ABSTRACT
INTRODUCTION: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes. METHODS: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 µg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA1c) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA1c level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose. RESULTS: The change in HbA1c level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA1c level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups. CONCLUSION: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control. TRIAL REGISTRATION: This trial has been registered with UMIN (No. 000010769).
ABSTRACT
AIMS/INTRODUCTION: Increased glycemic variability is an important contributing factor to coronary artery disease. Although various parameters of glycemic variability can be derived by continuous glucose monitoring, the clinical relevance of individual parameters has remained unclear. We have now analyzed the relationship of such parameters to coronary plaque vulnerability. MATERIALS AND METHODS: The standard deviation of glucose levels (SD glucose), mean amplitude of glycemic excursions (MAGE), continuous overlapping net glycemic action calculated every 1 h (CONGA-1) and mean of daily differences (MODD) were calculated from continuous glucose monitoring data for 53 patients hospitalized for percutaneous coronary intervention. The relationship of these parameters to the percentage necrotic core of total plaque volume (%NC) as assessed by virtual histology-intravascular ultrasound (a predictor of coronary plaque rupture) was evaluated. RESULTS: All parameters of glycemic variability were significantly correlated with %NC, with correlation coefficients of 0.593, 0.626, 0.318, and 0.388 for log(SD glucose), log(MAGE), CONGA-1 and log(MODD), respectively. Simple linear regression analysis showed that the coefficients of determination for %NC and either log(SD glucose; 0.352) or log(MAGE; 0.392) were greater than those for %NC and either CONGA-1 (0.101) or log(MODD; 0.151), whereas the residual sums of squares for the former relationships (1045.1 and 979.5, respectively) were smaller than those for the latter (1449.3 and 1369.6, respectively). CONCLUSIONS: The present data suggest that SD glucose and MAGE are more highly correlated with coronary plaque vulnerability than are CONGA-1 and MODD, and are thus likely better predictors of coronary artery disease.
ABSTRACT
AIMS/INTRODUCTION: Whereas some clinical studies have shown that excessive fat accumulation in the pancreas is associated with impairment of insulin secretion, others have not found such an association. 1 H magnetic resonance spectroscopy allows quantitative fat analysis in various tissues including the pancreas. The pathological relevance of pancreatic fat content (PFC) in Japanese individuals remains unclear, however. MATERIALS AND METHODS: We analyzed PFC in 30 Japanese individuals with normal glucose tolerance by 1 H magnetic resonance spectroscopy, and then investigated the relationships between PFC and indexes of insulin secretion and insulin sensitivity-resistance determined by an oral glucose tolerance test. We also measured hepatic fat content and intramyocellular lipid content by 1 H magnetic resonance spectroscopy, as well as visceral fat area and subcutaneous fat area by magnetic resonance imaging, and we examined the relationships between these fat content measures and oral glucose tolerance test-derived parameters. RESULTS: PFC was correlated with indexes of insulin sensitivity-resistance, but not with those of insulin secretion. Hepatic fat content and visceral fat area were correlated with similar sets of parameters as was PFC, whereas subcutaneous fat area was correlated with parameters of insulin secretion, and intramyocellular lipid content was not correlated with any of the measured parameters. The correlation between PFC and homeostasis model assessment of insulin resistance remained significant after adjustment for age, body mass index and sex. Among fat content measures, PFC was most highly correlated with hepatic fat content and visceral fat area. CONCLUSIONS: PFC was correlated with indexes of insulin resistance, but not with those of insulin secretion in non-obese Japanese individuals with normal glucose tolerance.
