BACKGROUND Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and it makes them to have high risk for development of type 2 diabetes. Evaluation of insulin sensitivity would be important to predict their risks. Although the euglycemic-hyperinsulinemic clamp technique is the gold standard for measuring insulin sensitivity, it is too hard to practice in large epidemiologic studies. The aim of this study is to verify the validity of various insulin sensitivity indexes from oral glucose tolerance test (OGTT) in women with PCOS. METHODS: We performed euglycemic-hyperinsulinemic clamp (target glucose; 90 mg/dL, insulin ;~1 mU/kg.min) to obtain insulin-mediated glucose disposal rate (M-value) in 62 non-diabetic women with PCOS (BMI < 23 kg/m2; n = 37, BMI > or = 23 kg/m2; n = 25). Homeostasis model assessment [HOMA(IR)], quantitative insulin sensitivity check index (QUICKI), glucose to insulin ratio (G/I ratio), whole body insulin sensitivity index [ISI(COMP)], metabolic clearance rate of glucose [MCR(est)-OGTT(1,2)], and insulin sensitivity indexes [ISI(est)-OGTT(1,2)] were calculated from plasma glucose and insulin levels from standard 75-g OGTT. The correlations of various insulin sensitivity indexes from OGTT with M-value were evaluated. RESULTS: In lean women with PCOS (BMI < 23 kg/m2, n = 37), ISI(COMP) (r = 0.36, P < 0.05), MCRest-OGTT1 (r = 0.49, P < 0.01), ISI(est)-OGTT(1) (r = 0.50, P < 0.01), MCR(est)-OGTT(2) (r = 0.45, P < 0.01) and ISI(est)-OGTT(2) (r = 0.40, P < 0.05) were significantly correlated with M-value. In overweight and obese women with PCOS (BMI > or = 23 kg/m2, n = 25), HOMA(IR) (r = -0.40, P < 0.05), QUICKI (r = 0.40, P < 0.05), MCR(est)-OGTT(1) (r = 0.76, P < 0.001), ISI(est)-OGTT(1) (r = 0.63, P < 0.001), MCR(est)-OGTT(2) (r = 0.58, P < 0.01) and ISI(est)-OGTT(2) (r = 0.42, P < 0.05) showed significant correlations with M-value. CONCLUSION: MCR(est)-OGTT(1) and ISI(est)-OGTT(1) were the most reliable and easily accessible insulin sensitivity indexes obtained from OGTT for measuring of insulin sensitivity in women with PCOS regardless of obesity.
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Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes Flavia Tosi, Enzo Bonora, Paolo Moghetti Human Reproduction.2017; 32(12): 2515. CrossRef
BACKGROUND Resistance to insulin-stimulated glucose uptake is present in the majority of patients with obesity, glucose intolerance, hypertension, dyslipidemia, and coronary artery disease. It is known that values for insulin-stimulated glucose uptake(insulin sensitivity) vary widely within individuals with normal glucose tolerance. We investigated the variations in insulin sensitivity and related factors in the nonobese healthy young men. METHODS: Insulin sensitivity was considered as whole body insulin-stimulated glucose uptake rate(M), determined by euglycemic hyperinsulinemic clamp technique in 44 non-obese healthy young men with normal glucose tolerance. Plasma glucose, insulin, and C-peptide concentrations after a standard oral glucose tolerance test and total cholesterol, triglyceride, and HDL-cholesterol levels were measured after 12-hours fasting. The subjects were divided into four quartiles based on the insulin sensitivity (M) and their clinical and biochemical characteristics were compared. RESULTS: Glucose disposal rates (M-values) were ranged from 4.14 to 11.06 mg/kg/min and distributed normally. The plasma glucose levels were not different between quartiles but plasma insulin levels of quartile 1 were significantly higher than the other three quartiles during oral glucose tolerance test. There was a curvilinear relationship between insulin sensitivity and acute insulin response (Ins[o-30]) to oral glucose challenge. There were negative cnrrelations between insulin sensitivity and BMI, percent ideal body weight, WHR, body fat content, fasting insulin level, insulin response area during OGTT, and fasting serum triglyceride level. HDL-cholesterol concentration was positively correlated with insulin sensitivity. In multiple linear regression analysis, body fat content, fasting insulin, and HDL-cholesterol were independent variables, which were related to the insulin sensitivity. CONCLUSION: There were considerable variations in insulin sensitivity in the nonobese healthy young men with normal glucose tolerance and the related independent factors were body fat content, fasting insulin, and HDL-cholesterol cancentrations.
Seok Won Park, Yong Seok Yun, Churl Woo Ahn, Jae Hyun Nam, Suk Ho Kwon, Min Kyung Song, Seol Hye Han, Bong Soo Cha, Young Duk Son, Hyun Chul Lee, Kap Bum Huh
Korean Diabetes J. 1998;22(2):199-208. Published online January 1, 2001
BACKGROUND The euglycemic hyperinsulinemic clamp technique is currently regarded as gold standard for measuring insulin sensitivity, but it requires sophisticated equipment and highly trained personnel. We investigated the reliability of short insulin tolerance test as a simple tesl to measure in vivo insulin sensitivity. METHODS: Short insulin tolerance test(SITT) and euglyeemic hyperinsulinemic clamp test were performed at random order in 14 healthy subjects and 10 abnormal glucose tolerant subjects. The plasma glucose disappearance rate(kitt: %/min) after iv injection of regular insulin(0.1U/kg) was determinecl and compared to insulin sensitivitv indices(M, M/I) of euglycemic hyperinsulinemic clamp test. RESULTS: The mean Kitt value of healthy subjects was 3.50+0.75%/min and that of subjects with abnormal glucose tolerance was 2.56+0.56%/min. Changing sampling time from 15 min to 18~21 min and sampling interval from 3 min to 1.5 min had no influence on Kitt value. Kitt values were reproducible in six subjects, with a CV of 8.8+2.0%. There was a highly significant correlations between the Kitt value derived from SITT and M or M/I derived from euglycemic hyperinsulinemic clamp test. There were no significant adverse effects including hypoglycemic symptom while performing SITT. CONCLUSION: SITT is simple, safe, rapid to perform, and provides reliable index of in vivo insulin sensitivity. It seems particularly suitable for studies involving large series of subjects or including repeated evaluation of insulin sensitivity.
BACKGROUND Increased FFA availability is known to induce insulin resistance by decrease in peripheral glucose utilization and increase in hepatic glucose procluction. However, there are conflicting results about the time dependence of the developrnent of insulin resistance with increased availability of FFA. METHODS: To elucidate the time dependence of the development of insulin resistance associated with increased availability of FFA, peripheral glucose utilization rate and hepatic glucose production rate were measured by euglycemic hyperinsulinemic clamp with 3-3H glucose infusion in rats fed high fat diet (1 week or 3 weeks) or control diet(ordinary chow diet). RESULTS: Basal plasrna FFA levels and steady state plasma insulin levels increased after high fat diet. After 1 week of high fat diet, suppressibility of hepatic glucose production rate by insulin was impaired(p<0.05 vs control). Insulin sensitivity index(glucose utilization rates/steady state plasma insulin concentrmtions X100) was decreased only after 3 weeks of high fat diet(p<0.05 vs control) which was accompanied by decreased glycogen synthase activity. CONCLUSION: High fat diet induces hepatic insulin resistance before peripheral insulin resistance and decreased glycogen synthase activity may contribute to the development of peripheral insulin resistance in rats fed high fat diet.