Steady-state Plasma Glucose Research Articles

Adiponectin levels among patients with chronic hepatitis B and C infections and in response to IFN‐α therapy

The study was designed to survey the change of adiponectin levels before and after interferon-alpha (IFN-alpha) therapy in patients with chronic hepatitis B and C infections. Twenty-one biopsy-proved patients with chronic hepatitis B (10 cases) and hepatitis C (11 cases) were given IFN-alpha for a total of 24 weeks. Fasting plasma glucose, insulin and adiponectin levels were obtained before and 12 weeks after completion of IFN-alpha therapy. Insulin suppression test was conducted before and within 1 week after IFN-alpha therapy. The change of adiponectin levels differed significantly between responders (eight cases) and non-responders (13 cases) to IFN-alpha treatment (-4.8+/-2.2 vs. 0.5+/-1.0 microg/ml, P=0.03). After adjusting for age, gender and change in body mass index, the study found the change of adiponectin levels still significantly related to the response to IFN-alpha (P=0.04). When hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected patients were separately analyzed, the adiponectin levels reported a trend to decrease in HCV responders (11.9+/-3.2 vs. 10.8+/-3.0 microg/ml, P=0.02, n=4) and HBV responders (17.7+/-4.1 vs. 9.2+/-1.0 microg/ml, P=0.10, n=4). In addition, a significant decrease of steady-state plasma glucose in insulin suppression test was noted in responders (13.6+/-1.8-11.7+/-1.2 mmol/l, P=0.03), but not in non-responders (12.3+/-1.1-11.0+/-1.0 mmol/l, P=0.20), after IFN-alpha therapy. IFN-alpha resulted in a decrease of serum adiponectin levels but an improvement of insulin resistance in responders to the treatment. The result contradicts previous concept of the relationship between insulin resistance and adiponectin levels. Whether and how the augmented immune response, which was supposed to result from the disappearance or the profound down-regulation of the virus or viral antigens in responders to IFN-alpha treatment, contributes to the lowering of adiponectin levels needs to be further investigated.

Second World Congress on the Insulin Resistance Syndrome

This is the first in a series of articles on the Second World Congress on the Insulin Resistance Syndrome, Universal City, California, 18–20 November 2004. Yehuda Handelsman (Tarzana, CA) introduced the Second World Congress on the Insulin Resistance Syndrome, noting the importance of ICD-9 diagnostic code 277.7, which allows one to use insulin resistance syndrome as a specific medical diagnosis, although the nomenclature of the syndrome is complex (1). There is a continuous relationship between the number of risk factors and associated conditions and the severity of insulin resistance, so that it may be incorrect to suggest that a specific number of components is needed to determine the presence of this condition, a potential advantage of the American Association of Clinical Endocrinologists diagnostic criteria, which appears to be more strongly associated with diabetes than other criteria for the insulin resistance syndrome. Gerald M. Reaven (Stanford, CA) discussed the relationship between obesity and the insulin resistance syndrome, noting that mean fat and energy intake increased between 1990 and 2000 from 81 to 86 g and from 1,969 to 2,200 calories daily, respectively, so that “we’re getting heavier because we’re eating more.” Obesity is associated with increased mortality, with insulin resistance the link between obesity and coronary heart disease. Reaven used 3-h somatostatin, insulin, and glucose infusion to measure the steady-state plasma glucose (SSPG), which is inversely related to insulin sensitivity. There is tremendous variability in healthy individuals, with SSPG in 490 people with normal glucose tolerance 300 mg/dl in the 10th decile. The lowest quartile of insulin sensitivity is strongly predictive of development of diabetes and of coronary artery disease. Both BMI and waist circumference correlate with SSPG, but “with enormous variation,” as some obese individuals have normal and some lean individuals have high …

Change in Vascular Adhesion Protein‐1 and Metabolic Phenotypes after Vertical Banded Gastroplasty for Morbid Obesity

The association between circulating vascular adhesion protein-1 (VAP-1) and metabolic phenotypes has been shown to be inconsistent. The current study explored whether the changes in serum VAP-1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery. Clinical characteristics and serum VAP-1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m(2)) were measured before and after vertical banded gastroplasty. Before surgery, serum VAP-1 levels correlated positively with fasting plasma glucose (gamma = 0.56, p = 0.01) and negatively with insulin levels (gamma = -0.51, p = 0.021). After surgery, the changes in serum VAP-1 levels were negatively correlated with the changes in waist circumference (gamma = -0.57, p = 0.011), diastolic blood pressure (DBP) (gamma = -0.56, p = 0.015), and mean arterial pressure (gamma = -0.46, p = 0.055). In multivariate regression, serum VAP-1 levels were negatively correlated with waist circumference (beta = -2.36, p = 0.014) and DBP (beta = -3.02, p = 0.017) after adjusting for age and gender. The change in DBP was negatively correlated with the change in VAP-1 levels after adjusting for age, gender, and steady-state plasma glucose. The results suggest that VAP-1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects. After surgery, the changes in VAP-1 levels were associated with changes in visceral adiposity and DBP. Serum VAP-1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people.

The −514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population

Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.

Increased plasma concentration of nitric oxide in type 2 diabetes but not in nondiabetic individuals with insulin resistance

Insulin resistance (IR) is a key element in the pathogenesis of type 2 diabetes. The results of recent experiments on insulin-mediated vasodilatation have suggested that vascular insensitivity is a component of IR. However, it is still controversial that patients with type 2 diabetes have a decreased ability of insulin to increase endothelial nitric oxide (NO) release. Plasma concentration of NO was examined in 26 patients with type 2 diabetes and 78 nondiabetic volunteers during an insulin suppression test. The test measured the efficacy of insulin in promoting disposal of the infused glucose load, in which the steady state plasma glucose (SSPG) during the 150-180 min of the test was used as an index of IR. Plasma NO levels were assayed by measurement of the stable end products of their metabolism. Comparison of plasma NO levels between groups were performed by Mann-Whitney test and relationships between SSPG and different variables were analyzed by partial correlations. Our results showed that the plasma NO levels were significantly higher in the diabetic group. When the nondiabetic subjects were analyzed according to their SSPG levels, there was no difference of plasma NO levels between those with SSPG>160 mg/dl and those with SSPG<160 mg/dl. There were also no difference of NO levels between those with a family history of type 2 diabetes and those without. In the nondiabetic group, SSPG correlated with BMI, fasting insulin, triglyceride and HDL-cholesterol, but neither with plasma NO levels nor fasting plasma glucose. Our data suggests that the impairment of NO activity in patients with type 2 diabetes is due to an impaired effect rather than its production. This altered NO signaling pathway is not an early event in insulin resistant individuals. Any such changes will not be apparent until type 2 diabetes with overt hyperglycemia develops.

Relationship between several surrogate estimates of insulin sensitivity in non-diabetic patients with coronary artery disease.

Insulin resistance plays an important role in the pathogenesis of coronary artery disease (CAD). Thus, there is a need for accurate and accessible tools for measurement of insulin sensitivity in patients with this disease. This study explored the relationship between several surrogate estimates of insulin sensitivity in non-diabetic patients with angiographic evidence of CAD. The study population consisted of 1363 non-diabetic subjects with angiography results which revealed evidence of CAD in 660 and no evidence of CAD in 703 subjects. After overnight fasting, blood samples were drawn for determination of glucose and insulin concentrations in order to determine the homeostasis model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). In addition, steady-state plasma glucose (SSPG) concentrations obtained from insulin suppression tests were carried out in 54 subjects with and 194 subjects without CAD. The correlation of QUICKI with other surrogate estimates of insulin sensitivity in obese and non-obese subjects was also evaluated. The QUICKI correlated significantly with other methods for estimating insulin sensitivity in the CAD and non-CAD groups. The QUICKI also had a closer correlation with SSPG and log fasting plasma insulin (log FPI) in subjects with CAD (r = -0.573 and -0.869, respectively) than HOMA-IR (r = 0.508 and 0.777, respectively). QUICKI had a closer correlation with SSPG in the obese subjects than in the non-obese subjects, irrespective of the presence of CAD. The QUICKI was more closely related with SSPG, insulin area, and log FPI than other measurements of insulin sensitivity. These findings suggest that the QUICKI may provide a convenient, efficient method to measure insulin sensitivity in non-diabetic patients with CAD.

A Polymorphism Exon 1 Variant at the Locus of the Scavenger Receptor Class B Type I (SCARB1) Gene Is Associated with Differences in Insulin Sensitivity in Healthy People during the Consumption of an Olive Oil-Rich Diet

Scavenger receptor class B type I (SCARB1) was described as the first high-density lipoprotein receptor. Increasing evidence indicates that SCARB1 plays additional roles particularly in type 2 diabetes mellitus. Our aim was to determine whether the presence of an exon 1 (G-->A) polymorphism at the SCARB1 gene modifies the insulin sensitivity to dietary fat. We studied 59 healthy volunteers (30 men and 29 women, 42 G/G homozygous and 17 G/A heterozygous). Subjects consumed three diets for 4 wk each: a saturated fatty acid (SFA)-rich diet (38% fat, 20% SFA), followed by a carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a monounsaturated fatty acid (MUFA)-rich diet (38% fat, 22% MUFA) after a randomized crossover design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. Steady-state plasma glucose after the MUFA diet was lower in G/A compared with G/G subjects (P = 0.030). This effect was not observed after CHO and SFA diets (P = 0.177 and 0.957, respectively). Plasma nonesterified free fatty acid values were lower in subjects carrying the A allele for all the diet periods. Our findings show that carriers of the G/A genotype have significant increases in insulin sensitivity after a MUFA-rich diet compared with G/G individuals.

Divergent Effects of Unilateral and Subtotal Nephrectomy on Insulin Sensitivity in Rats

Objectives. Insulin resistance is associated with chronic renal failure, which may amplify its cardiovascular pathologic manifestations. We previously showed the presence of insulin resistance in mild renal insufficiency due to chronic glomerulonephritis. These observations may be explained by a decrease in insulin sensitivity due to renal dysfunction. The aim of the present study was to evaluate the effects of unilateral and subtotal nephrectomy on insulin sensitivity. Methods. Unilateral heminephrectomy and five-sixths nephrectomy (5/6Nx) were performed in male Sprague–Dawley rats, measuring steady-state plasma glucose (SSPG) during the insulin suppression test. Results. The glomerular filtration rate (GFR) decreased significantly from sham-operated rats, to unilateral heminephrectomy group, to 5/6Nx rats. SSPG was unexpectedly lower in the unilateral heminephrectomy group than in controls, suggesting that unilateral heminephrectomy increased the sensitivity to insulin despite a mild decrease in renal function. However, when the analysis was limited to the 5/6Nx group, SSPG was inversely correlated with GFR (r = − 0.65, p < 0.05). When renal failure caused by 5/6Nx had reached end stage, the rats became insulin resistant, despite a profound reduction in renal mass. Conclusion. It is suggested that unilateral heminephrectomy reduced GFR and increased the sensitivity to insulin. When rats became uremic, insulin sensitivity decreased, even, in 5/6Nx.

Comparative effects of rosuvastatin and gemfibrozil on glucose, insulin, and lipid metabolism in insulin-resistant, nondiabetic patients with combined dyslipidemia

To evaluate the pharmacologic intervention most likely to decrease cardiovascular disease risk in insulin-resistant patients with combined dyslipidemia, 39 patients with this abnormality were assessed before and after 3 months of treatment with gemfibrozil (1,200 mg/day) or rosuvastatin (40 mg/day) with regard to: (1) steady-state plasma glucose concentration at the end of a 180-minute infusion of octreotide, insulin, and glucose; (2) fasting lipid, lipoprotein, and apolipoprotein concentrations; and (3) daylong glucose, insulin, triglyceride, and remnant lipoprotein cholesterol concentrations in response to breakfast and lunch. The 2 groups were similar at baseline in age, gender, body mass index and in measurements of carbohydrate and lipoprotein metabolism. Neither gemfibrozil nor rosuvastatin enhanced insulin sensitivity or lowered daylong glucose and insulin concentrations in insulin-resistant patients with combined dyslipidemia, but both drugs significantly decreased fasting triglyceride concentrations. However, only rosuvastatin treatment significantly (p <0.05 to <0.001) reduced fasting low-density lipoprotein cholesterol, apolipoprotein B-100, apolipoprotein C-III, apolipoprotein C-III:B particles, the apolipoprotein B-100:apolipoprotein A-I ratio, and increased apolipoprotein A-I (p <0.05). The degree of improvement in fasting and postprandial remnant lipoprotein cholesterol concentrations was significantly greater (p <0.05) in rosuvastatin-treated patients, and this difference in the relative effectiveness of the drugs was also true of the decrease in non-high-density lipoprotein cholesterol concentrations.

Impact of degree of obesity on surrogate estimates of insulin resistance.

To evaluate the role of adiposity in the relationship between specific and surrogate estimates of insulin-mediated glucose uptake (IMGU) in a large nondiabetic population. Healthy volunteers were classified by BMI into normal weight (<25.0 kg/m(2), n = 208), overweight (25.0-29.9 kg/m(2), n = 168), and obese (>or=30.0 kg/m(2), n = 109) groups. We then assessed how differences in BMI affect the correlation between steady-state plasma glucose (SSPG) concentration at the end of a 180-min infusion of octreotide, glucose, and insulin (a specific measure of IMGU) and five surrogate estimates: fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and area under the curve for insulin in response to oral glucose (I-AUC). Correlation coefficients (r values) between SSPG and surrogate measures of IMGU were all significant (P < 0.05), but the magnitude varied between BMI groups: normal weight: fasting plasma glucose 0.20, fasting plasma insulin 0.33, HOMA-IR 0.36, QUICKI -0.33, and I-AUC 0.69; overweight: fasting plasma glucose 0.19, fasting plasma insulin 0.55, HOMA-IR 0.55, QUICKI -0.54, and I-AUC 0.72; and obese: fasting plasma glucose 0.40, fasting plasma insulin 0.56, HOMA-IR 0.60, QUICKI -0.61, and I-AUC 0.69. The relationship between direct and surrogate estimates of IMGU varies with BMI, with the weakest correlations seen in the normal-weight group and the strongest in the obese group. In general, I-AUC is the most useful surrogate estimate of IMGU in all weight groups. Fasting plasma insulin, HOMA-IR, and QUICKI provide comparable information about IMGU. Surrogate estimates of IMGU based on fasting insulin and glucose account for no more than 13% of the variability in insulin action in the normal-weight group, 30% in the overweight group, and 37% in the obese group.

Physiological Measurement of Insulin Action across a Range of Insulin Sensitivities

2265 Resistance to insulin action, i.e. decreased uptake of glucose from the blood at a given plasma insulin concentration, is a large public health problem in the U.S. Insulin action is quantifiable using 2 broad classes of methods. Open-loop techniques in which endogenous insulin production is replaced by exogenous infusion, e.g. the hyperinsulinemic clamp, allow quantitative assessment of peripheral glucose uptake (PGU) but do not closely approximate physiological conditions. Closed-loop techniques based on endogenous insulin secretion, e.g. the oral glucose tolerance test (OGTT), better simulate physiological conditions but do not allow calculation of PGU. The CIGMA technique (Continuous Infusion of Glucose with Model Assessment) is a closed-loop system developed and validated to quantitatively measure glucose uptake under “physiological” conditions. CIGMA is useful to characterize insulin resistance in a population but not to assess changes before and after an intervention. Purpose: To compare insulin action measured with by CIGMA, modified by scaling the infusion rate to fat free mass and including a glucose stable isotope to quantify glucose (m- CIGMA), to the Composite Insulin Sensitivity Index (C-ISI) derived from the glucose and insulin responses to a standard OGTT. Methods: On 2 separate mornings, in balanced order, insulin action was measured by m-CIGMA or C-ISI in 18 individuals (8 F, 9 M) who were expected to encompass a wide range of insulin actions. In the m-CIGMA test, [6,62H]glucose was infused for 90' in the fasted state followed by infusion of 20% dextrose (2% enriched with [6,62H]glucose) at 8.45 mg/kg FFM for 60'. During the steady-state period (last 10 minutes of the infusion) glucose (SSPG) and insulin (SSPI) concentrations were used to calculate insulin action (SSPG/SSPI). Insulin action was calculated from Glucose and insulin concentrations measured every 30' during the OGTT were incorporated into a mathematical model to derive C-ISI. Measures of whole-body insulin action generated by the 2 methods were compared with Pearson's correlation analysis. Results: There was a statistically significant relationship (r=.707, p =.003) between insulin action measured by M-CIGMA and C-ISI. Conclusion: These results suggest that for individuals with a range of insulin sensitivities, steady-state plasma glucose and insulin responses to the m-CIGMA infusion simulate the responses to a typical mixed meal. Insulin action measured by the m-CIGMA method is in good agreement with estimates based on the OGTT and can be used in conjunction with stable isotope dilution to assess peripheral and hepatic insulin action under physiological conditions

Plasma Ghrelin Concentrations Are Decreased in Insulin-Resistant Obese Adults Relative to Equally Obese Insulin-Sensitive Controls

Ghrelin, an orexigenic hormone that may play a role in body weight regulation, is reduced in states of obesity. Because obesity is associated with insulin resistance and compensatory hyperinsulinemia, we determined whether these metabolic characteristics were independently associated with suppressed ghrelin concentrations. To investigate this hypothesis, using steady-state plasma glucose concentrations, we identified 20 insulin-resistant (IR) and 20 insulin-sensitive (IS) individuals who were equally obese. The mean body mass indexes were 32.5 +/- 0.4 and 32.0 +/- 0.4 kg/m(2) for the IR and IS groups, respectively. Fasting insulin concentrations were 19.5 and 7.4 micro U/ml (P < 0.001), respectively. Ghrelin concentrations were suppressed in the IR group (252 +/- 19 pg/ml) relative to the IS group (412 +/- 35 pg/ml; P < 0.001). Ghrelin correlated inversely with both insulin resistance (r = -0.64; P < 0.001) and fasting insulin concentration (r = -0.58; P < 0.001). Multivariate analysis confirmed that both insulin resistance and hyperinsulinemia independently predicted low ghrelin concentrations. Our results demonstrate that in obese individuals, insulin resistance and hyperinsulinemia are inversely associated with ghrelin concentrations. Thus, insulin resistance or related metabolic abnormalities may constitute part of a feedback mechanism by which body weight is regulated in humans.

Prevalence of insulin resistance and associated cardiovascular disease risk factors among normal weight, overweight, and obese individuals

Obese individuals tend to be both insulin resistant and at increased risk to develop cardiovascular disease (CVD). Given the increased prevalence of obesity in the US population, we thought it important to define the relationship between degree of obesity and insulin-mediated glucose disposal in the population at large, as well as the relationship between obesity, insulin resistance, and CVD risk in these individuals. To do this we quantified insulin-mediated glucose disposal in 465 healthy volunteers by determining the steady-state plasma glucose (SSPG) concentrations at the end of a 180-minute infusion of somatostatin, insulin, and glucose. Adiposity was estimated by body mass index (BMI) and the relationship between BMI and SSPG defined. In addition, a series of CVD risk factors were measured, including blood pressure, plasma glucose, and insulin concentrations, before and after 75 g of oral glucose, and fasting plasma lipid and lipoprotein concentrations. The results indicated that SSPG concentration and BMI were significantly correlated ( r = 0.54, P > .001), and 36% of individuals in the most insulin-resistant tertile were obese (BMI ≥ 30.0 kg/m 2). However, 16% of those in the most insulin-resistant tertile were of normal weight (BMI < 25.0 kg/m 2). Although CVD risk factors were accentuated in general with progressive increases in either BMI or SSPG concentration, important differences were noted. Thus, the higher the SSPG concentration, the more the increase in plasma glucose, insulin, and triglyceride (TG) concentrations, whereas the greater the BMI, the higher the low-density lipoprotein concentration. Furthermore, while CVD risk factors increased significantly with each tertile of insulin resistance, significant differences in CVD risk were only apparent when the lowest BMI tertile was compared with the other 2, with the values in the middle and upper BMI differing from each other. These results show that while BMI and insulin resistance are related, they are not synonymous, and that they make independent and different contributions to increasing CVD risk.

1160-197 Decreased serum ghrelin and insulin-like growth factor-I levels associated with insulin resistance in patients with acute heart failure: Analysis by steady-state plasma glucose method

1160-197 Decreased serum ghrelin and insulin-like growth factor-I levels associated with insulin resistance in patients with acute heart failure: Analysis by steady-state plasma glucose method

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension

Background Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening. Methods We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening. A total of 41 subjects with nondiabetic essential hypertension were studied. Endothelial function of brachial artery and carotid wall thickening were assessed noninvasively using ultrasound technique. In brachial artery, we measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate–induced endothelium-independent vasodilation (GTN). We estimated intima-media thickness of the common carotid artery (IMT). Insulin sensitivity was measured according to the steady-state plasma glucose (SSPG) method. High SSPG levels indicated insulin resistance. Results On univariate analysis, there were significant negative correlations between FMD and SSPG ( r = −0.695, P < .0001) or IMT ( r = −0.449, P < .004). The FMD was negatively correlated significantly with age and with systolic and diastolic blood pressures (BP). A significant negative correlation was observed between GTN and SSPG. There was a significant positive relation between SSPG and IMT. On multiple regression analysis including systolic BP, SSPG, and age as independent variables and FMD as a dependent variable, FMD was independently related to SSPG ( P < .03) and systolic BP ( P < .02). If the presence of SSPG, diastolic BP, and age were entered as independent variables against FMD, FMD was independently related to SSPG ( P < .002). Conclusions One of the major determinants of endothelial function was insulin resistance. Our findings suggest that endothelial dysfunction and early structural vascular changes were related to insulin resistance.

Plasma adiponectin concentrations do not increase in association with moderate weight loss in insulin-resistant, obese women

Plasma adiponectin concentrations were measured before and after moderate weight loss in 20 obese women, divided at baseline into insulin-resistant (IR) and insulin-sensitive (IS) subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, glucose, and insulin. The groups were similar in age and body weight and lost comparable amounts of weight (8 to 9 kg) during the weight loss period. Fasting plasma insulin and SSPG concentrations were significantly higher ( P < .001) and adiponectin concentrations somewhat lower ( P = .10) in the IR group ( P < .001) at baseline. Both SSPG and plasma insulin concentrations decreased in IR subjects ( P < .001), but did not change in IS individuals. Adiponectin concentrations did not change with weight loss in either group. Thus, neither weight loss, per se, nor enhanced insulin sensitivity resulted in a change in plasma adiponectin concentrations.

The 1st World Congress on the Insulin Resistance Syndrome.

This is the first of two articles covering the 1st World Congress on the Insulin Resistance Syndrome (IRS), which was held in Los Angeles, 21–22 November 2003. Yehuda Handlesman (Tarzana, CA), the conference organizer, noted that it reflects an endeavor to bring an understanding of basic science into the clinical practice of medicine. Contributory causes of insulin resistance include obesity, sedentary lifestyle, and many other characteristics and conditions. Handlesman noted that the syndrome has been assigned International Classification of Disease (ICD)-9 code 277.7 as the dysmetabolic syndrome. Many aspects of the IRS are pharmacologically treatable when lifestyle modification is ineffective, and we need tools to determine which approaches are appropriate for particular individuals. Gerald Reaven (Stanford, CA) reviewed the six- to eightfold variation in steady-state plasma glucose (SSPG) with continuous octreotide, insulin, and glucose infusion among apparently healthy persons. He attributed the lack of glycemic abnormality of persons with insulin resistance to compensatory hyperinsulinemia, although noting that there is great variation in insulin levels for a given level of insulin sensitivity. Similarly, there is variation in the correlations between obesity and insulin resistance, as well as between maximal aerobic capacity, a measure of physical fitness, and insulin sensitivity. Reaven suggested that adiposity and physical fitness each account for ∼25% of the variability in insulin sensitivity, with genetic factors, which he illustrated with the differences in insulin sensitivity between persons of European and persons of South Asian or Mexican ancestry and with the similarity in insulin sensitivity of related persons in a family, responsible for an additional 50% of this variation. Syndrome X, as Reaven originally termed it, included insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and increased risk of both diabetes and coronary heart disease. Other abnormalities associated with the IRS include glucose intolerance, small LDL particle size, postprandial accumulation of triglyceride-rich …

Use of metabolic markers to identify overweight individuals who are insulin resistant.

Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful. To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant. Cross-sectional study. General clinical research center. 258 nondiabetic, overweight volunteers. Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power. Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%). Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.

Interferon-alpha reduces insulin resistance and beta-cell secretion in responders among patients with chronic hepatitis B and C.

This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

Methods for quantifying insulin resistance in human immunodeficiency virus-positive patients

Various indirect indices have been used in human immunodeficiency virus (HIV)-infected individuals to assess insulin resistance, but the validity of these measures has not been rigorously assessed by comparison with physiologic methods of quantifying insulin-mediated glucose uptake (IMGU). We directly measured IMGU in 50 nondiabetic HIV-positive subjects by determining the steady-state plasma glucose (SSPG) concentration in response to a 3-hour continuous infusion of insulin, glucose, and somatostatin. Because steady-state plasma insulin concentrations were similar (∼60 μU/mL) in all subjects, the SSPG concentrations provided direct assessments of insulin action. Relationships between SSPG levels and various surrogate measures of IMGU derived from the 75-g oral glucose tolerance test (OGTT) were determined. The indirect measure of IMGU most closely related to SSPG concentrations was the total integrated insulin response to a 75-g glucose load ( r = 0.78, P < .01), accounting for approximately two thirds of the variability in SSPG ( r 2 = 0.61). Other indirect measures of IMGU, including the homeostasis assessment for insulin resistance (HOMA-IR), were also significantly related to SSPG values, but had lower magnitudes of correlation ( r = 0.43 to 0.61), thereby possessing limited ability to predict SSPG variability ( r 2 = 0.18 to 0.37). In conclusion, indirect measures of IMGU need to be applied with caution when evaluating insulin action in HIV-infected patients.