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Biomedical subjects

G S Meneilly

Publications and source records attributed to G S Meneilly.

At least 19 recordsLinked to original sources
PubMed1998

Responses to influenza vaccination in different T-cell subsets: a comparison of healthy young and older adults.

T-lymphocyte responses to influenza vaccination were measured in healthy young and older adult volunteers. All participants were vaccinated with the 1995-96 trivalent influenza vaccine. Cytokine and granzyme B levels were measured in peripheral blood mononuclear cells (PBMC) cultures after virus stimulation, prior to and 4 and 12 weeks after vaccination. The major findings in the older adult group were the different types of helper T-cell (Th) responses to each of the vaccine strains of virus and a very poor cytotoxic T lymphocyte (as measured by granzyme B) response to vaccination. IL-10, which is produced in a Th-type 2 response, was higher in PBMC stimulated with A/Texas/36/91 (H1N1) compared with A/Johannesburg/33/94 (H3N2); this difference was more marked in the PBMC from older compared with younger adults. In contrast, IL-2, which is produced in a Th-type 1 response, was measured in the same cultures and was significantly higher in A/Johannesburg/33/94-stimulated PBMC. IFN- gamma levels were highest in the PBMC stimulated with B/Harbin/7/94. The greatest age-related difference was the level of granzyme B in all virus-stimulated PBMC from the young compared with the older adult group. The strain of influenza virus contained in the vaccine, as well as the age of the subject, appear to be very important determinants of the T-cell response to vaccination.

Adult↗
PubMed1998

Assessment of insulin sensitivity in older adults using the hyperglycemic clamp technique.

OBJECTIVE: The euglycemic glucose clamp technique is the gold standard for the measurement of insulin sensitivity in older adults, whereas the hyperglycemic glucose clamp technique is used to assess insulin release. The objective of this study was to evaluate the ability of the hyperglycemic glucose clamp technique to assess insulin sensitivity and insulin release in older people. RESEARCH DESIGN AND METHODS: Healthy older controls (n = 26, age 72 +/- 1) and older non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 35, age 75 +/- 1) underwent a 2-hour hyperglycemic glucose clamp study (glucose 5.4 mM above basal) and a 3-hour euglycemic clamp study (insulin infusion rate 40 mU/m2/min). The average glucose infusion rate (last 30 minutes) of each clamp was divided by the average insulin value (last 30 minutes). This value was then divided by the average plasma glucose value to give glucose clearance per plasma insulin concentration. RESULTS: In control subjects (Eug: 0.80 +/- .05 mL/kg/min/pM; Hyper: 0.88 +/- .07 mL/kg/min/pM, P = .357) and NIDDM patients (Eug: 0.48 +/- .03 mL/kg/min/pM; Hyper: 0.42 +/- .03 mL/kg/min/pM, P = .162), glucose clearance values were similar whether calculated from the euglycemic or the hyperglycemic clamp. The correlation between glucose clearance values derived from the euglycemic and hyperglycemic clamp was excellent in normal controls (r = .76, P < .001) and patients with NIDDM (r = .71, P < .001). CONCLUSIONS: We conclude that the hyperglycemic glucose clamp technique can reliably assess both insulin release and insulin sensitivity in older people.

Aged↗
PubMed1998

The effect of age and glycemic level on the response of the beta-cell to glucose-dependent insulinotropic polypeptide and peripheral tissue sensitivity to endogenously released insulin.

Normal aging is characterized by a progressive impairment in glucose tolerance. An important mechanism underlying the glucose intolerance of aging is an impairment in glucose-induced insulin release. These studies were conducted to determine whether the age-related impairment in insulin release was caused by a decreased beta-cell sensitivity to glucose-dependent insulinotropic polypeptide (GIP). Thirty-one Caucasian men were divided into four groups: two young groups (age range: 19-26 yr, n = 15) and two old groups (age range: 67-79 yr, n = 16). Each volunteer participated in three studies (n = 93 clamps). Hyperglycemic clamps were conducted at two doses [basal plasma glucose (G) + 5.4 mmol/L and G + 12.8 mmol/L] for 120 min. In the initial hyperglycemic clamp, only glucose was infused. In subsequent studies, GIP was infused at a final rate of 2 or 4 pmol/ kg(-1) x min(-1) from 60-120 min. Basal plasma insulin and GIP levels were similar in the young (41 +/- 6 and 51 +/- 6 pmol/L) and the old subjects (42 +/- 6 and 66 +/- 12 pmol/L) in all studies. First- and second-phase insulin responses were similar during the control study and during the first 60 min of each GIP infusion study in both groups. The 90-120 min GIP values were similar between groups and between hyperglycemic plateaus during the 2 and 4 pmol/kg(-1) x min(-1) GIP infusion (young: 342 +/- 28 and 601 +/- 44 pmol/L, old: 387 +/- 45 and 568 +/- 49 pmol/L). In response to the GIP infusions, significant increases in insulin occurred in young and old at both glucose levels (P < 0.01). The potentiation of the insulin response caused by GIP was greater in the young subjects than in the old, in the G + 5.4 mmol/L studies (P < 0.05). However, the insulin response to GIP was similar in both young and old during the G + 12.8 mmol/L clamps. The insulinotropic effect of the incretin was higher in the young and in the old, in the G + 12.8 mmol clamps, than in the G + 5.4 mmol/L clamps. We conclude that normal aging is characterized by a decreased beta-cell sensitivity to GIP during modest hyperglycemia, which may explain, in part, the age-related impairment in glucose-induced insulin release. We also find that the insulinotropic effect of GIP is increased with increasing levels of hyperglycemia.

Adult↗
PubMed1998

Alterations in non-insulin-mediated glucose uptake in the elderly patient with diabetes.

It is increasingly recognized that alterations in non-insulin-mediated glucose uptake (NIMGU) play an important pathogenic role in disorders of carbohydrate metabolism. This study was conducted to determine whether NIMGU is impaired in elderly patients with type 2 diabetes. Healthy elderly control subjects (n = 19, age 76 +/- 1 years, BMI 26.8 +/- 1.1 kg/m2) and elderly patients with type 2 diabetes (n = 19, age 76 +/- 2 years, BMI 27.5 +/- 0.9 kg/m2) underwent a 240-min glucose clamp study. Octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose uptake and disposal rates. For the first 180 min, glucose was kept at fasting levels. From 180 to 240 min, glucose was increased to 11 mmol/l. At fasting glucose levels, glucose uptake was similar in both groups. However, glucose clearance was reduced in patients with diabetes (control 1.68 +/- 0.05 ml x kg(-1) x min(-1); diabetes 1.34 +/- 0.07 ml x kg(-1) x min(-1), P < 0.0001). During hyperglycemia, glucose uptake was reduced in patients with diabetes (control 3.16 +/- 0.09 mg x kg(-1) x min(-1); diabetes 2.57 +/- 0.11 mg x kg(-1) x min(-1), P < 0.0001). Peripheral glucose effectiveness (SG) was less in patients with diabetes (control 1.28 +/- 0.04 ml x kg(-1) x min(-1); diabetes 0.94 +/- 0.08 ml x kg(-1) x min(-1), P < 0.0001). Hepatic glucose output and hepatic SG were not different between groups. We conclude that the effect of glucose on glucose uptake is impaired in elderly patients with type 2 diabetes, a finding that may have therapeutic implications for this patient population.

Adipose Tissue↗
PubMed1998

Physiological importance of first-phase insulin release in elderly patients with diabetes.

OBJECTIVE: To assess the physiological role of first-phase insulin release in obese elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Moderately obese elderly patients (n = 14, mean age 77 +/- 2 years, BMI 28.4 +/- 0.7 kg/m2) with type 2 diabetes underwent three 180-min hyperglycemic clamp studies. In the control study, glucose alone was infused. In the first-phase study, human insulin was infused for the first 4 min at 12 mU/m2 to mimic first-phase insulin release. In the first-phase enhanced study, insulin was infused for the first 4 min at 24 mU.m-2 .min-1. Tritiated glucose methodology was used in all studies to measure glucose production and disposal rates. RESULTS: Glucose values were similar in all studies. In the control study, first-phase insulin response was absent. The peak insulin response occurred at 4 min in the first-phase and first-phase enhanced studies, but insulin values were substantially higher in the latter study (528 +/- 40 vs. 340 +/- 24 pmol/l, P < 0.0001). Second-phase insulin responses were not different among the studies. Glucose production and disposal rates were not significantly different among the studies. CONCLUSIONS: While absent first-phase insulin secretion is a marker of abnormal pancreatic function in obese elderly patients with type 2 diabetes, it is not important in the regulation of hepatic glucose output or peripheral glucose disposal.

Aged↗
PubMed1997

Substrate utilisation during exercise and shivering.

It is generally assumed that exercise and shivering are analogous processes with regard to substrate utilisation and that, as a consequence, exercise can be used as a model for shivering. In the present study, substrate utilisation during exercise and shivering at the same oxygen consumption (VO2) were compared. Following an overnight fast, eight male subjects undertook a 2-h immersion in cold water, designed to evoke three different intensities of shivering. At least 1 week later they undertook a 2-h period of bicycle ergometry during which the exercise intensity was varied to match the VO2 recorded during shivering. During both activities hepatic glucose output (HGO), the rate of glucose utilisation (Rd), blood glucose, plasma insulin, free fatty acid (FFA) and beta-hydroxybutyrate (B-HBA) concentrations were measured. The VO2 measured during the different levels of shivering averaged 0.49 l.min-1 (level 1: low), 0.6 l.min-1 (level 2: low-moderate), and 0.9 l.min-1 (level 3: moderate), and corresponded closely to the levels measured during exercise. HGO and Rd were greater (P < 0.05) during exercise than during shivering at the same VO2 (9.5% and 14.7%, respectively). The average (SD). HGO during level 3 exercise was 3.0 (0.91) mg.kg-1.min-1 compared to 2.76 (1.0) mg.kg-1.min-1 during shivering. The values for Rd were 3.06 (0.98) mg.kg-1.min-1 during level 3 exercise and 2.68 (0.82) mg.kg-1.min-1 during shivering. Blood glucose levels did not differ between conditions averaging 5.4 (0.3) mmol.l-1 over all levels of shivering and 5.2 (0.3) mmol.l-1 during exercise. Plasma FFA and B-HBA were higher (P < 0.01) during shivering than during corresponding exercise (12.3% and 33.3%, respectively). FFA averaged 0.61 (0.2) mmol.l-1 over all levels of shivering and 0.47 (0.16) mmol.l-1 during exercise. The figures for L-HBA were 0.44 (0.13) mmol. l-1 during all levels of shivering and 0.32 (0.1) mmol.l-1 during exercise. Plasma insulin was higher (P < 0.05) during level 2 and 3 shivering compared to corresponding exercise; at these levels the average value for plasma insulin was 95.9 (21.9) pmol.l-1 during shivering and 80.6 (16.1) pmol.l-1 during exercise. On the basis of the present findings it is concluded that, with regard to substrate utilisation, shivering and exercise of up to 2 h duration should not be regarded as analogous processes.

3-Hydroxybutyric Acid↗
PubMed1997

Increased disorderliness of basal insulin release, attenuated insulin secretory burst mass, and reduced ultradian rhythmicity of insulin secretion in older individuals.

Insulin is secreted in a pulsatile fashion. Rapid pulses are considered to be important for inhibiting hepatic glucose output, and ultradian pulses for stimulating peripheral glucose disposal. Aging is characterized by a progressive impairment in carbohydrate tolerance. We undertook the current studies to determine whether alterations in pulsatile insulin release accompany the age-related changes in carbohydrate metabolism. Healthy young (n = 8; body mass index, 21 +/- 1 kg/m2; age, 24 +/- 1 yr) and old (n = 9; body mass index, 24 +/- 1 kg/m2; age, 77 +/- 2 yr) volunteers underwent two studies. In the first study, insulin was sampled every 1 min for 150 min, and pulse analysis was conducted using a recently validated multiparameter deconvolution technique. In the second study, insulin was sampled every 10 min for 600 min, and insulin release was evaluated by Cluster analysis. In the 150-min studies, insulin secretory burst mass (P < 0.05) and amplitude (P < 0.01) were reduced in the elderly. In addition, approximate entropy, a measure of irregularity or disorderliness of insulin release, was increased in the aged (P < 0.01). In the 600-min studies, interpulse interval was greater in the aged (P < 0.05), and burst number was less (P < 0.05). We conclude that normal aging is characterized by more disorderly insulin release, a reduction in the amplitude and mass of rapid insulin pulses, and a decreased frequency of ultradian pulses. Whether these alterations in insulin pulsatility contribute directly to the age-related changes in carbohydrate metabolism will require further study.

Activity Cycles↗
PubMed1996

Passive temperature lability in the elderly.

Thermoregulatory responses of nine healthy elderly [seven men and two women; mean age (SD) 73.9 (4.8) years] were compared to those of nine young adult men [26.6 (5.2) years]. They exercised on a cycle ergometer for 20 min at an intensity inducing a heart rate equivalent to 65% of their predicted maximum, and were thereafter immersed in 28 degrees C water. The exercise was conducted to elevate tympanic temperature (Tty) and initiate a steady rate of sweating. The post-exercise immersion period induced gradual cooling of Tty, and changes in Tty relative to resting levels (delta Tty) at which sweating abated and shivering commenced were defined as the delta Tty thresholds for the cessation of sweating (Tsw) and onset of shivering (Tsh), respectively. In addition to Tty, oxygen uptake (VO2; l.min-1), sweating rate (g.m-2.min-1), and forehead skin blood perfusion were also measured during the trials. The mean (SD) Tsw occurred at a significantly (P < 0.005) higher delta Tty [0.48 (0.18) degrees C] in the elderly than in the young adults [0.21 (0.06) degrees C], while the Tsh occurred at significantly (P < 0.005) lower delta Tty in the elderly [-0.64 (0.34) degrees C] than in young adults [-0.22 (0.10) degrees C]. Decreases in delta Tty below the shivering threshold were met with a significantly (P < 0.01) reduced VO2. The range of temperature lability between Tsw and Tsh, defined as the null-zone, was significantly greater in the elderly [1.12 (0.39) degrees C] than in the young adults [0.43 (0.12) degrees C], and the slope of the vasoconstrictor response in the null-zone was significantly (P < 0.001) lower in the elderly subjects. The present study demonstrates a greater passive core temperature lability in older individuals, since the effector responses of sweating and shivering were initiated at higher and lower levels of Tty, respectively. The magnitudes of the effector responses beyond the thresholds were also significantly reduced, suggesting that the elderly may be more susceptible to hypo-/hyperthermia during periods of endogenous and/or exogenous thermal stress.

Adult↗
PubMed1996

Helper and cytotoxic T lymphocyte responses to influenza vaccination in healthy compared to diabetic elderly.

This study was designed to determine the effect of Type II diabetes mellitus in older adults on two measures of the cell-mediated immune response to influenza vaccination. Twenty-two elderly persons with diabetes mellitus were compared to 20 healthy seniors, all of whom were living independently in the community. Peripheral blood mononuclear cells (PBMC) were challenged in vitro with live influenza virus, pre-vaccination and 4 and 12 weeks post-vaccination. PBMC culture supernatants were assayed for IL-2 activity as a measure of the helper T-cell response to vaccination. The cytotoxic T-lymphocyte response was determined using an assay of granzyme B activity in PBMC lysates. Initial analysis of the data showed increased IL-2 production in post-vaccination PBMC cultures from the diabetic group compared to the healthy group. However, when vaccination histories were used in an analysis of variance, it was found that the difference between the two groups was related to vaccination history. Study subjects vaccinated one year prior to participation in this study compared to those who had not been previously vaccinated, demonstrated a significantly suppressed IL-2 response to vaccination. Type II diabetes mellitus had no effect on the IL-2 response to vaccination. The granzyme B response to vaccination was not significantly affected by previous vaccination and results were similar for the healthy and diabetic elderly groups.

Aged↗
PubMed1996

Effect of hypoglycemia on thermoregulatory responses.

The effects of hypoglycemia on sweating, skin blood perfusion, and shivering responses were investigated in 10 healthy male volunteers. They exercised on an underwater cycle ergometer while immersed to the neck in 28 degrees C water for 20 min at 50% of their maximal work rate. The exercise-induced elevation in esophageal temperature (T(es)) initiated the sweating response (Esw) and increased skin blood perfusion (SkBP) as measured at the forehead. In the 99-min postexercise immersion period, the values of T es relative to resting level (delta T(es)) at which Esw abated, SkBP reached preexercise values, and shivering commenced were defined as the delta T(es) thresholds for cessation of sweating, passive vasodilation, and onset of shivering, respectively. Two trials were conducted 1 wk apart. The subject was hypoglycemic in one trial and euglycemic in the other (plasma glucose was maintained at 2.8 and 5 mM, respectively) with the use of the hyperinsulinemic (insulin infusion rate = 60 mU.m-2.min-1) glucose-clamp technique. Oxygen uptake, Esw, T(es), mean skin temperature, heat flux from the skin, and SkBP were recorded at minute intervals. Although heat flux and SkBP attained significantly higher end-exercise levels during euglycemia, the responses were similar during the postexercise cooling period. Hypoglycemia did not affect the Esw response during the exercise and cooling periods. Whereas the exercise delta T(es) response was unaffected by hypoglycemia, the decrease in T(es) was greater (P < or = 0.005) during the hypoglycemic than during the euglycemic condition. Hypoglycemia did not alter the delta T(es) threshold for cessation of sweating and passive vasodilation but reduced (P < or = 0.001) the delta T(es) threshold for onset of shivering (from -0.09 +/- 0.07 degrees C in the euglycemic condition to -0.65 +/- 0.12 degrees C in the hypoglycemic condition). The present results indicate that hypoglycemia (2.8 mM) does not affect the delta T(es) threshold for cessation of thermoregulatory sweating or the threshold for passive vasodilation during recovery from exercise-induced moderate heat stress but that it decreases the core temperature threshold for shivering during cold exposure.

Adult↗
PubMed1996

NIDDM in the elderly.

OBJECTIVE: We conducted this study to assess the metabolic alterations in elderly patients with NIDDM. RESEARCH DESIGN AND METHODS: Healthy, lean (n = 15; age, 73 +/- 1 years; BMI, 23.8 +/- 0.5 kg/m2), and obese (n = 10; age, 71 +/- 1 years; BMI, 28.9 +/- 1.2 kg/m2) control subjects and lean (n = 10; age, 75 +/- 2 years; BMI, 24.0 +/- 0.5 kg/m2) and obese (n = 23; age, 73 +/- 1 years; BMI, 29.9 +/- 0.7 kg/m2) NIDDM patients underwent a 3-h glucose tolerance test, a 2-h hyperglycemic glucose clamp study, and a 3-h euglycemic glucose clamp study with tritiated glucose methodology to measure glucose production and disposal rates. RESULTS: Waist-to-hip ratio (WHR) was greater in both lean and obese NIDDM patients than in control subjects. Insulin responses during the oral glucose tolerance test were similar in obese subjects (control subjects: 417 +/- 64 pmol/l; NIDDM patients: 392 +/- 47 pmol/l) but were reduced in lean NIDDM patients (control subjects: 374 +/- 34 pmol/l; NIDDM patients: 217 +/- 20 pmol/l, P < 0.01). Lean and obese NIDDM patients had absent first-phase insulin responses during the hyperglycemic clamp. Second-phase insulin responses were reduced in lean (P < 0.01 vs. control subjects by analysis of variance) but not obese NIDDM patients. Hepatic glucose output was not increased in lean or obese NIDDM patients. Steady-state (150-180 min) glucose disposal rates were 16% less in lean NIDDM patients (control subjects: 8.93 +/- 0.37 mg.kg LBM (lean body mass)-1.min-1; NIDDM patients: 7.50 +/- 0.28 mg.kg LBM-1.min-1, P < 0.05) and 37% less in obese NIDDM patients (control subjects: 8.17 +/- 0.38 mg.kg LBM-1.min-1; NIDDM patients: 5.03 +/- 0.36 mg.kg LBM-1.min-1, P < 0.001). CONCLUSIONS: Lean elderly NIDDM patients have a profound impairment in glucose-induced insulin release but mild resistance to insulin-mediated glucose disposal. Obese elderly NIDDM patients have adequate circulating insulin, but marked resistance to insulin-mediated glucose disposal. Hepatic glucose output is not increased in elderly NIDDM patients.

Aged↗
PubMed1995

Vaccine-related determinants of the interleukin-2 response to influenza vaccination in healthy young and elderly adults.

This study was designed as a parallel-groups comparison of trivalent preparations of split-virus vaccine (SVV) and whole-virus influenza vaccine (WVV) in healthy young and elderly adults. Interleukin-2 (IL-2) was measured in the supernatants of peripheral blood mononuclear cell (PBMC) cultures stimulated with live virus preparations of the two strains of influenza A contained in the vaccine. The duration of increased in vitro IL-2 production after vaccination was significantly different between the two strains of virus. A/Beijing/353/89 resulted in an IL-2 response that was quite short (< 7 weeks) while the response to A/Texas/16/89 was much more prolonged (> 12 weeks). In the first 12 weeks after vaccination, there was no difference in IL-2 levels between SVV and WVV recipients in either the young or elderly groups. The duration of the response to A/Texas/16/89 was slightly longer in WVV recipients as measured at 26 weeks postvaccination. The viral strain contained in the vaccine appears to be an important variable in determining the duration of the IL-2 response to vaccination.

Adult↗
PubMed1995

Diabetes in the elderly.

Diabetes affects at least 20% of the population over the age of 65. Half of these patients are unaware that they have the disease. Diabetes in middle-aged subjects is characterized by an impairment in glucose induced insulin release, increased fasting hepatic glucose output and resistance to insulin mediated glucose disposal. In contrast, diabetes in the elderly is primarily associated with insulin deficiency. The presentation of diabetes in the aged is often non-specific. The elderly have an increased frequency of complications from diabetes. They are particularly susceptible to hypoglycaemia, because of reduced awareness of hypoglycaemic warning symptoms and altered release of counterregulatory hormones. Although no data are yet available from randomized controlled trials, there is abundant epidemiological evidence to suggest that adequate control of blood glucose can be expected to reduce the risk of long-term complications. A team approach is ideal for the management of the elderly patient with diabetes. Little data is available on which to base a diet and exercise prescription for elderly patients. Gliclazide appears to be the sulphonylurea of choice in the aged because it is associated with a lower frequency of hypoglycaemic reactions. Urine glucose testing is unreliable, and capillary glucose monitoring is preferred. Fructosamine may prove to be superior to haemoglobin A1C for monitoring long-term control.

Aged↗
PubMed1995

Changes in CD45 isoform expression vary according to the duration of T-cell memory after vaccination.

Healthy young (< 40 years) and elderly (< 60 years) adults were immunized with the 1992-1993 preparation of trivalent influenza vaccine, and changes in CD45 isoform expression on peripheral blood lymphocytes were measured in the pre- and postvaccination periods. Fluorescence-activated cell sorter analysis was used to study T-cell subsets in fresh peripheral blood lymphocytes (day 0) and after 6 days of culture with live influenza virus. We have reported previously that the interleukin-2 response to the stimulating strain of virus, A/Texas/16/89, did not decline until 26 weeks postvaccination. In ex vivo CD4+ subsets, this interleukin-2 response was paralleled by a > 10% increase in the proportion of cells expressing the CD45RO+ phenotype following vaccination (p < 0.0001). In vitro stimulation had no effect on CD4+ subsets prior to vaccination but, after vaccination, was associated with a > 10% increase in CD45RA+RO+ cells (P < 0.0001). In addition, we have identified a change in the population of cells that express a CD45 isoform that is neither CD45RA nor CD45RO (CD45RA-RO-). At 26 weeks postvaccination, the proportion of CD45RA-RO- cells in ex vivo CD4+ peripheral blood mononuclear cells increased by approximately 15% from that measured at the earlier postvaccination time points (P < 0.0001). In vitro stimulation with influenza virus resulted in a further 20% increase in the proportion of CD45RA-RO- cells (P < 0.0001). The CD45RA-RO- phenotype may identify a population of cells undergoing apoptosis (programmed cell death) that limits the duration of helper T-cell (CD4+) memory after vaccination.

Adult↗
PubMed1995

Insulin-mediated increase in blood flow is impaired in the elderly.

It has recently been recognized that the ability of insulin to augment blood flow is reduced in insulin-resistant conditions such as obesity and noninsulin-dependent diabetes mellitus. Normal aging is characterized by resistance to insulin-mediated glucose uptake. We undertook the following studies with the hypothesis that the resistance to insulin-mediated glucose uptake that occurs with aging is caused in part by a reduction in insulin-mediated blood flow. These experiments were conducted on healthy young (n = 13; age, 24 +/- 1 yr; body mass index: 22.2 +/- 0.6 kg/m2) and old (n = 13; age, 77 +/- 1 yr; body mass index: 24.2 +/- 0.5 kg/m2) subjects. Each subject underwent two studies. In the control study, saline was infused for 4 h. In the euglycemic clamp study, insulin was infused for 4 h at a rate of 40 mU/m2.min in the young subjects and 34 mU/m2.min in the old subjects. Blood samples were taken, and calf blood flow was measured using venous occlusion plethysmography at regular intervals in each study. Basal calf blood flow was lower in the elderly (young subjects: 1.51 +/- .08 mL/100 mL tissue per min; old subjects: 1.15 +/- 0.07 mL/100 mL tissue per min, P < 0.002). During the euglycemic clamp studies, steady-state insulin and glucose values were similar in the two age groups. Glucose disposal rates were significantly higher in the young subjects (P = 0.01 by analysis of variance). Mean arterial pressure values were significantly higher in the elderly (P < 0.001 by analysis of variance) throughout the clamp, but there was no significant change over time in either age group. The mean incremental blood flow rate at steady-state (180-240 min) was significantly higher in the young subjects (0.76 +/- 0.23 mL/100 mL tissue per min) than in the old subjects (0.05 +/- 0.09 mL/100 mL tissue per min, P < 0.01). There was a significant correlation between steady-state glucose disposal rate values and incremental blood flow rates in the young subjects (r = 0.59, P < 0.05) but not in the old subjects (r = 0.21, P = NS). We conclude that normal aging is characterized by an impairment in the ability of insulin to modulate blood flow, which may contribute in part to the insulin resistance of aging.

Adult↗
PubMed1995

Differential effects of human and animal insulin on the responses to hypoglycemia in elderly patients with NIDDM.

Recent studies suggest that insulin-dependent diabetes mellitus patients switched from animal to human insulin may have decreased awareness of hypoglycemic warning symptoms. The risk of severe or fatal hypoglycemia associated with the treatment of diabetes increases with age. We conducted these studies to determine if awareness of hypoglycemic warning symptoms was greater with animal than with human insulin in elderly patients with diabetes. Nonobese elderly patients with non-insulin-dependent diabetes mellitus (NIDDM) (n = 13; age, 74 +/- 1 years; body mass index, 26.6 +/- 0.7 kg/m2) underwent paired hyperinsulinemic glucose clamp studies (insulin infusion rate 60 mU.m-2.min) in random order. In one study, regular human insulin was infused, and in the other study, regular beef/pork insulin was infused. In all studies, plasma glucose was decreased from fasting levels to 5 mmol/l during the first 60 min and was then allowed to fall to 4.4, 3.8, 3.3, and 2.8 mmol/l in each subsequent hour. Subjects were blinded as to which study they were undergoing. In each study, a hypoglycemic symptom checklist was administered, and counterregulatory hormones were measured every 15 min. Neuropsychological tests were performed every hour. Counterregulatory hormone responses to the two insulin preparations were similar. Autonomic (P < 0.05) and neuroglycopenic (P < 0.01) symptom scores were significantly higher during the beef/pork insulin studies. The responses on the neuropsychological tests were not significantly different. We conclude that beef/pork insulin results in greater awareness of hypoglycemic warning symptoms than does human insulin in elderly patients with NIDDM.

Aged↗
PubMed1994

The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects.

Despite similar glycemic profiles, higher insulin levels are achieved following oral versus intravenous administration of glucose. This discrepancy is due to the incretin effect and is believed to be mediated via stimulation of beta-cells by hormone(s) released from the gut. The leading gut hormone candidates are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP-1). To determine the relative insulinotropic activity of these peptides, we infused GLP-1(7-37) and GIP into normal subjects and patients with non-insulin dependent diabetes mellitus (NIDDM). In normal subjects during euglycemia, GLP-1(7-37) stimulated insulin release, whereas GIP did not. Using the Andres clamp technique, we established stable hyperglycemia for 2 h (5.4 mmol/l above the basal level). During the second hour, either GIP, GLP-1(7-37), or both were infused in normal healthy volunteers and in patients with NIDDM. In normal subjects, at a glucose level of 10.4 mmol/l, the 90-120 min insulin response was 279 pmol/l. GIP at a dose of 1, 2 or 4 pmol/kg/min augmented the 90-120 min insulin response by 69, 841 and 920 pmol/l, while GLP-1(7-37), at a dose of 1.5 pmol/kg/min augmented the insulin response by 2106 pmol/l. When both hormones were administered simultaneously, the augmentation was additive--2813 pmol/l. In the diabetic subjects, GIP had no effect, while GLP-1(7-37) augmented the insulin response by 929 pmol/l. We conclude that in normal healthy subjects, GLP-1(7-37), on a molar basis, is several times more potent than GIP at equivalent glycemic conditions. The additive insulinotropic effect suggests that more than one incretin may be responsible for the greater insulin levels observed following oral administration of glucose compared to the intravenous route. In NIDDM, GIP had no insulinotropic effect, while GLP-1(7-37) had a marked effect. This suggests that GLP-1(7-37) may have therapeutic potential as a hypoglycemic agent in NIDDM patients.

Administration, Oral↗