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Biomedical subjects

F Abbasi

Publications and source records attributed to F Abbasi.

At least 19 recordsLinked to original sources
PubMed2003

Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents.

AIMS: To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET. METHODS: The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter. RESULTS: The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different. CONCLUSIONS: The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.

Blood Glucose↗
PubMed2002

Evaluation of the quantitative insulin sensitivity check index as an estimate of insulin sensitivity in humans.

The goal of this study was to compare estimates of insulin resistance generated by the quantitative insulin sensitivity check index (QUICKI) with a direct measure of insulin-mediated glucose disposal in healthy, nondiabetic volunteers. For this purpose, the results of measurements of plasma glucose and insulin concentrations in 490 nondiabetic, healthy subjects were used to compute several surrogate estimates of insulin resistance, and these values were compared with a direct measure of insulin-mediated glucose disposal. The results of this analysis showed that estimates of insulin resistance derived from use of QUICKI were significantly correlated (r = -.60, P <.001) with direct measures of insulin-mediated glucose in the 490 subjects studied. It was also noted that QUICKI estimates of insulin resistance were highly correlated with fasting insulin concentrations (r = -.98) and the homeostasis model assessment for insulin resistance (HOMA-IR, r = -.99). On the other hand, the correlation between all 3 of the surrogate methods for estimating insulin resistance and the direct assessment of insulin-mediated glucose disposal was relatively weak, i.e., r =.61, r =.64, and r = -.60) for fasting insulin concentration, HOMA-IR, and QUICKI, respectively. The results of these comparisons do not provide support for the superiority of QUICKI over other commonly used surrogate measures of insulin resistance based upon use of fasting insulin concentration or equations utilizing fasting insulin and glucose concentration. Furthermore, none of the 3 surrogate estimates can account for more than approximately 40% of the variability of the difference in insulin-mediated glucose disposal measured directly in 490 healthy, nondiabetic volunteers.

Homeostasis↗
PubMed2002

Relationship between fasting and day-long plasma glucose concentrations in diet-treated patients with type 2 diabetes.

To define the relationship between fasting and postprandial hyperglycemia, plasma glucose concentrations were determined before and after breakfast and lunch in 42 diet-treated patients with type 2 diabetes. Breakfast was consumed at 8:00 AM and lunch at 12:00 PM, with blood drawn hourly from 8:00 AM to 4:00 PM for measurement of plasma glucose concentration. The results demonstrated highly significant correlation coefficients (r) between fasting plasma glucose concentration and any individual hourly value (r values varying between 0.86 and 0.91). Furthermore, fasting plasma glucose concentrations and the total integrated glucose response areas, post-breakfast (8:00 AM to 12:00 PM), post-lunch (12:00 PM to 4:00 PM), and day-long (8:00 AM to 4:00 PM) were also highly correlated, with r values of 0.95, 0.91, and 0.94, respectively. These results demonstrate that fasting and postprandial glucose concentrations are almost perfectly correlated in diet-treated patients with type 2 diabetes, and that determination of fasting plasma glucose concentrations in these individuals provides an excellent estimate of degree of glycemic control.

Adult↗
PubMed2002

Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes.

This study was initiated to see if plasma asymmetric dimethylarginine (ADMA) concentrations decreased in hyperglycemic patients with type 2 diabetes following metformin treatment, either as monotherapy or following its addition to sulfonylurea-treated patients. Fasting plasma glucose, dimethylarginine, and L-arginine concentrations were measured before and 3 months after the administration of a maximally effective dose of metformin to 31 patients with type 2 diabetes in poor glycemic control (fasting plasma concentrations > 9.7 mmol/L), while being treated with either diet (n = 16) or a maximal amount of a sulfonylurea compound (n = 15). Fasting plasma glucose concentration (mean +/- SEM) decreased to a similar degree (P <.01) in patients treated with either metformin alone (12.4 +/- 0.5 to 9.5 +/- 0.5 mmol/L) or when it was added to a sulfonylurea compound (14.1 +/- 0.5 to 10.6 +/- 0.9 mmol/L). The improvement in glycemic control was associated with similar decreases (P <.01) in ADMA concentrations in metformin (1.65 +/- 0.21 to 1.18 +/- 0.13 micromol/L) and sulfonylurea + metformin-treated patients (1.75 +/- 0.13 to 1.19 +/- 0.08 micromol/L). Plasma L-arginine concentrations were similar in the 2 groups at baseline and did not change in response to metformin. Thus, metformin treatment was associated with a favorable increase in the plasma L-arginine/ADMA ratio. These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment.

Arginine↗
PubMed2001

Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone.

OBJECTIVE: To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS). DESIGN: Case report. SETTING: Academic clinical practice and General Clinical Research Center. PATIENT(S): A 25-year-old woman with PCOS. INTERVENTION(S): Rosiglitazone maleate, 4 mg daily for 5 months until conception. MAIN OUTCOME MEASURE(S): Insulin sensitivity by steady-state plasma glucose technique; serum androgens, progesterone, and hCG; and pelvic ultrasound images. RESULT(S): Rosiglitazone treatment for 5 months improved insulin sensitivity, lowered serum free testosterone, and resulted in spontaneous ovulation and conception. CONCLUSION(S): Rosiglitazone is a promising insulin sensitizer for treatment of PCOS. Clinical trials are warranted.

Adult↗
PubMed2001

Insulin resistance, dietary cholesterol, and cholesterol concentration in postmenopausal women.

Questions remain concerning the effect of variations in cholesterol intake on plasma cholesterol concentration, as well as on the role of factors modulating the metabolic impact of this dietary intervention. To define the impact of wide variations in dietary cholesterol intake on plasma total and low-density lipoprotein (LDL) cholesterol concentrations, as well as testing the hypothesis that resistance to insulin-mediated glucose disposal would accentuate the increase in plasma total and LDL cholesterol concentrations in response to a given increment in dietary cholesterol intake, we performed a prospective, randomized study comparing diets varying in cholesterol content in 65 healthy, postmenopausal women, 31 defined as insulin-resistant and 34 as insulin-sensitive. The changes in total and LDL cholesterol in response to increments in dietary cholesterol of up to approximately 800 mg/day were modest in magnitude, without evidence of a statistically significant diet-induced increase in cholesterol concentration, or of any difference in the responses of insulin-resistant as compared with insulin-sensitive women. These results indicate that relatively large increments in dietary cholesterol intake had little effect on total or LDL cholesterol concentrations in healthy, postmenopausal women, irrespective of whether they were insulin-resistant or insulin-sensitive.

Apolipoproteins A↗
PubMed2001

Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.

Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutraminine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. Weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant.

Appetite Depressants↗
PubMed2001

Metabolic changes following sibutramine-assisted weight loss in obese individuals: role of plasma free fatty acids in the insulin resistance of obesity.

The relationship between insulin-mediated glucose disposal and daylong free fatty acid (FFA) concentrations before and after sibutramine-assisted weight loss was investigated in 24 healthy, normotensive, nondiabetic, obese women (body mass index [BMI] >30.0 kg/m(2)). The 24 volunteers were defined as being insulin-resistant (IR) or insulin-sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration in response to a 180-minute continuous intravenous infusion of octreotide, insulin, and glucose. The mean (+/- SEM) SSPG concentrations were significantly higher (P <.001) in the IR group (219 +/- 7 v 69 +/- 6 mg/dL) at baseline. The IR group also had significantly higher plasma glucose (P =.002), insulin (P <.001), and FFA (P =.02) concentrations measured at hourly intervals from 8 AM to 4 PM, before and after breakfast (8 AM) and lunch (noon). Weight loss in response to an energy-restricted diet for 4 months and sibutramine (15 mg/d) was comparable in the 2 experimental groups (8.6 +/- 1.3 v 7.9 +/- 1.4 kg). SSPG concentrations decreased significantly (P <.001) following weight loss (219 +/- 7 to 144 +/- mg/dL) in the IR group, but there was no change in the SSPG of the IS group (69 +/- 6 to 73 +/- 7 mg/dL. The improvement in insulin sensitivity in the IR group after weight loss was associated with a significant decline in daylong plasma glucose (P >.001) and insulin (P =.02) concentrations, without a weight-loss-associated decrease in daylong plasma FFA responses. In contrast, there was no significant change in plasma glucose, insulin, and FFA concentrations following weight loss in the IS group. These results indicate that daylong FFA concentrations vary substantially in obese individuals as a function of whether they are IR or IS. Furthermore the observation that the IR group was more insulin-sensitive after weight loss, associated with lower daylong insulin concentrations in the absence of a significant decrease in circulating FFA concentrations, suggests that resistance to insulin-mediated glucose disposal in obese individuals cannot be entirely due to high FFA levels.

Adipose Tissue↗
PubMed2001

Effect of insulin resistance on postprandial elevations of remnant lipoprotein concentrations in postmenopausal women.

BACKGROUND: Questions remain as to why postmenopausal women are at a higher risk of coronary artery disease (CAD) than are premenopausal women. Studies have shown that plasma concentrations of remnant lipoproteins (RLPs) are elevated in patients with CAD and that increases in plasma RLP concentrations may be related to variations in insulin-mediated glucose disposal. OBJECTIVE: We sought to evaluate the possibility that postprandial accumulation of plasma RLPs will be accentuated in insulin-resistant, postmenopausal women. DESIGN: Postmenopausal women were divided into insulin-sensitive (n = 15) and insulin-resistant (n = 15) groups according to their steady state plasma glucose concentrations in response to a 180-min infusion of octreotide, insulin, and glucose. Plasma insulin, triacylglycerol, and RLP-cholesterol concentrations were measured either hourly (insulin) or every 2 h (triacylglycerol and RLP cholesterol) for 8 h, before and after breakfast (0800) and lunch (1200). RESULTS: By selection, insulin-resistant women had higher steady state plasma glucose concentrations than did insulin-sensitive women (10.8 +/- 0.5 compared with 4.1 +/- 5 mmol/L, respectively; P < 0.001), associated with higher fasting triacylglycerol (1.58 +/- 0.04 compared with 1.00 +/- 0.03 mmol/L; P = 0.01) and lower HDL-cholesterol (1.06 +/- 0.08 compared with 1.34 +/- 0.05; P = 0.01) concentrations. In addition, measurements of daylong concentrations of insulin, triacylglycerol, and RLP cholesterol were also significantly greater in insulin-resistant than in insulin-sensitive women (P < 0.001). CONCLUSIONS: Postprandial accumulation of RLPs is accentuated in insulin-resistant, postmenopausal women. This may contribute to the increased risk of CAD in these individuals.

Blood Glucose↗
PubMed2001

Insulin resistance as a predictor of age-related diseases.

The current study was initiated to evaluate the ability of insulin resistance to predict a variety of age-related diseases. Baseline measurements of insulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m2) individuals, who were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary heart disease, stroke, cancer, and type 2 diabetes. The effect of insulin resistance on the development of clinical events was evaluated by dividing the study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary heart disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of the total 40 clinical events were seen in 25 individuals (36%) in the most insulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple logistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy individuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the most insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-related diseases.

Age Factors↗
PubMed2000

High carbohydrate diets, triglyceride-rich lipoproteins, and coronary heart disease risk.

In this study we compared the effects of variations in dietary fat and carbohydrate (CHO) content on concentrations of triglyceride-rich lipoproteins in 8, healthy, nondiabetic volunteers. The diets contained, as a percentage of total calories, either 60% CHO, 25% fat, and 15% protein, or 40% CHO, 45% fat, and 15% protein. They were consumed in random order for 2 weeks, with a 2-week washout period in between. Measurements were obtained at the end of each dietary period of plasma triglyceride, cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, remnant lipoprotein (RLP) cholesterol, and RLP triglyceride concentrations, both after an overnight fast and throughout an 8-hour period (8 A.M. to 4 P.M.) in response to breakfast and lunch. The 60% CHO diet resulted in higher (mean +/- SEM) fasting plasma triglycerides (206 +/- 50 vs 113 +/- 19 mg/dl, p = 0.03), RLP cholesterol (15 +/- 6 vs 6 +/- 1 mg/dl, p = 0.005), RLP triglyceride (56 +/- 25 vs 16 +/- 3 mg/dl, p = 0.003), and lower HDL cholesterol (39 +/- 3 vs 44 +/- 3 mg/dl, p = 0.003) concentrations, without any change in LDL cholesterol concentration. Furthermore, the changes in plasma triglyceride, RLP cholesterol, and RLP triglyceride persisted throughout the day in response to breakfast and lunch. These results indicate that the effects of lowfat diets on lipoprotein metabolism are not limited to higher fasting plasma triglyceride and lower HDL cholesterol concentrations, but also include a persistent elevation in RLPs. Given the atherogenic potential of these changes in lipoprotein metabolism, it seems appropriate to question the wisdom of recommending that all Americans should replace dietary saturated fat with CHO.

Apolipoproteins↗
PubMed2000

The relationship between plasma glucose and insulin responses to oral glucose, LDL oxidation, and soluble intercellular adhesion molecule-1 in healthy volunteers.

This study was initiated to describe the relationships between plasma glucose and insulin responses to oral glucose and the concentrations of partially oxidized low density lipoprotein (poxLDL) and soluble intercellular adhesion molecule-1 (sICAM-1) in 23 healthy, non-diabetic volunteers. Results demonstrated that plasma glucose (r=0.65, P<0.002) and insulin (r=0.58, P<0.007) responses to a 75-g oral glucose challenge were highly correlated to poxLDL concentrations. Plasma glucose (r=0.63, P<0.002) and insulin (r=0.68, P<0.001) concentrations also significantly correlated with sICAM-1 concentrations. Furthermore, concentrations of poxLDL and sICAM-1 were significantly related (r=0.55, P<0.001). These relationships remained statistically significant when adjusted for differences in age, gender, body mass index, and lipoprotein concentrations. These results provide further evidence that circulating LDL particles are more highly oxidized in insulin resistant states, and demonstrate the presence of an in vivo relationship between insulin resistance, LDL oxidized state, and sICAM-1 concentrations. These results help explain why soluble forms of adhesion molecules are increased in clinical conditions characterized by insulin resistance, and support the possibility that LDL oxidizability is increased in insulin resistant subjects, and that the increase in sICAM-1 results from stimulation of cellular adhesion molecules by more highly oxidized LDL.

Administration, Oral↗
PubMed2000

Plasma insulin concentration is more tightly linked to plasma leptin concentration than is the body mass index.

This study tested the hypothesis that the integrated plasma insulin response to oral glucose is a more sensitive predictor of the fasting plasma leptin concentration than the body mass index (BMI) or waist to hip ratio (WHR). For this purpose, we determined the fasting plasma leptin concentration and plasma insulin response to a 75-g oral glucose challenge in 76 healthy female subjects, with a BMI of 19.1 to 36.6 kg/m2 and a WHR of 0.57 to 1.1. The results demonstrated that fasting plasma leptin concentrations were significantly correlated with both the BMI (r = .64, P < .001) and the plasma insulin response to glucose (r = .61, P < .001), but not with the WHR (r = .27). Since the BMI and the insulin response were also significantly related (r = .34, P = .003), multivariate analysis was performed to determine if the BMI and insulin response were independent determinants of the fasting leptin concentration. This analysis indicated that both the BMI and insulin response were significantly related to plasma leptin (P < .001). To pursue this issue further, the population was divided into tertiles on the basis of the (1) plasma leptin concentration, (2) BMI, and (3) integrated insulin response. The two variables that were most closely linked to each other were the leptin concentration and insulin response. In contrast, the BMI was relatively easily disassociated from the other two variables. These results indicate that while both the plasma insulin response to glucose and the BMI are significantly associated with the fasting plasma leptin concentration, the plasma insulin response appears more closely associated with the plasma leptin concentration.

Administration, Oral↗
PubMed2000

Insulin regulation of plasma free fatty acid concentrations is abnormal in healthy subjects with muscle insulin resistance.

This study evaluated the ability of insulin to regulate free fatty acid (FFA) concentrations in healthy nondiabetic subjects selected to be either insulin-resistant or -sensitive on the basis of insulin-mediated glucose disposal by muscle. Comparisons of steady-state plasma glucose (SSPG), insulin (SSPI), and FFA concentrations were made at the end of 3 infusion periods: (1) under basal insulin conditions (approximately 10 microU/mL), (2) in response to isoproterenol-induced stimulation of lipolysis at the same basal insulin concentration, and (3) following inhibition of isoproterenol-induced lipolysis by a 2-fold increase in the insulin concentration. The results showed that steady-state FFA concentrations were significantly higher under basal conditions (360 +/- 73 v 158 +/- 36 microEq/L, P = .02), in response to isoproterenol-induced lipolysis (809 +/- 92 v433 +/- 65 microEq/L, P = .005), and following insulin inhibition of isoproterenol-induced lipolysis (309 +/- 65 v 159 +/- 37 microEq/L, P = .06). These differences were found despite the fact that SSPG concentrations were also higher in insulin-resistant individuals during all 3 infusion periods. These results demonstrate that the ability of insulin to regulate plasma FFA concentrations is impaired in healthy subjects with muscle insulin resistance, indicating that insulin-resistant individuals share defects in the ability of insulin to stimulate muscle glucose disposal and to inhibit adipose tissue lipolysis.

Adrenergic beta-Agonists↗
PubMed2000

Relation between insulin resistance and plasma concentrations of lipid hydroperoxides, carotenoids, and tocopherols.

BACKGROUND: It is not known whether total circulating lipid hydroperoxides are increased in insulin-resistant individuals and whether this correlates with depletion of liposoluble antioxidant vitamins that are consumed during lipid peroxidation. OBJECTIVE: The goal of this study was to define the relation between resistance to insulin-mediated glucose disposal and plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins in healthy volunteers. DESIGN: Insulin-mediated glucose disposal was determined in 36 healthy, nondiabetic volunteers by measuring their steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations in response to a 180-min constant infusion of octreotide, insulin, and glucose. In addition, fasting plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins were determined by using the FOX 2 assay and liquid chromatography. RESULTS: Statistically significant direct relations were observed between SSPG and mean arterial blood pressure (r = 0.44, P: = 0.008) and plasma lipid hydroperoxide concentrations (r = 0.42, P: = 0.01), whereas significant inverse correlations were found between SSPG and alpha-carotene (r = -0.58, P: = 0.0002), beta-carotene (r = -0.49, P: = 0.004), lutein (r = -0.35, P: = 0.04), alpha-tocopherol (r = -0. 36, P: = 0.04), and delta-tocopherol (r = -0.45, P: = 0.007). CONCLUSIONS: Variations in insulin-mediated glucose disposal in healthy individuals are significantly related to plasma concentrations of lipid hydroperoxides and liposoluble antioxidant vitamins. These findings suggest that total plasma lipid peroxidation is increased in insulin-resistant individuals at an early, preclinical stage, ie, well before the development of glucose intolerance and type 2 diabetes.

Blood Glucose↗
PubMed2000

Roles of insulin resistance and obesity in regulation of plasma insulin concentrations.

Plasma glucose, insulin, and C-peptide concentrations were determined in response to graded infusions of glucose, and insulin secretion rates were calculated over each sampling period. Measurements were also made of insulin clearance, resistance to insulin-mediated glucose, uptake, and the plasma glucose, insulin, and C-peptide concentrations at hourly intervals from 8:00 AM to 4:00 PM in response to breakfast and lunch. Plasma glucose, insulin, and C-peptide concentrations were significantly (P < 0.01) higher in obese women in response to the graded intravenous glucose infusion, associated with a 40% (P < 0.005) greater insulin secretory response. Degree of insulin resistance correlated positively (P < 0.05) with the increase in insulin secretion rate in both nonobese (r = 0.52) and obese (r = 0.58) groups and inversely (P < 0.05) with the decrease in insulin clearance in obese (r = -0.46) and nonobese (r = -0.39) individuals. Weight loss was associated with significantly lower plasma glucose, insulin, and C-peptide concentrations in response to graded glucose infusions and in day-long insulin concentrations. Neither insulin resistance nor the insulin secretory response changed after weight loss, whereas there was a significant increase in the rate of insulin clearance during the glucose infusion. It is concluded that 1) obesity is associated with a shift to the left in the glucose-stimulated insulin secretory dose-response curve as well as a decrease in insulin clearance and 2) changes in insulin secretion and insulin clearance in obese women are more a function of insulin resistance than obesity.

C-Peptide↗
PubMed2000

The relationship between glucose disposal in response to physiological hyperinsulinemia and basal glucose and free fatty acid concentrations in healthy volunteers.

This study was initiated to see if defects in the ability of physiological hyperinsulinemia (approximately 60 microU/mL) to stimulate glucose uptake in healthy, nondiabetic volunteers are associated with increases in concentrations of plasma glucose and free fatty acid (FFA) when measured at basal insulin concentrations (approximately 10 microU/mL). We recruited 22 volunteers (12 women and 10 men) for these studies, with a (mean +/- SEM) body mass index of 24.8 +/- 0.5 kg/m2. Resistance to insulin-mediated glucose disposal during physiological hyperinsulinemia was determined by suppressing endogenous insulin and determining the steady-state plasma glucose (SSPG) and steady-state plasma insulin (SSPI) concentrations at the end of a 3-h infusion, period during which glucose (267 mg/m2 x min) and insulin (32 mU/m2 x min) were infused at a constant rate. Glucose, insulin and FFA concentrations were also measured in response to infusion rates of glucose (50 mg/m2 x min) and insulin (6 mU/m2 x min). The SSPI concentration (mean +/- SEM) during physiological hyperinsulinemia was 64 +/- 3 microU/mL), in contrast to 12 +/- 0.4 microU/mL during the basal insulin study. The results demonstrated a significant relationship between SSPG concentration in response to physiological hyperinsulinemia (SSPG60) and SSPG(Basal) (r = 0.57, P < 0.01) and FFA(Basal) (r = 0.73, P < 0.001). Furthermore, FFA(Basal) and SSPG(Basal) were significantly correlated (r = 0.47, P < 0.05). Comparison of the seven most insulin-resistant and seven most insulin sensitive individuals (SSPG60 values of 209 +/- 16 vs. 64 +/- 8 mg/dL) revealed that the insulin-resistant group also had significantly higher SSPG(Basal) (105 +/- 5 vs. 78 +/- 7 mg/dL, P < 0.01) and FFA(Basal) (394 +/- 91 vs. 104 +/- 41, P < 0.02) concentrations. However, random fasting plasma glucose and FFA concentrations of the two groups were not different. The results presented demonstrate that individual differences in the ability of elevated insulin concentrations to stimulate muscle glucose disposal are significantly correlated with variations in insulin regulation of plasma glucose and FFA concentrations at basal insulin concentrations.

Adult↗