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Biomedical subjects

A N Peiris

Publications and source records attributed to A N Peiris.

At least 19 recordsLinked to original sources
PubMed1996

Interstitial insulin during euglycemic-hyperinsulinemic clamp in obese and lean individuals.

Transcapillary insulin transport has been considered a rate-limiting step of insulin action. However, direct measurement of interstitial insulin levels during physiologic levels of insulinemia have not been performed. We determined changes in interstitial insulin in eight healthy non-obese men and seven healthy obese men by microdialysis during a euglycemic-hyperinsulinemic clamp. Interstitial insulin was determined in the subcutaneous tissue of the abdomen and thigh. Steady-state insulin concentrations were reached approximately 10 minutes after the start of insulin infusion in the subcutaneous tissue of the abdomen and thigh and returned to basal levels approximately 10 minutes after the infusion was discontinued. There was no difference in the rapidity of change in interstitial insulin between obese and lean individuals at either site studied, irrespective of the pattern of fat distribution. The relative change in dialysate insulin concentration during the euglycemic clamp did not differ between obese and lean individuals at either site studied. It was also unaffected by the waist to hip ratio. The rapid change in interstitial insulin concentration could be of physiologic significance in determining the effects of changes in circulating insulin concentration. We conclude that transcapillary insulin transport in adipose tissue is unaffected by obesity and the pattern of fat distribution in healthy men. It is also concluded that when interstitial insulin is determined directly, transcapillary insulin transport is rapid and does not demonstrate a significant lag phase.

Adult↗
PubMed1995

The effect of body fat distribution on pulmonary function tests.

Although the influence of obesity on pulmonary function tests has been examined, the role of body fat distribution has received limited attention. Pulmonary studies of patients severely affected by upper body obesity suggest they have more severely compromised lung volumes than obese patients with lower body obesity. We examined 42 healthy but normal or mildly obese men to determine if body fat distribution influences pulmonary function tests. Multiple measures of adiposity showed a significant inverse relationship with both spirometry and static lung volumes. However, the biceps skinfold thickness had the strongest inverse relationship with total lung capacity (TLC) compared to other anthropometric measures. The waist-to-hip ratio (WHR) demonstrated a significant inverse relationship with static lung volumes only when controlling for cigarette smoking. However, comparing pulmonary function tests between patients with a WHR less than 0.950 (lower body fat distribution) and subjects with a WHR of 0.950 or greater (upper body fat distribution) revealed that FVC, FEV1, and TLC were significantly lower in the patients with upper body fat distribution. Stepwise multiple regression analysis was done using all anthropometric variables and age which generated predictive equations that included the biceps skinfold thickness for residual volume (RV) and TLC. This suggests that upper body fat distribution may be associated with a modest impairment of lung volumes in normal and mildly obese men. Until the findings of this study can be applied to a larger, ethnically and anthropometrically diverse population, and to women, we believe caution is warranted when standard equations are used to predict pulmonary function tests in an anthropometrically diverse population.

Adipose Tissue↗
PubMed1994

Lack of delay in hepatic insulin transit as indicated by concordance of insulin secretory and peripheral insulin pulses.

The liver is an important site of insulin metabolism and action. It has often been assumed that the liver may diminish the amplitude of the insulin secretory waveform without altering hepatic insulin transit time. However, the significant extraction and metabolism of hepatic insulin has the potential to delay hepatic insulin transit. To examine hepatic insulin transit, we studied the concordance of calculated insulin secretory peaks with peripheral insulin peaks in 12 healthy men of varying body weight and fat distribution. Adiposity was determined by percent body fat, and fat distribution by the waist to hip ratio. Arterialized peripheral venous samples for insulin and C-peptide assays were obtained every 2 minutes for 90 minutes. Pancreatic insulin secretion rates were estimated with individual C-peptide kinetics using a two-compartment model. Concordance between insulin secretory peaks and peripheral insulin peaks was assessed by the hypergeometric probability model. A significant concordance between secretory and peripheral insulin pulses was demonstrated in seven of 12 subjects (P < .00001). The mean pulse intervals for insulin secretion were similar to the mean pulse intervals for peripheral insulin. The degree of concordance between the insulin secretory peaks and peripheral insulin pulses was unrelated to adiposity or body fat distribution. Significant synchronicity exists between insulin secretory peaks and peripheral insulin peaks in healthy men. We conclude that despite significant hepatic insulin extraction and metabolism, hepatic insulin transit may not be delayed in healthy men.

Adult↗
PubMed1993

Drug-induced disorders of glucose tolerance.

PURPOSE: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism. DATA SOURCES: Data were obtained from a MEDLINE search back to 1966 and included animal and human studies published in the English language. STUDY SELECTION: Approximately 80% of original publications were included after review by the authors. Case reports were included if they provided additional information. DATE EXTRACTION: The original data from the literature were included on the basis of independent extraction by the authors. DATA SYNTHESIS: Many common therapeutic agents influence glucose metabolism. Multiple mechanisms of action on glucose metabolism exist through pancreatic, hepatic, and peripheral effects. Based on circumstances at the time of use, a drug may cause both hyper- and hypoglycemia in a patient. The patient's previous pancreatic reserve, nutritional state, use of other medication, or exposure to alcohol may influence the direction of the plasma glucose alterations. CONCLUSION: Hyperinsulinemia and insulin resistance form an intrinsic component of diabetes, hyperlipidemia, and atherosclerotic vascular disease (syndrome X). The induction of hyperinsulinemia and insulin resistance by medication may therefore counteract intended benefits. An extensive review of recent medication in patients with disorders of glucose tolerance and the avoidance of polypharmacy are recommended. It is prudent to monitor plasma glucose values when it is not possible to avoid prescription of medication with known effects on carbohydrate metabolism.

Animals↗
PubMed1993

Lack of insulin feedback inhibition in non-obese and obese men.

The existence of insulin feedback inhibition is a controversial issue. The present study adopted a novel approach to determine whether insulin feedback inhibition exists in vivo during physiologic hyperinsulinemia and if it could contribute to enhanced insulin secretion in obesity. Serial plasma insulin and C-peptide levels were determined during a basal state and a hyperinsulinemic clamp (287 pmol/min/m2) and following discontinuation of the insulin infusion under euglycemic conditions. Insulin secretion rates were derived from plasma C-peptide levels and individual C-peptide kinetics using a two-compartment model. Eight non-obese and nine obese men were recruited for the studies, which were performed in random order. Men with significant variations in glucose levels during hyperinsulinemia were excluded from the analysis. Plasma glucose levels were similar between the non-obese and obese groups during all phases of the study, and similar plasma insulin levels were achieved in both groups during euglycemic hyperinsulinemia. In obese men, C-peptide levels were significantly greater compared with non-obese men during euglycemic hyperinsulinemia (P < .05). However, neither the non-obese nor the obese group demonstrated significant suppression of insulin secretion rates during euglycemic hyperinsulinemia. Expressing the data in absolute terms or as a percent of basal did not alter the results. Moreover, there was no significant change between the non-obese and the obese group during the rapid onset and cessation of hyperinsulinemia. Under euglycemic conditions, physiologic hyperinsulinemia does not induce suppression of endogenous insulin secretion in non-obese or obese men.

Adult↗
PubMed1993

Relationship of insulin secretory pulses to sex hormone-binding globulin in normal men.

Insulin has emerged as a regulator of sex hormone-binding globulin (SHBG) production in vitro and in vivo. A role for insulin in regulating SHBG exists in insulin resistant states such as obesity and polycystic ovary syndrome. The relationship of in vivo insulin secretion rates to SHBG levels in healthy normal men is less well documented. Hepatic synthesis of SHBG may be influenced by quantitative insulin exposure as well as qualitative characteristics such as frequency and amplitude of insulin secretory pulses. The present study was undertaken to assess these relationships in 10 normal men. Adiposity was determined by the body mass index and fat distribution by the waist hip ratio. Peripheral insulin sensitivity was determined by the euglycemic clamp technique at an insulin infusion rate of 287 pmol/min.m2. SHBG levels were determined in the fasting state by RIA. Arterialized venous samples for C-peptide were obtained every 2 min for 90 min in the basal state. Individual C-peptide kinetics were derived after a bolus injection of biosynthetic human C-peptide and a previously validated two compartmental model. Insulin secretion rates at each time point were calculated using the plasma C-peptide values and the C-peptide kinetics. Insulin secretion rates were unrelated to SHBG concentrations (r = -0.29, P > 0.05). The insulin secretory pulse interval had a significant positive association with SHBG levels (r = 0.86, P < 0.05). Insulin secretory pulse amplitude, body mass index, waist hip ratio, and peripheral insulin sensitivity were not associated with SHBG concentrations in a regression analysis. We postulate that insulin secretory pulse frequency may be an important determinant of SHBG synthesis in normal man.

Adipose Tissue↗
PubMed1992

Body fat distribution and peripheral insulin sensitivity in healthy men: role of insulin pulsatility.

Abdominal fat distribution is associated with insulin resistance in healthy young men. Factors modulating this phenomenon remain unclear. Pulsatile insulin release has been implicated as a potential regulator of insulin action. The relationship of pulsatility of peripheral insulin levels to fat distribution and peripheral insulin sensitivity was examined in 10 healthy men. Fat distribution was determined by the waist to hip ratio. Peripheral insulin sensitivity was assessed by the euglycemic clamp at an insulin infusion rate of 287 pmol/min.m2. Pulsatility of insulin was assessed by sampling every 2 min for 90 min in the basal state. The characteristics of insulin pulses were assessed by the computer program Pulsar. The waist to hip ratio was negatively associated with insulin sensitivity (r = -0.70, P less than 0.05) and insulin pulse interval (r = -0.66, P less than 0.05). The insulin pulse interval was positively correlated with peripheral insulin sensitivity (r = 0.73, P less than 0.05). The insulin interpulse interval was the primary determinant of insulin sensitivity. The increased frequency of insulin pulses may play a role in inducing insulin resistance in individuals with abdominal fat distribution.

Abdomen↗
PubMed1991

Relationship of regional fat distribution and obesity to electrocardiographic parameters in healthy premenopausal women.

Abdominal obesity is an independent cardiovascular risk factor. The coexistence of abdominal obesity and electrocardiographic abnormalities may facilitate the development of cardiac arrhythmias and sudden death. We determined the relationship of body fat distribution and obesity to ECG indices in 27 obese premenopausal women on an isocaloric diet. Intra-abdominal fat distribution was assessed by computerized tomography, and obesity was assessed by hydrostatic weighing. The PR, QRS, and QTc intervals, the P and QRS axes, and the P-QRS angle were determined from a resting electrocardiogram. Cardiovascular risk profile was assessed by systolic and diastolic blood pressure and plasma cholesterol and triglyceride levels. Increased deposition of intra-abdominal fat was significantly associated with prolongation of the QTc interval independent of obesity and other cardiovascular risk factors. The prolongation of the QTc interval seen with increasing intra-abdominal fat distribution may enhance susceptibility to cardiac arrhythmias. These subjects should have electrocardiographic monitoring during periods of weight loss achieved by intensive regimens.

Abdomen↗
PubMed1989

Adiposity, fat distribution, and cardiovascular risk.

STUDY OBJECTIVE: To determine the relative importance of adiposity and fat distribution to cardiovascular risk profile. DESIGN: A cross-sectional study. SETTING: Clinical research center funded by the National Institutes of Health. PATIENTS: Convenience sample of 33 healthy premenopausal women with a wide range of body weight who did not have diabetes mellitus, hirsutism and virilism, gynecologic disorder, cardiac disease, or hypertension. Women participating in exercise or dietary programs or taking medication were excluded. All subjects completed the study. INTERVENTIONS: Total body fat mass was determined by hydrostatic weighting, and fat distribution was assessed by subscapular skinfold thickness, subscapular-to-triceps skinfold ratio, the waist-to-hip ratio, and computed tomography. Cardiovascular risk was assessed by the serum insulin response during oral glucose stimulation; levels of triglycerides and total cholesterol; high-density lipoprotein cholesterol to total cholesterol concentrations; and systolic and diastolic blood pressures. MEASUREMENTS AND MAIN RESULTS: The anthropometric parameters chosen were significantly associated with the cardiovascular risk profile (P less than 0.001). Visceral fat distribution assessed by computed tomography accounted for a significantly greater degree of variance in the cardiovascular risk factors than the total body fat mass (P less than 0.05). The cumulative insulin response was the primary metabolic variable relating the anthropometric indices to cardiovascular risk. CONCLUSIONS: Intra-abdominal fat deposition constitutes a greater cardiovascular risk than obesity alone. Hyperinsulinemia may constitute an important component of the increased cardiovascular risk of abdominal obesity.

Adipose Tissue↗
PubMed1989

Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus.

Our studies support the view that body fat distribution and the accompanying metabolic abnormalities could be exacerabated by variability in the androgenic/estrogenic balance. Sensitivity to the androgenic milieu might be initiated by an early developmental aberration in sexual dimorphism. The possible direct and indirect sites of interaction between androgenic activity and the abnormal metabolic pathways in upper body obesity are summarized in Figure 19.

Adipose Tissue↗
PubMed1989

The relationship of insulin to sex hormone-binding globulin: role of adiposity.

The role of adiposity in the relationship of insulin to sex hormone-binding globulin (SHBG) concentration was examined in 31 healthy premenopausal women of varying body weight. Fat mass was estimated by hydrostatic weighing. Concentrations of SHBG and testosterone (T) and cumulative insulin response during an oral glucose tolerance test were measured. The cumulative insulin response was inversely related to SHBG (r = -0.56, P less than 0.01). The relationship between SHBG and cumulative insulin response remained significant (r = -0.47, P less than 0.01) after adjusting for fat mass and T. The fat mass correlated significantly with SHBG (r = -0.51, P less than 0.01). The relationship of SHBG to fat mass remained significant after adjusting for T (r = -0.45, P less than 0.01). However, the relationship between fat mass and SHBG was no longer significant (r = -0.34, P greater than 0.05) after adjusting for cumulative insulin response. Hyperinsulinemia may play an important role in the progressive reduction of SHBG observed with increasing adiposity.

Adult↗
PubMed1989

Health risks of obesity.

Evidence implicating obesity as a risk-factor disease is critically reviewed. Possible reasons for the many conflicting findings are addressed. The classification of obesity, based upon the site of body fat distribution, and possible biologic mechanisms associating regional adiposity with morbidity, are discussed.

Adipose Tissue↗
PubMed1989

Relative contribution of obesity and body fat distribution to alterations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women.

Obesity and fat topography are risk factors for hyperinsulinemia, insulin resistance, and diabetes mellitus. The relative contribution of obesity and body fat distribution indices to fasting and oral glucose-stimulated C peptide, insulin, and glucose concentrations were determined in 33 healthy premenopausal women. Obesity level was assessed by hydrostatic weighing and fat topography by computerized tomography-derived intraabdominal fat area, waist to hip ratio, subscapular skinfold thickness and the ratio of subscapular to triceps skinfold thickness. Both fat mass and regional fat distribution indices were associated closely with changes in insulin secretion. Fat topography indices were more closely correlated (p less than 0.001) to insulin response than were fat mass indices (p less than 0.01). The subscapular skinfold thickness had the greatest integrity for reflecting fat mass and fat distribution as they relate to the metabolic profile. The subscapular skinfold thickness may help identify individuals at risk for noninsulin dependent diabetes mellitus.

Adipose Tissue↗
PubMed1989

The relative contributions of hepatic and peripheral tissues to insulin resistance in hyperandrogenic women.

Insulin resistance is associated with hyperandrogenic states. To determine the mechanisms by which androgen excess can affect insulin action, we studied insulin sensitivity in five nonobese hyperandrogenic women and six normal women. After oral glucose administration, the hyperandrogenic women had higher serum insulin concentrations than the normal women (P = 0.05). The mean cumulative peripheral serum insulin response in the hyperandrogenic women [79.6 +/- 30.8 (+/- SD) nmol/L.300 min] was significantly greater than that in the normal women (46.6 +/- 15.1 nmol/L.300 min; P less than 0.05). In the basal state and during hyperinsulinemic (20 mU/min.m2) euglycemic clamp studies serum insulin levels were similar in the two groups. Basal and insulin-mediated suppressions of hepatic glucose production determined from [3-3H]glucose specific activity were similar in the two groups. Peripheral glucose utilization was markedly diminished in the hyperandrogenic women compared to that in the normal women (27.8 +/- 6.7 vs 48.9 +/- 12.8 mumol/min.kg fat-free mass; P less than 0.01). We conclude that the insulin resistance in nonobese hyperandrogenic women is due to peripheral, but not hepatic, resistance to the action of insulin. This marked peripheral insulin resistance may result from the effects of hyperandrogenemia on skeletal muscle fiber morphology and metabolism.

Adult↗
PubMed1988

Relationship of anthropometric measurements of body fat distribution to metabolic profile in premenopausal women.

Regional fat distribution has emerged as an independent predictor of metabolic aberrations including glucose intolerance, hyperinsulinemia, insulin resistance, hyperlipidemia and hypertension. We investigated the comparative efficacy of various body fat distribution indices in predicting these aberrations. The relationship of circumferential ratios, skinfold measurements, and computerized tomography (CT)-derived indices of intra- and extra-abdominal fat distribution to the metabolic variables and blood pressure was examined in a cohort of healthy premenopausal women. All indices denoting preponderance of fat in the central, upper body or abdominal region were predictive of the metabolic profile. The subscapular skinfold, subscapular-triceps ratio, waist-hip ratio (WHR), and the CT derived intra-abdominal fat area (CT-IFA) were closely related to alterations in glucose and insulin concentrations independent of age and obesity. The WHR and CT-IFA were better predictors of plasma triglyceride levels and blood pressure profile and thus the overall aberrations than skinfold measurements. Despite a high degree of intercorrelation between the anthropometric indices measured, only the relationship of WHR to CT-IFA remained significant after adjusting for the effects of age and degree of adiposity, suggesting that WHR indexes not only the relative distribution of truncal to gluteofemoral subcutaneous fat but also the abundance of intra-abdominal or visceral fat depots. The greater reproducibility of CT-IFA and WHR also suggests that these measurements are the most useful in predicting the regional obesity-associated metabolic abnormalities with their morbidity and mortality risks.

Adipose Tissue↗
PubMed1988

Glucose metabolism in obesity: influence of body fat distribution.

The dose-response relationships between portal venous insulin concentrations and hepatic glucose production and between peripheral insulin concentrations and peripheral glucose utilization were determined in 8 nonobese and 17 obese premenopausal women with either upper or lower body fat localization. The glucose production dose-response curves for the two obese groups were shifted to the right at all levels of portal insulinemia. The upper body obese women had a greater rightward shift compared to the lower body obese women. The peripheral glucose utilization dose-response curve was shifted to the right in the lower body obese women, but maximal glucose utilization was normal. The upper body obese women had both a greater rightward shift and a marked reduction in maximal glucose utilization. The insulin concentrations that had half-maximal effects on glucose production and utilization were similar in each group. These results indicate that the liver is not inherently more sensitive to insulin than peripheral tissues. Obesity is associated with a moderate diminution of hepatic and peripheral insulin sensitivity. Upper body fat localization in obese women is characterized by a greater diminution in insulin sensitivity and decline in peripheral insulin responsivity than is lower body fat localization. The marked peripheral insulin resistance in the former group may account for the increased prevalence of glucose intolerance.

Adult↗
PubMed1987

Relationship of androgenic activity to splanchnic insulin metabolism and peripheral glucose utilization in premenopausal women.

The importance of androgenic activity in mediating the effects of obesity and body fat topography on splanchnic insulin metabolism and peripheral insulin sensitivity was studied in 19 nonhirsute premenopausal women with a wide range of ideal body weight [percent ideal body weight (% IBW), 78-202%] and body fat distribution pattern [waist to hip girth ratio (WHR), 0.67-0.91]. Turnover kinetics of peripheral plasma C-peptide and insulin were measured, and estimates of pancreatic insulin production (PIP) and the hepatic extraction fraction (HEF) were calculated. The peripheral insulin sensitivity index (M/I) was determined during an euglycemic insulin clamp study. Androgenic activity was assessed by estimating the plasma level of sex hormone-binding globulin (SHBG) and percentage of free testosterone (% FT). After iv glucose stimulation, PIP ranged from 40-254 mU/min X m2 and correlated highly with % IBW (r = 0.78; P less than 0.01). Insulin HEF ranged from 5-69% of the pancreatic production and was inversely proportional to WHR (r = -0.60; P less than 0.01). Increasing WHR also correlated with the diminution in M/I (r = -0.47; P less than 0.05), which, in turn, correlated with the decline in the HEF of insulin (r = 0.60; P less than 0.01). Since PIP, HEF, and M/I correlated with SHBG and % FT, and since the degree of androgenic activity correlated with % IBW and WHR, partial regression analysis was performed. After adjusting for the effects of SHBG and % FT, the relationship between % IBW and PIP remained unaltered, whereas the correlation between WHR and HEF or M/I and their relationship to each other were either markedly reduced or became insignificant. Thus, in premenopausal women, the increase in pancreatic insulin production with increasing weight is independent of the degree of androgenic activity. On the other hand, the decline in hepatic insulin extraction and diminution in peripheral insulin sensitivity with upper body fat localization are in part mediated by increased androgenic activity. This association may account for the pronounced hyperinsulinemia and insulin resistance characteristic of this form of obesity.

Adipose Tissue↗