Showing papers by "Bastiaan E. de Galan published in 2012"
TL;DR: The linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels and reversible Michaelis-Menten kinetic parameters were calculated, in line with previously published data obtained under hyperglycemic conditions.
Abstract: The objective of this study was to investigate the relationship between plasma and brain glucose levels during euglycemia and hypoglycemia in healthy subjects and patients with type 1 diabetes mellitus (T1DM). Hyperinsulinemic euglycemic (5 mmol/L) and hypoglycemic (3 mmol/L) [1-13C]glucose clamps were performed in eight healthy subjects and nine patients with uncomplicated T1DM (HbA1c 7.7 ± 1.4%). Brain glucose levels were measured by 13C magnetic resonance spectroscopy. Linear regression analysis was used to fit the relationship between plasma and brain glucose levels and calculate reversible Michaelis-Menten (MM) kinetic parameters. Brain glucose values during euglycemia (1.1 ± 0.4 μmol/g vs. 1.1 ± 0.3 μmol/g; P = 0.95) and hypoglycemia (0.5 ± 0.2 μmol/g vs. 0.6 ± 0.3 μmol/g; P = 0.52) were comparable between healthy subjects and T1DM patients. MM kinetic parameters of combined data were calculated to be maximum transport rate/cerebral metabolic rate of glucose (Tmax/CMRglc) = 2.25 ± 0.32 and substrate concentration at half maximal transport (Kt) = 1.53 ± 0.88 mmol/L, which is in line with previously published data obtained under hyperglycemic conditions. In conclusion, the linear MM relationship between plasma and brain glucose can be extended to low plasma glucose levels. We found no evidence that the plasma to brain glucose relationship or the kinetics describing glucose transport over the blood–brain barrier differ between healthy subjects and patients with uncomplicated, reasonably well-controlled T1DM.
49 citations
TL;DR: This review summarizes the best available evidence favoring these positive pleiotropic effects of incretin mimetics as well asincretin enhancers on elevated cardiovascular risks in patients with type 2 diabetes.
Abstract: PURPOSE OF REVIEW: Type 2 diabetes mellitus is a chronic dysmetabolic condition characterized by hyperglycemia and accompanied by dyslipidemia (low HDL, high triglycerides), and hypertension associated with insulin resistance in obesity. In addition to the glucose-reducing effects, incretin-based therapies have been found to have cardiovascular protective properties. This review summarizes the best available evidence favoring these positive pleiotropic effects of incretin mimetics as well as incretin enhancers. RECENT FINDINGS: Studies in animals and humans are accumulating showing the direct as well as indirect actions of the glucagon-like peptide 1 analogues and dipeptidyl peptidase 4 inhibitors on the cardiovascular system. This class of agents appear to have effects on the cardiomyocytes, blood vessels, adipose tissue, regulation of blood pressure, and postprandial intestinal lipoprotein metabolism. SUMMARY: Long-term hard outcome trials are under way that investigate the effects of incretin-based treatments on elevated cardiovascular risks in patients with type 2 diabetes.
16 citations
TL;DR: An overview of recent developments in rapid-acting insulin analogs is provided and potential benefits with respect to postprandial glucose control are discussed.
Abstract: SUMMARY Many patients with Type 1 or insulin-requiring Type 2 diabetes fail to achieve the widely recommended glycemic target of HbA1c below 7%. Insufficient control of postprandial glucose excursion plays an important role in this failure. The pharmacological profile of rapid-acting insulin analogs is still far from mimicking the physiological profile of endogenous insulin secretion. Several products are under development that aim to bring this goal closer. These developments include the use of jet injectors for insulin administration, coadministration of hyaluronidase, insulin agents that are resistant to hexamer formation, and insulin products that use an alternative route of administration. This review provides an overview of recent developments and discusses potential benefits with respect to postprandial glucose control.