1 (treatment convenience) score was significantly higher in the linagliptin group than in the metformin group. The overall DTR-QOL score did not differ between the two groups; however, the DTR-QOL scores significantly improved after 24 weeks of linagliptin treatment, but not after metformin treatment. CONCLUSION: We did not find significantly better treatment-related QOL with linagliptin among Japanese patients with T2DM. In terms of treatment convenience, our data showed that linagliptin was superior to metformin. FUNDING: This study was financially supported by Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company. The journal's article processing fees were covered by a research fund from Juntendo University. CLINICAL TRIAL REGISTRATION: UMIN000022953.

Study Protocol for the Initial Choice of DPP-4 Inhibitor in Japanese Patients with Type 2 diabetes Mellitus: Effect of Linagliptin on QOL (INTEL-QOL) Trial.

INTRODUCTION: Consideration of treatment-related quality of life (QOL) is important in diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus metformin on treatment-related QOL when used as first-line therapy in patients with type 2 diabetes mellitus. METHODS: This study is a prospective, randomized, open-label, multicenter, parallel-group, comparative study. Between June 2016 and December 2017, 44 participants who failed to achieve glycemic control despite diet and exercise therapy were recruited at 14 clinics and randomly allocated to linagliptin or metformin therapy. Treatment-related QOL was assessed with the Oral Hypoglycemic Agent Questionnaire, version 2 (OHA-Q ver. 2) and the self-administered Diabetes Therapy-Related QOL (DTR-QOL) questionnaire. The primary study outcome is the difference in total OHA-Q ver. 2 score between the two treatment groups at the end of the study. The secondary outcomes include differences in the scores for each OHA-Q ver. 2 subscale between the two treatment groups at the end of the study, change in total DTR-QOL score and for each domain from baseline to the end of treatment, changes in glycemic control, and adverse events. PLANNED OUTCOME: The present study is designed to assess the effects of linagliptin on the treatment-related QOL. Results will be available in the near future. Study findings are expected to provide useful information on how to maintain or improve QOL in patients with type 2 diabetes mellitus treated with insulin. FUNDING: Nippon Boehringer Ingelheim Co., Ltd. and Eli Lilly and Company. CLINICAL TRIAL REGISTRATION: UMIN000022953.

Effects of linagliptin versus voglibose on treatment-related quality of life in patients with type 2 diabetes: sub-analysis of the L-STEP study.

Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.

Dapagliflozin improves treatment satisfaction in overweight patients with type 2 diabetes mellitus: a patient reported outcome study (PRO study).

BACKGROUND: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. METHODS: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. RESULTS: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). CONCLUSIONS: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.

Distribution of cardiac troponin I in the Japanese general population and factors influencing its concentrations.

BACKGROUND: The 99th percentile of cardiac troponin I level in the general population is accepted as the cut-off for the diagnosis of acute myocardial infarction (AMI). However, it is not clear whether the cut-offs derived in racially and geographically different populations are applicable in Japan. METHODS: Troponin I was determined using the Abbott ARCHITECT STAT high-sensitive troponin I immunoassay in 698 apparently healthy individuals who visited the Japanese Red Cross Medical Center for a health checkup. RESULTS: The 99th percentile of the hsTnI in the overall population was 22.5 (95% confidence interval (CI), 16.8-36.6) pg/mL, 17.7 (95% CI 12.0-22.8) pg/mL for females and 30.6 (95% CI 17.1-53.4) pg/mL for males. The median of the hsTnI in the overall population was 3.2 (95% CI, 3.0-3.3) pg/mL, 2.6 (95% CI 2.4-2.8) pg/mL for females and 4.0 (95% CI 3.8-4.3) pg/mL for males. The age and gender had a significant influence on these values. The troponin I level also showed significant associations with the body mass index (BMI), the gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), estimated glomerular filtration rate (eGFR), and cardiac abnormalities by electrocardiography (ECG) but not with the high-sensitive C-reactive protein (hsCRP) level. CONCLUSIONS: The 99th percentiles of the troponin I measured in the general population in Japan were comparable as the ones derived in the US, Germany, and Singapore. The troponin I level was dependent on the gender, age, BMI, and cardiac abnormalities found by ECG but not by the hsCRP level.

Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes.

Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.

Isolated Adrenocorticotropic Hormone Deficiency Caused by Nivolumab in a Patient with Metastatic Lung Cancer.

Nivolumab has promising efficacy for treating various advanced malignant tumors, although it has been reported to induce a wide range of autoimmune adverse effects. We herein report the case of a patient with metastatic lung adenocarcinoma who developed adrenal insufficiency after 12 cycles of nivolumab treatment. Endocrine test results supported a diagnosis of isolated adrenocorticotropic hormone deficiency due to hypophysitis, and replacement therapy using hydrocortisone has been successful. Although hypophysitis is a rare immune-related adverse event that is associated with nivolumab therapy, clinical awareness is essential, as this condition can be life-threatening and requires prompt treatment.

Antithyroid Arthritis Syndrome: A Case Report and Review of the Literature.

We herein report the case of a 38-year-old Japanese woman with antithyroid arthritis syndrome who experienced severe migratory polyarthritis after the initiation of thiamazole therapy. The patient's symptoms promptly disappeared without any sequelae after the withdrawal of the drug. Antithyroid arthritis syndrome is poorly characterized, and the findings from our literature review indicate that this syndrome exhibits serological features that are distinct from those of antithyroid agent-induced vasculitis syndrome. The absence of autoantibodies, especially anti-neutrophil cytoplasmic antibodies, may help characterize and diagnose antithyroid arthritis syndrome. Furthermore, physicians' awareness of this syndrome is essential for its diagnosis in clinical practice.

Effects of linagliptin monotherapy compared with voglibose on postprandial blood glucose responses in Japanese patients with type 2 diabetes: Linagliptin Study of Effects on Postprandial blood glucose (L-STEP).

AIMS: To compare the efficacy on glycemic parameters between a 12-week administration of once-daily linagliptin and thrice-daily voglibose in Japanese patients with type 2 diabetes. METHODS: In a multi-center, randomized, parallel-group study, 382 patients with diabetes were randomized to the linagliptin group (n=192) or the voglibose group (n=190). A meal tolerance test was performed at weeks 0 and 12. Primary outcomes were the change from baseline to week 12 in serum glucose levels at 2h during the meal tolerance test, HbA1c levels, and serum fasting glucose levels, which were compared between the 2 groups. RESULTS: Whereas changes in serum glucose levels at 2h during the meal tolerance test did not differ between the groups, the mean change in HbA1c levels from baseline to week 12 in the linagliptin group (-0.5±0.5% [-5.1±5.4mmol/mol]) was significantly larger than in the voglibose group (-0.2±0.5% [-2.7±5.4mmol/mol]). In addition, there was significant difference in changes in serum fasting glucose levels (-0.51±0.95mmol/L in the linagliptin group vs. -0.18±0.92mmol/L in the voglibose group, P<0.001). The incidences of hypoglycemia, serious adverse events (AEs), and discontinuations due to AEs were low and similar in both groups. However, gastrointestinal AEs were significantly lower in the linagliptin group (1.05% vs. 5.85%; P=0.01). CONCLUSIONS: These data suggested that linagliptin monotherapy had a stronger glucose-lowering effect than voglibose monotherapy with respect to HbA1c and serum fasting glucose levels, but not serum glucose levels 2h after the start of the meal tolerance test.

Lack of predictive power of plasma lipids or lipoproteins for gestational diabetes mellitus in Japanese women.

AIMS/INTRODUCTION: To determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20-28 weeks of gestation who underwent a glucose challenge test (GCT). MATERIALS AND METHODS: A total of 1,161 Japanese women at 20-28 weeks of gestation underwent a GCT. Participants with a positive test (GCT[+]) underwent a subsequent oral glucose tolerance test. Clinical and biochemical parameters were determined and quantification of apolipoproteins (Apo), including ApoB, ApoB48, ApoA-I and ApoC-III, was carried out. RESULTS: The prevalence of GCT(+; with a 130 mg/dL glucose cut-off) and GDM was 20% and 4%, respectively. There was a trend for increased triglycerides and ApoC-III in GDM(+) participants. However, the difference in plasma triglycerides, ApoC-III or ApoB48 did not reach statistical significance between GDM(+) and GDM(-) women. Values of 1-h glucose (P < 0.001) and fasting glucose (P = 0.002) were significant risk factors for GDM. CONCLUSIONS: Prediction of GDM using only the ApoC-III value is not easy, although triglycerides and ApoC-III were higher in the GDM(+) group. The present findings show no significant difference in plasma lipid levels between women diagnosed with GDM and those with normal glucose tolerance.

Fear of hypoglycemia and its determinants in insulin-treated patients with type 2 diabetes mellitus.

The aim of the present study was to investigate the prevalence of fear of hypoglycemia, in association with severe hypoglycemia and social factors, in insulin-treated patients with type 2 diabetes mellitus. A questionnaire survey on hypoglycemia and patient-physician communication was carried out in 355 patients with insulin-treated type 2 diabetes mellitus patients at 16 hospitals and clinics. A fear of hypoglycemia was reported by 27.7% of patients. A stepwise logistic regression analysis found that severe hypoglycemia during the past 1 year was a significant determinant of fear of hypoglycemia (odds ratio 2.16, 95% confidence interval 1.06-4.41; P = 0.034), and age (odds ratio 1.02, 95% confidence interval 1.00-1.05, P = 0.038) and living alone (odds ratio 1.93, 95% confidence interval 1.00-3.73, P < 0.05) were significantly higher in patients with fear of hypoglycemia than in those without it.

Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins.

BACKGROUND: There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks. METHODS: Lipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin) plus ezetimibe (EAT: n = 53) with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin) (DST: n = 56) in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol) and sd-LDL-C, two characteristic atherogenic risks of DM. RESULTS: The reduction of LDL-C (%), the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST). In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7) and RLP-C (-19.7 vs. +5.5). In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3) and non-HDL-C (-20.7 vs. -8.3) differed significantly between the two groups. CONCLUSION: Ezetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin) was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin) treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response. TRIAL REGISTRATION: The UMIN Clinical Trials Registry UMIN000002593.

Glucagon underutilized among type 1 diabetes mellitus patients in Japan.

AIM: Glucagon is recommended to treat severe hypoglycemia in nonhospital environments, when a patient with type 1 diabetes mellitus (T1DM) is unconscious and unable to eat or drink. However, the actual possession rate of glucagon in Japan has not been investigated. SUBJECTS AND METHODS: We recruited 208 T1DM patients older than 15 years of age. The patients were treated at 16 hospitals and clinics in different regions of Japan. Answers were obtained using a self-administered questionnaire about the possession, the experience of usage, and the preference to possess glucagon after reading what is glucagon and when it is used. A stepwise logistic regression analysis was performed to assess the influence of various factors on the possession of glucagon. RESULTS: The possession rate of glucagon was 15.9%, and the rate of those who had experience of using glucagon to treat severe hypoglycemia was 6.0%. The rate of preference to possess glucagon at home after reading the description of glucagon was 39.0%. The possession of glucagon was significantly associated with results of the Glucagon Knowledge Test (odds ratio=24.1; 95% confidence interval, 3.2-183.3; P=0.002) and the history of severe hypoglycemia within 1 year (odds ratio=4.8; 95% confidence interval, 2.0-12.0; P=0.001). CONCLUSIONS: Glucagon as a measure to treat severe hypoglycemia was underutilized among T1DM patients in Japan.

Comparison between sitagliptin and nateglinide on postprandial lipid levels: The STANDARD study.

AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism. METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A1c (HbA1c) > 6.5% despite diet and exercise; HbA1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially. RESULTS: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m(2); the nateglinide group: 21.39 ± 2.24 kg/m(2)). Fasting levels of HbA1c, glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P < 0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P = 0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group. CONCLUSION: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.

A retrospective, longitudinal study to evaluate healing lower extremity wounds in patients with diabetes mellitus and ischemia using standard protocols of care and platelet-rich plasma gel in a Japanese wound care program.

Chronic wounds, especially in patients with diabetes mellitus (DM), are a major health challenge in Japan. The goal of wound care centers (WCCs) in Japan is to facilitate healing and prevent lower extremity amputations (LEAs) using standardized protocols of patient and wound care. The standard treatment algorithm includes a complete patient and wound assessment, history, physical exam, and a variety of diagnostic tests that determine the need for infection control intervention, revascularization, excision and debridement, growth factor/platelet rich plasma (PRP) gel therapy, skin graft/ flap, wound protection, and education. All patient and wound data are entered in a secure central database for all WCCs. To evaluate the outcomes of standard care regimens compared to the use of a topical PRP gel treatment in patients with a variety of complex wounds, a retrospective, longitudinal study was conducted. Wound outcomes from 39 patients with 40 chronic, nonhealing, lower extremity wounds were evaluated between two time periods: between first presentation at the WCC (T1) and after using standard topical treatments (T2) and between T2 and after using the PRP gel treatment (T3). Patient average age was 66.8 years (SD: 10.60) and mean wound duration was 99.7 days before treatment (SD: 107.73); and the majority of patients (85%) had DM. Wounds were classified as ischemic diabetic (n = 24), diabetic (n = 10), ischemic (n = 5), and pressure ulcer (n = 1). DFUs were Wagner III (77%) and lV (23%). Of those, 60% were in patients with arteriosclerotic obliterans (ASO). Infection (abscess, cellulitis, osteomyelitis, and/or gangrene) was present in all wounds and treated using debridement, antibiotic therapy, and surgery as deemed appropriate. During the first treatment period (T1 to T2) of 75.3 days, which included revascularization and/or debridement along with standard of care, none of the wounds healed and the average wound area, depth, and volume increased. Following topical PRP gel treatment, 83% of wounds healed within 145.2 days (T2 to T3) (P = 0.00002). Only one patient required an LEA. The results of this study suggest that good healing outcomes and a low amputation rate can be obtained with a protocol of supportive care (including revascularization procedures) and the PRP gel treatment. Prospective controlled studies comparing the use of this PRP gel to other advanced treatments are warranted.