1.
Pramlintide reduced markers of oxidative stress in the postprandial period in patients with type 2 diabetes.
Ceriello, A, Lush, CW, Darsow, T, Piconi, L, Corgnali, M, Nanayakkara, N, Frias, JP, Maggs, D
Diabetes/metabolism research and reviews. 2008;(2):103-8
Abstract
BACKGROUND The production of oxidative stress as a result of postprandial hyperglycaemia is now recognized as an important contributing factor in the development of diabetes complications. The objective of this study was to examine the effects of pramlintide on plasma concentrations of glucose and several markers of oxidative stress in patients with type 2 diabetes following a standardized meal. METHODS This was a randomized, single-blind, placebo-controlled, crossover study conducted at two clinical research centres in the United States. A total of 19 subjects (9 men and 10 women) with type 2 diabetes using mealtime insulin participated in the study. Pramlintide (120 microg), or placebo, and rapid-acting mealtime insulin were administered prior to a standardized meal on two separate study days. Plasma concentrations of glucose, nitrotyrosine (NT), oxidized-LDL cholesterol (OxLDL-C), and total radical trapping parameter (TRAP) were assessed during the 4-h postprandial period. RESULTS Compared to placebo, pramlintide treatment reduced postprandial excursions of glucose, NT, and OxLDL-C and protected TRAP from consumption. Correlation analysis revealed positive associations between placebo-corrected glucose incremental AUC(0-4 h) and both NT and OxLDL-C and a negative association between placebo-corrected glucose incremental AUC(0-4h) and TRAP. CONCLUSIONS The reduction in postprandial glucose excursions achieved with addition of pramlintide to rapid-acting insulin in type 2 diabetes was associated with a reduction in postprandial markers of oxidative stress.
2.
Postprandial glucose regulation: new data and new implications.
Leiter, LA, Ceriello, A, Davidson, JA, Hanefeld, M, Monnier, L, Owens, DR, Tajima, N, Tuomilehto, J, ,
Clinical therapeutics. 2005;:S42-56
Abstract
BACKGROUND Type 2 diabetes is characterized by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) to guide management. OBJECTIVES The objectives of this article are to review current data on postprandial hyperglycemia and to assess whether, and how, management of type 2 diabetes should change to reflect new clinical findings. METHODS Articles were selected from MEDLINE searches (key words: postprandial glucose, postprandial hyperglycemia, and cardiovascular disease) and from our personal reference files, with emphasis on the contribution of postprandial hyperglycemia to overall glycemic load or cardiovascular (CV) risk. RESULTS About 33% of people diagnosed as having type 2 diabetes based on postprandial hyperglycemia have normal FPG. PPG contributes > or =70% to the total glycemic load in patients who are fairly well controlled (HbA1c <7.3%). Furthermore, there is a linear relationship between the risk of CV death and the 2-hour oral glucose tolerance test (OGTT). Increased mortality is evident at OGTT levels of approximately 90 mg/dL (5 mmol/L), which is well below current definitions of type 2 diabetes. Biphasic insulin aspart was shown to be more effective at reducing HbA1c below currently recommended levels than basal insulin glargine (66% vs 40%; P < 0.001), and it reduced endothelial dysfunction more effectively than regular insulin (P < 0.01). Repaglinide achieved regression of carotid atherosclerosis (intima-media thickness) in 52% of patients versus 18% for glyburide (P < 0.01) over 1 year, although levels of HbA1c and CV risk factors were similar for both treatment groups. Finally, acarbose reduced the relative risk of CV events by 49% over 3.3 years versus placebo in patients with impaired glucose tolerance (2.2% vs 4.7%; P = 0.03) and by 35% over > or =1 year in patients with type 2 diabetes (9.4% vs 6.1%; P = 0.006). CONCLUSIONS All components of the glucose triad (ie, FPG, HbA1c, and PPG) should be considered in the management of type 2 diabetes. Therapy targeted at PPG has been shown to improve glucose control and to reduce the progression of atherosclerosis and CV events; therefore, physicians should consider monitoring and targeting PPG, as well as HbA1c and FPG, in patients with type 2 diabetes.