Effects of Switching from Insulin Glargine 100 to Insulin Glargine 300 on Glycemic Control and Treatment Satisfaction In Japanese People with Type 1 and Type 2 Diabetes

Aims: To investigate how switching from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) affects glycemic control and treatment satisfaction in Japanese people with type 1 and 2 diabetes. Methods: We enrolled 152 outpatients with diabetes (type 1, n = 29; type 2, n = 123) being treated with basal-bolus therapy (BBT; n = 95) or basal only using as insulin therapy (n = 57) with Gla-100 and switched them all to Gla-300. The dose of Gla-300 was initially the same as that of Gla-100 and was then titrated up. We investigated changes in hemoglobin A1c (HbA1c), body weight, glargine insulin dose over three months, and diabetes treatment satisfaction questionnaire scores over three months. Results: Three months after patients had switched to Gla-300, HbA1c and body weight had not changed significantly. In the whole group, the basal dose of Gla-300 insulin was significantly higher than that of Gla-100 (14.2 ± 8.1 vs 13.7 ± 7.9 units, respectively; P < 0.001). Separate analyses of the BBT and Basal only groups showed that in both the BBT and the Basal only group, the basal insulin dose was significantly higher with Gla-300 than with Gla-100. Patient treatment satisfaction scores did not change significantly after switching to Gla-300. In the BBT group, hypoglycemia was less frequent with Gla-300. Conclusions: HbA1c, body weight, and treatment satisfaction were similar with Gla-100 and Gla-300. In people treated with BBT, Gla-300 may be associated with less frequent hypoglycemic episodes.journal articl

A case of Hyperglycemic Hyperosmolar State with Hyponatremia and Subsequent Gastrointestinal Bleeding due to Acute Gastric Mucosal Lesions

We present a case of hyperglycemic hyperosmolar state with hyponatremia and subsequent bleeding from acute gastric mucosal lesions. An 84-year-old man with a long history of type 2 diabetes was repeat-edly hospitalized for treatment of congestive heart failure due to coronary artery disease during the past decade and therefore received combination therapy with loop and thiazide diuretics. He was admitted for hyperglycemic hyperosmolar state with hyponatremia and, while hospitalized, developed anemia and bloody stools. Gastroscopy showed gastrointestinal bleeding due to acute gastric mucosal lesions（erosions and ulcers）. Clinicians should keep in mind that acute gastric mucosal lesions can develop as a complica-tion of hyperglycemic hyperosmolar state.journal articl

Effect of Insulin on Aortic Rings Isolated from Wistar Rats

Background:Insulin increases nitric oxide (NO) production via the phosphatidylinositol 3-kinase(PI3K) pathway and endothelin( ET)-1 secretion via the mitogen-activated protein kinase( MAPK) pathwayin vascular endothelial cells. In normal vascular endothelial cells, the insulin effect via the PI3K pathwayis thought to occur slightly earlier than that via the MAPK pathway. However, the direct effect of insulinon vascular rings isolated from an animal model has not been fully examined. The main purpose of studywas to investigate the potential vasodilation-effect of insulin on the isolated vascular rings of rats.Material and Methods:Descending aorta rings isolated from Wister rats were used in exo-vivo study.In study using culture cells, bovine aortic endothelial cells were used, and the effect of insulin on the productionof nitric oxide( NO) and the secretion of endothelin( ET)-1 was investigated. NO production was evaluatingusing diaminofluorescein-2, a NO-specific dye.Results:Insulin (250 nM)-stimulated NO production evaluated using diaminofluorescein-2 (DAF-2) dependencyon the NO concentration in BAECs indicated a significant increase in NO compared with controls.Addition of 250 nM insulin also significantly increased ET-1 secretion and phosphorylation of Akt at Ser473and eNOS at Ser1177 (Ser1179 in bovine eNOS) in BAECs, compared with controls. Insulin treatmentshowed a slight tendency to increase phosphorylation of extracellular signal-regulated kinase (ERK) 1/2,but this change did not reach statistical significance. A cumulative insulin concentration of 3×10&#8722;6 M producedonly a small change in the diameter of aortic rings from Wister rats( 7.3±3.5% vs. 3.6±3.5% with 3×10&#8722;6 M saline;both n=3). Addition of acetylcholine to these rings caused dilatation of almost 100 %.Conclusion:Insulin increases production of NO and secretion of ET-1 in BAECs, but has little effect onaortic rings isolated from Wister rats.原著Originaljournal articl

A Randomized Trial of Step-up Treatment with Premixed Insulin Lispro-50/50 vs. Aspart-70/30 in Patients with Type 2 Diabetes Mellitus

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 <7.4% after an additional 16 ± 2 weeks, a pre-lunch insulin injection was added (step 3). Hypoglycemic episodes were also recorded. RESULTS: The cumulative percentages of subjects who achieved HbA1c <7.4% were 36.1% (13/36) for both Mix50 and BIAsp 30 in step 1, 62.9% (23/36) for BIAsp 30 and 52.8% (19/36) for Mix50 in step 2, and 66.7% (24/36) in BIAsp 30 and 72.2% (26/36) in Mix50 in step 3. The achievement rates of HbA1c <7.4% were not statistically different between the two groups. A total of ten hypoglycemic episodes occurred in this study. However, there were no severe hypoglycemic episodes. All cases recovered by taking glucose and drinking juice. CONCLUSION: Mix50 step-up treatment has a clinical effect in achieving good glycemic control equal to that of BIAsp 30 treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13300-014-0078-7) contains supplementary material, which is available to authorized users

Fixed-dose combination of alogliptin/pioglitazone improves glycemic control in Japanese patients with type 2 diabetes mellitus independent of body mass index

2017-02This study investigated the effects of switching from combination therapy with either alogliptin (Alo) or pioglitazone (Pio) to fixed-dose combination therapy (FDCT) with alogliptin and pioglitazone (Alo-Pio FDCT). The usefulness and efficacy of Alo-Pio FDCT were investigated. A total of 50 outpatients with type 2 diabetes mellitus (T2DM) treated with Alo and 47 outpatients with T2DM treated with Pio were switched to Alo-Pio FDCT, and its efficacy and usefulness were evaluated. Significant improvements were observed in hemoglobinA1c (HbA1c), alanine transaminase (ALT), and γ-glutamyl transpeptidase (GGT) levels after switching to Alo-Pio FDCT for 16 weeks in both groups. Only the group switching from Alo to Alo-Pio FDCT showed significant improvements in high-density lipoprotein cholesterol (HDL) levels and triglyceride levels. In a multivariate logistic regression model of the variation in the change of HbA1c at 16 weeks, ALT and GGT were independent predictors of the change of HbA1c at 16 weeks. In addition, the switch to Alo-Pio FDCT improved glycemic control to a certain degree regardless of BMI. Switching from either Alo or Pio to Alo-PIO FDCT may, unlike monotherapy with a DPP-4 inhibitor, be effective for patients with T2DM regardless of whether they are obese or lean.departmental bulletin pape

Macrophage HIF-1α increases liver tumor

Aims/Introduction: Chronic inflammation of the liver is often observed with obesity or type 2 diabetes. In these pathological conditions, the immunological cells, such as macrophages, play important roles in the development or growth of liver cancer. Recently, it was reported that hypoxia‐inducible factor‐1α (HIF‐1α) is a key molecule for the acquisition of inflammatory M1 polarity of macrophages. In the present study, we examined the effects of altered macrophage polarity on obesity‐ and diabetes‐associated liver cancer using macrophage‐specific HIF‐1α knockout (KO) mice. Materials and Methods: To induce liver cancer in the mice, diethylnitrosamine, a chemical carcinogen, was used. Both KO mice and wild‐type littermates were fed either a high‐fat diet (HFD) or normal chow. They were mainly analyzed 6 months after HFD feeding. Results: Development of liver cancer after HFD feeding was 45% less in KO mice than in wild‐type littermates mice. Phosphorylation of extracellular signal‐regulated kinase 2 was also lower in the liver of KO mice. Those effects of HIF‐1α deletion in macrophages were not observed in normal chow‐fed mice. Furthermore, the size of liver tumors did not differ between KO and wild‐type littermates mice, even those on a HFD. These results suggest that the activation of macrophage HIF‐1α by HFD is involved not in the growth, but in the development of liver cancer with the enhanced oncogenic extracellular signal‐regulated kinase 2 signaling in hepatocytes. Conclusions: The activation of macrophage HIF‐1α might play important roles in the development of liver cancer associated with diet‐induced obesity and diabetes

SIADH induced by pneumonia in a patient with Shy-Drager syndrome

Patients with Shy-Drager syndrome have impaired baroreceptor-mediated vasopressin release when inan upright position. We report a case of Shy-Drager syndrome in which the syndrome of inappropriate secretionof antidiuretic hormone (SIADH) developed with pneumonia. It has been speculated that pneumonia-induced SIADH is caused by baroreceptor-mediated vasopressin release. Our case presents the possibilitythat pneumonia-induced SIADH is caused by non-baroreceptor-mediated ADH release

Association Between Nerve Conduction Velocity and Clinical Parameters Related to Diabetic Complications inPatients with Type 2 Diabetes

The main purpose of the study was to investigate the association of median motor nerve conduction velocity(MCV) and sural sensory nerve conduction velocity( SCV) with parameters related to diabetic complicationsin patients with type 2 diabetes. A total of 263 patients hospitalized for glycemic control from 1999to 2006 who underwent single or multiple nerve conduction velocity tests (at least a right median MCVtest) were enrolled in the study retrospectively. Right median MCV showed a significant negative correlationwith age and diabetic duration, and was also significantly negatively correlated with systolic blood pressure(SBP) and log urinary albumin excretion (UAE). Right median MCV showed strong positive correlationswith left median MCV and right median SCV, and significant but relatively mild positive correlationswith right peroneal MCV and right sural SCV. In multiple regression analysis, only SBP and diabetic durationshowed a significant association with right median MCV. Although right sural SCV showed significantnegative correlations with SBP and log UAE, the correlations were relatively weak compared with those forright median MCV. Of 215 patients who underwent complete sural SCV measurements, right and left suralSCV were detected in 159( 74%) and 163 patients( 76%), respectively. In conclusion, these results suggestthat median MCV is more closely associated with markers related to diabetic complications such as SBP orUAE, compared with sural SCV, but that sural SCV is more sensitive than median MCV for detection of diabeticneuropathy

Greater Efficacy and Improved Endothelial Dysfunction in Untreated Type 2 Diabetes with Liraglutide versus Sitagliptin

Objective:The incretin hormone glucagon-like peptide 1 (GLP-1) and its analogs, including the glucagonlike peptide 1 receptor agonist liraglutide, use a simple once-daily regimen and can be easily introduced in the outpatient setting. We compared treatment with liraglutide monotherapy and dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy in patients with untreated type 2 diabetes( T2DM).Methods:This study included 40 outpatients with untreated T2DM who were randomized to receive liraglutide (0.9 mg/day, n=24) or DPP-4 inhibitors (n=16:sitagliptin, 50 mg/day) as initial treatment for 6 months. Glycemic control, urinalysis, blood pressure, body weight, lipid levels, vascular endothelial function, and inflammatory factors were assessed before and after treatment.Results:Significant improvement was observed in HbA1c and fasting blood glucose levels after treatment in both groups;improvements in the liraglutide group were significantly better than in the sitagliptin group. Only the liraglutide group demonstrated significant improvements in blood pressure, low-density lipoprotein cholesterol levels, urinary albumin excretion, flow-mediated dilatation, and high-sensitivity C-reactive protein levels. Linear regression analysis demonstrated a significant negative relation between change in flow-mediated dilatation and high-sensitivity C-reactive protein levels.Conclusion:Liraglutide provided significant glycemic control and improved blood pressure, lipid levels, endothelial function, and inflammatory factors in untreated T2DM. In addition to its impact on blood glucose levels, liraglutide may have beneficial effects on the cardiovascular system in patients with T2DM

A case in which water intoxication due to excessive water ingestion did not inhibit the secretion of arginine vasopressin

We experienced a case of water intoxication due to excessive water ingestion that was complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 60-year-old Japanese woman with nervous depression drank too much lemon tea within several hours, vomited ten times, and developed disturbed consciousness and dysarthria. Her plasma arginine vasopressin (AVP) concentration was not inhibited,although her plasma osmolality was low. Nausea and/or stress may stimulate AVP secretion regardless of the hypo-osmolality. We believe that dilatation of her stomach due to excessive liquid ingestion and cerebral edema due to hypo-osmolality brought on her nausea. Stress induced by a psychiatric problem and/or admission to a hospital may also stimulate AVP secretion by the central nervous system. Treatingnausea and stress may help reduce AVP secretion and resolve hyponatremia