Insulin After 75 Years: Still A Heroic Hormone

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111083/1/j.1532-5415.1997.tb05183.x.pd

Endocrine markers of aging

Sophisticated methods available to quantitate hormone secretion and hormone action provide opportunities to identify potential endocrine biomarkers of aging. However, there are many challenges facing the investigator who wishes to establish an endocrine biomarker. Circulating levels of many hormones fluctuate on a circadian rhythm, and a variety of other short-term fluctuations may occur. Hormone secretion is generally tightly regulated and often affected by multiple, redundant feedback mechanisms. Interpretation of circulating hormone levels must also take into account factors affecting hormone metabolism and degradation which may be influenced by age. The rate of hormone secretion and circulating hormone levels are related to the sensitivity to hormone action by feedback control mechanisms. Thus interpretation of potential circulating endocrine markers of aging must take into account changes in sensitivity to that hormone as well.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27554/1/0000598.pd

Geriatrics program development at the University of Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31253/1/0000159.pd

Geriatrics Attitudes and Knowledge Among Surgical and Medical Subspecialty House Officers

To examine geriatrics knowledge and attitudes of non-primary care house officers (HOs) before and after a multidisciplinary faculty development program. DESIGN : Serial cross-sectional surveys. PARTICIPANTS : HOs. SETTING : A large midwestern academic medical center. INTERVENTION : Faculty from seven surgical and six medical subspecialties participated in weekly seminars for 9 months and implemented geriatrics curricula in their HO programs. MEASUREMENTS : HO geriatrics attitudes and knowledge were measured using the University of California at Los Angeles Geriatrics Attitudes Scale (GAS; 14 items), two scales of the Maxwell Sullivan test (Therapeutic Potential and Time/Energy; six items each; lower scores denote more-favorable attitudes), and the Geriatrics Clinical Knowledge Assessment (20 multiple choice items; range 0–100%). Repeat surveys were administered in seven disciplines after geriatrics curriculum implementation. RESULTS : Baseline (n=175) geriatrics attitudes were favorable (e.g., 3.7 for GAS; 2.1 for Time/Energy), with more-favorable attitudes among medical subspecialty than surgical HOs (e.g., mean GAS 3.8 and 3.6, respectively; P =.001), and with advanced training. Mean baseline knowledge scores were 65.1% among all HOs. No differences in attitudes or knowledge were observed between the first (n=100) and second (n=90) cohorts in the seven disciplines that administered subsequent tests. CONCLUSION : Geriatrics attitudes of non-primary care HOs are positive, and knowledge is moderate, suggesting need for and potential effect of geriatrics curricula. Demonstrating effects on learner outcomes of faculty development programs may require more than one faculty member per discipline and measures that are curriculum-specific and detailed rather than general and brief.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66180/1/j.1532-5415.2007.01475.x.pd

Comparison of Safety and Efficacy of Insulin Glargine and Neutral Protamine Hagedorn Insulin in Older Adults with Type 2 Diabetes Mellitus: Results from a Pooled Analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90150/1/jgs3773.pd

Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 ± 3 years) ( ± 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 ± 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 ± 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays; ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise.The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing

The interplay between endogenous catecholamines and induced ventricular tachycardia during electrophysiologic testing

Plasma epinephrine and norepinephrine concentrations were measured before, during, and shortly after induced ventricular tachycardia (VT) in 22 selected patients. Sustained, unimorphic VT was induced by programmed ventricular stimulation and terminated after 45 to 384 seconds by overdrive pacing in all patients. In no patient did VT result in loss of consciousness. The baseline plasma catecholamine concentrations did not correlate with the baseline right ventricular effective refractory period, the cycle length of induced VT, or the number of extrastimuli required to induced VT. Induced VT was not associated with a significant increase in the mean plasma epinephrine concentration. In contrast, the plasma norepinephrine concentration increased from a mean baseline level of 317 +/- 136 pg/ml (mean +/- standard deviation) to 418 +/- 220 pg/ml during VT (p = 0.01) and increased further to 569 +/- 387 pg/ml shortly after VT (p p < 0.05 for each). In eight patients the same configuration of VT was induced on two sequential attempts; in five patients the same number of extrastimull were required for the second induction of VT as for the first, whereas in three patients fewer extrastiuli were required. Plasma cateholamine concentrations were not higher in patients requiring fewer extrastimuli to induce the second episode of VT, either shortly after the first episode of VT or shortly after the second episode of VT. In conclusion, plasma catecholamines do not influence baseline ventricular refractoriness, the cycle length of induced VT, or the VT induction technique. Induced VT, which does not require termination by direct-current countershock, is generally associated with little or no increase in plasma epinephrine and a variable increase in plasma norepinephrine concentration, depending on the severity and duration of hypotension during VT. The plasma catecholamine response to VT does not affect a second induction of VT. Therefore, endogenous catecholamines exert little influence on the results of electrophysiologic testing in patients with sustained VT which does not require termination by direct-current countershock.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26830/1/0000389.pd

Reverse geroscience: how does exposure to early diseases accelerate the age‐related decline in health?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135360/1/nyas13297.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135360/2/nyas13297_am.pd

Peripheral sympathectomy and adrenal medullectomy do not alter cerebrospinal fluid norepinephrine

Despite a blood-brain barrier for norepinephrine, the concentration of norepinephrine in plasma and cerebrospinal fluid has been observed to be similar. This relationship between plasma and cerebrospinal fluid norepinephrine levels suggests that peripheral sympathetic neurons innervating blood vessels to brain and spinal cord may contribute significantly to cerebrospinal fluid norepinephrine levels, and questions the validity of cerebrospinal fluid norepinephrine as an index of central nervous system noradrenergic activity. We demonstrate that extensive destruction of the peripheral sympathetic nervous system and the adrenal medulla has no effect on rat cerebrospinal fluid norepinephrine. It is therefore unlikely that peripheral sources of norepinephrine contribute significantly to cerebrospinal fluid norepinephrine levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26232/1/0000312.pd

Glucose regulation in non-insulin-dependent diabetes mellitus: Interaction between pancreatic islets and the liver

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25595/1/0000139.pd