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Biomedical subjects

M F Saad

Publications and source records attributed to M F Saad.

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

Familial and metabolic factors related to blood pressure in Pima Indian children.

High blood pressure, abnormal glucose tolerance, and obesity are frequently associated with each other, but the mechanism of these associations is poorly understood. Studying them in children may help in understanding the pathogenesis of hypertension. Blood pressure, height, weight, and plasma glucose and serum insulin concentrations during a 75-g oral glucose tolerance test were measured in 1,698 Pima Indian children aged 6-17 years who participated in an ongoing epidemiologic study. Weight relative to height was used as an index of obesity. The parents of many of the children were also examined. Fasting and 2-hour glucose and insulin concentrations, adjusted for age, sex, and relative weight, were positively related to systolic blood pressure but not to diastolic blood pressure. Relative weight, 2-hour glucose, and fasting insulin concentrations were independently and significantly associated with systolic blood pressure in a stepwise regression analysis that included age and sex. After parental hypertension was taken into account, maternal but not paternal non-insulin-dependent diabetes mellitus, controlled for the child's relative weight and glucose and insulin concentrations, was significantly associated with higher blood pressure in children. The stronger association with maternal diabetes suggests a greater sharing of environmental factors between mother and child than between father and child, but familial similarities in obesity and glucose and insulin concentrations, the diabetic intrauterine milieu, and shared environmental factors probably all contribute to this association.

Adolescent↗
PubMed1994

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Analysis of Variance↗
PubMed1994

Decreased polymorphonuclear leukocyte deformability in NIDDM.

OBJECTIVE: To determine the rheological properties of polymorphonuclear leukocytes (PMN) from non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: The deformability of PMN from 33 NIDDM subjects, 13 with impaired glucose tolerance (IGT), and 22 with normal glucose tolerance (NGT) was studied. A Cell Transit Analyzer that measures the transit time of PMN through 8-microns pores was used. Studies were performed under three different conditions: 1) basal state; 2) after incubation with cytochalasin B (20 microM) to dissociate f-actin from the cytoskeleton; and 3) following activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 nM). RESULTS: PMN from diabetic patients were more rigid (i.e., had longer transit time) than those from subjects with NGT or IGT under basal conditions and after cytochalasin B, but not after stimulation with fMLP. The deformability of PMN from subjects with IGT was similar to those of the NGT group. In the pooled data, basal transit time correlated with age; systolic and diastolic blood pressure; HbA1c; and serum creatinine, cholesterol, and triglyceride concentrations (r = 0.29, 0.34, 0.37, 0.48, 0.25, 0.36, 0.29, respectively, P < 0.05 for each). Hypertensive diabetic patients had less deformable PMN than normotensive ones. No relation was found between PMN deformability and the duration of diabetes, type of treatment, or the presence of retinopathy. CONCLUSIONS: These data indicate increased rigidity of PMN in NIDDM that may contribute to development of microcirculatory disturbances and microangiopathy.

Adult↗
PubMed1994

Insulin and hypertension: are they related?

It has been postulated that insulin resistance and the concomitant compensatory hyperinsulinemia contribute to the pathogenesis of hypertension; possible by stimulating the sympathetic nervous system, promoting renal sodium reabsorption, modulating cation transport, and/or stimulating vascular smooth muscle hypertrophy. The purpose of this article is to present a comprehensive up-to-date review of the literature and critically examine the insulin resistance-hyperinsulinemia-hypertension hypothesis.

Animals↗
PubMed1993

Serum androgens in hyperinsulinemic Pima Indian and obese Caucasian women and their response to short-term insulin infusion.

Insulin resistance and its attendant hyperinsulinemia has been linked with hyperandrogenism. Insulin resistance is characteristic of the Pima Indians of the Gila River Indian community in central Arizona. Serum androgens, testosterone and dehydroepiandrosterone sulfate (DHEA-S) were quantitated at baseline and in response to low- and high-dose insulin infusion in 11 obese, hyperinsulinemic Pima Indian and 10 obese, hyperinsulinemic Caucasian women and were compared with baseline androgens in 16 nonobese Caucasian women. While there was no significant testosterone or DHEA-S response to short-term insulin infusion in either Pimas or obese Caucasians, both these groups had higher baseline testosterone concentrations (67 +/- 6.5 ng/dl in the Pimas, 55 +/- 5.9 ng/dl in the obese Caucasians) as compared with the nonobese Caucasians (28 +/- 2 ng/dl; p < 0.001). Baseline DHEA-S concentrations were not significantly different in the three groups. Given the hyperinsulinemic status of both the Pimas and the obese Caucasians, the finding of higher testosterone concentrations in these subjects as compared with nonobese Caucasians supports a role for insulin in ovarian androgen production and demonstrates that hormonal interactions that may be operating in obese hyperinsulinemic Caucasian subjects also operate in obese, hyperinsulinemic Pima Indians.

Adipose Tissue↗
PubMed1993

Insulin and hypertension: are they related?

It has been postulated that insulin resistance and the concomitant compensatory hyperinsulinemia contribute to the pathogenesis of hypertension, possibly by stimulating the sympathetic nervous system, promoting renal sodium reabsorption, modulating cation transport, and/or stimulating vascular smooth muscle hypertrophy. The purpose of this article is to present a comprehensive up-to-date review of the literature and critically examine the insulin resistance-hyperinsulinemia-hypertension hypothesis.

Animals↗
PubMed1993

Determinants of diabetes mellitus in the Pima Indians.

OBJECTIVE: To review the research findings on the determinants of diabetes mellitus in Pima Indians. RESEARCH DESIGN AND METHODS: Pima Indians in Arizona have participated in a longitudinal diabetes study that has provided data on and hypotheses about the development of NIDDM. Findings from this study are reviewed and updated. RESULTS: Frequency distributions of plasma glucose and HbA1 are bimodal in Pima adults, and substantial risk of the specific vascular complications of diabetes is confined to those in the higher components of these distributions. These findings contributed to the adoption of internationally recognized criteria for classification of glucose tolerance. Diabetes in the Pimas is strongly familial, and probably of genetic origin, although the precise nature of the gene or genes involved remains unknown. Obesity, which is at least in part environmentally determined, is a major factor interacting with the presumed genetic susceptibility to result in diabetes. The incidence of diabetes in the Pimas has increased during the last several decades, providing further evidence for environmental-genetic interaction. Longitudinal studies suggest that the progression from normal to diabetes can be considered to involve two stages. The first, primarily attributable to insulin resistance, leads to impaired glucose tolerance, and the second, which depends on insulin secretory failure, leads to worsening hyperglycemia and overt diabetes. CONCLUSIONS: The Pimas and many other American Indian populations suffer from a high incidence of diabetes and its characteristic disabling or fatal complications, and would benefit from continued research on the pathogenesis and prevention of the disease.

Adolescent↗
PubMed1993

Diabetes and obesity in the offspring of Pima Indian women with diabetes during pregnancy.

OBJECTIVE: To review the long-term effects of the diabetic pregnancy on the offspring among the Pima Indians of Arizona. RESEARCH DESIGN AND METHODS: Studies published by the Phoenix Epidemiology and Clinical Research branch of the National Institute of Diabetes and Digestive and Kidney Diseases, since the inception of the longitudinal diabetes studies in 1965 were reviewed. In addition, pertinent studies from other centers, mentioned as references in these publications, were reviewed. As far as possible, all original articles and abstracts on this aspect of the Pima Indian studies were discussed. RESULTS: The offspring of women who had diabetes during pregnancy, on average, were more obese and had higher glucose concentrations and more diabetes than the offspring of women who developed diabetes after pregnancy or who remained nondiabetic. Although no new analyses were attempted, several of the older publications were updated by repeating the analyses on later, expanded data sets. CONCLUSIONS: The diabetic pregnancy, in addition to its effects on the newborn, has effects on the subsequent growth and glucose metabolism of the offspring. These effects are in addition to genetically determined traits.

Adolescent↗
PubMed1993

Diabetic kidney disease in Pima Indians.

OBJECTIVE--To describe the natural history of kidney disease in Pima Indians with NIDDM. RESEARCH DESIGN AND METHODS--Review of previous studies describing diabetic kidney disease in this Native-American population and in other populations. RESULTS--NIDDM is the leading cause of renal failure in Pima Indians, among whom the incidence of ESRD is 23 times that of the general U.S. population. The high incidence of NIDDM and its early onset in the Pima undoubtedly contribute to this difference. The incidence of overt nephropathy and ESRD, as a function of diabetes duration, is at least as high in Pima Indians with NIDDM as that reported in other populations with IDDM. Furthermore, nearly all of the excess mortality associated with NIDDM is found in individuals with overt nephropathy. Mild elevations of UAE, which may be present even shortly after the onset of diabetes, predict the development of overt nephropathy in diabetic Pimas. Additional predictors include high blood pressure, level of glycemia, duration of diabetes, family history of diabetic nephropathy, and type of diabetes treatment. CONCLUSIONS--Diabetic kidney disease is a major cause of morbidity and mortality in Pima Indians. The natural history of diabetic kidney disease in this population is similar, in many ways, to the natural history described in individuals with IDDM.

Diabetes Mellitus, Type 1↗
PubMed1993

Development of impaired glucose tolerance with or without weight gain.

OBJECTIVE: To evaluate whether risk factors and changes in insulin concentrations differ in subjects who develop impaired glucose tolerance with or without weight gain. Hyperinsulinemia is a risk factor for impaired glucose tolerance, and insulin concentrations increase further with the development of impaired glucose tolerance. Its development, however, often is accompanied by weight gain, which, by itself, is associated with high insulin concentrations. RESEARCH DESIGN AND METHODS: Participants for this study were adult Pima Indians involved in an ongoing epidemiological study. Initially, all had normal glucose tolerance. During follow-up, 80 of 387 who did not gain weight developed impaired glucose tolerance, as did 295 of 1026 who gained weight. Risk factors for impaired glucose tolerance and the relationships between changes in weight and glucose and changes in insulin were evaluated by multivariate analyses. RESULTS: High baseline fasting insulin predicted impaired glucose tolerance regardless of weight after adjustment for age, sex, body mass index, and glucose. The development of impaired glucose tolerance was accompanied by a further increase in fasting and 2-h insulin, whether or not subjects gained weight. In both weight-change groups, impaired glucose tolerance was associated with more centralized fat distribution. CONCLUSIONS: Fasting hyperinsulinemia, a reflection of insulin resistance, is associated with the risk of developing impaired glucose tolerance whether or not weight is gained. Impaired glucose tolerance occurs when insulin resistance increases further. Weight gain is the most common precipitating factor. Aging and physical inactivity are other possible precipitating factors.

Adult↗
PubMed1993

Insulinemia in children at low and high risk of NIDDM.

OBJECTIVE: Fasting hyperinsulinemia in the presence of normoglycemia usually indicates insulin resistance and is characteristic of populations at high risk for developing NIDDM. Hyperinsulinemia predicts the development of impaired glucose tolerance and NIDDM in Pima Indians, a population with a high incidence of NIDDM. Insulin concentrations in population-based samples of children who have different risks of developing NIDDM later in life have not been reported previously. RESEARCH DESIGN AND METHODS: We compared fasting insulin concentrations in two populations of nondiabetic children, 6-19 yr of age: Pima Indians from southern Arizona and Caucasians from Minnesota. RESULTS: Insulin concentration varied with age, sex, glucose concentration, and relative weight. Mean fasting insulin concentration was 140.3 pM in Pima Indian males, 94.4 pM in Caucasian males, 171.5 pM in Pima Indian females, and 107.1 pM in Caucasian females. For each sex, the mean fasting insulin concentration, controlled for age, glucose, and relative weight, was significantly higher in the Pima Indians than in the Caucasians (P < 0.001). CONCLUSIONS: From a young age, Pima Indian children have higher fasting insulin concentrations than Caucasian children. As hyperinsulinemia predicts subsequent NIDDM, these data suggest that the susceptibility to NIDDM is manifest at a young age as fasting hyperinsulinemia.

Adolescent↗
PubMed1992

Tyrosine kinase activity of skeletal muscle during insulin infusion in humans.

Insulin receptor tyrosine kinase is stimulated by insulin in vivo, and this provides a mechanism by which the signal from insulin is transmitted into target cells. This study examined the time course of the in vivo activation of the kinase. Five nondiabetic Pima Indians had a euglycemic clamp at an insulin dose of 600 mU/min.m2, resulting in plasma insulin concentrations of about 15 nM by 30 min. Percutaneous muscle biopsies were taken from the vastus lateralis before and at regular intervals during insulin infusion, and the in vivo and in vitro tyrosine kinase activities were measured. There was a rapid in vivo activation of the kinase, detectable at less than 10 min and reaching a maximum within 30 min of insulin infusion. The time course of in vivo kinase activity, plasma insulin concentrations, and insulin-mediated glucose disposal rates displayed parallel patterns, indicating close interrelationships among these variables. The insulin concentration at which the kinase activity was maximal was about 10 nM both in vivo and in vitro. In vitro, however, this maximum increased with the degree of the kinase activation in vivo, indicating that the kinase potential in vitro is dependent on previous insulin exposure in vivo. We conclude that in vivo activation of the insulin receptor tyrosine kinase in human skeletal muscle is a rapid process, related to insulin action on glucose disposal, and that circulating insulin primes inactive insulin receptor molecules for subsequent tyrosine kinase activation by a mechanism that remains to be elucidated.

Adult↗
PubMed1992

Insulin treatment, endogenous insulin concentration, and ECG abnormalities in diabetic Pima Indians. Cross-sectional and prospective analyses.

The prevalence and incidence of CHD, defined by ECG abnormalities according to the Tecumseh criteria for Minnesota Codes, were determined in Pima Indians greater than or equal to 25 yr of age. In a cross-sectional analysis, the age-sex-adjusted prevalence (+/- SE) of ECG abnormalities was higher in 1454 NIDDM patients (6.86 +/- 0.65%) than in 1696 nondiabetic subjects (3.23 +/- 0.63%; prevalence rate ratio = 2.12; 95% CI 1.39-3.25). In a prospective analysis, the age-sex-adjusted incidence (+/- SE) of ECG abnormalities was higher in 824 NIDDM patients (12.77 +/- 1.67) than in 935 nondiabetic subjects (5.93 +/- 1.43 cases/1000 person-yr; incidence rate ratio = 2.15; 95% CI 1.26-3.69). The prevalence of ECG abnormalities in insulin-treated NIDDM patients was significantly higher than in NIDDM patients not treated with insulin (age-sex-adjusted OR = 2.83; 95% CI 1.84-4.33); and this association persisted when adjusted for other factors such as sBP, BMI, duration of diabetes, serum cholesterol concentration, and oral hypoglycemic agents (OR = 2.12; 95% CI 1.34-3.37). In the prospective analysis, the incidence of ECG abnormalities in NIDDM patients treated with insulin was higher than in those NIDDM patients not treated with insulin, but, when controlled for age, sex, duration of diabetes, and oral hypoglycemic agents in a proportional-hazards model, the relationship with insulin treatment was not statistically significant (incidence rate ratio = 1.36; 95% CI 0.80-2.31). This suggests that insulin treatment may be a marker of more severe diabetes, and that factors associated with clinical indications for insulin treatment, rather than insulin treatment per se, are related causally to CHD. On the other hand, endogenous fasting and 2-h postload serum insulin concentrations were not associated with ECG abnormalities among 761 NIDDM patients not treated with insulin nor among 1226 nondiabetic subjects. Furthermore, in the prospective study, neither endogenous fasting nor 2-h postload serum insulin was associated with the subsequent development of ECG abnormalities in NIDDM patients or nondiabetic subjects.

Adult↗
PubMed1992

Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies.

We examined distribution characteristics of the body mass index (BMI; weight/height; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs > or = 40 kg/m2.

Adolescent↗
PubMed1991

Racial differences in the relation between blood pressure and insulin resistance.

BACKGROUND: Insulin resistance and the concomitant compensatory hyperinsulinemia have been implicated in the pathogenesis of hypertension. However, reports on the relation between insulin and blood pressure are inconsistent. This study was designed to investigate the possibility of racial differences in this relation. METHODS: We studied 116 Pima Indians, 53 whites, and 42 blacks who were normotensive and did not have diabetes; the groups were comparable with respect to mean age (29, 30, and 31 years, respectively) and blood pressure (113/70, 111/68, and 113/68 mm Hg, respectively). Insulin resistance was determined by the euglycemic-hyperinsulinemic clamp technique during low-dose (40 mU per square meter of body-surface area per minute) and high-dose (400 mU per square meter per minute) insulin infusions. RESULTS: The Pima Indians had higher fasting plasma insulin concentrations than the whites or blacks (176, 138, and 122 pmol per liter, respectively; P = 0.002) and lower rates of whole-body glucose disposal during both the low-dose (12.7, 17.1, and 19.5 mmol per minute; P less than 0.001) and the high-dose (38.0, 43.1, and 45.7 mmol per minute; P less than 0.001) insulin infusions. After adjustment for age, sex, body weight, and percentage of body fat, mean blood pressure (calculated as 1/3 systolic pressure + 2/3 diastolic pressure) was significantly correlated with the fasting plasma insulin concentration (r = 0.42) and the rate of glucose disposal during the low-dose (r = -0.41) and high-dose (r = -0.49) insulin infusions (P less than 0.01 for each) in whites, but not in Pima Indians (r = -0.06, -0.02, and -0.04, respectively) or blacks (r = -0.10, -0.04, and 0.02, respectively). CONCLUSIONS: The relations between insulinemia, insulin resistance, and blood pressure differ among racial groups and may be mediated by mechanisms active in whites, but not in Pima Indians or blacks.

Adult↗
PubMed1991

Obesity in the Pima Indians: its magnitude and relationship with diabetes.

Members of the Pima Indian population are obese, on average, as estimated by the body mass index (BMI). Young adults have had the highest BMIs and there have been modest increases in age- and sex-specific mean BMIs for the past 25 y. These observations suggest that the older adults have had less exposure to factors leading to obesity than have the younger adults. Compared with children studied early in this century, present-day Pima children are much heavier for height, suggesting that the degree of obesity has increased since that time. Obesity in the Pimas is familial and has complex relationships with non-insulin-dependent diabetes mellitus, a common disease in this population. Obesity predicts the development of diabetes; once people have diabetes, however, they tend to lose weight. Thus, obesity should not be studied in this population without also considering diabetes, which tends to limit the degree of obesity.

Aged↗
PubMed1991

Ethnic differences in sympathetic nervous system-mediated energy expenditure.

The impact of sympathetic nervous system (SNS) activity on energy expenditure (EE) was evaluated in nondiabetic Caucasian and Pima Indian men while on a weight-maintenance diet using two approaches as follows. 1) The relationship between 24-h EE, measured in a respiratory chamber, and 24-h urinary norepinephrine was studied in 36 Caucasians [32 +/- 8 (SD) yr, 95 +/- 41 kg, 22 +/- 13% fat] and 33 Pimas (29 +/- 6 yr, 103 +/- 28 kg, 30 +/- 9% fat). There was no difference between the two groups in 24-h EE (2,422 vs. 2,523 kcal/24 h) and in urinary norepinephrine (28 vs. 31 micrograms/24 h), even after adjusting for body size and composition. Twenty-four-hour EE correlated significantly with 24-h urinary norepinephrine in Caucasians (r = 0.78, P less than 0.001) but not in Pimas (r = 0.03), independent of fat-free mass (FFM), fat mass, and age. 2) The effect of beta-adrenoceptor blockade with propranolol (120 micrograms/kg FFM bolus and 1.2 micrograms.kg FFM-1.min-1 for 45 min) on the resting metabolic rate (RMR) was evaluated in 36 Caucasians (30 +/- 6 yr, 103 +/- 36 kg, 25 +/- 11% fat) and 32 Pimas (28 +/- 6 yr, 100 +/- 34 kg, 27 +/- 10% fat). The RMR was similar in the two groups (2,052 vs. 1,973 kcal/24 h) even after adjustment for FFM, fat mass, and age and dropped significantly after propranolol infusion in Caucasians (-3.9%, P less than 0.001) but not in Pimas (-0.8%, P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗