Biomedical subjects

M F Saad

Publications and source records attributed to M F Saad.

At least 37 records · Page 2Linked to original sources

PubMed1998

Changes in plasma leptin during the menstrual cycle.

OBJECTIVE: To measure the plasma concentration of leptin, which is expressed in ovarian follicles and may have a reproductive function, in healthy women during the menstrual cycle. DESIGN: This study included nine women with regular menstrual cycles (mean+/-S.E.M. age 28+/-2 years: body mass index 23.9+/-1.8 kg/m2). From the onset of menses, fasting blood samples were collected every 1-2 days throughout the menstrual cycle. As a control, plasma leptin was measured in six postmenopausal women and six men every other day for 28 days. RESULTS: In menstruating women, plasma leptin increased from 14.9+/-2.9 ng/ml in the early follicular phase to 20.4+/-4.2 ng/ml (P<0.01) at the midluteal phase and returned to the baseline by the subsequent menses. In contrast, leptin concentrations did not change significantly in postmenopausal women or men. The changes in plasma leptin during the menstrual cycle were not related to changes in sex hormones. CONCLUSIONS: The cause of the increase in plasma leptin during the late follicular and luteal phases of the menstrual cycle is not clear. It may be attributed to augmented adipocyte production of leptin in response to increased caloric intake or hypothalamic release of neuropeptide Y. or to release of leptin from mature ovarian follicles. Leptin may have a role in regulating the menstrual cycle and preparing the body for the metabolic demands of pregnancy.

Adipose Tissue↗

PubMed1998

Physiological insulinemia acutely modulates plasma leptin.

Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/-2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0 kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by 37+/-2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.

Adult↗

PubMed1998

Association of hormone replacement therapy and carotid wall thickness in women with and without diabetes.

OBJECTIVE: Atherosclerosis is the major underlying cause of death for women with type 2 diabetes. We examined the relationship between use of postmenopausal hormone replacement therapy(HRT) and subclinical atherosclerosis among women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was conducted among 623 postmenopausal women in the Insulin Resistance Atherosclerosis Study (IRAS). Current users of HRT, n = 200, were compared with 104 former users and 319 never users. Intimal-medial wall thicknesses (IMTs) of the common carotid (CCA) and internal carotid (ICA) arteries were used as measures of atherosclerosis. RESULTS: Significant differences between HRT user groups were noted for certain demographic, socioeconomic, and lifestyle factors. After adjustment for these and other coronary heart disease risk factors, current users had a 69 microm thinner ICA IMT than never users (P = 0.06). Former users had a 96 pm thinner ICA IMT than never users (P = 0.03). No significant difference was observed for the CCA. Although women with type 2 diabetes had thicker carotid IMT than women without diabetes, the association between HRT use and thinner IMT was similar in both groups. The difference between current and never users was attenuated by adjustment for HDL and LDL cholesterol. Neither duration of HRT use nor HRT regimen was associated with IMT in either artery. CONCLUSIONS: This analysis suggests that current and former use of HRT is associated with reduced atherosclerosis and that women with type 2 diabetes may receive the same benefit from HRI as women without diabetes.

Adult↗

PubMed1997

Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non-insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non-insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.

Aged↗

PubMed1997

Duration of diabetes and carotid wall thickness. The Insulin Resistance Atherosclerosis Study (IRAS).

BACKGROUND AND PURPOSE: Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. However, the role of the primary metabolic abnormality of diabetes (chronic hyperglycemia) in this disease process has not been fully elucidated. METHODS: A cross-sectional analysis was conducted among 489 persons with non-insulin-dependent diabetes mellitus; 299 were established diabetics (diagnosed previously) and 190 were newly diagnosed at the time of the Insulin Resistance Atherosclerosis Study (IRAS) examination. These men and women, of three different ethnic groups, were participants in IRAS. Established diabetes (versus newly diagnosed diabetes) and mean fasting glucose level were used as measures of hyperglycemic burden. Intimal-medial wall thickness (IMT) of the internal (ICA) and common (CCA) carotid arteries were used as indices of atherosclerosis. RESULTS: The mean duration of disease among established diabetics was 7 years. The mean CCA IMT and ICA IMT were 872 and 946 microns, respectively. Established diabetes and mean fasting glucose level were positively associated with increased CCA IMT (P < .05) but not ICA IMT, even after adjustment for numerous cardiovascular disease risk factors. CCA IMT was increased by 70 microns in established diabetics (versus newly diagnosed diabetics) and by 26 microns per 1 SD of fasting glucose. Among established diabetics, however, duration of known diabetes (number of years) was not significantly related to IMT. CONCLUSIONS: Among diabetics in IRAS, established diabetes and fasting glucose level were each independently associated with CCA IMT, suggesting that chronic hyperglycemia or its associated metabolic abnormalities may lead to increased risk of atherosclerosis.

Arteriosclerosis↗

PubMed1997

Sexual dimorphism in plasma leptin concentration.

Leptin, the obese (ob) gene product, is thought to be a lipostatic hormone that contributes to body weight regulation through modulating feeding behavior and/or energy expenditure. The determinants of plasma leptin concentration were evaluated in 267 subjects (106 with normal glucose tolerance, 102 with impaired glucose tolerance, and 59 with noninsulin-dependent diabetes). Fasting plasma leptin levels ranged from 1.8-79.6 ng/mL (geometric mean, 12.4), were higher in the obese subjects, and were not related to glucose tolerance. Women had approximately 40% higher leptin levels than men at any level of adiposity. After controlling for body fat, postmenopausal women had still higher leptin levels than men of similar age, and their levels were not different from those in younger women. Multiple regression analysis showed that adiposity, gender, and insulinemia were significant determinants of leptin concentration, explaining 42%, 28%, and 2% of its variance, respectively. Neither age nor the waist/hip ratio was significantly related to leptin concentration. Thus, our data indicate that gender is a major determinant of the plasma leptin concentration. This sex difference is not apparently explained by sex hormones or body fat distribution. Leptin's sexual dimorphism suggests that women may be resistant to its putative lipostatic actions and that it may have a reproductive function.

Adipose Tissue↗

PubMed1997

The effect of a desogestrel-containing oral contraceptive on glucose tolerance and leptin concentrations in hyperandrogenic women.

Ovarian hyperandrogenism can be associated with insulin resistance, hyperinsulinemia, glucose intolerance, and obesity. High levels of the lipostatic hormone, leptin, have also been reported in this condition. The purpose of the present study was to examine the effect of an oral contraceptive (OC) of low androgenicity containing desogestrel on glucose tolerance in hyperandrogenic women and the impact of changes in androgenic/estrogenic status on leptin concentrations. Sixteen nondiabetic hyperandrogenic women, aged 29 +/- 1 yr with a body mass index (BMI) of 36.8 +/- 1.8 kg/m2, underwent an oral glucose tolerance test before and after 6 months of therapy with the OC. Free testosterone decreased and sex hormone-binding globulin increased after therapy (P < 0.001). Glucose tolerance deteriorated significantly, and two women developed diabetes. Body weight, BMI, and leptin did not change significantly. Leptin correlated with BMI before (r = 0.56; P = 0.02) and after (r = 0.51; P = 0.04) treatment, but not with glucose, insulin, total and free testosterone, or sex hormone-binding globulin before or after treatment. In conclusion, 1) glucose tolerance should be monitored in hyperandrogenic women using OC, even those of low androgenicity; and 2) changes in androgenic/estrogenic status had no effect on the leptin concentration, suggesting that its sexual dimorphism is not related to sex steroids.

Adult↗

PubMed1997

Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic whites, and Hispanics with NIDDM: the Insulin Resistance Atherosclerosis Study.

NIDDM is usually characterized by beta-cell failure and decreased insulin sensitivity. It has been reported that a high proportion of African-American NIDDM subjects are insulin sensitive. To examine this issue, we determined insulin sensitivity (S(I)) in 479 NIDDM subjects by minimal model analyses of frequently sampled intravenous glucose tolerance (FSIGT) from the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular risk in African-Americans, Hispanics, and non-Hispanic whites. The African-Americans and non-Hispanic whites were sampled in Los Angeles and Oakland, California. The non-Hispanic whites and Hispanics were sampled in San Antonio, Texas, and San Luis Valley, Colorado. We defined the proportion of insulin-sensitive (S(I)) subjects as > or =1.61 min-1 x microU-1 x ml-1, which is above the median for nondiabetic subjects of all ethnic groups in the IRAS. Using this definition, the proportion of insulin-sensitive diabetic subjects was very low in all ethnic groups (non-Hispanic whites [14.3%] vs. African-Americans [6.5%], P = 0.039 in Los Angeles and Oakland; non-Hispanic whites [6.8%] vs. Hispanics [4.9%], P = 0.737 in San Luis Valley and San Antonio). These results were also similar in newly diagnosed mildly hyperglycemic diabetic subjects. In addition, these results were not affected by the adjustment for differences in obesity, body fat distribution, and severity of hyperglycemia. Even in nonobese subjects (with BMI <30 kg/m2), the proportion of insulin-sensitive subjects (S(I) > or =1.61 min-1 x microU-1 x ml-1) was low (3.6-9.7%). The acute insulin response (AIR) was significantly higher in African-Americans than in non-Hispanic whites; there were no ethnic differences in AIR between Hispanics and non-Hispanic whites. There were no significant ethnic differences for non-insulin-mediated glucose disposal (S(G)). We conclude that the number of insulin-sensitive NIDDM subjects is low and similar among non-Hispanic whites, Hispanics, and African-Americans in the U.S.

Black or African American↗

PubMed1997

Method of insulin administration has no effect on insulin sensitivity estimates from the insulin-modified minimal model protocol.

The effect of the method of insulin administration on insulin sensitivity estimates from the insulin modified minimal model (MINMOD) protocol was evaluated using the tolbutamide-boosted protocol as a reference. The study included 21 nondiabetic men ages 40 +/- 2 years (mean +/- SE) with a BMI of 26.6 +/- 1.1 kg/m2. Each subject underwent four frequently sampled intravenous glucose tolerance tests (FSIGTT), one with tolbutamide and three with the same insulin dosage (0.03 U/kg) given as a bolus or infusion over 5 or 10 min. The insulin sensitivity index (SI) of each subject was calculated from each FSIGTT with MINMOD. Insulin sensitivity indexes from the four FSIGTTs were highly correlated (r > 0.85, P < 0.001). SI(insulin) from the bolus and the 5- and 10-min infusion protocols were similar, but were 21 +/- 5, 29 +/- 5, and 23 +/- 4% lower than SI(tolbutamide), respectively. SG(tolbutamide) and SG(insulin) were not different among the four protocols and were significantly correlated (r > 0.55, P < 0.01). Thus the tolbutamide and insulin protocols must not be used interchangeably in any single cross-sectional or longitudinal study. When the same insulin dosage is used, the method of its administration has no bearing on insulin sensitivity estimates from the insulin-modified FSIGTT. The same method of insulin administration should be used, however, in any single study for purpose of standardization.

Adult↗

PubMed1997

Differences between the tolbutamide-boosted and the insulin-modified minimal model protocols.

The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 +/- 2 years [mean +/- SE], BMI 27.2 +/- 0.9 kg/m2). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU x m(-2) x min(-1)). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes (S(I)) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.001), but S(I(insulin)) was 29 +/- 4% lower than S(I(tolbutamide)). Both S(I(insulin)) and S(I(tolbutamide)) correlated significantly with S(I(clamp)) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same units (dl/min per pU/ml), S(I(tolbutamide)) was on average 13 +/- 6% lower than S(I(clamp)) (4.51 +/- 0.40 vs. 5.36 +/- 0.36 x 10(-2), P = 0.009), whereas S(I(insulin)) was 44 +/- 4% lower. S(G(tolbutamide)) and S(G(insulin)) were not different (1.88 +/- 0.10 vs. 2.01 +/- 0.09 x 10(-2) min(-1), P = 0.167) and were significantly correlated (r = 0.50, P = 0.002). Thus, insulin sensitivity estimates from both protocols correlate significantly with each other and with the clamp. They are quantitatively discrepant, however, possibly due to differences in the route of insulin delivery, saturation of insulin action, and/or tolbutamide-induced proinsulin release. Data obtained from these two MINMOD protocols are not directly comparable, and the same protocol must be used in any single cross-sectional or longitudinal study.

Adult↗

PubMed1996

Insulin sensitivity and atherosclerosis. The Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

BACKGROUND: Reduced insulin sensitivity has been proposed as an important risk factor in the development of atherosclerosis. However, insulin sensitivity is related to many other cardiovascular risk factors, including plasma insulin levels, and it is unclear whether an independent role of insulin sensitivity exists. Large epidemiological studies that measure insulin sensitivity directly have not been conducted. METHODS AND RESULTS: The Insulin Resistance Atherosclerosis Study (IRAS) evaluated insulin sensitivity (SI) by the frequently sampled intravenous glucose tolerance test with analysis by the minimal model of Bergman. IRAS measured intimal-medial thickness (IMT) of the carotid artery as an index of atherosclerosis by use of noninvasive B-mode ultrasonography. These measures, as well as factors that may potentially confound or mediate the relationship between insulin sensitivity and atherosclerosis, were available in relation to 398 black, 457 Hispanic, and 542 non-Hispanic white IRAS participants. There was a significant negative association between SI and the IMT of the carotid artery both in Hispanics and in non-Hispanic whites. This effect was reduced but not totally explained by adjustment for traditional cardiovascular disease risk factors, glucose tolerance, measures of adiposity, and fasting insulin levels. There was no association between SI and the IMT of the carotid artery in blacks. The association between SI and the IMT was stronger for the internal carotid artery than for the common carotid artery in all ethnic groups. CONCLUSIONS: Higher levels of insulin sensitivity are associated with less atherosclerosis in Hispanics and non-Hispanic whites but not in blacks. This effect is partially mediated by traditional cardiovascular risk factors.

Adult↗

PubMed1996

Ethnic differences in carotid wall thickness. The Insulin Resistance Atherosclerosis Study.

BACKGROUND AND PURPOSE: Ethnic differences in cardiovascular disease (CVD) morbidity and mortality have been observed in US adults. However, little data exist on differences in indices of preclinical atherosclerosis such as carotid wall intima-media thickness (IMT) for US non-Hispanic whites, Hispanics, and blacks. This study was undertaken to determine whether there were ethnic differences in carotid wall IMT. METHODS: Internal carotid artery (ICA) IMT and common carotid artery (CCA) IMT, indices of atherosclerosis, were assessed with the use of B-mode ultrasound in 1020 nondiabetic participants in the Insulin Resistance Atherosclerosis Study, a multicenter study designed to examine the association between insulin resistance and carotid atherosclerosis. The study included 281 blacks, 329 Hispanics, and 410 non-Hispanic whites aged 40 to 69 years. RESULTS: Blacks had significantly greater CCA IMT than non-Hispanic whites (865 versus 808 microns); this remained significant after adjustment for major CVD risk factors and insulin sensitivity (864 versus 823 microns). There were no significant differences in ICA IMT between blacks and non-Hispanic whites. Hispanics had significantly lesser CCA IMT than non-Hispanic whites (749 versus 776 microns), and these differences remained significant after adjustment for traditional cardiovascular risk factors and insulin sensitivity (750 versus 778 microns). There were no significant differences in ICA IMT between non-Hispanic whites and Hispanics. CONCLUSIONS: We conclude that ethnic differences exist in CCA but not in ICA IMT in nondiabetic subjects. These differences in IMT, which are indicators of atherosclerosis, are a non-invasive measure that is consistent with some of the data on clinical end points. These differences may be associated with the observed differences in CVD morbidity and mortality among major ethnic groups in the United States.

Arteriosclerosis↗

PubMed1996

Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women. The Insulin Resistance and Atherosclerosis Study.

Increased abdominal obesity has been related to lower insulin sensitivity (SI), independent of overall obesity, but it has been suggested that this relationship may be weaker in non-whites. In the Insulin Resistance and Atherosclerosis Study (IRAS), SI was estimated using a minimal model analysis of the frequently sampled intravenous glucose tolerance test in 1,625 men and women aged 40-69 years. Subjects included African-Americans, Hispanics, and non-Hispanic whites from Oakland and Los Angeles, CA, San Antonio, TX, and the San Luis Valley, CO. Minimum waist circumference was significantly (P = 0.0001) associated with SI after adjusting for age, sex, height, BMI, glucose tolerance status, ethnicity, and clinic. This relationship was significantly (P = 0.0001) stronger in subjects with normal glucose tolerance (NGT) (beta = -0.030, P = 0.0001) than in those with impaired glucose tolerance (IGT) (beta = -0.010, P = 0.02; NIDDM: beta = -0.013, P = 0.0001). There were no significant ethnic differences in effect size across the spectrum of glucose tolerance. Waist circumference was also positively related to fasting insulin, an indirect measure of insulin sensitivity, in NGT (P = 0.0001), IGT (P = 0.0003), and NIDDM (P = 0.0002). The waist-fasting insulin relationship was significantly weaker in African-Americans, relative to non-Hispanic whites, in NGT and IGT (tests of statistical interaction: P = 0.04 and P = 0.02, respectively). In general, these patterns were similar in models specifying waist-to-hip ratio (WHR), rather than waist circumference, as the independent variable. While some ethnic variability exists, a negative relationship between abdominal obesity and insulin sensitivity was confirmed for all three ethnic groups across the spectrum of glucose tolerance.

Adult↗

PubMed1996

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Africa↗

PubMed1995

Exploration of simple insulin sensitivity measures derived from frequently sampled intravenous glucose tolerance (FSIGT) tests. The Insulin Resistance Atherosclerosis Study.

Both abnormal insulin levels and low insulin sensitivity have been implicated as risk factors for Type II diabetes mellitus and cardiovascular disease. While insulin level is relatively simple to assess, direct measurement of insulin sensitivity is much more invasive, costly, and time-consuming. The authors considered eight previously described measures or indices of indices of insulin sensitivity derived from the frequently sampled intravenous glucose tolerance test (FSIGT). Each one was evaluated by strength and consistency of association with insulin sensitivity computed from glucose clamp (SI(clamp)), across three glucose tolerance groups, including participants with normal glucose tolerance (n = 11), impaired glucose tolerance (n = 20), and non-insulin-dependent diabetes mellitus (n = 24). Minimal model analysis (MINMOD SI(22)), based on the 22-sample FSIGT, performed best based on statistical criteria of strong and consistent association with SI(clamp). An insulin sensitivity measure similar to that of Galvin et al. (Diabetic Medicine 1990;9:921-8), defined as glucose disappearance (10-50 minutes) divided by insulin area under the curve above baseline from 0-50 minutes, performed best based on statistical criteria and time-savings. Galvin insulin sensitivity is simple to calculate, requires only a 50-minute FSIGT, and is significantly (p < 0.001) and not inconsistently (p = 0.12 for inconsistent association) associated with SI(clamp) over a wide range of glucose tolerance.

Analysis of Variance↗

PubMed1995

In vivo beta-cell function at the transition to early non-insulin-dependent diabetes mellitus.

Impaired insulin secretion occurs at some stage in the development of non-insulin-dependent diabetes mellitus (NIDDM), possibly during impaired glucose tolerance (IGT) or early NIDDM. To assess insulin secretion at these critical stages, we measured the first-phase insulin response (to glucose and arginine), maximal secretory capacity, and glucose potentiation slope for insulin secretion in Pima Indians with normal glucose tolerance (n = 20), IGT (n = 9), and mild (fasting glucose < 7.8 mmol/L) NIDDM (n = 7). We also measured oral glucose tolerance and insulin action. Subjects with IGT were more insulin-resistant (P < .05) than normals. A wide range of insulin secretion was noted, although as a group, no significant impairment was detected. Subjects with mild NIDDM were similarly insulin-resistant, but they also had impaired insulin secretion. The first-phase response to glucose was markedly reduced in absolute terms (P < .001), but all secretion indices were impaired relative to the degree of insulin resistance (P = .05 to P < .0001). These results suggest that in Pima Indians, impairment of insulin secretion, especially the first-phase response to glucose, is associated with mild NIDDM. Insulin secretion in IGT is variable and, overall, seems intact, although a subtle defect in the first-phase insulin response to glucose could not be ruled out in this study. Glucose sensing for first-phase secretion may be one of the early secretory defects in the progression of glucose intolerance and seems to be critical at the transition from IGT to early NIDDM.

Adult↗

PubMed1995

The insulin resistance atherosclerosis study (IRAS) objectives, design, and recruitment results.

The Insulin Resistance Atherosclerosis Study (IRAS) is the first epidemiologic study designed to assess the relationships between insulin resistance, insulinemia, glycemia, other components of the insulin resistance syndrome, and prevalent cardiovascular disease (CVD) in a large multiethnic cohort. Over 1600 men and women were recruited from four geographic areas to represent a range of glucose tolerance (normal, impaired, and diabetic) and ethnicity (hispanic, non-Hispanic white, and African-American). Insulin resistance was assessed directly using the frequently sampled intravenous glucose tolerance test with minimal model analysis. Intimal-medial carotid artery wall thickness, an indicator of atherosclerosis, was measured using B-mode ultrasonography. Prevalent CVD was assessed by questionnaire and resting electrocardiography. This report describes the design of the study and provides the recruitment results. Forthcoming cross-sectional analyses will help to disentangle the association between insulin resistance and CVD, apart from the concomitant hyperinsulinemia and related CVD risk factors.

Adult↗

PubMed1995

Results of pancreas transplantation with portal venous and enteric drainage.

PURPOSE: The standard method for pancreatic transplantation involves drainage of exocrine secretions into the urinary bladder with venous outflow into the systemic circulation. Despite the high success rate associated with this approach, it often leads to complications, including chemical cystitis, reflux pancreatitis, metabolic acidosis, and hyperinsulinemia. The authors developed a new technique of pancreatic transplantation with portal drainage of endocrine secretions and enteric drainage of exocrine secretions (PE), which theoretically should be more physiologic. PROCEDURES: All patients were insulin-dependent diabetics with end-stage renal disease who underwent combined kidney-pancreas transplantation. Between 1990 and 1994, 19 patients have been transplanted using intraperitoneal placement of the pancreas allograft with exocrine drainage into a Roux-en Y loop and venous drainage into the portal circulations (PE). A comparison group of all patients undergoing standard systemic-bladder (SB) transplantation between April 1989 and March 1993 (n = 28) also was studied. Patient follow-up ranges from 6 months to 5 years for the SB patients (mean = 2.5 years) and 6 months to 4 years for the PE patients (mean = 1.6 years). Routine follow-up includes documentation of the clinical course and detailed endocrine studies. FINDINGS: Patient and graft actuarial survival at 1 and 3 years is no different for SB and PE patients. Urinary tract infections occurred in 89.3% of the SB patients (2.8/patient) versus 26.3% of the PE patients (0.25/patient, p < or = 0.0001). None of the PE patients experienced hematuria compared with 53.6% of the SB patients (p < or = 0.0001); however, two PE patients had melanotic episodes. The incidence of urinary retention and reflux pancreatitis was 32.1% versus 5.3% (p < or = 0.028) for SB and PE groups, respectively. Patients in the SB group required sodium bicarbonate therapy (mean = 55 mEq/day) although no PE patient required routine therapy; despite this, SB patients experienced more episodes of acidosis (44 vs. 5). Endocrine studies indicate no difference in glycosylated hemoglobin or fasting and stimulated glucose values throughout the follow-up period. In contrast, hyperinsulinemia was evident in both fasting and stimulated tests for the SB patients, with values consistently two- to fivefold higher than those of the PE group. CONCLUSIONS: These results indicate that PE and SB pancreas transplantation are equivalent in terms of patient and graft survival and suggest that the PE approach is associated with a decreased incidence of metabolic and bladder-related complications. In addition, the PE approach eliminates the state of peripheral hyperinsulinemia that characterizes the SB procedure. Continued follow-up will be necessary to determine if long-term outcomes will differ for patients with PE and SB grafts.

Actuarial Analysis↗