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Biomedical subjects

Jeffrey B Halter

Publications and source records attributed to Jeffrey B Halter.

14 recordsLinked to original sources
PubMed2006

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. At the end of each treatment period, participants had a frequently sampled iv glucose tolerance test and ramp clamp, in which insulin secretion rates (ISR) were determined in response to a matched 5-10 mm glucose stimulus. MAIN OUTCOME MEASURES: Insulin sensitivity (S(I)), acute insulin response to iv glucose (AIRg), and disposition index (AIRg x S(I), or beta-cell compensation for insulin resistance) from frequently sampled iv glucose tolerance testing, and ISR area under the curve (or beta-cell sensitivity to glucose) from ramp clamp were determined. RESULTS: Progressive impairments in insulin secretion as assessed by AIRg, disposition index, and ISR area under the curve were identified in older people with NGT, with more marked defects in older people with IGT. Nicotinic acid treatment significantly reduced S(I) in all groups. beta-Cell compensation for nicotinic acid-induced insulin resistance was incomplete in all three groups, with greater defects in the two older groups. CONCLUSIONS: Human aging is associated with impaired beta-cell sensitivity to glucose and impaired beta-cell compensation to insulin resistance.

Adult↗
PubMed2006

Development of a standardized patient instructor to teach functional assessment and communication skills to medical students and house officers.

Professional societies have called for increased geriatrics training for all medical students and physicians. A Geriatrics Standardized Patient Instructor (GSPI) was developed in which learners assess the functional status of a patient preparing for hospital discharge. Standardized patients (SPs) rate learners on functional assessment and communication skills, and provide feedback. Seventeen SPs were trained. Correlations of ratings by SPs with ratings by three geriatricians of videotaped encounters indicated good reliability (correlation coefficient = 0.69 and 0.70 for functional assessment and communication skills, respectively). Results from two learner groups illustrated the utility and feasibility of the GSPI. First, 138 house officers in nine specialties experienced the GSPI as a formative evaluation during implementation of new geriatrics curricula. Mean scores+/-standard deviation (on a 100-point scale) for functional assessment and communication skills were 78+/-16 and 86+/-11, respectively. House officers rated the overall experience positively (mean rating (1 = poor, 5 = excellent) 3.9+/-0.8). Second, 171 first-year medical students (M1 s) encountered the GSPI as part of an intense, multimodal educational intervention. Mean scores on functional assessment and communication skills were 93+/-10 and 93+/-7, respectively. Mean overall rating of the experience by M1 s was 4.1+/-0.8. After demonstrated success as a teaching tool in these two groups of learners, the GSPI has been successfully used with second- and third-year (M3) medical students and house officers from a total of 12 specialties and incorporated into multistation Objective Standardized Clinical Examination exercises for incoming house officers and M3 s. Unlike existing diagnosis-oriented SPs, the GSPI can be used to assess and teach geriatrics skills to physician learners across disciplines and levels of training.

Aged↗
PubMed2006

Effects of a geriatrics interdisciplinary experience on learners' knowledge and attitudes.

This study examines the impact of an interdisciplinary training program on knowledge and attitudes of learners from four health care programs: medicine, pharmacy, social work, and nursing. Sixty-two learners participated in a 4-day educational program (one day each week for 4 weeks) focusing on interdisciplinary geriatric care. After completing the program, learner scores improved on a knowledge test and two attitudinal subscales, and they reported a positive training experience. A short-term interdisciplinary educational intervention can have an impact on learners' knowledge of and attitudes toward older adults, and improve their understanding and confidence in participating in an interdisciplinary collaborative care team.

Education, Professional↗
PubMed2005

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. MAIN OUTCOME MEASURE: Sensitivity to insulin (S(I)) and acute insulin response to glucose (AIRg) from FSIGT were compared with HOMA models. RESULTS: S(I) and HOMA-IR measures identified similar patterns of increasing insulin resistance in the two older groups, compared with younger people with NGT, with the greatest degree of insulin resistance in older people with IGT (P < 0.05 vs. young and old NGT for both S(I) and HOMA-IR). Agreement between HOMA-IR and S(I) was moderate (weighted kappa = 0.51). AIRg was similar in young and old NGT but was markedly decreased in old IGT (P < 0.05 vs. young and old NGT). HOMA-beta-cell was similar in the three groups. Agreement between HOMA beta-cell and AIRg was weak (weighted kappa = 0.35). CONCLUSIONS: HOMA-IR may detect age-related insulin resistance when comparing large populations of older people. However, dynamic testing appears to be necessary to quantitate diminished insulin secretion in older people.

Adult↗
PubMed2004

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. Baseline and posttreatment studies included 1) an oral glucose tolerance test (OGTT), 2) 1-h postprandial glucose monitoring, 3) a frequently sampled intravenous glucose tolerance test (insulin sensitivity, or S(I)), and 4) glucose ramp clamp (insulin secretion rates, or ISR), in which a variable glucose infusion increases plasma glucose from 5 to 10 mM. The treatment groups had similar baseline body mass index; fasting, 2-h OGTT, and 1-h postprandial glucose levels; and S(I). In these carefully matched older people with IGT, both fasting (5.7 +/- 0.2 vs. 6.3 +/- 0.2 mM, P = 0.002) and 1-h postprandial glucose levels (6.9 +/- 0.3 vs. 8.2 +/- 0.4 mM, P = 0.02) were significantly lower in the acarbose than in the placebo group. Despite this reduction of chronic hyperglycemia in the acarbose vs. placebo group, measures of insulin secretion (ISR area under the curve: 728 +/- 55 vs. 835 +/- 81 pmol/kg, P = 0.9) and acute insulin response to intravenous glucose (329 +/- 67 vs. 301 +/- 54 pM, P = 0.4) remained unchanged and impaired. Thus short-term improvement of chronic hyperglycemia does not reverse beta-cell dysfunction in older people with IGT.

Acarbose↗
PubMed2004

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). Laplace's approximation for nonlinear mixed effects models. Biometrika 80:791-795) that enable model calculation to take place within the interaction matrix language SAS/IML (SAS Institute Inc. (1999a). SAS/IML User's Guide Version 7. Cary, NC: SAS Institute Inc.). They provide greater flexibility and scope for the specification and analysis of complex nonlinear mixed models. For example, using data from a frequently sampled intravenous glucose test, we fit a two-compartment kinetics model that has no closed-form representation. It is derived as the solution of a system of ordinary differential equations and specified as such in SAS/IML. Additional details and example NLINMIX code are available in Appendix A.

Humans↗
PubMed2003

Effects of age and nerve-repair grafts on reinnervation and fiber type distribution of rat medial gastrocnemius muscles.

Aging is associated with a decline in skeletal muscle function. Previous research suggests that this decline in skeletal muscle function may, in part, be explained by an age-associated decline in the ability of skeletal muscle to reinnervate and/or age-associated changes in fiber types and distribution during reinnervation. This study used a nerve-repair graft model to investigate age-associated changes in the ability to reinnervate via expression of neural cell adhesion molecule (NCAM), a marker of denervated and recently reinnervated muscle fibers and changes in fiber type and Type I fiber grouping in medial gastrocnemius (MG) muscles of 6-, 12- and 24-month-old male Fischer 344 rats. Age had no effect on total MG muscle fiber number. Aging and nerve-repair grafting led to an increase in percent Type I and a decrease in percent Type IIB fibers. Aging and nerve-repair grafting led to an increase in NCAM positive fibers and an increase in the percentage of enclosed Type I muscle fibers, which was greatest in the 24 month nerve-repair grafted group. Thus, we conclude that diminished contractile function of aged and/or nerve-repair grafted MG muscle may be explained, in part, by an increase in the percentage of denervated fibers.

Aging↗
PubMed2003

Relating medical students' knowledge, attitudes, and experience to an interest in geriatric medicine.

PURPOSE: This study examined medical students' interest in geriatrics: Are knowledge, positive attitudes, and prior experience with older adults associated with an interest in geriatric medicine? DESIGN AND METHODS: Entering University of Michigan medical students completed three surveys: the Revised Facts on Aging Quiz, the University of California at Los Angeles Geriatric Attitudes Scale, and the Maxwell-Sullivan Attitudes Scale. The students were also asked questions about their prior experience with older adults and their interest in geriatric medicine. RESULTS: The results indicate that incoming medical students have minimal knowledge about aging, moderately positive attitudes toward older adults, and low interest in geriatric medicine. Having more positive attitudes toward older adults (ss =.28) and having cared for older persons prior to medical school (ss =.14) were associated with greater interest in geriatric medicine. IMPLICATIONS: These findings suggest that interventions to increase the number of geriatric-oriented physicians should focus on influencing learners' attitudes through experiences in the care of older adults.

Adult↗
PubMed2003

Aging and insulin secretion.

Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes and postchallenge hyperglycemia in the older population. Age-related glucose intolerance in humans is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people. Under some conditions of hyperglycemic challenge, insulin levels are lower in older people, suggesting beta-cell dysfunction. When insulin sensitivity is controlled for, insulin secretory defects have been consistently demonstrated in aging humans. In addition, beta-cell sensitivity to incretin hormones may be decreased with advancing age. Impaired beta-cell compensation to age-related insulin resistance may predispose older people to develop postchallenge hyperglycemia and type 2 diabetes. An improved understanding of the metabolic alterations associated with aging is essential for the development of preventive and therapeutic interventions in this population at high risk for glucose intolerance.

Adult↗
PubMed2003

Combined infusion of epinephrine and norepinephrine during moderate exercise reproduces the glucoregulatory response of intense exercise.

Intense exercise (IE) (>80% O(2max)) causes a seven- to eightfold increase in glucose production (R(a)) and a fourfold increase in glucose uptake (R(d)), resulting in hyperglycemia, whereas moderate exercise (ME) causes both to double. If norepinephrine (NE) plus epinephrine (Epi) infusion during ME produces the plasma levels and R(a) of IE, this would prove them capable of mediating these responses. Male subjects underwent 40 min of 53% O(2max) exercise, eight each with saline (control [CON]), or with combined NE + Epi (combined catecholamine infusion [CCI]) infusion from min 26-40. In CON and CCI, NE levels reached 7.3 +/- 0.7 and 33.1 +/- 2.9 nmol/l, Epi 0.94 +/- 0.08 and 7.06 +/- 0.44 nmol/l, and R(a) 3.8 +/- 0.4 and 12.9 +/- 0.8 mg. kg(-1). min(-1) (P < 0.001), respectively, at 40 min. R(d) increased to 3.5 +/- 0.4 vs. 11.2 +/- 0.8 mg. kg(-1). min(-1) and glycemia 5.2 +/- 0.2 mmol/l in CON vs. 6.5 +/- 0.2 mmol/l in CCI (P < 0.001). The glucagon-to-insulin ratio did not differ. Comparing CCI data to those from 14-min IE (n = 16), peak NE (33.6 +/- 5.1 nmol/l), Epi (5.32 +/- 0.93 nmol/l), and R(a) (13.0 +/- 1.0 mg. kg(-1). min(-1)) were comparable. The induced increments in NE, Epi, and R(a), all of the same magnitude as in IE, strongly support that circulating catecholamines can be the prime regulators of R(a) in IE.

Adult↗
PubMed2003

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 +/- 4.2 kg/m(2), HbA(1c) 6.5 +/- 0.8%) in a randomized, double-blind, placebo-controlled, crossover study. A single injection (7.5 micro g/kg) of NN2211 or placebo was administered 9 h before the study. beta-cell sensitivity was assessed by a graded glucose infusion protocol, with glucose levels matched over the 5-12 mmol/l range. Insulin secretion rates (ISRs) were estimated by deconvolution of C-peptide levels. Findings were compared with those in 10 nondiabetic volunteers during the same glucose infusion protocol. In type 2 diabetic subjects, NN2211, in comparison with placebo, increased insulin and C-peptide levels, the ISR area under the curve (AUC) (1,130 +/- 150 vs. 668 +/- 106 pmol/kg; P < 0.001), and the slope of ISR versus plasma glucose (1.26 +/- 0.36 vs. 0.54 +/- 0.18 pmol x l[min(-1) x mmol(-1) x kg(-1)]; P < 0.014), with values similar to those of nondiabetic control subjects (ISR AUC 1,206 +/- 99; slope of ISR versus plasma glucose, 1.44 +/- 0.18). The long-acting GLP-1 derivative, NN2211, restored beta-cell responsiveness to physiological hyperglycemia in type 2 diabetic subjects.

Aged↗
PubMed2002

Effect of age on skeletal muscle proteolysis in extensor digitorum longus muscles of B6C3F1 mice.

The purpose of this study was to determine if age-related muscle atrophy is associated with an increased rate of protein degradation in extensor digitorum longus (EDL) muscles from young (YG; 2-4 months), middle-aged (MA; 12-17 months), and aged (AG; 22-24 months) B6C3F1 mice. EDL muscles from AG mice weighed less than EDL muscles from MA mice (p =.01). EDL muscles from MA mice weighed more than EDL muscles from YG mice (p =.02). The rate of protein degradation, as assessed by tyrosine release during in vitro incubations, was higher in EDL muscles from AG mice than it was in those from MA mice (p =.03). The rate of protein degradation was higher in EDL muscles from YG mice than it was in those from MA mice (p =.04). An inverse relationship existed between muscle mass and protein degradation (r = -.67; p =.0001). We conclude that skeletal muscle protein degradation rates decrease with maturation and increase with advancing age.

Aging↗