Serial changes in norepinephrine kinetics associated with feeding dogs a high-fat diet.

The role of increased sympathetic nervous system (SNS) activity in the pathogenesis of obesity hypertension and insulin resistance is controversial. Eight dogs were instrumented and fed a high-fat diet (HFD) for 6 weeks. Dogs were evaluated for changes in weight, blood pressure, insulin resistance, and norepinephrine (NE) kinetics using a two-compartment model.

Impaired beta-cell function in human aging: response to nicotinic acid-induced insulin resistance.

Context: Glucose tolerance declines with age and may involve impaired beta-cell sensitivity to glucose and beta-cell compensation for insulin resistance.

Objective: We investigated beta-cell sensitivity to glucose and beta-cell compensation for nicotinic acid-induced insulin resistance in young (age <35 yr) people with normal glucose tolerance (NGT) and old (age >60 yr) people with NGT and impaired glucose tolerance (IGT). DESIGN/PATIENTS/SETTING/INTERVENTION: Fifteen young NGT, 16 old NGT, and 14 old IGT were randomized to 2-wk treatment with nicotinic acid or placebo in a double-blind, crossover study in a university medical setting.

Limitation of the homeostasis model assessment to predict insulin resistance and beta-cell dysfunction in older people.

Context: Studies in older people have shown inconsistent agreement between homeostasis model assessment of insulin resistance (HOMA-IR) and dynamic measures of insulin action and have not evaluated HOMA beta-cell.

Objective: We compared measures of insulin sensitivity and beta-cell function from the frequently sampled iv glucose tolerance test (FSIGT) to HOMA models. DESIGN/PATIENTS/SETTING/INTERVENTION: Two hundred fourteen young and old with normal glucose tolerance (NGT) and old with impaired glucose tolerance (IGT) participated in a retrospective analysis of FSIGT data in a university medical setting.

Effect of lowering postprandial hyperglycemia on insulin secretion in older people with impaired glucose tolerance.

Glucose tolerance declines with age, resulting in a high prevalence of diabetes and impaired glucose tolerance (IGT) in the older population. Hyperglycemia per se can lead to impaired beta-cell function (glucose toxicity). We tested the role of glucose toxicity in age-related beta-cell dysfunction in older people (65 +/- 8 yr) with IGT treated with the alpha-glucosidase inhibitor acarbose (n = 14) or placebo (n = 13) for 6 wk in a randomized, double-blind study.

Ordinary differential equation PK/PD models using the SAS macro NLINMIX.

We describe some theory and recent enhancements for the SAS macro NLINMIX (Wolfinger, R. D. (1993).

Changes in systemic sympathetic nervous system activity after mitral valve surgery and their relationship to changes in left ventricular size and systolic performance in patients with mitral regurgitation.

Background: We have shown that the systemic sympathetic nervous system (SNS) is activated in patients with chronic mitral regurgitation (MR). However, the fate of systemic SNS activity after surgical correction of MR is currently unknown.

Methods: We examined 14 patients with MR who had normal sinus rhythm with an investigational, preoperative cardiac catheterization, including arterial norepinephrine (NE) sampling and [(3)H]-NE infusions and arterial blood sampling to determine NE kinetic parameters using a 2-compartment modeling analysis.

The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose.

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion in a glucose-dependent manner, but its short half-life limits its therapeutic potential. We tested NN2211, a long-acting GLP-1 derivative, in 10 subjects with type 2 diabetes (means +/- SD: age 63 +/- 8 years, BMI 30.1 +/- 4.

Compared with control subjects, the systemic sympathetic nervous system is activated in patients with mitral regurgitation.

Background: Whether the systemic sympathetic nervous system is activated as a compensatory mechanism in response to mitral regurgitation (MR) in humans is unknown. We tested the hypotheses that the systemic sympathetic nervous system would be activated in patients with MR in comparison with control subjects and that this activation would occur early in the disease process as a compensatory mechanism for chronic left ventricular (LV) volume overload.

Methods: We studied 37 patients with MR who underwent right heart catheterization and biplane cineventriculography to obtain LV end-diastolic and end-systolic volumes, ejection fractions, and regurgitant volumes.