Mark Rosenthal

Demonstration of a Relationship Between Level of Physical Training and Insulin-stimulated Glucose Utilization in Normal Humans

The relationship between level of physical training and in vivo insulin-stimulated glucose utilization was investigated in 33 healthy nonobese subjects. Status of physical training was estimated by maximal oxygen consumption (VO2 max) during graded bicycle ergometry, and insulin action by the insulin clamp technique. Within the study population we defined a significant (r = 0.63, P < 0.001) correlation between these two variables. This relationship was independent of age and obesity and accounted for over 40% of the variance in insulin-stimulated glucose utilization among these subjects. In addition, significant correlations existed between VO2 max and the plasma glucose (r = −0.35, P < 0.05) and insulin (r = −0.37, P < 0.05) responses to an oral glucose load. These results suggest that differences in level of physical training play a regulatory role in control of in vivo insulin action.

Hospitalization and Mortality of Diabetes in Older Adults: A 3-year prospective study

OBJECTIVE In light of increased fatality from acute events and the increased frequency of chronic complications, life expectancy might well be shortened in older patients with diabetes. The current studies investigated factors affecting the likelihood of dying or being hospitalized in older patients with diabetes. RESEARCH DESIGN AND METHODS A total of 135 older patients with diabetes were followed for 3 years after predictive factors were evaluated and compared with a cohort of patients without diabetes. RESULTS Mortality was only 3,250 per 100,000 patient-years, similar to that for patients without diabetes, but the frequency of hospitalizations was more than twice as high in patients with diabetes. Five factors predicted hospitalization and death. Of these, the geriatric depression score was the best predictor of these poor outcomes. CONCLUSIONS Older patients with diabetes were hospitalized more often than those without diabetes, but mortality was similar. Dysphoria is a major predictor of poor outcomes in older patients with diabetes.

Effect of Sulfonylurea Treatment on In Vivo Insulin Secretion and Action in Patients With Non-insulin-dependent Diabetes Mellitus

The effect of glipizide treatment on diabetic control and on in vivo insulin secretion and action was studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Patients were examined before and after a minimum of 3 mo treatment. Mean (± SEM) fasting plasma glucose level fell from 264 ± 12 mg/dl to 172 ± 10 mg/dl (P < 0.001) after glipizide treatment, and this was associated with a fall in total plasma glucose response to a test meal of approximately 35﹪. Mean (±SEM) fasting plasma insulin levels increased slightly from 15 ± 2 μU/ml to 18 ± 2 μU/ml following sulfonylurea treatment, and the total plasma insulin response to the test meal increased by 63﹪. However, there was no correlation (r = −0.20) between the increase in plasma insulin response and the fall in plasma glucose levels that occurred as the result of sulfonylurea therapy. Glipizide treatment also led to enhanced in vivo insulin action, whether measured by the insulin clamp technique (P < 0.001) or the insulin suppression test (P < 0.02). Furthermore, in this instance there was a significant correlation (r = 0.69, P < 0.001) between the enhanced insulin action and the improvement on diabetes control. Thus, chronic therapy with glipizide, a new sulfonylurea agent, led to increased in vivo insulin secretion and insulin action. These results lend direct support to the assumption that sulfonylurea compounds have a substantial extrapancreatic effect on glucose homeostasis, and suggest that this effect contributes to the therapeutic efficacy of these drugs.

Effect of Habitual Physical Activity on Regulation of Insulin‐stimulated Glucose Disposal in Older Males

The goal of this study was to evaluate the effect of differences in habitual level of physical activity on insulin action in healthy males between 60 and 75 years of age. The study population consisted of 20 non‐obese individuals with normal glucose tolerance: 13 older subjects (68 ± 4 years) not exercising regularly and 7 older subjects (66 ± 3 years) who exercised regularly. Measurements were made of body mass index (BMI), percentage body fat by underwater weighing, maximal O2 consumption by bicycle ergometry (V̇O2max), and insulin‐stimulated glucose disposal by the insulin clamp technique. The results demonstrated that insulin‐stimulated glucose disposal was significantly increased (P < 0.001) in the normal older subjects who exercised regularly. Furthermore, a direct relationship (r = 0.74, P < 0.001) existed between maximal aerobic capacity and in vivo insulin action, which was independent of either BMI or percentage body fat. These data are consistent with the view that the extensive variation previously noted in in vivo insulin‐stimulated glucose disposal of older subjects is related to differences in habitual physical activity.

Effect of Variations in Basal Plasma Glucose Concentration on Glucose Utilization (M) and Metabolic Clearance (MCR) Rates During Insulin Clamp Studies in Patients with Non-insulin-dependent Diabetes Mellitus

Two insulin clamp studies were performed at different steady-state plasma glucose concentrations in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM). Steady-state plasma insulin concentrations were comparable, with mean ± SEM levels of 94 ± 3 and 95 ± 4 μU/ml being achieved during the two studies. Glucose utilization rate (M) varied directly with plasma glucose concentration in each subject. Thus, the mean ± SEM value of M was 4.92 ± 0.73 mg/kg/min when patients were studied at a mean ± SEM plasma glucose concentration of 226 ± 15 mg/dl, and M was 2.71 mg/kg/min when the same subjects were studied at a glucose concentration of 118 ± 6 mg/dl. In contrast, the values for glucose metabolic clearance rate (MCR), which were 2.35 ± 0.50 and 2.49 ± 0.47 ml/kg/min, respectively, during the two studies, did not vary significantly with plasma glucose concentration. These data indicate that the glucose metabolic clearance rate (MCR), but not glucose utilization rate (M), can be used to compare in vivo insulin action when insulin clamp studies are performed in subjects with different basal plasma glucose concentrations.

Effect of Age on Glucose Tolerance, Insulin Secretion, and in Vivo Insulin Action

The effect of age on glucose tolerance, insulin secretion, and in vivo insulin action (insulin clamp) was studied in 48 nonobese subjects, all of whom were fully ambulatory and in good general health. The observed age‐related increase in fasting plasma glucose (r = 0.35, P < 0.01) was not due to an increase in relative body weight (RBW). Plasma insulin levels, both fasting and postprandial, tended to rise with age, but these changes were not significant. There was a marginally significant correlation (r = −0.21) between age and insulin‐stimulated glucose utilization, which fell to −0.13 when controlled for RBW. However, steady‐state insulin levels during the insulin‐clamp period were higher in the older subjects, suggesting that age leads to an impairment in insulin catabolism; thus it is likely that the impairment of in vivo insulin action with age was underestimated. The variation in in vivo action between individuals was much greater among the older subjects. It was concluded that the glucose intolerance associated with aging is of relatively minor magnitude when ambulatory, generally healthy, nonobese, and nondiabetic subjects are studied. The cause of the glucose intolerance associated with aging seems to be loss of normal in vivo insulin action. On the other hand, this defect is not shared by all older persons, and in many over the age of 70, glucose transport is as efficient as in persons in their 20s.

Effects of age on complications in adult onset diabetes.

The prevalence of diabetes is greatest among older persons, yet few studies have specifically addressed the impact of age on diabetic complications. The present study examines the prevalence of four diabetic complications: retinopathy, peripheral neuropathy, autonomic neuropathy, and hypertension, as well as depression, in older male patients with noninsulin‐dependent diabetes. Participants ranged in age from 53 to 80 years. Multiple risk factors, including age, duration of illness, type of treatment, metabolic control, and obesity were evaluated as predictors of these complications using logistic regression. Results suggest a significant increase in the prevalence of retinopathy with aging, independent of the effects of metabolic control, duration of illness, and other risk variables. Age was also related to prevalence of peripheral neuropathy symptoms, hypertension, and impotence. Current metabolic control was significantly associated with retinopathy, peripheral neuropathy, and hypertension prevalence. Time since diagnosis was only independently related to impotence and hypertension. These findings suggest that the increase in many diabetic complications in older persons cannot be wholely accounted for by simple disease status variables, and may result from an interaction of diabetes variables and general age‐related changes.

Does Insulin Removal Rate from Plasma Decline with Age

The effect of age on the rate of insulin removal from plasma was studied in both rat and man. The experimental approach was based on measurement of the steady-state plasma insulin concentration achieved during a period in which endogenous insulin secretion was suppressed and exogenous insulin infused. Rats, 1½ and 12 mo of age, were infused with 2.5, 5.0, and 10.0 μU/kg of insulin during a 180-min period in which endogenous insulin secretion was suppressed by epinephrine and propranolol. Steady-state plasma insulin concentrations were approximately twice as high in the older rats at every insulin infusion rate. Similar results were seen in man; significant correlations were observed between height of steady-state plasma insulin concentration and advancing age during infusion of exogenous insulin and suppression of endogenous insulin with either exogenous insulin (r = 0.66, P < 0.001) or epinephrine and propranolol (r = 0.47, P < 0.01). Since infusion rates of exogenous insulin were identical in all studies, these results suggest that there is an age-related decrease in insulin catabolism.

Central nervous system IgG synthesis rates in Alzheimer disease: possible differences in early-onset and late-onset subgroups

SummaryCentral nervous system IgG synthesis rates were determined for 51 patients with autopsy-confirmed Alzheimer disease and 23 age-matched controls. Rates were no different between patients and controls when overall groups were compared. Age-at-dementia-onset data were available on 37 patients. Comparisons of 11 early-onset (< 65 years of age) patients with 26 late-onset patients revealed significantly increased intrathecal IgG synthesis rates for the late-onset group. These results suggest that IgG synthesis may be a contributing pathogenic factor in a subgroup of patients with late-onset Alzheimer disease.

Geriatrics An Updated Bibliography

This is the authors fourth revision of a geriatrics bibliography. Approximately one‐third of the previous references have been replaced by more current or more detailed articles. Because the literature pertinent to geriatrics has continued to grow ever more rapidly, it has been necessary to omit many informative articles from the bibliography. Preference is given to recent publications; almost all of the references date from the past four years. Some articles were selected to highlight current controversies or changes in viewpoint. An occasional unrefereed article is cited to amplify geriatric aspects of common diseases.