INTEGRATED PHYSIOLOGY—INSULINCATEGORY SECRETION IN VIVO 1926-P Twenty patients [mean fasting plasma glucose (FPG) 7.3 mmol/L, HbA1c How to Transform a Metabolic Syndrome Score in an Insulin Sen- 7.5%, BMI 28.4 kg/m2] underwent a MTT and a glucose clamp. Participants sitivity Value? were given a test meal (460 kcal). Plasma glucose, insulin, and C-peptide im- MICHEL P. HERMANS, EVARISTE BOUENIZABILA, K. DANIEL AMOUSSOU- munoreactivity (CPR) were measured at 0, 30, 60, and 120 min. HOMA-IR and GUENOU, SYLVIE A. AHN, MICHEL F. ROUSSEAU, Brussels, Belgium, Brazzaville, Hepatic Insulin Clearance (HIC: AUC-Insulin/AUC-CPR ratio) were calculated Congo, Republic of the, Cotonou, Benin from the MTT results. The glucose disposal rate (GDR) was measured during The metabolic syndrome (MetS) predicts cardiovascular risk and incident hyperinsulinemic-euglycemic glucose clamps. type 2 diabetes mellitus (T2DM). The presence of a MetS is defi ned by the The mean GDR in all patients was 5.08 mg·kg-1·min-1. The index 20/(F- clustering of ≥3 out of 5 cardiometabolic criteria (hyperglycemia; hyperten- CPR × FPG) was correlated strongly with GDR (R=0.72), better than HOMA-IR sion; enlarged waist; low HDL-cholesterol; and hypertriglyceridemia), each (R=−0.53). 20/(F-CPR × FPG) was able to estimate GDR, we would like to of which is connected with insulin resistance (IR). It is not known whether name this index “CPR-IR.” The median value of HIC in all patients was 6.0. the severity of MetS, ranked from the sextet of scores’ range [0/5 to 5/5], In the patients with low hepatic insulin clearance (HIC<6.0), HOMA-IR and is linearly related to reduced insulin sensitivity (IS) and/or lesser hyperbolic CPR-IR were correlated equally with GDR (R=-0.68 and 0.69). In the patients product across the glycemic spectrum. with high hepatic insulin clearance (HIC>6.0), whereas HOMA-IR did not cor- We analyzed 839 adults (54 normoglycemic; 785 with abnormal glucose relate with GDR (R=-0.21), CPR-IR correlated with GDR (R=0.64). homeostasis, among whom 711 T2DM), whose IS was assessed together CPR-IR is a simple and effective index of insulin resistance in the patients with their cardiometabolic phenotype. with T2DM, and performs better than HOMA-IR with small effect of hepatic There was a signifi cant gradient according to interval-scale MetS score insulin clearance. in insulinemia; BMI; (visceral) fat; hepatic steatosis; and macroangiopathy. Table. The Correlation between GDR and CPR-IR, HOMA-IR. There was an inverse linear relationship between increasing MetS scores CPR-IR HOMA-IR and decreased IS, allowing to defi ne an IR-predicting linear equation: IS (%) = [-15.1*MetS score] + 109.4 (R2 = 0.221). For each MetS category, mean IS All patients R=0.72 R=-0.53 values did not signifi cantly differ between groups of patients across the gly- Low hepatic insulin clearance (HIC<6.0) R=0.69 R=-0.68 cemic spectrum. The hyperbolic product (β-cell function x IS) and/or its loss High hepatic insulin clearance (HIC>6.0) R=0.64 R=-0.21 rate were inversely related to MetS severity. In conclusion, IS is linearly and inversely related to MetS severity across the 6 scores. This novel way to exploit information intrinsic to the MetS cri- teria provides an easy and costless means to quantify IS across the glycemic INTEGRATED PHYSIOLOGY—INSULIN SECRETION spectrum. Moreover, MetS severity is associated with a lesser hyperbolic IN VIVO product, and a higher loss of the latter. 1927-P Guided Audio Tour: Insulin Secretion In Vivo (Posters: 1929-P to 1934-P), Possible Involvement of Undercarboxylated Osteocalcin upon Reg- see page 13. ulating Insulin Secretion in Patients with Type 2 Diabetes YUICHI TAKASHI, YOKO MATSUZAWA, JUN SAITO, MASAO OMURA, TETSUO & 1929-P NISHIKAWA, Yokohama, Japan Limitations of Standardized C-Peptide Kinetics for Estimation of We examined the effect of undercarboxylated osteocalcin (ucOC) on β-Cell Responsivity the ability of insulin secretion, evaluated by glucagon loading test (GLT) RON T. VARGHESE, FRANCESCA PICCININI, MEERA SHAH, CHIARA DALLA MAN, and meal tolerance test (MTT). UcOC has been shown to regulate insulin ROBERT A. RIZZA, CLAUDIO COBELLI, ADRIAN VELLA, Rochester, MN, Padova, secretion in rodents. However, data on the correlation between ucOC and Italy glucose metabolism in humans is limited and controversial. We recruited 50 Standard kinetics of C-Peptide clearance enable deconvolution of insu- patients (41 men and 9 postmenopausal women) with type 2 diabetes under lin secretion from changing plasma C-Peptide concentrations. However, written informed consent, and performed both GLT and MTT, and analyzed it is uncertain if standard parameters apply to all conditions under which the relationship between ucOC and C-peptide response (CPR). All patients β-cell function is measured. As part of a series of experiments examining the were free of insulin therapy and drugs known to infl uence bone metabolism, mechanisms underlying prediabetes, we studied 60 nondiabetic individuals such as vitamin D, bisphosphonate. Number of patients who were treated (38.7±2.2 years, BMI 28.3±0.8 Kg/M2) on 2 occasions in random order using with DPP-4 inhibitor, sulfonylurea, glinide, metformin, thiazolidinedione and an oral glucose challenge. On one occasion, free fatty acid (FFA) elevation alpha-glucosidase inhibitor were 17, 19, 15, 19, 4 and 12 patients. The av- to cause insulin resistance, was achieved by infusion of intralipid + heparin. erage of age, duration of diabetes, BMI, and HbA1c of the subjects were On the other study day subjects received the same amount of glycerol pres- 59.2 y.o., 7.8 years, 26.2 kg/m2 and 9.4%, respectively. UcOC was shown to ent in the intralipid. On a 3rd study day, after a euglycemic clamp where correlate positively with ১CPR in GLT and CPR after meal taking (r = 0.32, somatostatin inhibited endogenous insulin secretion, subjects received a C- p = 0.025; r = 0.29, p = 0.047). Furthermore, we focused on the patients Peptide bolus to calculate individual kinetic for clearance. β-cell responsivity with HbA1c less than 8.0% because we thought they had little infl uence of (ϕTotal) in the presence or absence of FFA elevation was estimated using the glucose toxicity. UcOC was shown to correlate positively more strongly with oral C-Peptide minimal model using either standard or individual C-Peptide CPR after glucagon loading and ১CPR in GLT (r = 0.60, p = 0.0088; r = 0.67, p = kinetics. ϕTotal estimated using individual kinetics correlated well with those 0.0025) than with CPR after meal taking (r = 0.51, p = 0.035). In both groups, estimated using standard kinetics in the presence (46±4 vs. 46±4 10-9 min-1, ucOC was not shown to correlate with CPR before glucagon loading or meal R2 =0.59, p<0.01) or absence (56±4 vs. 53±4 10-9 min-1, R2 =0.66, p<0.01) of taking. It is suggested that ucOC correlate with not basal but bolus insulin FFA elevation. Analysis of the components of ϕTotal reveals generally worse 2 secretion and may directly induce insulin secretion from β-cells without in- correlation for ϕDynamic in the presence (R =0.42, p<0.01) compared to the 2 volving gut-related insulin stimulation in patients with type 2 diabetes. UcOC absence (R =0.68, p<0.01) of FFA elevation. Similarly, ϕStatic in the presence 2 2 Obesity is suggested to be a new marker to evaluate the reserve capacity of β-cell (R =0.50, p<0.01) and absence (R =0.76, p<0.01) of FFA elevation. The great- POSTERS function, such as the bolus insulin secretion ability. est discrepancies arise in basal β-cell responsivity during FFA elevation 2 2 (ϕBasal - R <0.01, p=0.71) compared to glycerol infusion (R =0.79, p<0.01). We Integrated Physiology/ 1928-P conclude that results obtained with standard C-Peptide kinetics correlate 20/(Fasting C-Peptide × Fasting Plasma Glucose) Is a Novel Index of well with those obtained using individual kinetics. However individual pa- Insulin Resistance with Small Effect of Hepatic Insulin Clearance rameters are required for optimal measurement of ϕBasal at least in response TSUYOSHI OKURA, YOUHEI FUJIOKA, RISA NAKANISHI, HIDEKI SHIOCHI, to acute decreases in insulin action. KEISUKE SUMI, KYOKO SHOJI, AYUMI MURAWAKI, KAZUHIKO MATSUZAWA, Supported By: National Institutes of Health (R01DK078646) SCHOICHIRO IZAWA, CHIEKO SAKAI, MASAHIKO KATO, SHIN-ICHI TANIGUCHI, KAZUHIRO YAMAMOTO, Yonago, Japan We developed a simple and new insulin resistance index derived from a glucose clamp and a meal tolerance test (MTT) in Japanese patients with type 2 diabetes mellitus. For author disclosure information, see page A810. & Guided Audio Tour poster ADA-Funded Research A496 INTEGRATED PHYSIOLOGY—INSULINCATEGORY SECRETION IN VIVO & 1930-P Exposition to Glucocorticoids during Fetal Life Is Associated with Insulin Secretion Defect at Adult Age JEAN-PIERRE RIVELINE, JEAN-LOUIS NGUEWA, BAZ BAZ, PHILIPPE BOUDOU, BERTRAND BLONDEAU, BERNADETTE BRÉANT, YVES MOREL, JEAN-FRANCOIS GAUTIER, Paris, France, Lyon, France Objective: Animal studies suggest that glucocorticoids (GCs) inhibit the development of beta cells during fetal life. In order to address if such inhibi- tion may occurs in humans, we investigated in a case-control study beta-cell function in healthy subjects who have been exposed to GCs during early fetal life, at a period of beta cells development. Patients and Methods: Women carrying congenital adrenal hyperplasia (CAH) mutation are treated by dexamethasone (DXM) during pregnancy to avoid sexual ambiguity in affected fetus. DXM is stopped around the 18th week as soon as the mutation is excluded in the fetus.