Insulin resistance is one of the major aggravating factors for metabolic disease. There are many methods available for estimation of insulin resistance which range from complex techniques down to simple indices. For all methods of assessing insulin resistance, it is essential that their validity and reliability be established before using them in clinical investigations. The reference techniques of hyperinsulinemic euglycemic clamp and its alternative,the frequently sampled intravenous glucose tolerance test, are the most reliable methods available for estimating insulin resistance. However, there are many simple methods from which indices can be derived that have been assessed and validated, which include homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). Given the increasing number of simple indices of insulin resistance, it may be difficult for clinicians and researchers to select the most appropriate index for their studies. In planning studies on insulin resistance and selecting a suitable index, a number of important factors need to be considered by investigators, the principle one being the nature of the study to be undertaken.
Glucose Clamp Technique ; Glucose Tolerance Test ; Homeostasis ; Humans ; Insulin Resistance* ; Metabolic Diseases ; Reproducibility of Results ; Research Personnel

The effect of persistant mild hyperglycemic hyperinsulinemia on the development of the insulin resistance in rats was studied in vivo. Also, the characteristics of the insulin resistance compared with the insulin resistance of STZ diabetic rats. Persistant mild hyperglycemic hyperinsulinemic rat model was produced by ingestion of glucose polymer for 8 days. The glucose disappearance and infusion rate was measured by hyperinsulinemic euglycemic clamp to"Imique at steady state of blood glucose and insulin levels. The clamped level of blood glucose was 100 mg/dl, and the clamped levels of insulin were 70 pU/ml (physiologic condition) and 3000 pU/ml (supramaximal condition). Hepatic glucose producticon rate was calculated using measured data. And the glycogen synthetic capacity of skeletal muscle(soleus) and liver was measured after 2 hours of hyperinsulinemic euglycemic clamp study. The glucose disappearance and glucose infusion rate in glucose polymer group was decreased in the both physiological and supramaximal insulin level compared to the rate of the normal control group. The rate of STZ diabetic group wase lowest at supramaximal insulin level among two another experimental groups. The hepatic glucose production rate of glucose polymer group was decreased compared to normal control but increased in STZ diabetic group.
Animals ; Blood Glucose ; Eating ; Glucans ; Glucose ; Glucose Clamp Technique ; Glycogen ; Hyperinsulinism* ; Insulin Resistance* ; Insulin* ; Liver ; Models, Animal ; Rats*

OBJECTIVETo investigate the relationship between adiponectin and beta-cell function in abdominal visceral obesity women.

METHODSNine abdominal visceral obesity women (VO), 9 normal subjects (C) and 7 patients with type 2 diabetes mellitus (T2DM) were enrolled in the study. Beta-cell function and insulin sensitivity were determined by hyperglycemic clamp, fasting serum adiponectin was assayed by ELISA and regional body fat was measured by MRI.

RESULTThe levels of first phase insulin release (FPIR), glucose disposal rates (GDR), insulin sensitivity index (ISI) and adiponectin were significantly elevated in control group compared with VO group and T2DM group. As compared with T2DM group, the levels of adiponectin, FPIR, second phase insulin release (SPIR) and maximum insulin release (INS(max)) increased significantly in VO group. Multiple stepwise regression analysis showed that age, FPIR and GDR were positively correlated to adiponectin (B=0.145, 0.194, 0.277 respectively, all P<0.05), while waist-hip ratio was negatively correlated with adiponectin (B=-7.424, P<0.05).

CONCLUSIONThe visceral obesity women have lower adiponectin levels, and hyperadiponectinemia may be the link with insulin secretion.

Abdominal Fat ; Adiponectin ; blood ; Adult ; Female ; Glucose Clamp Technique ; Humans ; Insulin-Secreting Cells ; physiology ; Middle Aged ; Obesity ; blood ; physiopathology

OBJECTIVES: Insulin resistance is a major pathophysiology in polycystic ovary syndrome (PCOS), and assessment of insulin sensitivity is important. Various insulin sensitivity indices from fasting state or oral glucose tolerance test (OGTT) have been compared with euglycemic hyperinsulinemic clamp. We aimed to evaluate the usefulness of these indices in young Korean women with PCOS. METHODS: Euglycemic hyperinsulinemic clamp test and 75 g OGTT were performed in 290 women with PCOS. Insulin mediated glucose uptake (IMGU), the insulin sensitivity index from clamp, was compared with various insulin sensitivity indices such as composite insulin sensitivity index (ISIcomp), estimated metabolic clearance rate (MCRest) of glucose and estimated insulin sensitivity index (ISIest), area under the curve of glucose and insulin ratio (AUC-GIR), OGTT-derived Belfiore index, and oral glucose insulin sensitivity index (OGSI) by Kazama. Fasting state indices such as glucose insulin ratio (GIR), homeostasis model assessment for insulin resistance (HOMA-IR), fasting Belfiore index, and quantitative insulin sensitivity check index (QUICKI) were also compared with IMGU. RESULTS: The correlation coefficients of ISIcomp, MCRest, ISIest, AUC-GIR, OGTT-Belfiore index, and OGSI with IMGU were all about 0.5 (Ps'<0.001) in PCOS women as a whole. The MCRest and ISIest were significantly correlated with IMGU in both obese (r=0.58 and 0.58, P<0.0001) and non-obese subjects (r=0.33 and 0.32, P<0.001). Fasting glucose and insulin-derived indices showed worse correlation with IMGU than OGTT-derived ones. CONCLUSION: The MCRest and ISIest from OGTT might be the best replacement for the insulin sensitivity index from hyperinsulinemic euglycemic clamp independent of obesity.
Fasting ; Female ; Glucose ; Glucose Clamp Technique ; Glucose Tolerance Test ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Metabolic Clearance Rate ; Obesity ; Polycystic Ovary Syndrome

BACKGROUND: Insulin resistance is a central feature of polycystic ovary syndrome (PCOS), and hyperinsulinemia contributes to anovulation, oligo or amenorrhea, hyperandrogenism and infertility in women with PCOS. The use of insulin sensitizers, such as metformin or thiazolidinedione, in PCOS is becoming increasingly accepted. The purpose of our study was to evaluate the therapeutic effects of metformin and rosiglitazone on the metabolic and reproductive derangement, and find parameters predicting their therapeutic efficacy in Korean PCOS women. METHODS: Sixty-two women with PCOS were recruited. The baseline characteristics, including BMI, glucose tolerance test, lipid profiles, sex hormones and hyperinsulinemic euglycemic clamp test, were assessed. After the administration of the insulin sensitizer (metformin 1.5g/day or rosiglitazone 4mg/day) for 3 months, the insulin sensitivity was reassessed. A drug response was defined as menstrual restoration or pregnancy. RESULTS: Of the 62 women with PCOS, 36 gained restored regular menstruation, and a further 5 conceived (a drug response rate of 66.7%). There were no significant clinical differences between responders and nonresponders. Twelve weeks after taking the drugs, the insulin sensitivity was significantly improved (M-value 4.7+/-0.2 vs. 5.5+/-0.4mg/kg/min, P<0.05), and the free testosterone levels(72.5+/-39.9 vs. 45.8 +/-3.8pmol/L, P<0.05) were significantly decreased, without significant weight reduction. CONCLUSION: Metformin and rosiglitazone restored menstruation in 66.1% of women with PCOS. Hyperandrogenemia and insulin sensitivity were significantly improved with the use of the two drugs. However, metabolic or hormonal markers for predicting the drug response could not be found.
Amenorrhea ; Anovulation ; Female ; Glucose Clamp Technique ; Glucose Tolerance Test ; Gonadal Steroid Hormones ; Humans ; Hyperandrogenism ; Hyperinsulinism ; Infertility ; Insulin ; Insulin Resistance ; Menstruation ; Metformin* ; Polycystic Ovary Syndrome* ; Pregnancy ; Testosterone ; Weight Loss

BACKGROUND: The glucose uptake rate is the limiting step in glucose utilization and storage. The failure of insulin to stimulate glucose uptake in muscle appears to be a primary defect of insulin resistance. This study was undertaken to examine the effect of physiological hyperinsulinemia on the phosphorylation of the insulin receptor (IR-beta), insulin receptor substrate (IRS), Akt kinase and GSK-3 in isolated skeletal muscle, in people with type 2 diabetes (n=9) and control subjects (n=11). METHODS: 75g OGTT and euglycemic hyperinsulinemic clamp test were done. And vastus lateralis muscle was obtained before and 30 min into the euglycemic clamp. Western blots were performed for tyrosine phosphorylation of insulin receptor substrate (IRS) and phosphorylation of the insulin receptor(IR-beta), Akt and GSK-3. RESULT: There were no statistical differences in the mean age, BMI and body fat between the control subjects and diabetic patients. The fasting blood sugar and HbA1c in controls and diabetic patients were 98.+/-1.3 and 208.1+/-16.5 ng/dl, and 5.4+/-0.5 and 9.2+/-0.6%, and 1.4+/-0.2 in the control subjects, and 72.2+/-52.3% (p<0.01) and 10.2+/-6.3 (p<0.01) in the diabetic patients, respectively. The insulin resistance from the euglycemic hyperinsulinemic clamp tests were 8.2+/-0.6 mg/kg/min and 3.7+/-1.1 ng/kg/min in the control subjects and in the diabetic patients, respectively (p<0.01). Compared with the normal controls, insulin-stimulated IR phosphorylation was no different to that in the diabetic patients. However, insulin-stimulated IRS phosphorylation, insulin-stimulated Akt phosphorylation and insulin-stimulated GSK-3 phosphorylation were reduced in the diabetic patients compared with the normal controls by 24, 43 and 25%, respectively (p<0.05). CONCLUSION: In korean type 2 diabetic patients, the insulin resistance may be due to the impairment of the upstream insulin signal molecular network. Further studies will focus on determining whether these signaling defects are the cause of the development of insulin resistance, or secondary to the altered metabolic state, associated with type 2 diabetes mellitus
Adipose Tissue ; Blood Glucose ; Blotting, Western ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Glucose Clamp Technique ; Glucose Tolerance Test ; Glycogen Synthase Kinase 3 ; Humans ; Hyperinsulinism ; Insulin ; Insulin Resistance ; Muscle, Skeletal* ; Phosphorylation ; Phosphotransferases ; Quadriceps Muscle ; Receptor, Insulin ; Signal Transduction* ; Tyrosine

The sieving coefficient(S) representing convective transport of glucose during peritoneal dialysis(PD) with glucose containing dialysis solution has been reported to be anomalous, lower than 0 or higher than 1. During peritoneal dialysis using glucose containing dialysis solution, diffusive transport of glucose is from dialysate to blood, and convective transport in the opposite direction i.e., from blood to dialysate. Glucose intolerance and hyperinsulinemia are well known adverse effects of PD using glucose containing dialysis solutions. Insulin is required for glucose transport from extracelluar fluid to intracelluar fluid in adipocytes and muscell cells. Hyperinsulinemia in PD may alter peritoneal glucose transport. If extra to intracellular glucose transport mediated by insulin is involved in the peritoneal glucose transport during PD with conventional glucose containing dialysis solutions, the diffusive and convective transport characteristics for glucose calculated using membrane model between two well-mixed compartments may not represent true values. S can be calculated best when diffusion is minimized. Male Sprague-Dawley rats were used. To minimize the diffusive transport the glucose isochratic solutions containing approximately the same concentration as in serum were used. To maximize ultrafiltration 3.86% mannitol was used as an osmotic agent. To evaluate the effect of insulin on glucose transport two different glucose concentrations, 100mg/dl(NI) and 300mg/dl(HI), were used. During the dialysis with HI solution glucose clamp technique was performed to keep blood glucose level approximately 300mg/dl. A 2 hour peritoneal dialysis was performed in 13 rats(7 Nl and 6 Hl). Serum and dialysate insulin levels were measured in 3rats in Nl, 2 rats in Hl, and 4 rats without dialysis(NC). Intraperitoneal volume(VD) was calculated using volume marker, RISA, dilution method. The diffusive mass transport coefficient(KBD) and S for urea and glucose were calculated using the modified Babb- Randerson-Farrell model. D/P glucose in Nl was 0.61+/-0.05 due to high blood glucose level 187.2+/-17.9mg/dl vs. 114.3+/-7.6 mg/dl in dialysate and 0.99+/-0.26 in Hl(360.6+/-55.6mg/dl in blood vs. 345.0+/-55.6mg/dl in dialysate). VD did not differ between the two groups. KBD for urea and glucose, and S for urea did not differ between the two groups. S for glucose in Hl was negative value and significantly lower than that in Nl(-0.903+/-0.960 vs. 1.036+/-0.137, P<0.001). Plasma insulin level was significantly higher in Hl compared with values in Nl and NC. Dialysate insulin level was similar in Nl and Hl. Dialysate insulin level in Nl was higher than plasma insulin level. The present result that S for glucose at hyperinsulinemic condition was anomalous indicates that not only simple passive transport but also other transport mechanisms mediated by insulin such as glucose influx into cells may be involved in peritoneal glucose transport. The finding of dialysate insulin level higher than plasma concentration in Nl may suggest direct leakage of insulin from pancreas or portal vein into the peritoneal cavity.
Adipocytes ; Animals ; Blood Glucose ; Dialysis ; Dialysis Solutions ; Diffusion ; Glucose Clamp Technique ; Glucose Intolerance ; Glucose* ; Humans ; Hyperinsulinism ; Insulin ; Male ; Mannitol ; Membranes ; Pancreas ; Peritoneal Cavity ; Peritoneal Dialysis* ; Plasma ; Portal Vein ; Rats ; Rats, Sprague-Dawley ; Ultrafiltration ; Urea

OBJECTIVETo investigate the relationship between serum interleukin-10 (IL-10) level and insulin resistance (IR) in patients with metabolic syndrome (MS).

METHODSEighteen MS subjects and 18 age-matched normal subjects were enrolled. IR was evaluated by hyperinsulinemic-euglycemic clamp technique and serum IL-10 level measured by ELISA. Pearson's correlation analysis was used to investigate the relationship between serum IL-10 level and IR.

RESULTSSerum IL-10 levels were significantly higher in patients with MS than in the controls [1.3 (0.8/3.1) pg/ml vs 2.4 (1.1/4.5) pg/ml, P<0.05], and glucose metabolic rate (M value) derived from hyperinsulinemic-euglycemic clamp technique was lower in MS subjects than in controls [(5.76+/-1.81) mg/kg.min vs (8.39+/-1.25) mg/kg.min], P<0.05]. Serum IL-10 levels showed a positive correlation with M value (P<0.05).

CONCLUSIONPatients with MS have greater IR and lower serum IL-10 levels than normal subjects, and lowered IL-10 levels might be involved in the pathogenesis of IR in MS.

Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Glucose Clamp Technique ; Humans ; Insulin Resistance ; Interleukin-10 ; blood ; Male ; Metabolic Syndrome ; blood ; Middle Aged

BACKGROUNDThe persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery.

METHODSThirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression.

RESULTSWhen compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035.

CONCLUSIONSCIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.

Adipose Tissue ; metabolism ; Animals ; Blood Glucose ; metabolism ; Blotting, Western ; Glucose Clamp Technique ; Glucose Transporter Type 4 ; metabolism ; Hypoxia ; physiopathology ; Immunohistochemistry ; Insulin ; blood ; Insulin Resistance ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction

AIMTo observe the stability of BCG-induced insulin resistance model.

METHODSThe glucose tolerance, serum glucose, FFA, insulin, triglycerides, cholesterol, TNF-alpha and ALT level were measured. The change of GDR was measured by euglycemic clamp in model rats after given i.v. BCG 2, 4 and 8 weeks.

RESULTSAfter 2, 4 and 8 weeks, the GIR and glucose tolerance of the animals deceased significantly. After 2, 4 and 8 weeks, BCG infusion resulted in a pronounced reduction in glucose tolerance and insulin-stimulated glucose disposal rate [GDR = GDR: (29 +/- 6) vs (13 +/- 7) mg.kg-1.min-1 2 weeks; (29 +/- 6) vs (11 +/- 7) mg.kg-1.min-1 4 weeks and (23 +/- 3) vs (16 +/- 3) mg.kg-1.min-1 8 weeks, respectively, P < 0.01]. BCG infusion resulted in a pronounced increase in the weights of the liver [(6.2 +/- 0.9) vs (8.2 +/- 1.3) g, P < 0.05] and spleens [(0.51 +/- 0.11) vs (1.4 +/- 0.4) g, P < 0.01]. The histo-pathological results showed that BCG infusion resulted severe inflammation in the livers and spleens and the ratio of beta/alpha in pancreas increased. The serum levels of triglyceride, FFA and glucose were unchanged, but the level of serum TNF-alpha [543 +/- 60) vs (759 +/- 137) pg.mL-1, P < 0.05] and insulin [(31 +/- 5) vs (36 +/- 5) mu.L-1, P > 0.05] increased.

CONCLUSIONThis novel model of immune insulin resistance is completely and constantly established.

Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus ; metabolism ; Glucose Clamp Technique ; Glucose Tolerance Test ; Injections, Intravenous ; Insulin ; blood ; Insulin Resistance ; immunology ; Male ; Mycobacterium bovis ; Random Allocation ; Rats ; Rats, Wistar ; Spleen ; pathology ; Tumor Necrosis Factor-alpha ; metabolism