Search

AIM We compared the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice-daily to a free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide (IDeg + Lira) once-daily for patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs. SUBJECTS AND METHODS Eligible patients were randomly allocated at a 1:1 ratio to receive either the once-daily dual injection of IDeg + Lira (n = 24) or twice-daily single injection of IDegAsp (n = 28). The primary endpoints were as follows: HbA1c changes over 52 weeks of treatment and the percentage of participants achieving HbA1c

Aim: We compared the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice-daily to a free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide (IDeg+Lira) once-daily for patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs. Subjects and Methods: Eligible patients were randomly allocated at a 1:1 ratio to receive either the once-daily dual-injection of IDeg+Lira (n=24) or twice-daily single-injection of IDegAsp (n=28). The primary endpoints were: HbA1c changes over 52 weeks of treatment and the percentage of participants achieving HbA1c

Introduction and Hypothesis: White blood cell (WBC) count in healthy persons is reported to be associated with the risk of coronary artery disease (CAD) and all-cause death. The aim of our study was to determine whether WBC count predicts cardiovascular outcome, including heart failure and mortality, in consecutively registered patients with type 2 diabetes. Methods and Results: This was a post-hoc study from the Intensive Lipid and Blood Pressure Lowering and Cardiovascular Outcome Randomized Controlled Trial in Patients with CAD and type 2 diabetes. A total of 7,608 participants (mean age 68 years, 72% men) had WBC measured at baseline and were eligible for this study. Participants were followed for a mean of 1,328 days. We used Cox proportional hazards regression model to assess the hazard ratio (HR) and 95% confidence interval (CI). Participants with WBC count in the highest quartile had an adjusted HR for all-cause death of 1.66 (95% CI, 1.33 to 2.06, Figure) compared to those in the lowest quartile (WBC Conclusions: In patients with CAD and type 2 diabetes, higher WBC count may have potential as a predictor for all-cause death, myocardial infarction, and heart failure but not stroke. Disclosure A. Kawabe: None. Y. Nakatani: None. S. Ono: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. T. Yasu: None.

Introduction: Hemorheology (blood viscosity) was reported to be a strong predictor of cardiovascular events in the Edinburgh Artery Study. However, deterioration in hemorheology through microvessels is a potential adverse effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. This study aimed to clarify the effect of dapagliflozin on blood fluidity. Method: This multi-center, open-label, randomized, comparative study included 90 patients with type 2 diabetes mellitu. Patients were randomly divided into treatment groups with and without dapagliflozin treatment, and each item was investigated. The primary endpoint was the whole blood transit time, based on the difference from the baseline to 16 weeks after enrollment, as measured by a microchannel array flow analyzer (MC-FAN). To assess this outcome, a 15% noninferiority margin (clinically significant cut-off value) was used. To test the noninferiority of the treatment, a t-distribution was used to calculate the 95% confidence interval to assess the difference from the baseline. Results: The whole blood transit time in the dapagliflozin group was 41.8 ± 6.1 sec (mean ± SD) before administration, and 43.4 ± 6.8 sec at 16 weeks after dapagliflozin administration. In the control group, the whole blood transit time was 40.5 ± 3.0 sec before administration and 39.9 ± 3.8 sec after 16 weeks. The difference between groups from the baseline to 16 weeks after enrollment was 1.7 sec [0.2, 3.5] (95% C.I), confirming the noninferiority of dapagliflozin administration. Futher, the analysis Results of the differences between groups according to the some items (the baseline of hematocrit, HbA1c levels and the whole blood transit time) for baseline, demonstrating the noninferiority of dapagliflozin administration in these items. Conclusion: Dapagliflozin was unlikely to have negative effects on blood fluidity after administration irrespective of the baseline Hematocrit, HbA1c levels and the whole blood transit time. Disclosure S. Ono: None. Y. Nakatani: None. A. Kawabe: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. Y. Aso: None. T. Yasu: None. Funding AstraZeneca

This study evaluated the effects of a glucagon-like peptide-1 receptor agonist on gastrointestinal (GI) tract motility and residue rates by examining GI transit time and lumen using capsule endoscopy.GI motility and lumen were assessed by capsule endoscopy before and after liraglutide administration in 14 patients with type 2 diabetes mellitus (T2DM).Gastric transit time in the group with diabetic neuropathy (DN) was 1:12:36±1:04:30h before liraglutide administration and 0:48:40±0:32:52h after administration (nonsignificant difference, P=0.19). Gastric transit time in the non-DN group was 1:01:30±0:52:59h before administration and 2:33:29±1:37:24h after administration (significant increase, P=0.03). Duodenal and small intestine transit time in the DN group was 4:10:34±0:25:54h before and 6:38:42±3:52:42h after administration (not significant, P=0.09) and, in the non-DN group, 3:51:03±0:53:47h before and 6:45:31±2:41:36h after administration (significant increase, P=0.03). The GI residue rate in the DN group was 32.1±24% before administration and 90.0±9.1% after administration (significant increase, P0.001), and increased in all patients; in the non-DN group, it was 32.1±35.3% before and 78.3±23.9% after administration (significant increase, P0.001), and also increased in all patients.Liraglutide causes delayed gastric emptying and inhibits duodenal and small intestine motility. However, these GI movement-inhibiting effects may be decreased or absent in patients with DN-associated dysautonomia.

Introduction The efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM). Methods The subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180

Background: The efficacy of administering a sodium-glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM).Methods: The subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean blood glucose level, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC)(>180, 180, it decreased from 339.1 to 113.6 mg/dL(P

日本甲状腺学会から甲状腺クリーゼの診断基準が2008 年に発表された.2004 年4 月から2009 年3月に当院で臨床的に甲状腺クリーゼと診断,治療した20 症例を,その診断基準にあてはめ,治療と予後等について解析した.基礎疾患は全例バセドウ病だった.誘因として服用不規則や中断が9 例,感染症6 例,糖尿病性ケトアシドーシス3 例,情動ストレス2 例,脳血管障害1 例,外傷1 例だった.診断基準で確定診断例が15例,疑い例が1 例,除外症例が4 例だった.症状では中枢神経症状が疑い・確定診断例では11 例,脈拍130/分以上は12 例認められたが,除外例では認められなかった.治療としてはチアマゾールが全症例に使用されていた.ヨードは13 例,b ブロッカーは17 例,ステロイドは12 例の症例で使用されており全例救命できた.服用不規則や中断,感染症が誘引となりやすく,症状では中枢神経症状・脈拍が特にクリーゼの診断には重要と考えられた.後遺症を残す重症例は6 例で全て新診断基準によって確定診断された症例であり,新診断基準は予後への有用性も期待できると考えられた., The Japan Thyroid Association established diagnosticcriteria for thyroid crisis in 2008. Using these criteria, weanalyzed 20 cases clinically diagnosed as thyroid crisis andtreated in our hospital from April 2004 to March 2009. Allpatients had Basedow's disease at the basal disease. Thecauses were irregular compliance or interruption of treatment(9 cases), infection (6 cases), diabetic ketoacidosis (3cases), emotional stress( 2 cases), stroke( 1 case), and trauma(1 case). Fifteen cases were confirmed as thyroid crisis,1 case was suspected as thyroid crisis, and 4 cases were rejectedas thyroid crisis according to the diagnostic criteria.Central nervous symptoms were observed in 11 cases, andtachycardia (over 130 beats/min) in 12 cases in the definitiveand suspicious cases, although there were no centralnervous symptoms or tachycardia in the excluded cases.Thiamazole was administered to all patients. In addition, iodine(13 cases), b -blocker (17 cases), and corticosteroids(12 cases) were administered. All patients were recovered.Irregular internal use, stopping treatment, and infectionwere likely to induce thyroid crisis. In paticular, centralnervous symptoms and tachycardia were important factorsfor diagnosis. As 6 serious cases with aftereffect were diagnosedas definitive cases of thyroid crisis according to thenew criteria, these new criteria may be useful to predictthe prognosis.

Background Caloric restriction (CR) prevents senescent changes, in which reactive oxygen species (ROS) have a critical role. Left ventricular (LV) hypertrophy is a risk factor for cardiovascular diseases. We examined whether CR alters cardiac redox state and hypertrophy from chronic pressure overload. Methods and Results Male c57BL6 mice were subjected to ascending aortic constriction (AAC) with ad libitum caloric intake (AL + AAC group) or 40% restricted caloric intake (CR + AAC group). CR was initiated 2 weeks before AAC and was continued for 4 weeks. Two weeks after constriction, AAC increased LV wall thickness, impaired transmitral flow velocity, and augmented myocyte hypertrophy and fibrosis, in association with enhancement of BNP and collagen III expressions in the AL + AAC group. In the AL + AAC group, oxidative stress in cardiac tissue and mitochondria were enhanced, and NADPH oxidase activity and mitochondrial ROS production were elevated. These changes were significantly attenuated in the CR + AAC group. Additionally, in antioxidant systems, myocardial glutathione peroxidase and superoxide dismutase activities were enhanced in the CR + AAC group. Conclusions Chronic pressure overload increased cardiac oxidative damage, in association with cardiac hypertrophy and fibrosis. Short-term CR suppressed oxidative stress and improved cardiac function, suggesting that short-term CR could be a useful strategy to prevent pressure overload–induced cardiac injury.

Introduction When insulin treatment is started in patients with type 2 diabetes mellitus (T2DM), there are many regimens that control serum glucose levels to a normal range. Basal-bolus insulin therapy is one of the most effective treatments for improving glycemic control to prevent the progression of diabetic microvascular complications. This study was conducted to determine whether step-up insulin treatment with premixed insulin aspart-30/70 (BIAsp 30) or lispro-50/50 (Mix50) in Japanese patients with type 2 diabetes mellitus could achieve better glycemic control. Methods In this open label study, 72 insulin-naïve patients with poorly controlled T2DM (HbA1c ≥8.4%), who had been taking oral antidiabetic drugs for at least 12 months, were randomized to receive BIAsp 30 or Mix50 therapy. Patients started treatment of a pre-dinner injection of each type of insulin (Step 1). At 16 ± 2 weeks, a pre-breakfast injection of each type of insulin was added if HbA1c exceeded 7.4% (step 2). If patients had still not achieved HbA1c

A cyclopentenone-type prostaglandin, 15-deoxy-Δ12,14-prostaglandin J2(15-d-PGJ2), has been shown to induce the cellular stress response and to be a ligand for the peroxisome proliferator-activated receptor (PPAR)-γ. We studied its effect on the basal and thyrotropin (TSH)-induced production of thyroglobulin (TG) by human thyrocytes cultured in the presence of 10% FBS. In 15-d-PGJ2-treated cells in which the agent itself did not stimulate cAMP production, both the basal production of TG and the response to TSH were facilitated, including the production of TG and cAMP, whereas such production was decreased in untreated cells according to duration of culture. PGD2and PGJ2, which are precursors to 15-d-PGJ2, exhibited an effect similar to 15-d-PGJ2. However, the antidiabetic thiazolidinediones known to be specific ligands for PPAR-γ, and WY-14643, a specific PPAR-α ligand, lacked this effect. 15-d-PGJ2and its precursors, but not the thiazolidinediones, induced gene expression for heme oxygenase-1 (HO-1), a stress-related protein, and strongly inhibited interleukin-1 (IL-1)-induced nitric oxide (NO) production. Cyclopentenone-type PGs have been recently shown to inhibit nuclear factor-κB (NF-κB) activation via a direct and PPAR-independent inhibition of inhibitor-κB kinase, suggesting that, in human thyrocytes, such PGs may inhibit IL-1-induced NO production, possibly via an inhibition of NF-κB activation. On the other hand, sodium arsenite, a known activator of the stress response pathway, induced HO-1 mRNA expression but lacked a promoting effect on TG production. Thus 15-d-PGJ2and its precursors appear to facilitate TG production via a PPAR-independent mechanism and through a different pathway from the cellular stress response that is available to cyclopentenone-type PGs. Our findings reveal a novel role of these PGs associated with thyrocyte differentiation.

Long- and short-acting glucagon-like peptide 1 receptor agonists (GLP-1RAs) liraglutide and lixisenatide, which are available for diabetes therapy, may act on the autonomic nervous system to increase heart rate (1,2). We performed a prospective, single-center, randomized, open-label study with a 1:1 allocation ratio using a 24-h Holter electrocardiogram to compare the effects of these GLP-1RAs on the autonomic nervous system. All procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients participating in this study. The study is registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000017770). Sixty patients with type 2 diabetes who were admitted for diabetes treatment and had not received dipeptidyl peptidase-4 inhibitors or GLP-1RAs were randomly divided into a liraglutide (age 64.9 ± 12.7 years, HbA1c 10.3 ± 2.5% [89.1 mmol/mol], BMI 24.6 ± 4.8 kg/m2, diabetes duration 7.8 ± 7.8 years) or …

The aim of this study was to evaluate the effectiveness of re-education in the insulin injection technique for glycemic control. A preliminary experimental study was performed with 87 insulin-treated diabetic outpatients (11 with type 1 diabetes, 76 with type 2 diabetes; 43 men, 44 women). All patients had been treated with insulin for more than 3 years. After answering questions about the insulin injection technique, the patients’ knowledge levels were scored. Correct answers and explanation sheets were subsequently given to all patients. The physicians in charge gave a short lecture and provided 10 min of individual advice. Two, three, and four months after re-education the HbA1c and glycoalbumin levels were measured. The mean HbA1c levels of almost all patients significantly improved from 7.46 ± 0.09% to 6.73 ± 0.10% (P

We report a 32-year-old Japanese women with severe hypoglycemia accompanied with thyroid crisis. She complained of dyspnea, general fatigue, and leg edema. She was diagnosed with hyperthyroidism with congestive heart failure and liver dysfunction. Soon after admission, sudden cardiopulmonary arrest occurred. She was then transferred to the intensive care unit. Her serum glucose level was 7 mg/dl. Intravenous glucose, hydrocortisone, diuretics, and continuous hemodiafiltration (CHDF) saved her. We considered that hypoglycemia occurred due to heart failure and liver dysfunction due to thyroid crisis.

A 62-year-old woman was admitted with dry mouth, general fatigue, and severe back pain. Biochemistry examination showed extreme hypercalcemia (21.2 mg/dL). Bone marrow examination was negative, but needle biopsy of a metastatic lung tumor revealed abnormal plasma cells; thus, multiple myeloma stage III-A was finally diagnosed. Serum concentrations of both parathyroid hormone-related peptide (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) were markedly elevated (PTHrP 7.2 pmol/L, normal

The effects of a low dose of rosuvastatin (ROS) and pitavastatin (PIT) on lipid profiles and inflammation markers were assessed in subjects with type 2 diabetes mellitus.A total of 90 Japanese type 2 diabetes patients with hyperlipidemia (low-density lipoprotein cholesterol [LDL-C] ≥140 mg/dL) were enrolled in this study. They were randomly assigned to four groups with open-label treatment with ROS (2.5 mg daily) or PIT (2 mg daily); two groups were sequentially treated with both drugs, with crossover of medication after 12 weeks, and the other two groups underwent treatment with either ROS or PIT for 24 weeks. The primary endpoints were the percentage changes in LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglyceride, and the LDL-C/HDL-C ratio.Both ROS and PIT lowered LDL-C and triglyceride, and increased HDL-C. In particular, significantly greater reduction in LDL-C was seen with ROS (-44.1%) than with PIT (-36.9%, P0.01) in the crossover group from ROS to PIT, and the same result was detected in the crossover group from PIT (-34.8%) to ROS (-44.7%). The ratio of LDL-C/HDL-C was significantly reduced with ROS treatment (from 3.45 to 1.85) compared with that with PIT (from 3.45 to 2.22, P0.01). Both ROS and PIT lowered plasma levels of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-alpha, and plasminogen activator inhibitor-1 (PAI-1). In addition, the hsCRP level with the administration of ROS was significantly improved compared with the administration of PIT. There was no significant correlation between changes in LDL-C and hsCRP, TNF-alpha, and PAI-1 levels. ROS and PIT did not have an adverse effect on glycemic control in type 2 diabetes patients.Therapy with both statins improved lipid profiles and reduced proinflammatory responses; however, 2.5 mg of ROS have a potent LDL-C-lowering and hsCRP-lowering effect compared with 2 mg of PIT in patients with diabetes.

In this study, we examined the effects of the alpha-glucosidase inhibitors acarbose and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus.Twenty-one Japanese patients with type 2 diabetes were enrolled in this study. Subjects had been treated with voglibose for at least 3 months. They underwent a 400 kcal balanced food meal tolerance test before and 8 weeks after the changeover from voglibose to acarbose. Subjects were divided into two groups: the first group (low-dose group; n=11) was changed over from 0.6 mg/day voglibose to 150 mg/day acarbose, and the other (high-dose group; n=10) from 0.9 mg/day voglibose to 300 mg/day acarbose.The increment rate of postprandial plasma glucose ([plasma glucose 2 hours after test meal - fasting glucose]/fasting glucose) decreased from 34.7%+/-23.9% to 25.0%+/-24.6% (P=0.13) in the low-dose group, and decreased significantly from 56.1%+/-53.1% to 31.5%+/-36.0% (P=0.03) in the high-dose group after changeover. However, there were no significant changes in blood glycated hemoglobin (HbA(1c)) levels before and after changeover in either group. The increment rate of postprandial serum triglyceride (TG) ([serum TG 2 hours after test meal - fasting TG]/fasting TG) decreased significantly only in the high-dose group (52.4%+/-60.0% to 24.3%+/-16.6%) (P=0.05). No significant changes in serum high-density lipoprotein cholesterol levels were observed in either group, whereas serum low-density lipoprotein cholesterol levels decreased significantly from 3.20+/-0.25 to 2.65+/-0.18 mmol/L (P=0.04), only in the high-dose group.In patients with type 2 diabetes our findings suggest that acarbose 300 mg/day is superior to voglibose 0.9 mg/day in improving postprandial hyperglycemia and hypertriglyceridemia.

Objective: Our aim was to investigate the effect of 1-year treatment with raloxifene, a selective estrogen receptor modulator, on plasma lipid profiles in Japanese postmenopausal type 2 diabetic patients. Subjects and Methods: A total of 43 Japanese women with postmenopausal osteoporosis and type 2 diabetes with serum low-density lipoprotein cholesterol (LDL-C) 1.03 mmol/l, who took 60 mg/day of raloxifene for 12 months, were enrolled. For analysis, they were divided into 2 groups: nonhyperlipidemia (n = 23) and hyperlipidemia treated with statin (n = 20). Results: Raloxifene treatment significantly induced a mean reduction in serum LDL-C from 2.90 to 2.36 and 2.67 mmol/l in the nonhyperlipidemia and statin-treated group, respectively. However, the reduction ratio of serum LDL-C showed a significant difference in the nonhyperlipidemia group (17%) compared to the statin-treated group (7%; p = 0.03). Although serum HDL-C showed an increase in both groups (from 1.45 to 1.58 vs. from 1.40 to 1.47 mmol/l), the increase ratio of serum HDL-C was not significant between the two groups. Raloxifene administration showed 15% reduction in the nonhyperlipidemia group (p = 0.02) and 13% reduction in the statin-treated group (p = 0.02) of urinary N-telopeptide of type I collagen. No significant change in blood HbA1c was observed in either group. Conclusion: The administration of raloxifene to type 2 diabetic women showed favorable efficacy on serum lipid profiles, particularly in patients without statin treatment.

Bacterial lipopolysaccharide (LPS) and other immunostimulants induce an isoform of nitric oxide synthase (iNOS) gene expression in vascular smooth muscle cells (VSMC). This process is dependent on nuclear factor-kappa B (NF-kappaB) activation and is suppressed by glucocorticoids. The aim of this study was to investigate the molecular mechanisms of inhibition of iNOS expression by the synthetic glucocorticoid, dexamethasone (DEX), in rat VSMC. Treatment of VSMC with LPS plus interferon-gamma (LPS/IFN) caused activation of NF-kappaB and the iNOS promoter. LPS/IFN induced iNOS mRNA and NO synthesis. DEX markedly depressed LPS/IFN-stimulated iNOS mRNA expression and NO production. DEX also suppressed LPS/IFN-stimulated activity of a 1.7-kb iNOS promoter, indicating that the inhibition of iNOS expression by DEX occurs at the level of transcription. NF-kappaB activation by LPS/IFN was repressed by DEX. The inhibition of NF-kappaB by DEX exhibited dose-dependent kinetics, which corresponded to DEX suppression of iNOS promoter activation, iNOS mRNA expression, and NO production. However, activation of activator protein-1 (AP-1), which is also contained in the iNOS promoter, was not enhanced by LPS/IFN or inhibited by DEX. Thus, glucocorticoids appear to block iNOS expression, at least in part, through inhibition of NF-kappaB activation, which results in decreased NO production.

Proliferation of vascular smooth muscle cells (VSMC) contributes to the pathogenesis of atherosclerosis, and glycated serum albumin (GSA, Amadori adduct of albumin) might be a mitogen for VSMC proliferation, which may further be associated with diabetic vascular complications. In this study, we investigated the involvement of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), and protein kinase C (PKC), in GSA-stimulated mitogenesis, as well as the functional relationship between these factors. VSMC stimulation with GSA resulted in a marked activation of ERK. The MAPK kinase (MEK) inhibitor, PD98059, blocked GSA-stimulated MAPK activation and resulted in an inhibition of GSA-stimulated VSMC proliferation. GSA also increased PKC activity in VSMC in a dose-dependent manner. The inhibition of PKC by the PKC inhibitors, GF109203X and Rottlerin (PKCdelta specific inhibitor), as well as PKC downregulation by phorbol 12-myristate 13-acetate (PMA), inhibited GSA-induced cell proliferation and blocked ERK activation. This indicates that phorbol ester-sensitive PKC isoforms including PKCdelta are involved in MAPK activation. Thus, we show that the MAPK cascade is required for GSA-induced proliferation, and that phorbol ester-sensitive PKC isoforms contribute to cell activation and proliferation in GSA-stimulated VSMC.

Purpose: Premixed insulin is effective to improve glycemic control; however, clinicians may be less likely to know which premixed insulin is appropriate for which patients. This study aimed to evaluate the effects of twice-daily injections of premixed insulin lispro on glycemic control in type 2 diabetic patients. Materials and Methods: Forty type 2 diabetic patients, who had been treated with twicedaily injections of human protamine mixture 30/70 insulin for at least 12 months, were divided into two groups; one group whose blood glucose 2 hours after breakfast was greater than 200 mg/dL, was switched to lispro mix50, and the other group whose blood glucose 2 hours after breakfast < 200 was switched to lispro mix25. Results: Glycated haemoglobin (HbA1c) significantly improved in the Mix50 group from 8.3% to 7.5% (at 12 weeks; p < 0.05), and to 7.5% (at 24 weeks; p < 0.05). On the other hand, HbA1c levels in the Mix25 group were slightly decreased from 8.1% to 7.7% at 12 weeks (p < 0.05), and to 7.9% at 24 weeks (not significant). Both postprandial plasma glucose and fasting plasma glucose levels were significantly improved in the Mix50 group, but not in the Mix25 group. Overall, 95% of subjects preferred premixed lispro insulin from human insulin in the viewpoint of the timing of insulin injection by questionnaire analysis. Conclusion: Switching from human protamine mixture 30/70 insulin to lispro mix50 twice-daily injection therapy in patients with high postprandial plasma glucose could improve their glycemic control and quality of life.