Glucagon Stimulation Test and Insulin Secretory Capacity in Clinical Assessment of Incretin-Based Therapy for Diabetes.

Evaluation of insulin secretory capacity is essential to understand the pathophysiological condition of individuals with diabetes and to assess the efficacy of drugs used in treatment of the disease. The 1 mg intravenous glucagon stimulation test (GST) is widely used to evaluate residual ß cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, recent reports indicate that pharmacological concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The present studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). Our first study comprised individuals initiated with the treatment of GLP-1RAs evaluated by GSTs before and after treatment. Although the fasting C-peptide levels (CPR) were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and non-users, assessed by GST after propensity score matching. While the fasting CPR were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that GST might underestimate insulin secretory capacity under incretin-based therapy.

PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.

AIMS/INTRODUCTION: PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. MATERIALS AND METHODS: Adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34-44 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and ≥75 years. RESULTS: A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA1c and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA1c from baseline was -0.7 percentage points (-0.77, -0.61) overall, -0.8 percentage points (-0.86, -0.67) in the <75 years subgroup and -0.5 percentage points (-0.68, -0.41) in the ≥75 years subgroup (all P < 0.0001). Estimated change (95% CI) in bodyweight was -2.8 (-3.19, -2.50) kg overall, -2.9 (-3.38, -2.49) kg in the <75 years subgroup and - 2.7 (-3.18, -2.14) kg in the ≥75 years subgroup (all P < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and ≥75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation. CONCLUSIONS: In routine clinical practice, HbA1c and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged ≥75 years, with no new safety concerns.

Effect of Roxadustat on Thyroid Function in Patients With Renal Anemia.

CONTEXT: Roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, a recently developed class of drugs for treatment of anemia in chronic kidney disease (CKD), is reported to have a structure unlike that of other HIF-PH inhibitors but similar to that of triiodothyronine and bind to the thyroid hormone receptor in vitro. However, reports on the effects of roxadustat on thyroid function are limited and not detailed, and it remains unknown whether other HIF-PH inhibitors also affect thyroid function. OBJECTIVE: To compare the effect of roxadustat with daprodustat, another HIF-PH inhibitor, on thyroid function in patients with renal anemia in CKD. METHODS: This retrospective observational study included a total of 26 patients with anemia in CKD who were treated with roxadustat or daprodustat; thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were measured before and after treatment with the drugs. RESULTS: After initiation of roxadustat, TSH showed a significant decrease (2.4732 [1.7858-4.9016] µIU/mL before treatment and 0.659 [0.112-2.005] µIU/mL after treatment, P < .05); FT4 showed a significant decrease (0.93 [0.84-1.05] ng/dL before treatment and 0.70 [0.53-0.85] ng/dL after treatment, P < .01). After daprodustat initiation, neither TSH nor FT4 showed a significant change (TSH: 3.044 [1.853-4.171] µIU/mL before treatment and 2.893 [1.866-4.894] µIU/mL after treatment, P = .635; FT4 was 0.93 [0.81-1.00] ng/dL before treatment and 0.97 [0.87-1.05] ng/dL after treatment, P = .328). CONCLUSION: Roxadustat decreases TSH and FT4 levels while daprodustat does not.

Is caloric restriction enough to increase longevity? Fasting and circadian alignment.

Effects of caloric restriction, fasting and circadian alignment on longevity in mice and potential risks and benefits of extrapolation to humans.

Stigma evaluation for diabetes and other chronic non-communicable disease patients: Development, validation and clinical use of stigma scale - The Kanden Institute Stigma Scale.

AIMS/INTRODUCTION: The aim of this study was to develop a scale to evaluate disease stigma in patients with lifestyle-related chronic non-communicable diseases (LCNCDs), which we named the Kanden Institute Stigma Scale (KISS), and to consider its possible clinical application for patients with diabetes. MATERIALS AND METHODS: An initial 90 questions were drafted and categorized into six subscales according to the manifestations of stigma. The final version of the KISS was developed as a 24-item questionnaire comprising four items for each subscale. RESULTS: A total of 539 outpatients including 452 patients with diabetes and 87 patients without diabetes were recruited. Construct validity was confirmed by assessing the correlation with previously established measures. Confirmatory factor analysis showed the KISS to have good model fitness (adjusted goodness-of-fit index = 0.856). Test-retest reproducibility analysis showed that the intraclass coefficient of the first and a second KISS was 0.843 (P < 0.001), indicating excellent reproducibility. The KISS showed higher scores for patients with diabetes than for patients without diabetes (12.23 ± 0.49 vs 5.76 ± 0.73, P < 0.05). The KISS score was significantly higher in type 1 and type 2 diabetes patients taking insulin therapy than in type 2 diabetes patients not taking insulin (P < 0.05). CONCLUSION: The KISS is a validated and reliable questionnaire for assessment of stigma among patients with diabetes as well as other lifestyle-related chronic non-communicable diseases, and might contribute to identifying and rectifying diabetes stigma, as well promoting awareness among health care professionals of this very consequential health problem.

Association between height-corrected appendicular and regional skeletal muscle mass and insulin resistance in patients with type 2 diabetes.

[Purpose] The effect of height-corrected skeletal muscle masses on insulin resistance has not been fully investigated in patients with type 2 diabetes. In this study, we aimed to investigate the association between height-corrected appendicular and regional skeletal muscle masses and insulin resistance in patients with type 2 diabetes. [Participants and Methods] We included 136 male and 100 female patients with type 2 diabetes (average age, male 55.7 ± 12.3 years old, female 60.7 ± 11.3 years old, and average height, male 1.67 ± 0.06 m, female 1.54 ± 0.06 m) in this study. Bioelectrical impedance analysis was used to evaluate skeletal muscle mass. We calculated the appendicular skeletal muscle mass index by dividing the appendicular skeletal muscle mass by the square of the patient's height. The upper limb muscle mass, lower limb muscle mass, and trunk muscle mass figures were also divided by the square of the patient's height. We used the homeostasis model assessment of insulin resistance as a marker of insulin resistance. [Results] In multiple regression analysis, the homeostasis model assessment of insulin resistance was inversely associated with appendicular skeletal muscle mass index and lower limb muscle mass/height2 in male patients with type 2 diabetes when adjusted for age and body mass index. Similarly, the homeostasis model assessment of insulin resistance was inversely associated with appendicular skeletal muscle mass index and lower limb muscle mass/height2 in non-obese female patients with type 2 diabetes. [Conclusion] We have confirmed that there is an association between appendicular skeletal muscle mass index and lower limb muscle mass/height2 with insulin resistance in male and female patients with type 2 diabetes, except in females with obesity.

Effects of physician's diabetes self-management education using Japan Association of Diabetes Education and Care Diabetes Education Card System Program and a self-monitoring of blood glucose readings analyzer in individuals with type 2 diabetes: An exploratory, open-labeled, prospective randomized clinical trial.

AIMS/INTRODUCTION: This 6-month, single-center, prospective, open-labeled, randomized trial was designed to investigate whether physicians' diabetes self-management education using an education tool developed by the Japan Association of Diabetes Education and Care and a self-monitoring of blood glucose (SMBG) analyzer improves glycemic control in individuals with type 2 diabetes receiving insulin and SMBG. MATERIALS AND METHODS: Participants were randomized into intervention (I) and control (C) groups. Both groups received physicians' diabetes self-management education at each hospital visit, whereas the Japan Association of Diabetes Education and Care education tool and the SMBG readings analyzer was used in group I, but not group C. All participants filled out a diabetes treatment-related quality of life form and an original questionnaire on SMBG use with five questions (Q1-Q5) before and after the study period. RESULTS: A total of 76 individuals were recruited and randomized. Glycated hemoglobin (HbA1c) was significantly improved during the study period in group I, whereas no significant change was observed in group C. The change in HbA1c was greater in group I, although it did not reach statistical significance. The diabetes treatment-related quality of life total score was not changed in either group. Interestingly, the score of Q1 ("How important is SMBG to you?") in the SMBG questionnaire was unchanged in group I, whereas it was significantly decreased in group C. HbA1c change was independently associated with changes in insulin dose and SMBG Q1 score. CONCLUSION: Greater HbA1c-lowering by physicians' diabetes self-management education using the Japan Association of Diabetes Education and Care education tool and SMBG analyzer in individuals with type 2 diabetes receiving insulin and SMBG was suggested, but not confirmed.

Effects of glucagon-like peptide-1 receptor agonists on secretions of insulin and glucagon and gastric emptying in Japanese individuals with type 2 diabetes: A prospective, observational study.

AIMS/INTRODUCTION: Differences in the glucose-lowering mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been noted. Clarifying these differences could facilitate the choice of optimal drugs for individuals with type 2 diabetes and requires investigation in a clinical setting. MATERIALS AND METHODS: A single-arm, prospective, observational study was conducted to evaluate the effects of various GLP-1RAs on postprandial glucose excursion, secretions of insulin and glucagon as well as on the gastric emptying rate. Participants were subjected to meal tolerance tests before and 2 weeks and 12 weeks after GLP-1RA initiation. Effects on postprandial secretions of glucose-dependent insulinotropic polypeptide (GIP) and apolipoprotein B48 were also investigated. RESULTS: Eighteen subjects with type 2 diabetes received one of three GLP-1RAs, i.e., lixisenatide, n = 7; liraglutide, n = 6; or dulaglutide, n = 5. While 12-week administration of all of the GLP-1RAs significantly reduced HbA1c, only lixisenatide and liraglutide, but not dulaglutide, significantly reduced body weight. Postprandial glucose elevation was improved by all of the GLP-1RAs. Postprandial insulin levels were suppressed by lixisenatide, while insulin levels were enhanced by liraglutide. Postprandial glucagon levels were suppressed by lixisenatide. The gastric emptying rate was significantly delayed by lixisenatide, while liraglutide and dulaglutide had limited effects on gastric emptying. GIP secretion was suppressed by lixisenatide and liraglutide. Apolipoprotein B48 secretion was suppressed by all of the GLP-1RAs. CONCLUSIONS: All of the GLP-1RAs were found to improve HbA1c in a 12-week prospective observational study in Japanese individuals with type 2 diabetes. However, differences in the mechanisms of the glucose-lowering effects and body weight reduction were observed.

The COVID-19 world - Are we there yet?

The spreading of SARS-CoV-2 virus infection is still of great concern as well as clinical and social interest. The key to conquer this pandemic would be establishment of herd immunity by vaccination and of treatment, and I have discussed issues we are facing now.

Lifestyle changes as a result of COVID-19 containment measures: Bodyweight and glycemic control in patients with diabetes in the Japanese declaration of a state of emergency.

To clarify the association between lifestyle changes as a result of coronavirus disease 2019 containment measures and changes in metabolic and glycemic status in patients with diabetes, a cross-sectional, single-center, observation study was carried out. A self-reported questionnaire was provided to ascertain the frequency of various lifestyle activities before and after the coronavirus disease 2019 containment measures in Japan. Among 463 patients, change in glycated hemoglobin was significantly associated with change in bodyweight. After stratification by age 65 years, binary logistic regression analysis showed that increased frequency of snack eating increased bodyweight (odds ratio 1.709, P = 0.007) and glycated hemoglobin (odds ratio 1.420, P = 0.025) in the younger group, whereas in the older patients, reduced walking activities resulted in weight gain (odds ratio 0.726, P = 0.010). In conclusion, changes in eating behavior and physical activity increased bodyweight and reduced glycemic control among diabetes patients, but by different processes depending on age under the coronavirus disease 2019 containment measures in Japan.

Glutamate is an essential mediator in glutamine-amplified insulin secretion.

AIMS/INTRODUCTION: Glutamine is the most abundant amino acid in the circulation. In this study, we investigated cell signaling in the amplification of insulin secretion by glutamine. MATERIALS AND METHODS: Clonal pancreatic ß-cells MIN6-K8, wild-type B6 mouse islets, glutamate dehydrogenase (GDH) knockout clonal ß-cells (Glud1KOßCL), and glutamate-oxaloacetate transaminase 1 (GOT1) knockout clonal ß-cells (Got1KOßCL) were studied. Insulin secretion from these cells and islets was examined under various conditions, and intracellular glutamine metabolism was assessed by metabolic flux analysis. Intracellular Ca2+ concentration ([Ca2+ ]i ) was also measured. RESULTS: Glutamine dose-dependently amplified insulin secretion in the presence of high glucose in both MIN6-K8 cells and Glud1KOßCL. Inhibition of glutaminases, the enzymes that convert glutamine to glutamate, dramatically reduced the glutamine-amplifying effect on insulin secretion. A substantial amount of glutamate was produced from glutamine through direct conversion by glutaminases. Glutamine also increased [Ca2+ ]i at high glucose, which was abolished by inhibition of glutaminases. Glutamic acid dimethylester (dm-Glu), a membrane permeable glutamate precursor that is converted to glutamate in cells, increased [Ca2+ ]i as well as induced insulin secretion at high glucose. These effects of glutamine and dm-Glu were dependent on calcium influx. Glutamine also induced insulin secretion in clonal ß-cells MIN6-m14, which otherwise exhibit no insulin secretory response to glucose. CONCLUSIONS: Glutamate converted from glutamine is an essential mediator that enhances calcium signaling in the glutamine-amplifying effect on insulin secretion. Our data also suggest that glutamine exerts a permissive effect on glucose-induced insulin secretion.

Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial.

BACKGROUND: Given the unique phenotype of type 2 diabetes in Japanese patients, novel therapies such as oral semaglutide require evaluation in this population. PIONEER 9 aimed to assess the dose-response of oral semaglutide and to compare the efficacy and safety of oral semaglutide with placebo and a subcutaneous GLP-1 receptor agonist in a Japanese population. METHODS: PIONEER 9 was a 52-week, phase 2/3a, randomised, controlled trial done at 16 sites (clinics and university hospitals) in Japan. Japanese patients aged 20 years or older with uncontrolled type 2 diabetes managed by diet or exercise or with oral glucose-lowering drug monotherapy (washed out) were randomly assigned (1:1:1:1:1) to receive double-blind once-daily oral semaglutide (3 mg, 7 mg, or 14 mg) or placebo, or open-label subcutaneous once-daily liraglutide 0·9 mg. The primary endpoint was change in HbA1c from baseline to week 26 with the trial product (primary) estimand (which assumes all patients remained on trial product without rescue medication use) in all randomly assigned patients. This trial is registered with ClinicalTrials.gov, NCT03018028. FINDINGS: Between Jan 10, and July 11, 2017, 243 patients were randomly assigned to oral semaglutide 3 mg (n=49), 7 mg (n=49), or 14 mg (n=48), or placebo (n=49), or to liraglutide 0·9 mg (n=48). Changes in HbA1c from baseline (mean 8·2%) to week 26 were dose-dependent with oral semaglutide (mean change -1·1% [SE 0·1] for oral semaglutide 3 mg, -1·5% [0·1] for 7 mg, and -1·7% [0·1] for 14 mg), -0·1% (0·1) with placebo, and -1·4% (0·1) with liraglutide 0·9 mg. Estimated treatment differences for change in HbA1c compared with placebo were -1·1 percentage points (95% CI -1·4 to -0·8; p<0·0001) for oral semaglutide 3 mg, -1·5 percentage points (-1·7 to -1·2; p<0·0001) for oral semaglutide 7 mg, and -1·7 percentage points (-2·0 to -1·4; p<0·0001) for oral semaglutide 14 mg. Estimated treatment differences for change in HbA1c compared with liraglutide 0·9 mg were 0·3 percentage points (95% CI -0·0 to 0·6; p=0·0799) for oral semaglutide 3 mg, -0·1 percentage points (-0·4 to 0·2; p=0·3942) for oral semaglutide 7 mg, and -0·3 percentage points (-0·6 to -0·0; p=0·0272) for oral semaglutide 14 mg. Gastrointestinal events, predominantly of mild or moderate severity, were the most frequently reported class of adverse event with oral semaglutide: constipation was most common, occurring in five to six (10-13%) patients with oral semaglutide, three (6%) with placebo, and nine (19%) with liraglutide 0·9 mg. INTERPRETATION: This study showed that oral semaglutide provides significant reductions in HbA1c compared with placebo in a dose-dependent manner in Japanese patients with type 2 diabetes, and has a safety profile consistent with that of GLP-1 receptor agonists. FUNDING: Novo Nordisk.

A novel splice-site mutation of the HNF1B gene in a family with maturity onset diabetes of the young type 5 (MODY5).

SUMMARY: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes mellitus characterised by early onset and dominant inheritance. Delayed diagnosis or misdiagnosis as type 1 or type 2 diabetes mellitus is common. Definitive genetic diagnosis is essential for appropriate treatment of patients with MODY. The hepatocyte nuclear factor 1-beta (HNF1B) gene is responsible for MODY type 5 (MODY5), which has distinctive clinical features including renal disease. MODY5 should always be considered by clinicians in patients with early onset diabetes and renal anomalies. We report a case of a 30-year-old Japanese male with early-onset diabetes mellitus, renal anomalies and family history of diabetes that was suggestive of MODY5. Renal histology showed no evidence of diabetic nephropathy. Genetic testing revealed a novel heterozygous splice-site mutation of the HNF1B gene in the family members. It was strongly suggested that the mutation could underlie our patient's MODY5. LEARNING POINTS: Genetic diagnosis of MODY is relevant for appropriate treatment. Dominantly inherited early-onset diabetes mellitus with renal cysts suggests MODY5. Scanning the non-coding regions is important for not missing a mutation in HNF1B.

Dietary instructions focusing on meal-sequence and nutritional balance for prediabetes subjects: An exploratory, cluster-randomized, prospective, open-label, clinical trial.

BACKGROUND: Although lifestyle modifications are known to be effective in type 2 diabetes (T2D) as well as in prediabetes, adherence to a healthy diet is difficult for some, and interventions of lifestyle modifications need to be revised occasionally. Meal sequence has been gaining attention as a part of a healthy diet among T2D individuals to improve glycemia and body weight. In addition, a dietary instruction program, SMART Washoku®, which can help individuals to consume a more nutritionally balanced diet, has been developed. METHODS: The current exploratory trial was designed to examine the effects of dietary instructions focusing on meal sequence and nutritional balance in individuals with prediabetes in the Japanese national health check-up and guidance program. Participants were cluster-randomized into three groups: Group A, receiving a conventional health guidance program (n = 11); Group B, receiving health guidance with dietary instructions focusing on meal sequence (n = 18); and Group C, receiving health guidance with dietary instructions focusing on nutritional balance (n = 13). Participants received health guidance education and various measurements before and 6 months after the instructions. RESULTS: Body weight in Group B was significantly reduced compared to that in Group A, with similar adherence, while the effects on glycemia were similar between the two Groups. Body weight reduction was greater in Group C compared to that in Group A, although adherence in Group C was significantly lower than that in Group A. CONCLUSION: The group receiving health guidance with dietary instructions focusing on meal sequence exhibited similar adherence and greater reduction in body weight than the group receiving conventional health guidance.

Evaluation of skeletal muscle mass indices, assessed by bioelectrical impedance, as indicators of insulin resistance in patients with type 2 diabetes.

[Purpose] This study aimed to investigate the association between two skeletal muscle mass indices and insulin resistance, and to determine the skeletal muscle mass index that is beneficial in evaluating insulin resistance in patients with type 2 diabetes mellitus. [Participants and Methods] This study evaluated 136 male and 100 female patients with type 2 diabetes mellitus. The skeletal muscle mass was evaluated by bioelectrical impedance analysis. Two skeletal muscle mass indices were investigated as the appendicular skeletal muscle mass index (appendicular skeletal muscle mass divided by the square of height) and relative total skeletal muscle mass (total skeletal muscle mass as a percent of body weight). The homeostasis model assessment of insulin resistance was used as a marker of insulin resistance. Associations were investigated by grouping the participants according to gender and age (<60 or ≥60 years). [Results] The appendicular skeletal muscle mass index was positively associated with the homeostasis model assessment of insulin resistance, except in male patients aged ≥60 years, whereas the relative total skeletal muscle mass was significantly inversely associated with the homeostasis model assessment of insulin resistance, in all patient groups. The cutoff values of the relative total skeletal muscle mass for the presence of insulin resistance were 37.9% and 32.5% in male and female patients, respectively. [Conclusion] This finding suggests that relative total skeletal muscle mass may be a better indicator of insulin resistance than appendicular skeletal muscle mass index is, in patients with type 2 diabetes mellitus.

Reply to the comment of Wilbrink et al. on Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes: The association between remaining ß-cell function and the achievement of the HbA1c target 1 year after initiation.

We have reported that the HbA1c-lowering effects of liraglutide/basal insulin combination rely on remaining ß-cell function and that the cut-off value of the C-peptide immunoreactivity index (CPI), a ß-cell function-related index frequently used in Japanese clinical settings, is 1.103 for the achievement of HbA1c <7.0% at 54 weeks after initiating the liraglutide/basal insulin combination. Wilbrink et al claimed that glucose-lowering effects of glucagon-like peptide-1 receptor agonist liraglutide depend of duration of type 2 diabetes; while our resent study published in the Journal of Diabetes Investigation failed to detect such dependency. This discrepancy might be due to several reasons including co-administration of basal insulin with liraglutide in our study; ethnic difference in T2D pathophysiology between the two study; and difference in sample size (The Usui study on liraglutide/basal insulin, n = 38; the Usui study on liraglutide monotherapy or SU combination, n=88; and the Wilbrink study, n = 69).

Mental distress and health-related quality of life among type 1 and type 2 diabetes patients using self-monitoring of blood glucose: A cross-sectional questionnaire study in Japan.

AIMS/INTRODUCTION: The present multicenter, cross-sectional survey was initiated to evaluate self-monitoring of blood glucose (SMBG)-associated mental distress among patients with diabetes. MATERIALS AND METHODS: The survey was carried out in patients with type 1 diabetes and type 2 diabetes using SMBG recruited from 42 medical institutions. Profiles of Mood States 2 and diabetes therapy-related quality of life questionnaires were used to evaluate mood status and health-related quality of life. Two original questionnaires were also developed to evaluate SMBG 'importance,' 'painfulness' and 'confidence' among patients, and to evaluate physician attitudes to SMBG use. RESULTS: Questionnaires from 517 type 1 diabetes and 1,648 type 2 diabetes patients showed that 46.0% of type 1 diabetes and 37.5% of type 2 diabetes patients reported 'painfulness,' and that these patients reporting 'painfulness' showed significantly higher Profiles of Mood States 2 scores, lower diabetes therapy-related quality of life scores and higher glycated hemoglobin compared with those not reporting 'painfulness,' whereas the number of their daily SMBG tests were comparable. Patients reporting 'painfulness' also reported that SMBG use was significantly less important. Whether or not patients recognized the importance of SMBG use was well correlated with the frequency of physicians checking patient diaries. CONCLUSIONS: Type 1 diabetes and type 2 diabetes patients reporting 'painfulness' in SMBG use had more mental distress, lower health-related quality of life and higher glycated hemoglobin regardless of their number of daily SMBG tests. The importance of SMBG use was recognized less by patients experiencing pain, and the importance of SMBG use was recognized more in medical institutions in which physicians regularly checked SMBG diaries to provide meaningful feedback to patients in clinical settings.

Glucose excursions and hypoglycemia in patients with type 2 diabetes treated with mitiglinide/voglibose versus glimepiride: A randomized cross-over trial.

BACKGROUND: Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. METHODS: This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test. RESULTS: The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase. CONCLUSIONS: Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

Retrospective analysis of liraglutide and basal insulin combination therapy in Japanese type 2 diabetes patients: The association between remaining ß-cell function and the achievement of the glycated hemoglobin target 1 year after initiation.

AIMS/INTRODUCTION: The glucose-lowering effects of the glucagon-like peptide-1 receptor agonist, liraglutide, have been shown to rely on remaining ß-cell function. However, the possible associations of remaining ß-cell function with the glucose-lowering effects of liraglutide in combination with basal insulin remain unknown and warrant investigation. MATERIALS AND METHODS: This was a single-center, retrospective, observational study carried out in a private hospital in Osaka, Japan. Type 2 diabetes patients who received a prescription change from insulin therapy, both multiple-dose insulin and basal insulin-supported oral therapy, to liraglutide and basal insulin combination and continued the therapy for 54 weeks without additional oral antidiabetic drugs or bolus insulin were retrospectively analyzed. RESULTS: Among the 72 participants who received a prescription change from multiple-dose insulin and basal insulin-supported oral therapy to liraglutide and basal insulin combination, 57 continued the therapy for 54 weeks. Of those who continued the therapy without receiving additional oral antidiabetic drugs or bolus insulin, seven participants achieved glycated hemoglobin < 7.0% at 54 weeks, but 30 participants did not. The participants who achieved glycated hemoglobin < 7.0% at 54 weeks had a significantly higher C-peptide immunoreactivity index, a ß-cell function-related index frequently used in Japanese clinical settings. The receiver operating curve analysis showed that the C-peptide immunoreactivity index cut-off value for the achievement of glycated hemoglobin <7.0% at 54 weeks is 1.103. CONCLUSIONS: The current findings show that the glucose-lowering effects of liraglutide rely on remaining ß-cell function, even when used with basal insulin; and suggest that liraglutide and basal insulin combination might require additional bolus insulin to fully compensate insulin insufficiency in individuals with reduced ß-cell function.