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Biomedical subjects

G S Meneilly

Publications and source records attributed to G S Meneilly.

At least 55 records · Page 3Linked to original sources
PubMed1994

Glibenclamide vs gliclazide in type 2 diabetes of the elderly.

The objective of this study was to compare the effect of two sulphonylureas on the frequency of hypoglycaemic events and glycaemic control in elderly patients with Type 2 diabetes. Twenty-two untreated elderly patients were treated with glibenclamide or gliclazide in a randomized double-blind fashion. Prior to treatment, a biochemical profile, an oral glucose tolerance test, and a 2-h hyperglycaemic glucose clamp (glucose 5.4 mmol l-zs-1 above baseline) were performed. Patients were seen regularly over 6 months to assess glycaemic control and the frequency of hypoglycaemic reactions. Hyperglycaemic clamp studies and oral glucose tolerance tests were repeated at 1 and 6 months. The area under the curve for the oral glucose tolerance test (glibenclamide: 15.5 +/- 0.7; gliclazide: 14.9 +/- 0.8 mmol l-1 (p = NS)) and the haemoglobin A1C (glibenclamide: 7.4 +/- 0.2%; gliclazide: 7.9 +/- 0.5% (p = NS)) were similar at 6 months. Hypoglycaemic reactions were significantly more frequent with glibenclamide than with gliclazide: 17 vs 4 (p < 0.01). Insulin sensitivity index (ml kg-1 min-1 pmol-1 x 100) was increased significantly by glibenclamide but not gliclazide (glibenclamide: 0.284 +/- 0.116 (baseline) vs 0.518 +/- 0.102 (6 months) (p < 0.05), gliclazide: 0.260 +/- 0.048 (baseline) vs 0.358 +/- 0.048 (6 months) (p = NS)). We conclude that glycaemic control was equivalent with the two drugs but the incidence of hypoglycaemic reactions was significantly greater with glibenclamide probably because this drug increases insulin sensitivity to a greater degree.

Aged↗
PubMed1994

Altered responses to hypoglycemia of healthy elderly people.

Many elderly people are treated with medications or are subjected to diseases which can cause hypoglycemia. We conducted the following studies to assess whether alterations in counterregulatory hormone release, decreased awareness of warning symptoms or alterations in psychomotor performance might increase the susceptibility of the elderly to hypoglycemia. Healthy, nonobese young (n = 10, age < 30) and old (n = 9, age > 65) subjects underwent paired hyperinsulinaemic clamp studies (insulin infusion rate 60 mU/m2.min). In the control study, glucose was kept at 5.0 mmol/L for 5 h. In the hypoglycemic study, glucose was kept at 5 mmol/L for 1 h and was lowered in stepwise fashion 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. Counterregulatory hormones were measured and a hypoglycemic symptom checklist was administered every 15 min in each study. Neuropsychological tests were performed at regular intervals. The glucose threshold for release of counterregulatory hormones was defined as the glucose level at which the values during the hypoglycemic study first exceeded values during the control study by 2 SD. The glucose threshold for glucagon and epinephrine release was higher in the young (approximately 3.3 mmol/L) than the old (approximately 2.8 mmol/L) and the epinephrine responses to hypoglycemia were also greater in the young. The threshold for release of GH (approximately 3.3 mmol/L) and norepinephrine and cortisol (approximately 2.8 mmol/L) was similar in each age group, as was the magnitude of release of these hormones. Although the variance in symptoms scores was large, the elderly appeared to have reduced awareness of the autonomic but not neuroglycopenic symptoms of hypoglycemia. There was no difference between young and old in the effect of hypoglycemia on neuropsychologic tests. We conclude that healthy elderly people may have impaired release of glucagon and epinephrine in response to hypoglycemia and reduced awareness of the autonomic symptoms of hypoglycemia.

Adult↗
PubMed1994

Counterregulatory hormone responses to hypoglycemia in the elderly patient with diabetes.

In patients with non-insulin-dependent diabetes mellitus (NIDDM), the risk of severe or fatal hypoglycemia associated with the use of oral agents or insulin increases exponentially with age. We conducted this study with the hypothesis that this increased susceptibility to hypoglycemia is caused by alterations in release of counterregulatory hormones and psychomotor performance during hypoglycemia. Ten healthy nonobese elderly subjects (74 +/- 1 years of age; body mass index, 24.5 +/- 0.6 kg/m2) and 10 nonobese elderly NIDDM subjects (72 +/- 1 years of age; body mass index, 25.6 +/- 0.9 kg/m2) underwent two hyperinsulinemic glucose clamp studies (insulin infusion, 60 mU.m-2 x min-1). In the control study, glucose was maintained at 5 mM for 5 h; in the hypoglycemic study, glucose was kept at 5 mM for 1 h and then lowered in a stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mM in each subsequent hour. At regular intervals in each study, neuropsychological tests were performed, counterregulatory hormones were measured, and a hypoglycemic symptom questionnaire was administered. At a glucose level of 2.8 mM, NIDDM patients had reduced incremental glucagon (normal subjects, 114 +/- 18 ng/l; NIDDM subjects, 63 +/- 9 ng/l; P < 0.05) and growth hormone responses (normal subjects, 13.8 +/- 1.0 micrograms/l; NIDDM subjects, 7.0 +/- 2.0 micrograms/l; P < 0.01) and increased epinephrine (normal subjects, 925 +/- 198 pM; NIDDM subjects, 4175 +/- 824 pM; P < 0.001) and cortisol responses (normal subjects, 291 +/- 49 nM; NIDDM subjects, 524 +/- 92 mM; P < 0.05). Symptom scores were similar in both groups at all levels of glycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Changes in CD45 isoform expression after influenza vaccination.

In this study, we report the changes in the isoforms of CD45 expressed on T lymphocytes after influenza vaccination. Young adults were compared to an elderly group (26 participants/group) after vaccination with influenza split-virus vaccine. Peripheral blood mononuclear cells (PBMC) obtained pre-vaccination and 6 and 12 weeks post-vaccination were cultured with live influenza virus. Unstimulated and stimulated (5-day culture with virus) PBMC were labelled with fluorescent monoclonal antibody markers for CD3, CD4, CD8, CD45RA and CD45RO. When compared to the young controls, the elderly group had a higher proportion of CD45RO+RA- and, reciprocally, a lower proportion of CD45RA+RO- cells. In spite of these differences, both groups showed a progressive increase in the proportion of CD45RA+ T lymphocytes (CD4+ and CD8+) following influenza vaccination. In vitro stimulation with influenza virus resulted in a decrease in the proportion of CD45RA+RO- with a concomitant increase in the CD45RA-RO- population, both of which were observed only at 6 weeks post-vaccination. Although the phenotype of classical memory cells for recall antigen is CD45RO+, these results suggest that memory for influenza split-virus vaccine, exists in the CD45RO- population. More importantly, it should be noted that in spite of the decline in CD45RA+ cells with aging, the elderly group showed similar changes in the proportions of all cell phenotypes in response to vaccination, and to subsequent in vitro re-exposure to the virus.

Adult↗
PubMed1993

Antibody response to whole-virus and split-virus influenza vaccines in successful ageing.

The antibody response to influenza vaccination has been variably reported to be decreased in elderly individuals. To determine the effect of ageing alone on this antibody response, a group of carefully-screened healthy elderly subjects were compared with young adult controls. Antibody titres for several strains of influenza were measured before and after vaccination with whole-virus (WVV) and split-virus influenza vaccines (SVV) in two successive years. In general, the antibody response to WVV was greater than the response to SVV. Both groups showed a similar response to the H3N2 strain but the elderly group showed a lower response to the H1N1 and B strains of virus contained in the vaccine. Antibodies to older strains of influenza A but not B were stimulated by vaccination with SVV. In the elderly group, the response to older viral strains was relatively increased compared with newer strains. In contrast, the young control group had better antibody responses to the newer than to the older strains of influenza tested. Reductions in the antibody response to influenza vaccination may, therefore, be related to the phenomenon of original antigenic sin and the cohort effect of exposure to H1N1 during childhood in the elderly group studied. The increased immunogenicity of WVV must be considered in light of the current wide use of SVV in the elderly.

Adult↗
PubMed1993

The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes.

BACKGROUND: A number of studies have found that cognitive function is impaired in elderly patients with non-insulin dependent diabetes mellitus (NIDDM) when compared with age-matched non-diabetic controls. In addition, it has been reported that elderly NIDDM patients who have poor glycemic control have a greater impairment in cognition that elderly NIDDM patients with good control. We conducted the following prospective study to determine if improved glycemic control would result in an improvement in cognitive function in elderly patients with NIDDM: METHODS: Sixteen untreated elderly patients with NIDDM underwent a battery of neuropsychologic tests on two occasions, separated by at least two weeks. They were then started on an oral hypoglycemic agent. After they had been on a stable dose of medication for 6 months the neuropsychologic tests were repeated. RESULTS: Fasting glucose decreased significantly after treatment (before: 13.8 +/- 1.2 mmol/l; after 8.4 +/- 0.4 mmol/l, p < .01). After 6 months of treatment patients had improvement in their scores on the Grooved Pegboard, Trail Making-Part A, Stroop-Word Naming, Cued Recall and Picture Arrangement tests (all p < .05). CONCLUSIONS: Improved glycemic control in the elderly patient with NIDDM may have beneficial effects on selective areas of cognition.

Affect↗
PubMed1993

Alterations in glucose metabolism in patients with Alzheimer's disease.

OBJECTIVE: To determine the alterations in glucose metabolism that occur in patients with Alzheimer's Disease (AD). DESIGN: Cross-sectional comparison of AD and healthy controls. SETTING: A University teaching hospital. PATIENTS: Healthy controls (n = 14, BMI: 24.9 +/- 0.5 kg/M2, age 73 +/- 1 years) and patients with AD (n = 12, BMI: 23.9 +/- 1.0 kg/M2, age 72 +/- 1 years). All controls and patients with AD had a normal history and physical examination, a negative family history of diabetes, and took no medications. MEASUREMENTS: All patients and controls underwent an assessment of their dietary intake and physical activity, a 3-hour oral glucose tolerance test (OGTT), and a 2-hour hyperglycemic glucose clamp study. RESULTS: Total caloric intake (AD: 27.1 +/- 1.3 kcal/kg/day; CONTROL: 23.6 +/- 1.6 kcal/kg/day; P = ns) and intake of complex carbohydrates (AD: 5.9 +/- 0.4 kcal/kg/day; CONTROL: 6.5 +/- 0.3 kcal/kg/day; P = ns) were not different between groups. Leisure time physical activity was greater in controls (AD: 2970 +/- 411 kcal/week; CONTROL: 5229 +/- 864 kcal/week; P < 0.05). Patients with AD had higher fasting glucose (AD: 5.9 +/- 0.2 mmol/L; CONTROL: 5.1 +/- 0.1 mmol/L; P < 0.01) and insulin (AD: 144 +/- 20 pmol/L; CONTROL: 100 +/- 6 pmol/L; P < 0.05) values. In response to the OGTT, the area under the curve for glucose and insulin was similar in both groups. During the hyperglycemic clamp, steady-state glucose values were higher in the Alzheimer's patients (AD: 11.5 +/- 0.2 mmol/L; CONTROL: 10.9 +/- 0.1 mmol/L, P < 0.01). First- and second-phase insulin responses were similar in each group. The insulin sensitivity index (units: mL/kg.min per pmol/L x 100), a measure of tissue sensitivity to insulin, was reduced in the patients with AD (AD: 0.59 +/- 0.06; CONTROL: 0.79 +/- 0.07; P < 0.05). CONCLUSIONS: We conclude that early AD is characterized by alterations in peripheral glucose metabolism, which may relate, in part, to alterations in physical activity.

Aged↗
PubMed1993

The effect of glyburide on beta-cell sensitivity to glucose-dependent insulinotropic polypeptide.

OBJECTIVE: To assess whether treatment with glyburide alters beta-cell sensitivity to GIP in NIDDM patients. RESEARCH DESIGN AND METHODS: We studied 5 untreated NIDDM patients in a meal study (Ensure, 240 ml/M2) and a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above fasting). From 60 to 120 min of the clamp, GIP was infused in a primed continuous manner at a rate of 2 pmol.kg-1 x min-1. Subjects then were treated with glyburide. After they had been on a stable dose of medication for 1 mo, the meal study and glucose clamp studies were repeated. RESULTS: In response to treatment, a decrease in fasting glucose and an increase in weight was observed (12.8 +/- 1.8 vs. 8.5 +/- 0.8 mM and 74.3 +/- 6.3 vs. 76.1 +/- 6.3 kg, respectively, P < 0.05). In response to the meal study, the AUC for glucose was less, for insulin was increased, and for GIP was unchanged after treatment (16.9 +/- 2.1 vs. 12.6 +/- 6.9 mM, P < 0.05; 161 +/- 47 vs. 242 +/- 60 pM, P < 0.05; and 199 +/- 22 vs. 219 +/- 18 pM, respectively). During the hyperglycemic clamp, steady-state glucose and 90- to 120-min GIP values were equivalent before and after treatment (18.0 +/- 1.3 vs. 18.3 +/- 1.3 mM and 302 +/- 59 vs. 298 +/- 37 pM, respectively). The 90-120 min insulin responses to the hyperglycemic clamp were greater after therapy (123 +/- 37 vs. 283 +/- 80 pM, P < 0.05) reflecting increased beta-cell responses to GIP. CONCLUSIONS: We conclude that glyburide enhances beta-cell sensitivity to GIP.

Adult↗
PubMed1993

Alterations in glucose metabolism in the elderly patient with diabetes.

OBJECTIVE: To determine the alterations in glucose metabolism in elderly patients with NIDDM. RESEARCH DESIGN AND METHODS: We studied 9 healthy elderly control subjects (73 +/- 1 yr of age; body mass index 25.7 +/- 0.4 kg/m2) and 9 untreated elderly NIDDM patients (72 +/- 2 yr of age; BMI 25.9 +/- 0.5 kg/m2). Each subject underwent a 3-h oral glucose tolerance test (40 g/m2); a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above basal); and a 4-h euglycemic insulin clamp (40 mM.m2.min-1). Tritiated glucose methodology was used to measure glucose production and disposal rates during the euglycemic clamp. RESULTS: Patients with NIDDM had a higher fasting glucose (9.3 +/- 0.3 vs. 5.1 +/- 0.1 mM in control subjects vs. NIDDM patients, respectively, P < 0.001) and a greater area under the curve for glucose during the OGTT (16.0 +/- 0.6 vs. 6.7 +/- 0.3 mM in control subjects vs. NIDDM patients, respectively, P < 0.01) than the healthy control subjects. During the hyperglycemic clamp, patients with NIDDM had an absent first-phase insulin response (112 +/- 6 vs. 250 +/- 31 pM in control subjects vs. NIDDM patients, respectively, P < 0.01), and a blunted second-phase insulin response (159 +/- 11 vs. 337 +/- 46 pM in control subjects vs. NIDDM patients, respectively, P < 0.01). Before the euglycemic clamp, fasting insulin (99 +/- 5 vs. 111 +/- 10 pM in control subjects vs. NIDDM patients, respectively) and hepatic glucose production (11.8 +/- 0.7 vs. 11.5 +/- 0.5 mumol.kg-1-min-1 in control subjects vs. NIDDM patients, respectively) were similar. Steady-state (180-240 min) glucose disposal rates during the euglycemic clamp were slightly, but not significantly, higher in the normal control subjects (36.5 +/- 1.1 vs. 33.1 +/- 1.9 mumol.kg-1-min-1 in control subjects vs. NIDDM patients, respectively, NS). CONCLUSIONS: We conclude that NIDDM in nonobese elderly subjects is characterized by a marked impairment in insulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the beta-cell. When compared with age-matched control subjects, the NIDDM patients showed no increase in fasting insulin or hepatic glucose production, and insulin resistance was mild.

Aged↗
PubMed1992

The effect of influenza vaccination on IL2 production in healthy elderly: implications for current vaccination practices.

Age-related senescence of T-cell mediated responses is well recognized. This study was designed to determine how aging affects the T-cell mediated Interleukin 2 (IL2) response to influenza vaccination. A group of healthy elderly individuals were compared to a control group of healthy young adults for their response to the 1990 influenza vaccine. Cultures of peripheral blood mononuclear cells (PBMC) were prepared from venous blood samples taken prevaccination (pre) and 8 and 12 weeks post-vaccination (post). PBMC cultures stimulated with inactivated A/Shanghai/16/89 (contained in the 1990 vaccine) and A/Philippine/2/82 (not contained in the vaccine) were assayed for peak IL2 activity. We find that after influenza vaccination, there was an insignificant increase in IL2 activity when PBMC from the young control group were stimulated with A/Shanghai/16/89 (pre, 5.14 U/mL/10(6) PBMC; post, 6.64 U/mL/10(6) PBMC) but there was a significant increase in IL2 activity when stimulated with A/Phillippine/2/82 (pre, 1.5 U/mL/10(6) PBMC; post, 8.3 U/mL/10(6) PBMC). In similar cultures of PBMC from the elderly group, there was a significant increase in IL2 response to both A/Shanghai/16/89 (pre, 1.6 U/mL/10(6) PBMC; post, 3.5 U/mL/10(6) PBMC) and A/Philippine/2/82 (pre, 0.86 U/mL/10(6) PBMC; post, 8.3 U/mL/10(6) PBMC). Measurements of CD4+/CD8+ populations were not affected by vaccination and were not significantly different in the two groups. Subgroup analysis of the elderly group revealed that previous influenza vaccination in 1989 did not significantly affect IL2 levels measured in the present study. This study shows that in healthy elderly, influenza vaccination effectively restores IL2 activity to normal. There appears to be an age-related decrease in the duration of T-cell memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A pilot study of anabolic steroids in elderly patients with hip fractures.

OBJECTIVE: To determine the safety and efficacy of the anabolic steroid nandrolone in elderly patients with hip fractures. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: The orthopedic ward of a university teaching hospital. PARTICIPANTS: 29 frail elderly females with hip fractures. INTERVENTION: Subjects received nandrolone 2 mg/kg (n = 15) or placebo (n = 14) by weekly injection for 4 weeks or until discharge. MEASURES: Baseline functional status was assessed by the Lawton-Brody ADL and IADL. Hemoglobin, transferrin, thyroid-binding prealbumin, albumin, liver function tests, creatinine, weight, MAMC, bioelectric impedance, standard anthropometrics and grip strength were measured at baseline and weekly intervals. Rehabilitation parameters and length of stay were recorded. RESULTS: The placebo and nandrolone groups were similar in age, although the control group had slightly higher baseline ADL scores. There was no difference between groups in biochemical parameters, anthropometrics, body composition, grip strength, rehabilitation end points or length of stay. One subject in the nandrolone group had a doubling of AST and was withdrawn from the study. CONCLUSIONS: Nandrolone can be given safely to frail elderly subjects with hip fractures but is likely to be of minimal benefit at the doses we employed.

Activities of Daily Living↗
PubMed1991

Blood pressure, pulse, and neurohumoral responses to nitroprusside-induced hypotension in normotensive aging men.

In order to assess the effects of age on blood pressure, pulse, and neurohumoral responses to hypotensive stress, we infused nitroprusside into healthy young and old men until mean arterial blood pressure was reduced 20% from basal. Elderly subjects were much more sensitive to nitroprusside. Pulse increases in response to this hypotensive stress were markedly reduced in the elderly, but renin, vasopressin, and norepinephrine responses were not different between young and old. We conclude that cardioacceleration, one of the primary defenses against hypotension, is impaired with age. However, neurohumoral responses to hypotension are intact in the elderly.

Adult↗
PubMed1989

Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy.

Phenytoin sodium has been used to treat muscle cramps of diverse causes, and is known to increase insulin sensitivity during long-term use. We have previously described a syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy with continual muscle cramping. The effect of 300 mg/d of phenytoin (Dilantin) on muscle cramping and carbohydrate economy was studied in three affected patients and four control subjects. Oral glucose tolerance tests, euglycemic insulin infusion studies, and monocyte insulin binding tests were conducted before and after phenytoin administration. All three patients had notable improvement in muscle cramps. In response to phenytoin, metabolic improvements were variable, with improvement characteristically better in patients with less severe baseline metabolic abnormalities. Patient 1, with the mildest degree of glucose intolerance, had decreased fasting insulin and blood glucose levels, improved glucose tolerance, and insulin-mediated glucose disposal, associated with an increase in monocyte insulin receptors. Patient 2 had reduced fasting plasma glucose and insulin levels and improved oral glucose tolerance, suggesting a beneficial effect on carbohydrate metabolism. Patient 3, with the most severely impaired carbohydrate economy, showed no metabolic improvement despite marked lessening of muscle pain. These clinical characteristics were unaffected in control subjects. We conclude that phenytoin is of value in the therapy of muscle cramps and glucose intolerance in patients with this syndrome.

Acanthosis Nigricans↗
PubMed1989

Effect of insulin on plasma norepinephrine and 3,4-dihydroxyphenylalanine in obese men.

Increasing evidence relates serum insulin level and blood pressure in obese individuals. Although the connection between these two factors is not established, a common presumption is that the sympathetic nervous system is somehow involved, in part, because laboratory studies demonstrate insulin stimulation of sympathetic and cardiovascular activity. Because the obese may exhibit altered responsiveness to insulin action, the current investigation compared cardiovascular and neurohumoral responses to euglycemic insulin infusion (200 mU/m2/min) in obese and lean men. At baseline, obese men displayed higher glucose and insulin levels, faster pulse rates, and elevated mean arterial pressures (MAP) than lean controls; plasma norepinephrine (NE) and 3,4-dihydroxyphenylalanine (DOPA) concentrations, however, did not differ. During insulin infusion, pulse rate increased equally in obese and lean subjects (from 69 to 78 min-1 in obese and from 56 to 66 min-1 in lean subjects), while MAP remained unchanged in both groups. Elevations in plasma NE (+85 pg/mL in obese and +109 in lean pg/mL) and reductions in plasma DOPA (-233 pg/mL in obese and -376 pg/mL in lean) did not differ between groups. Sodium excretory rate decreased during insulin infusion in lean subjects by 2.2 mEq/h but increased in obese by 5.3 mEq/h (difference in response between groups, P = .024). Thus, in these obese men, cardiovascular and sympathetic responses to insulin persist despite evidence of moderate insulin resistance; increased sympathetic activity, as a cause for the resting tachycardia and borderline hypertension at baseline, seems unlikely.

Adult↗
PubMed1989

Escape of hepatic glucose production during hyperglycemic clamp.

The role of the pattern of insulin secretion on hepatic glucose production (HGP) was evaluated with hyperglycemic and euglycemic clamp studies in six normal young nonobese subjects. In the hyperglycemic studies, glucose levels were raised and maintained at 98 mg/dl above basal for 150 min. Each subject responded with a biphasic pattern of immunoreactive insulin (IRI) release. HGP was completely suppressed by 20 min, coincident with the first-phase insulin release. HGP then rose steadily, surpassing the basal rate by 100 min when IRI had reached the peak levels of the first phase. By 130 min, when IRI had surpassed the peak first-phase levels, HGP began to fall. In the euglycemic studies with a square wave of hyperinsulinemia (approximately 25 microU/ml), HGP was suppressed to approximately 60% of basal and remained at that rate. We next repeated the hyperglycemic studies with somatostatin, glucagon, and insulin infusions. In these studies with a square wave of hyperinsulinemia (approximately 40 microU/ml, the level observed during the first phase IRI of the previous hyperglycemic clamps), HGP was suppressed to approximately 43% of basal rate and remained at that rate. These studies indicate insulin regulation of HGP is not only dependent on insulin level but may be strongly influenced by the pattern, over time, of insulin secretion.

Adult↗
PubMed1989

Impairment of noninsulin-mediated glucose disposal in the elderly.

While normal aging is characterized by resistance to insulin-mediated glucose disposal (IMGU), the effect of age on noninsulin-mediated glucose disposal (NIMGU), which is responsible for the majority of basal glucose uptake, has not been completely evaluated. These studies were conducted on healthy nonobese young (n = 10; age, 20-30 yr) and old (n = 10; age, 62-80 yr) men. Each subject underwent two paired studies in random order. In all studies a [3H]glucose infusion was used to measure glucose uptake and production rates, and somatostatin (500 micrograms/h) was infused to suppress endogenous insulin release. In study A, plasma glucose was kept close to fasting levels (approximately 5.6 mmol/L) using an euglycemic clamp protocol for 4 h. Plasma insulin decreased to less than 20 pmol/L within 15 min and remained suppressed thereafter in all studies. Steady state (15-240 min) plasma glucagon levels were slightly greater in the elderly [young, 86 +/- 5 (+/- SE); old, 98 +/- 2 ng/L; P less than .05]. Basal glucose uptake was similar in both groups (young, 877 +/- 21; old, 901 +/- 24 mumol/min). Glucose uptake during the last hour of the study (180-240 min) was used to represent NIMGU, because insulin action was assumed to be absent by this time. NIMGU was less in the elderly (young, 744 +/- 18; old, 632 +/- 32 mumol/min; P less than 0.01). In study B, plasma glucose was kept at about 11 mmol/L for 4 h using a hyperglycemic clamp protocol. Plasma insulin decreased to less than 20 pmol/L within 15 min and remained suppressed thereafter in all studies. Steady state plasma glucagon levels were slightly but not significantly higher in the elderly (young, 88 +/- 6; old, 100 +/- 4 ng/L). Basal glucose uptake (young, 910 +/- 27; old, 883 +/- 25 mumol/min) and NIMGU (young, 933 +/- 36; old, 890 +/- 16 mumol/min; P = NS) were similar in both young and old subjects. We conclude that aging is associated with impairment in NIMGU only in the basal state, which may explain in part the increase in fasting glucose with age.

Adult↗
PubMed1988

Insulin-mediated hypokalemia and paralysis in familial hypokalemic periodic paralysis.

To elucidate a potential role for insulin-mediated extra-renal potassium disposal in the clinical syndrome of hypokalemic periodic paralysis, an obese affected man was studied using the euglycemic insulin clamp, which, in normal and obese subjects, produces predictable, insulin dose-dependent declines in plasma potassium levels. During a 20 mU/m2/minute euglycemic clamp (insulin level, 88 microU/ml) procedure, while the patient with hypokalemic periodic paralysis demonstrated severe resistance to insulin-mediated glucose uptake (glucose uptake 50 percent of that of normal control subjects, n = 17), his plasma potassium declined to a degree similar to that seen in normal subjects. During a subsequent higher dose, 200 mU/m2/minute insulin infusion (insulin level, 914 microU/ml), plasma potassium declined to 2.5 meq/liter, a value significantly below that seen in normal (n = 19) (3.3 +/- 0.1 meq/liter) and obese (n = 6) (3.2 +/- 0.1 meq/liter) subjects. During this study, paralysis began in the patient's hand and forearm at the potassium nadir and lasted three hours, despite restoration of normokalemia 30 minutes after paralysis began. Glucose disposal rates during this high-dose insulin infusion were one-half that seen in lean control subjects (n = 19) and similar to those in obese control subjects. If these findings are representative of hypokalemic periodic paralysis and can be generalized to larger numbers of patients, they indicate several new features of this syndrome. The ability of insulin to induce hypokalemia is enhanced in this syndrome even in the presence of marked coexistent obesity-related resistance to the action of insulin to promote glucose utilization. Enhanced sensitivity of potassium uptake systems to activation by insulin (and other factors) may be a central feature of this syndrome. Additionally, paralytic hypokalemia can be induced during a euglycemic insulin clamp procedure, which could be utilized as a diagnostic test for this syndrome.

Adult↗