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

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

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

BACKGROUNDHyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitivity, but it is too complicated and expensive to use in clinic. We tried to find an alternative indicator to reflect insulin sensitivity. To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.

METHODSIn this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship between the different adipokines and glucose disposal rate (M value), as well as insulin sensitivity index (M value/insulin, M/I), which are the "gold standard" indices of insulin sensitivity.

RESULTSThere were significant differences in mean leptin values in the four adipokines from the four different groups (P < 0.001; comparison of the variation between different groups was analyzed by variance analysis). Compared to controls (using multiple comparison two-way Dunnett t test), only the leptin level showed significant differences in the four adipokines from the four different groups at the same time (P < 0.001). The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or M/I values (r = -0.56, P < 0.001); there was no relationship between the other three adipokines and M or M/I values.

CONCLUSIONOnly leptin was associated with M or M/I values. Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Adipokines ; blood ; Adiponectin ; blood ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 1 ; blood ; Diabetes Mellitus, Type 2 ; blood ; Glucose Clamp Technique ; Humans ; Insulin Resistance ; physiology ; Leptin ; blood ; Obesity ; blood ; Resistin ; blood ; Tumor Necrosis Factor-alpha ; blood

BACKGROUND: Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function. METHODS: In Sprague-Dawley (SD) rats treated with SIN-1 for 4 weeks, insulin sensitivity was measured by a glucose clamp study. Triglyceride content and fatty acid oxidation were measured in the skeletal muscle. In addition, mitochondrial DNA content and mRNA expression of mitochondrial biogenesis markers were assessed by real-time polymerase chain reaction and expression of insulin receptor substrate (IRS)-1 and Akt were examined by Western blot analysis in skeletal muscle. In C2C12 cells, insulin sensitivity was measured by 2-deoxyglucose uptake and Western blot analysis was used to examine the expression of IRS-1 and Akt. RESULTS: SIN-1 improved insulin sensitivity in C2C12 cells and skeletal muscles of SD rats. In addition, SIN-1 decreased triglyceride content and increased fatty acid oxidation in skeletal muscle. Mitochondrial DNA contents and biogenesis in the skeletal muscle were increased by SIN-1 treatment. Moreover, SIN-1 increased the expression of phosphor-IRS-1 and phosphor-Akt in the skeletal muscle and muscle cells. CONCLUSION: Our results suggest that NO mediates glucose uptake in skeletal muscle both in vitro and in vivo by improving mitochondrial function and stimulating insulin signaling pathways.
Animals ; Organelle Biogenesis ; Blotting, Western ; Deoxyglucose ; DNA, Mitochondrial ; Glucose ; Glucose Clamp Technique ; Humans ; Insulin ; Insulin Resistance ; Mitochondria ; Muscle Cells ; Muscle, Skeletal ; Muscles ; Nitric Oxide ; Rats ; Real-Time Polymerase Chain Reaction ; Receptor, Insulin ; RNA, Messenger ; Signal Transduction ; Tissue Donors

OBJECTIVETo investigate the role of c-Jun NH (2)-terminal kinase (JNk) in insulin resistance after burn and its mechanism.

METHODSTwenty-four Sprague-Dawley rats were randomized to control, burn and burn + anisomycin groups. The rats in control group received sham burn trauma, and burn and burn + anisomycin groups received 30% total body surface area (TBSA) full thickness burn injury. Anisomycin (5 mg/kg) together with 250 microl dimethyl sulfoxide (DMSO) was injected to the rats in anisomycin group intravenously, and only 250 microl DMSO in the other two groups. Euglycemic-hyperinsulinemic glucose clamps was performed 2 hours after the injection. The changes of phospho-serine 307, phospho-tyrosine of insulin receptor substrate (IRS)-1 and phospho-JNK in muscle tissues were determined and compared using immunoprecipitation and Western blot analysis or immunohistochemistry in the three groups.

RESULTSThe infusing rates of total 10% glucose (mg x kg(-1) x min(-1)) in control, burn and burn + anisomycin group were 12.3 +/- 0.4, 6.6 +/- 0.3, 6.5 +/- 0.4, respectively. The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn.

CONCLUSIONSThe activation of JNK elevates the level of IRS-1 phospho-serine 307 and might play a role in insulin resistance after burn in rats.

Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Anisomycin ; administration & dosage ; Anti-Bacterial Agents ; administration & dosage ; Blotting, Western ; Burns ; enzymology ; metabolism ; physiopathology ; Dimethyl Sulfoxide ; administration & dosage ; Disease Models, Animal ; Female ; Glucose Clamp Technique ; Immunohistochemistry ; Injections, Intravenous ; Insulin ; administration & dosage ; Insulin Receptor Substrate Proteins ; Insulin Resistance ; physiology ; JNK Mitogen-Activated Protein Kinases ; metabolism ; Male ; Muscles ; metabolism ; Phosphorylation ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serine ; metabolism ; Tyrosine ; metabolism

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

OBJECTIVETo study the changes of insulin sensitivity in individuals with impaired glucose tolerance and diabetes and the relationship between insulin sensitivity and over weight/obesity (OW/OB) .

METHODSFifty-two individuals were divided into 4 groups according to WHO diagnostic criteria of obesity (1998) and diabetes (1999): normal weight with normal glucose tolerance (NW-NGT) group, OW/OB with normal glucose tolerance (OW/OB-NGT) group, OW/OB with impaired glucose tolerance (OW/OBIGT) group and OW/OB with diabetes mellitus (OW/OB-DM) group. Individuals in OW/OB-NGT group were further classified into 3 subgroups: over weight subgroup, mild obesity subgroup, and mediate obesity subgroup. Abdominal fat area was measured with magnetic resonance imaging. Visceral obesity was defined as intra-abdominal fat area over 100 cm(2). All subjects with NGT were divided into visceral obesity (VA) group and non-visceral obesity ( Non-VA) group. Extended hyperinsulinemic euglycemic clamp was performed to assess the peripheral tissue insulin sensitivity in all subjects.

RESULTSThe rates of insulin mediated glucose disappearance (Rd) were (3. 25+/-0. 13) mg x kg (-1) min (-1) in OW/OB-NGT group, (3. 06+/-0. 26) mg x kg(-1) x min(-1) in OW/OB-IGT group, and (3.19+/-0.44) mg x kg(-1) x min (-1) in OW/OB-DM group, which were significantly lower than that in NW-NGT group [ (5. 86+/-0. 65) mg x kg (-1) min (-1) ] (P < 0. 05, P < 0.01). The Rd in over weight subgroup [(3.50+/-0. 19) mg kg(-1) x min(-1) ] , mild obesity subgroup [(3. 03+/-0. 13) mg x kg (-1) min(-1)] , and mediate obesity subgroup [(2. 75 +/-0. 24) mg x kg (-1) min(-1)] were significantly lower than that of NW-NGT group (P <0. 05, P <0. 01). The Rd [ (2. 97+/-0. 12) mg kg(-1) x min(-1) vs (4.55+/-0.43) mg x kg(-1) x min(-1)] and glucose oxidation [(1.47 +/-0. 19) mg x kg(-1) min(-1) vs (2.24 +/-0. 19) mg kg(-1) x min(-1) in VA group were significantly decreased than that in non-VA group (P < 0. 05, P < 0. 01). Body mass index, waist and hip ratio, waist circumference, and intra-abdominal fat area were negatively correlated with Rd, respectively (P < 0. 01). Multiple regression analysis showed that body mass index, intra-abdominal fat area and abdominal subcutaneous fat area were the main risk factors of insulin sensitivity.

CONCLUSIONSInsulin sensitivity decreased in OW/OB individuals with or without hyperglycemia. Insulin sensitivity is lower in subjects with visceral obesity. Total body fat and abdominal fat are the main risk factors of insulin sensitivity.

Adolescent ; Adult ; Body Mass Index ; Female ; Glucose Clamp Technique ; methods ; Glucose Intolerance ; etiology ; Humans ; Insulin Resistance ; Intra-Abdominal Fat ; metabolism ; Male ; Middle Aged ; Obesity ; complications ; physiopathology ; Subcutaneous Fat, Abdominal ; metabolism

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

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