Insulin exposure mitigates the increase of arterial stiffness in patients with type 2 diabetes and albuminuria: an exploratory analysis

Aims Insulin possesses both vasodilatory and sympathomimetic activities. The aim was to examine the relationship between changes in insulin exposure and arterial stiffness in type 2 diabetes (T2D). Methods Patients with T2D with (n = 22) or without (n = 24) albuminuria, and non-diabetic controls (n = 25) were randomized to a crossover study having a breakfast with or without pre-meal rapid-acting insulin. Pulse wave velocity (PWV) was measured at 30 min before and at 60-min intervals up to 240 min after the breakfast. Results At baseline, both postprandial aortic (p = 0.022) and brachial (p = 0.011) PWV were higher in individuals with T2D than in healthy controls irrespective of the presence of albuminuria. In patients with albuminuria, weight-adjusted insulin dose correlated inversely with the excursion of the aortic (r = - 0.412, p = 0.006) and brachial (r = - 0.372; p = 0.014) PWV. Similarly, circulating endogenous insulin concentrations correlated inversely with the aortic (r = - 0.347, p = 0.026) and brachial (r = - 0.622, p =Peer reviewe

The Canadian conversion loan of 1958 : a study in debt management

World War II was partially financed through the issue of Victory Bonds. By 1958, Victory Bonds amounting to roughly 50% of the public debt were still outstanding, maturing at discrete intervals over the following seven years. In September, 1958, the Canadian Government launched the Conversion Loan — a successful attempt to refund the Victory Bonds. This enormous debt management operation raised the average term to maturity of the public debt from 8 to 14.75 years. Debt management operations, and the Conversion Loan in particular, have received little attention in the Canadian context. The scant existing literature has not rigorously examined the effects of the Loan on the level and term structure of interest rates, nor has it investigated its impact on the real sector of the economy. In this thesis regression analysis and simulation -- using the Bank of Canada RDX2 model -- were used to investigate these problems. The following conclusions were reached. There is convincing evidence that the Loan increased long rates and some less convincing evidence that it decreased short rates. In contrast to the U.S. there is no doubt that, in Canada, debt management operations significantly affect the term structure of interest rates. Other determinants of the term structure are expectations, monetary policy, transactions requirements, private sector wealth and the U.S. term structure of interest rates. The Loan was contractionary. Its effect during 1958 is estimated at 1% of GNE, increasing to 5% between 1959 and 1961, and decreasing thereafter. The overall cumulative effect is likely to have exceeded $1 billion. Contrary to conventional wisdom, it was the interest sensitivity of investment rather than the reduction in Canada's competitive position in world markets -- the Loan raised interest rates, attracted "hot capital" and led to an exchange rate appreciation --that engendered the depression.Arts, Faculty ofVancouver School of EconomicsGraduat

Influence of Postprandial Hyperglycemic Conditions on Arterial Stiffness in Patients With Type 2 Diabetes

Context: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. Objective: The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. Design: Asingle-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n = 22), 2) T2D patients without albuminuria (n = 24), and 3) nondiabetic controls (n = 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). Main Outcome Measures: Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. Results: At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P = .032) and high (P = .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P = .014) and high (P = .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. Conclusions: In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed.Peer reviewe