Matsuda Insulin Sensitivity Index Research Articles

Reduced Skeletal Muscle Volume and Increased Skeletal Muscle Fat Deposition Characterize Diabetes in Individuals after Pancreatitis: A Magnetic Resonance Imaging Study.

Background: Skeletal muscle has been implicated in the pathogenesis of type 2 diabetes but it has never been investigated in diabetes after pancreatitis. The aim was to investigate the relationship between psoas muscle volume (PMV) and diabetes in individuals after pancreatitis, as well as its associations with ectopic fat phenotypes and insulin traits. Methods: Individuals after an attack of pancreatitis and healthy individuals were studied in a cross-sectional fashion. All participants underwent magnetic resonance imaging, based on which PMV, skeletal muscle fat deposition (SMFD), as well as liver and intra-pancreatic fat depositions were derived. Fasting and postprandial blood samples were collected to calculate indices of insulin sensitivity and secretion. Linear regression analyses were conducted, adjusting for possible confounders (age, sex, body composition, comorbidities, use of insulin, and others). Results: A total of 153 participants were studied. PMV was significantly decreased in the diabetes group compared with healthy controls (β = −30.0, p = 0.034 in the most adjusted model). SMFD was significantly inversely associated with PMV (β = −3.1, p < 0.001 in the most adjusted model). The Matsuda index of insulin sensitivity was significantly directly associated with PMV (β = 1.6, p = 0.010 in the most adjusted model). Conclusions: Diabetes in individuals after pancreatitis is characterized by reduced PMV. Reduced PMV is associated with increased SMFD and decreased insulin sensitivity in individuals after pancreatitis.

Different pathogenesis of glucose intolerance in two subtypes of primary aldosteronism: Aldosterone-producing adenoma and idiopathic hyperaldosteronism.

Aims/IntroductionAn increased risk of diabetes mellitus has been reported in primary aldosteronism, but the pathogenesis of glucose intolerance between the primary aldosteronism subtypes remains unclear. This study aimed to evaluate glucose metabolism in oral glucose tolerance test between aldosterone‐producing adenoma and idiopathic hyperaldosteronism, and characterize patients with improved glucose intolerance after primary aldosteronism treatment.Materials and MethodsOral glucose tolerance test was carried out in 116 patients who were diagnosed with primary aldosteronism and received adrenal venous sampling for subtyping. Oral glucose tolerance test was re‐evaluated after starting the treatment of primary aldosteronism for those who had glucose intolerance before the treatment.ResultsA total of 46.4% and 52.3% of patients with aldosterone‐producing adenoma and idiopathic hyperaldosteronism, respectively, were diagnosed with impaired glucose tolerance or diabetes. The insulinogenic index was significantly lower in aldosterone‐producing adenoma than in idiopathic hyperaldosteronism (P = 0.045), whereas the Matsuda insulin sensitivity index was significantly higher in aldosterone‐producing adenoma than in idiopathic hyperaldosteronism (P = 0.022). After the treatment of primary aldosteronism, glucose intolerance was improved in 66.6% and 45.8% of aldosterone‐producing adenoma and idiopathic hyperaldosteronism, respectively. The presence of obesity and central obesity were significantly lower in patients who improved glucose intolerance after the treatment of primary aldosteronism as compared with those not improved (P = 0.013 and P = 0.033, respectively).ConclusionsInsulin secretion impairment and insulin resistance play pathogenic roles for glucose intolerance in aldosterone‐producing adenoma and idiopathic hyperaldosteronism, respectively. In addition, primary aldosteronism treatments can ameliorate glucose intolerance more effectively in patients without obesity and/or central obesity.

Relationship between Decreased Serum Superoxide Dismutase Activity and Metabolic Syndrome: Synergistic Mediating Role of Insulin Resistance and β-Cell Dysfunction.

The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06 ± 16.89 U/mL vs. 56.25 ± 22.61 U/mL, P = 0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend = 0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.

Association of [1H]-MRS quantified liver fat content with glucose metabolism status

BackgroundPrevious literatures have implied that the liver fat deposition plays a crucial role in the development and progression of insulin resistance. In the present study, we aimed to investigate the association of liver fat content (LFC) with glucose metabolism status in the population of newly diagnosed type 2 diabetes mellitus (nT2DM), prediabetes mellitus (PDM) and normal controls (NC), and assessing if the LFC could as an indicator for the prediction of T2DM.MethodsA total of 242 subjects (including 141 nT2DM patients, 48 PDM subjects and 53 NC) were enrolled. The levels of LFC were quantified by using the proton magnetic resonance spectroscopy ([1H]-MRS) technique. Clinical and laboratory parameters of study subjects were collected by medical records and biochemical detection. One-way ANOVA or nonparametric test (Kruskal–Wallis) was applied for intergroup comparisons; intergroup comparison was performed in using of Bonferroni multiple-significance-test correction.ResultsThere were significantly increased LFC levels in nT2DM (14.72% ± 6.37%) than in PDM (9.62% ± 4.41%) and that of NC groups (5.11% ± 3.66%) (all p < 0.001). The prevalence of nonalcoholic fatty liver disease (NAFLD) was also found to be increased in nT2DM (91.48%) than in PDM (85.41%) and that of NC (32.07%) groups. Correlation analysis revealed that the increase of LFC positively associated with fast plasma glucose (FPG), 2 h plasma glucose (PG), Delta G30 and homeostatic model assessment of insulin resistance (HOMA-IR), negatively associated with Delta Ins30, Delta C30, Ins30/G30 AUC, CP30/G30 AUC, Ins AUC/G AUC, CP AUC/G AUC, homeostatic model assessment for β-cell function index (HOMA-β) and matsuda insulin sensitivity index (Matsuda ISI). Multilinear regression analysis showed that LFC, body mass index (BMI) and diastolic blood pressure (DBP) contributed for the prediction of HOMA-IR, and total cholesterol (TC), age, waist circumference (WC) and low-density lipoprotein cholesterol (LDL-C) were the significant contributors for HOMA-β.ConclusionsOur study revealed an increased LFC level and prevalence of NAFLD in nT2DM than in PDM and that of NC groups, the increase of LFC was closely associated with insulin resistance and impaired glucose metabolism status, may be regarded as potential indicator contributing to the development and progression of T2DM.

5-LB: Consuming High-Fructose Corn Syrup or Sucrose-Sweetened Beverages Increases Hepatic Lipid Content and Decreases Insulin Sensitivity in Young Adults

Rodent studies demonstrate that compared with diets sweetened with sucrose, high fructose corn syrup (HFCS) produces greater metabolic dysfunction. However, the effects of sustained consumption of HFCS and sucrose have not been adequately compared in humans. The objective of this study was to compare HFCS-, sucrose-, or aspartame- sweetened beverage (-SB) consumption on hepatic lipid content and insulin sensitivity in young adults. In a parallel, double-blinded study, adult men and women (18-40 yrs) were assigned to beverage groups matched for sex, BMI and fasting triglycerides. Inpatient magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests were performed at baseline and intervention 15 days later. For 12 outpatient days subjects consumed their usual diets with 3 servings/day of HFCS- (n=28) or sucrose-SB (n=24) providing 25% energy requirement (Ereq), or aspartame-SB (n=23). Matched standardized diets were provided during inpatient testing with the sugar in beverages replacing complex carbohydrate during intervention. Hepatic lipid content was increased by consumption of HFCS-SB (LS means of absolute Δ±SEM: 0.5%±0.2, P&amp;lt;0.05) and sucrose-SB (Δ: 0.5%±0.2, P&amp;lt;0.01) compared with baseline levels and compared with aspartame-SB (Δ: -0.2%±0.2, P&amp;lt;0.05 vs. HFCS- or sucrose-SB). The 3-hr Matsuda insulin sensitivity index was decreased by consumption of HFCS-SB (Δ: -0.3±0.2) and sucrose-SB (Δ: -0.5±0.2, P&amp;lt;0.01 vs. baseline) compared with aspartame-SB (Δ: 0.3±0.2, P&amp;lt;0.05 vs. HFCS- or sucrose-SB). The 2-hr Oral Glucose Insulin Sensitivity index was also decreased by consumption of HFCS-SB (Δ: -13.6±7.5) and sucrose-SB (Δ:-11.5±7.9) compared with aspartame-SB (Δ: +17.9±8.3, P&amp;lt;0.05 vs. HFCS- or sucrose-SB). Consumption of SB providing 25% of Ereq as HFCS or sucrose for 2 weeks increased hepatic lipid content and reduced insulin sensitivity in young adults compared with consumption of aspartame-SB. Disclosure D. Sigala: None. B. Hieronimus: None. C. Price: None. V. Lee: None. M. Nunez: None. V. Medici: None. A.J. Chaudhari: None. J.P. McGahan: None. Y. Abdelhafez: None. N.L. Keim: None. M.I. Goran: Advisory Panel; Self; Yumi. Other Relationship; Self; Penguin Random House. G. Pacini: None. A. Tura: None. P.J. Havel: Research Support; Self; Arrowhead Pharmaceuticals, Inc., Magnamosis, Inc. Other Relationship; Self; None. K.L. Stanhope: None. Funding National Institutes of Health (R01HL091333, R01HL107256)

1836-P: Nonalcoholic Steatohepatitis (NASH) Significantly Contribute to ß-Cell Function Impairment Independently of Glucose Tolerance Status

ß-cell dysfunction is a strong risk factor for type 2 diabetes (T2D). The liver plays a central role since insulin clearance (ClearIns) is up to 80% of the insulin secretion rate (ISR). ClearIns is reduced with insulin resistance (IR) and in patients with nonalcoholic fatty liver disease (NAFLD) . Our aim was to evaluate if ISR and ß-cell function were decreased in NASH vs. NAFL thus increasing their risk of T2D and the impact of ClearIns and IR. We measured glucose, insulin and c-peptide during a 3h oral glucose tolerance test in 341 subjects with liver biopsy and evaluated ISR (from deconvolution of c-peptide), ClearIns, Matsuda insulin sensitivity index (ISI) and disposition index (DI=ISI∙ΔAUC-I/ΔAUC-G); a low DI indicates a risk to develop T2D. Subjects were grouped according to glucose tolerance, normal (NGT), impaired (IGT) or T2D, and liver histology (noNAFL, NAFL, NASH-Fibrosis F0-F1 and F2-F4). The groups had similar BMI (∼34kg/m2). Severity of NAFLD was associated with increased IR, fasting and postprandial ISR and decreased ClearIns, after adjusting for age and BMI. DI was significantly lower in NASH-F24 in each glucose tolerance group (Figure). Conclusion: Disposition index is reduced in relation to presence and severity of NASH independent of glucose tolerance status supporting an independent role of NASH in the development of T2D. Disclosure L. Vonghia: None. E. Dirinck: None. F. Carli: None. A. Verrijken: None. J. Weyler: None. P. Michielsen: None. T. Vanwolleghem: None. A. Driessen: None. L. Van Gaal: None. S. Francque: None. C. De Block: Advisory Panel; Self; A. Menarini Diagnostics, Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD, Novartis AG, Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. Funding Horizon2020 (634413)

Contributions of Prenatal Exposures and Child Lifestyle to Insulin Sensitivity.

Prenatal exposures and lifestyle factors are important for metabolic health. Determine how prenatal exposures to maternal obesity and/or gestational diabetes mellitus (GDM) and childhood lifestyle factors independently contribute to child insulin sensitivity. Ninety children aged 7 to 11 years (56% girls, 60% exposed to GDM), born at Kaiser-Permanente Southern California, completed an oral glucose tolerance test (OGTT) as part of the BrainChild Study. Matsuda insulin sensitivity index (ISI) was used to estimate insulin sensitivity. Participants completed two 24-hour dietary recalls, and daily energy intake (EI), dietary added sugar, and total sugar were calculated. The 3-day physical activity recall determined the average minutes per day of moderate to vigorous physical activity (MVPA) and the average minutes per day spent sedentary. Maternal prepregnancy body mass index (BMI) and GDM status were extracted from electronic medical records. Matsuda-ISI. Linear regression showed that children who spent more time in MVPA had better ISI (β = 0.33; P = 0.001), and results remained after adjustment for maternal prepregnancy BMI, GDM exposure, child age, sex, daily EI, dietary added sugar (β = 0.34; P = 0.001), and further adjustment for child adiposity (β = 0.29; P = 0.001). Time spent sedentary, maternal prepregnancy BMI, GDM exposure, dietary added sugar, total sugar, and EI were not associated with ISI. Physical activity was the only predictor of ISI at this age, suggesting that engaging in physical activity during childhood is beneficial for insulin sensitivity and may ameliorate future risk for metabolic disease.

Effect of fructose and its epimers on postprandial carbohydrate metabolism: A systematic review and meta-analysis.

To synthesize the evidence of the effect of small doses (≤30-g/meal) of fructose and its epimers (allulose, tagatose, and sorbose) on the postprandial glucose and insulin response to carbohydrate-containing meals. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through to April 9, 2019. We included randomized (RCTs) and non-randomized acute, single-meal, controlled feeding trials that added ≤30-g of fructose or its epimers either prior to or with a carbohydrate-containing meal compared with the same meal alone. Outcomes included the incremental area under the curve (iAUC) for glucose and insulin, the Matsuda Insulin Sensitivity Index, and the Early Insulin Secretion Index. Data were expressed as ratio of means (RoM) with 95% CIs and pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE. Forty trial comparisons (n=400) were included (none for sorbose). Allulose significantly reduced the postprandial iAUC glucose response by 10% (0.90 [0.84 to 0.96], P<0.01). Tagatose significantly reduced the postprandial iAUC insulin response by 25% (0.75 [0.62 to 0.91], P<0.01) and showed a non-significant 3% reduction in the postprandial iAUC glucose response (0.97 [0.94 to 1.00], P=0.07). There was no effect of fructose on any outcome. The certainty of the evidence was graded as low to moderate for fructose, moderate for allulose, and low for tagatose. Small doses of allulose and tagatose, but not fructose, lead to modest improvements on postprandial glucose and insulin regulation. There is a need for long-term RCTs to confirm the sustainability of these improvements.

Cholecystectomy is an independent factor of enhanced insulin release and impaired insulin sensitivity

AimsCholecystectomy is a risk factor for insulin resistance and diabetes, but the association between cholecystectomy and insulin release/sensitivity remains obscure. We investigated the association between cholecystectomy and the factors related to glycemia and glucose tolerance. MethodsA cross-sectional study was conducted in 2011 with 10,027 participants aged ≥40 in Nanjing, China. After applying exclusion criteria, 8,030 participants were divided into three groups: 1, without gallbladder disease (n = 6783); 2, with gallbladder disease but without cholecystectomy (n = 857); and 3, with cholecystectomy (n = 390). ResultsVarious indexes of blood glucose and insulin level after the oral glucose tolerance test (OGTT) were assessed. The association between gallbladder disease or cholecystectomy and diabetes was evaluated with logistic regression models. Group 3 had a higher prevalence of newly diagnosed diabetes by OGTT criteria compared with groups 2 and 1, respectively (20.5% vs. 12.4% vs. 10.6%, P < 0.001). The adjusted odds ratio and 95% confidence interval of diabetes associated with cholecystectomy were 1.546 (1.168, 2.046) (P = 0.002). Pattern 2, which was characterized by a lasting late insulin response, was more frequent in group 3 compared with groups 2 and 1, respectively (61.0% vs. 54.3% vs.48.3%, P < 0.001). After adjusting for confounding factors, a higher total insulin release and lower Matsuda insulin sensitivity index (P < 0.001) were found in group 3 compared with the other two groups. ConclusionsCholecystectomized subjects demonstrated a higher prevalence of diabetes characterized by lower peripheral insulin sensitivity and higher total insulin release.

HDL cholesterol is an independent predictor of β-cell function decline and incident type 2 diabetes: A longitudinal study.

Experimental evidence indicates that high-density lipoprotein (HDL) may stimulate glucose uptake and improve β-cell function. The aim of this study was to evaluate whether lower levels of HDL may affect the risk to develop type 2 diabetes. Incident rate of type 2 diabetes and changes in insulin sensitivity and β-cell function over 5.5-year follow-up were examined in 670 non-diabetic subjects stratified in tertiles according to basal HDL levels. As compared to the highest tertile of HDL, individuals with lower levels of HDL have an increased risk to develop type 2 diabetes independently from several cardiometabolic risk factors (odds ratio: 2.88, 95% confidence interval: 1.05-7.91), and exhibited a greater deterioration of β-cell function, estimated by the disposition index, over 5.5-year follow-up. Conversely, changes in Matsuda index of insulin sensitivity over the follow-up were not significantly different amongst the three HDL groups. In a multivariable regression analysis model including age, sex, waist circumference, triglycerides, total cholesterol, C-reactive protein, fasting and 2-hour post-load glucose, family history of type 2 diabetes and smoking habit, HDL concentration at baseline was an independent predictor of β-cell function decline over the follow-up (β = .30, P = .0001). Mediation analysis showed that the association between lower HDL levels at baseline and increased risk of incident diabetes was mediated by β-cell function deterioration during the follow-up (t = -3.32, P = .001). Subjects with lower levels of HDL have an increased risk to develop type 2 diabetes likely due to a greater β-cell function decline over time.

β-Cell Glucose Sensitivity determines hyperglycaemia in Polycystic Ovary Syndrome

AimsTo investigate the mechanism of hyperglycaemia in women with Polycystic Ovary Syndrome (PCOS) by modelling physiological insulin secretion. Methods45 non-diabetic women with PCOS (defined by Rotterdam criteria) and 47 controls were studied. Insulin secretion was modelled from glucose and C-peptide concentrations during a 6-point oral glucose tolerance test (OGTT) and insulin resistance (IR) was determined by the Matsuda Insulin Sensitivity Index (ISI). Results(1). β-Cell Glucose Sensitivity (βCGS) is not intrinsically impaired in PCOS, but IR is increased. (2) However, women with PCOS and 2-hour hyperglycaemia (glucose >7.5 mmol/l]) were characterized by worse βCGS compared with women with 2-hour glucose <7.5 mmol/l (mean [SD]) 43.5 [23.6] versus 109.0 [68.5] pmol/min/ml/mmol; p = 0.04), and had higher waist circumference (116.8 [15.8] vs 93.5 [15.9] cm; p < 0.01) and 120 minute insulin concentrations (964.0 [579.2–1214.7] vs 328.2 [242.2–475.7] pmol/l; p = 0.01). (3). In contrast, lean, insulin sensitive women with PCOS were euglycemic, even in the presence of poor βCGS, and exhibited favourable cardiometabolic risk profiles. ConclusionsβCGS is not intrinsically impaired in PCOS, but it is the critical determinant of hyperglycaemia. Women with low βCGS, who also have central adiposity and IR exhibit 2-hour hyperglycaemia, whereas women with high βCGS are able to maintain euglycaemia despite central adiposity and IR. These findings show that (i) waist circumference and 2-hour glucose identify women at higher risk of diabetes, and confirm that (ii) obesity and IR are the key reversible targets for diabetes prevention in women with PCOS.

Longitudinal changes in glucose metabolism in women with gestational diabetes, from late pregnancy to the postpartum period.

This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34-37weeks gestation, T1), to early postpartum (1-5days, T2) and late postpartum (6-12weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI. ISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using the results of a 75g OGTT. Adipokines, cytokines and lipids were measured prior to each OGTT. Linear mixed-effects models were used to compare changes across each time point. Changes in ISOGTT, insulin response and DI were correlated with changes in maternal adipokines, cytokines and lipids at each time point. A total of 27 women completed all assessments. Compared with T1, ISOGTT was 11.20 (95% CI 8.09, 14.31) units higher at 1-5days postpartum (p < 0.001) and was 5.49 (95% CI 2.38, 8.60) units higher at 6-12weeks postpartum (p < 0.001). Compared with T1, insulin response values were 699.6 (95% CI 957.5, 441.6) units lower at T2 (p < 0.001) and were 356.3 (95% CI 614.3, 98.3) units lower at T3 (p = 0.004). Compared with T1, the DI was 6434.1 (95% CI 2486.2, 10,381.0) units higher at T2 (p = 0.001) and was 4262.0 (95% CI 314.6, 8209.3) units higher at T3 (p = 0.03). There was a decrease in mean cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol from T1 to T2 (all p < 0.001), and an increase in mean C-reactive protein, IL-6 and IL-8 from T1 to T2 (all p < 0.001). Mean leptin decreased from T1 to T2 (p = 0.001). There was no significant change in mean adiponectin (p = 0.99) or TNF-α (p = 0.81) from T1 to T2. The mean maternal BMI decreased from T1 to T2 (p = 0.001) and T3 (p < 0.001). There were no significant correlations between any measure of change in ISOGTT, insulin response and DI and change in maternal cytokines, adipokines, lipids or weight from T1 to T2. In women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6-12weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight. ClinicalTrials.gov NCT02082301.

Association of serum lipids with β-cell function in obese children and adolescents.

Few data are available on the association between serum lipids and insulin secretion (ISEC) in children. We evaluated the association of triglycerides (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) with ISEC in 1150 non-diabetic obese children and adolescents using multivariable robust median regression. The following models were employed: (1) IGI or incAUCR as the ISEC response variable; (2) QUICKI, OGIS, the Stumvoll index or the Matsuda insulin sensitivity index as the insulin sensitivity (ISEN) predictor; (3) TG, HDL-C and LDL-C as the predictors of interest; (4) 120-min glucose, age, sex and body mass index as confounders. LDL-C and TG were not associated with ISEC in any model. In three out of four IGI models, an increase of 1 interquartile range (IQR) of HDL-C was associated with a decrease of median incAUCR ranging from −9 (robust 95% CI −17 to −2) to −8 (−14 to −1) pmol/mmol. In two out of four incAUCR models, an increase of 1 IQR of HDL-C was associated with a decrease of median IGI ranging from −8 (−15 to −1) to −7 (−11 to −2) pmol/mmol. TG and LDL-C are not associated and HDL-C is inversely associated with ISEC in obese children and adolescents.

Gastric Emptying and Distal Gastrectomy Independently Enhance Postprandial Glucagon-Like Peptide-1 Release After a Mixed Meal and Improve Glycemic Control in Subjects Having Undergone Pancreaticoduodenectomy.

New-onset diabetes frequently resolves after pancreaticoduodenectomy (PD). Glucagon-like peptide-1 (GLP-1) conceivably is involved as its release is enhanced by rapid gastric emptying and distal bowel exposure to nutrients. We aimed at studying factors associated with GLP-1 release after PD. Fifteen PD subjects with distal gastrectomy (Whipple) and 15 with pylorus preservation were evaluated. A test meal containing 1 g paracetamol to measure gastric emptying was ingested. Blood for the measurement of paracetamol, glucose, insulin, and GLP-1 was drawn at baseline and 10, 20, 30, 60, 90, 120, 150, and 180 minutes thereafter. The Matsuda index of insulin sensitivity was calculated. In univariate analysis, gastric emptying correlated with GLP-1. Glucagon-like peptide-1 responses to the modes of operation did not differ. Multiple regression analysis confirmed gastric emptying and Whipple versus pylorus-preserving pancreaticoduodenectomy as independent predictors of GLP-1 release. The Matsuda index of insulin sensitivity correlated with GLP-1 concentrations and inversely with body mass index. Patients after Whipple procedure revealed lower glycated hemoglobin as compared with pylorus-preserving pancreaticoduodenectomy. Following PD, the postprandial GLP-1 release seems to be enhanced by rapid gastric emptying and to improve insulin sensitivity. Partial gastrectomy versus pylorus preservation enhanced the release of GLP-1, conceivably because of greater distal bowel exposure to undigested nutrients.

Relation of NT-probnp levels and cardiovascular disease risk factors in lean women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) often have cardiovascular disease (CVD) risk factors. N-terminal fragment of brain natriuretic peptide (Nt-probnp) is used as a diagnostic and prognostic marker for CVD. The aim of this study was to evaluate whether Nt-probnp is increased in lean PCOS patients. A total of 110 lean (BMI < 25 kg/m2) PCOS patients and 80 age and BMI matched healthy lean controls were included in this study. Serum Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), Matsuda insulin sensitivity index (ISI), Nt-probnp, C-reactive protein (CRP), androgen and lipid levels were measured. Serum Nt-probnp levels were significantly higher in the PCOS group. Hyperandrogenic PCOS patients had higher Nt-probnp levels. There were significant correlations between serum Nt-probnp and total testosterone, total cholesterol, HOMA and Matsuda levels. Linear regression analysis showed that Matsuda ISI and fasting insulin levels significantly affected the Nt-probnp levels (R2 of the model = 0.763; p<.0001).IMPACT STATEMENTWhat is already known on this subject? Many risk factors for cardiovascular disease (CVD) including insulin resistance, dyslipidaemia, hypertension and hyperandrogenism may be found in young women with polycystic ovary syndrome (PCOS), although evidence for CVD in lean women with PCOS is limited. N-terminal fragment of brain natriuretic peptide (NT-probnp) is a high predictive marker regarding of CVD, especially in patients without overt CVD. There have been contradictory results regarding Nt-probnp levels in PCOS patients and there have not been any effective studies regarding the relation between CVD risk factors and Nt-probnp levels for lean PCOS patients.What the results of this study add? This study found increased Nt-probnp levels in lean PCOS patients, which may indicate a positive correlation with risk for CVD. Strong relations were also found between Nt-probnp levels and increased insulin resistance, dyslipidaemia, decreased insulin sensitivity and hyperandrogenism. Lean PCOS patients have increased risk factors for CVD, and these risk factors are correlated with Nt-probnp levels. Nt-probnp is more affected by increased fasting insulin and decreased insulin sensitivity.What the implications are of these findings for clinical practice and/or further research? Lean PCOS patients should be evaluated for CVD. Further prospective controlled studies are needed in order to predict the long-term risk of developing CVD in lean PCOS patients.

274-OR: Beta-Cell Dysfunction Is Associated with Impaired Insulin-Mediated Suppression of Glucagon in Obese Hispanic Americans

Recent studies have demonstrated an increase in the glucagon:insulin ratio in lean versus obese subjects. We assessed insulin-mediated suppression of plasma glucagon levels in 260 obese Hispanic Americans (59 NGT, HbA1c= 5.1±0.1%, BMI= 32.6±0.7; 109 Prediabetes, HbA1c= 5.8±0.1%, BMI= 33.8±0.5; 92 T2D, HbA1c= 7.3±0.2%, BMI= 34±0.5) with varying glucose tolerance. Subjects participated in a 2-h OGTT with measurement of plasma glucose, insulin, glucagon concentrations. During the OGTT, we quantitated insulin-mediated suppression of plasma glucagon concentration, Matsuda Index of insulin sensitivity, and the insulin secretion/insulin sensitivity (disposition) index using plasma C-peptide concentration. There was no difference in fasting plasma glucagon level between obese subjects with normal glucose tolerance (NGT), prediabetes, and type 2 diabetes (T2D). However, there was a progressive decrease in fasting glucagon:insulin ratio from NGT to prediabetes to T2D (8.71±0.72 vs. 6.92±0.53 vs. 5.66±0.41, P&amp;lt;0.01). During OGTT at 60 min, glucagon:insulin ratio increased from NGT to T2D (0.93±0.09 vs. 0.89±0.07 vs. 2.33±0.20, P&amp;lt;0.001), and the suppression of plasma glucagon (compared to basal value) was markedly decreased (10.3±3.4% vs. 9.3±1.9% vs. 2.5±2.8%, P&amp;lt;0.05). At 120 min (OGTT), glucagon:insulin ratio was increased in T2D versus NGT (1.28±0.17 vs. 2.0±0.20, P&amp;lt;0.01). The glucagon:insulin ratio was closely correlated with whole body insulin sensitivity and β-cell function during the fasting state (Matsuda Index, r= 0.51, P&amp;lt;0.001; Disposition Index, r= 0.30, P&amp;lt;0.001) and with Disposition Index during the OGTT at 60 and 120 min (r= -0.41, P&amp;lt;0.001; r= -0.21, P&amp;lt;0.01), respectively. Collectively, these findings indicate that insulin-mediated suppression of glucagon secretion is impaired with increasing severity of glucose intolerance in obese Hispanic Americans and is closely associated with insulin resistance and β-cell dysfunction. Disclosure X. Chen: None. E.R. Maldonado Corchado: None. A. Merovci: None. E. Case: None. D. Tripathy: None. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.

2055-P: The Effect of Transcranial Direct Current Stimulation Associated with Hypocaloric Diet on Glucose Homeostasis in Overweight or Obese Adults

Aims: To test the effect of repetitive active transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) associated with a hypocaloric diet (HD) on glucose homeostasis in overweight or obese adults. Method: We selected in a RCT double-blind study, overweight or obese adults with different degrees of glucose tolerance to complete a 4-week (20 sessions; five consecutive weekdays) of fixed-dose tDCS (2mA, 20min) delivered over the right DLPFC associated with a standard HD. Subjects were randomly assigned (1:1) and stratified by sex to active tDCS group (AG) or sham tDCS group (SG). Changes on the glycemic and insulinemic response were assessed in a 4h liquid meal tolerance test (LMTT), performed before (t0) and after (t20) the 4-week intervention. Plasma glucose and insulin concentrations were used to determine glucose and insulin AUCs, indices of insulin sensitivity (MISI, Matsuda Insulin Sensitivity Index), insulin secretion (ISI, Insulin Secretion Index), and pancreatic β-cell function (DI, Disposition Index). Data were analyzed with generalized estimating equations adjusted for age, carbohydrate intake, and weight loss (%). Results: Twenty-eight participants were randomized (79% obese; 29% IGT, 4% T2D; 37.6 [5.8] years). Changes over the time (mean [95% CI]) for FPG was higher in AG than in SG (∆t20-t0 = −7.8 [−14.0, −1.6] vs. ∆t20-t0 = −0.9 [−4.0, 2.1] mg/dL; p = 0.043) after the intervention. Likewise, the MISI was improved in AG compared with SG (∆t20-t0 = 3.2 [1.5 to 4.9] vs. ∆t20-t0 = 0.5 [−1.5, 2.5] pmol-1x mmol-1; p = 0.044). There were no significant differences between groups in fasting insulin, glucose and insulin AUCs, ISI, or DI over the study. Conclusions: Repetitive active tDCS over the right DLPFC may be a promising non-invasive technique that could be used to improve glucose homeostasis in overweight or obese individuals on a low-calorie diet. ClinicalTrials.org: NCT02683902. Disclosure C. de Araujo: None. R.C. Fitz: None. G.R. Natividade: None. A.F. Osório: None. P.N. Merello: None. P. Schestatsky: None. F. Gerchman: Speaker's Bureau; Self; Novo Nordisk Inc. Other Relationship; Self; Sanofi-Aventis. Funding Hospital de Clínicas de Porto Alegre (FIPE15-0119, 16-0417)

196-LB: Prenatal and Lifestyle Contributions to Child Insulin Sensitivity

Background: Early life exposures play an important role in metabolic health throughout life. We examined how prenatal exposures to maternal obesity or gestational diabetes mellitus (GDM) and low levels of physical activity and increased food intake may contribute to reductions in insulin sensitivity in childhood. Methods: Participants were 7-10 year old children who were born at Kaiser Permanente Southern California. Maternal pre-pregnancy BMI and GDM status were extracted from electronic medical records. Child weight and height were measured, and oral glucose tolerance tests were performed. Insulin sensitivity was estimated using the Matsuda insulin sensitivity index (ISI). Diet was assessed using 24-hour dietary recalls and daily energy intake (EI) was calculated. Physical activity was assessed using a 3-day physical activity recall and average min/day of moderate to vigorous physical activity (MVPA) was calculated. Linear regression was used to assess ISI associations with the exposures. Results: 92 children (52 girls; 40 boys; 55 GDM-exposed; 37 unexposed) participated. Maternal pre-pregnancy BMI ranged from 19.0-50.4 kg/m2. Mean±SD child age was 8.3±0.9 years, BMI z-score: 0.60±1.1, ISI: 10.6±5.9, EI: 1790.7±444.2 kcal, and MVPA: 118.7±93.8 min/day. Children who spent more time in MVPA had better insulin sensitivity (β=0.82; P=.02). Adjusting for maternal pre-pregnancy BMI, GDM exposure, child age, sex, and EI, did not affect this relationship (β=0.87; P&amp;lt;.01), nor did further adjusting for BMI z-score (β=0.78; P=.01). Prenatal exposure to GDM and child ISI (β=0.19, P=.28) and maternal pre-pregnancy BMI were not significantly associated with child ISI (β=-0.01, P=0.40), nor was child’s EI associated with ISI (β=0.001; P=.59). Conclusions: Time spent in MVPA was the strongest predictor of child insulin sensitivity. Our findings suggest that engaging in MVPA during childhood is beneficial for insulin sensitivity and may help ameliorate future risk for metabolic disease. Disclosure J. Alves: None. T. Chow: None. J. Zink: None. S. Luo: None. M.P. Martinez: None. A. Romero: None. A. Xiang: None. K.A. Page: None. Funding American Diabetes Association (1-14-ACE-36 to K.A.P.); National Institutes of Health (1F31MH115640-01A1)

Effects of Avocado Consumption on Abdominal Adiposity and Glucose Tolerance: Findings from the Persea Americana for Total Health (PATH) Randomized Controlled Trial (P21-005-19)

ObjectivesOver 35% of adults have elevated abdominal obesity. This is concerning because abdominal obesity increases risk for type 2 diabetes. Therefore, dietary interventions with the potential to prevent abdominal obesity and its metabolic consequences have gained increasing importance. Habitual intake of the Hass avocado (Persea Americana) has been cross-sectionally linked to lower abdominal obesity; however, the effects of regular avocado consumption for abdominal adiposity and glycemic measures are unknown. Accordingly, we conducted a single-blind, randomized, controlled trial examining the effects of daily avocado consumption on abdominal adiposity and oral glucose tolerance (OGTT). Methods111 adults (65 females) between 25 and 45y with overweight or obesity (BMI >= 25 kg/m2) were randomized to an intervention group (N = 54) that received a daily meal with one fresh avocado or a control group (N = 57) that received an isocaloric meal without avocado for 3 months. DXA was used to assess abdominal fat distribution changes, calculated as the ratio of visceral adipose tissue to subcutaneous abdominal tissue (VS Ratio) and an OGTT was conducted following an overnight fast. ResultsA group by time effect (P = 0.04) was observed whereby the intervention group exhibited a reduction in the VS Ratio (0.02; 95% CI, 0.0003 to 0.04) whereas there was no change in the control group (0.003; 95% CI, −0.02 to 0.01). Changes in the VS ratio were driven by a reduction in visceral adipose tissue among intervention participants (28.3 g; 95% CI, 3.4 to 53.3). Avocado consumption did not affect the Matsuda Insulin Sensitivity Index (P = 0.28), Glucose AUC (P = 0.37), or Insulin AUC (P = 0.09). However, there was a group by time effect (P = 0.005) whereby the control group exhibited an increase in insulin concentration at 120 m (21.9 μU/ml; 95% CI, 3.3 to 40.5) whereas there was no change in the intervention group (6.1 μU/ml; 95% CI, −4.4 to 16.5). ConclusionsInclusion of one fresh avocado per day over 3 months had abdominal adiposity lowering effects. However, the effects for oral glucose tolerance were limited to insulin secretion 2 h postprandial. Our results demonstrate that avocados have beneficial effects on fat distribution while maintaining insulin sensitivity over time among adults with overweight and obesity. Funding SourcesThis work was supported by funds provided by the Hass Avocado Board. Partial support was also provided by the Department of Kinesiology and Community Health at the University of Illinois and the USDA National Institute of Food and Agriculture, Hatch project 1009249.

Abstract P255: Central Fat Distribution and Metabolic Health in Normoglycemic Young Women

Purpose: The purpose of this pilot study is to test the hypothesis that fat distribution, rather than overall obesity, is strongly related to insulin sensitivity in young, normoglycemic women. Methods: Thirty-eight non-diabetic young women completed the study (ages 20.7 ±2.8 years; BMI 27.6 ±3.6; 44% Caucasian (17 of 38). Matsuda Insulin Sensitivity Index was calculated from plasma glucose and insulin at 0, 30, 60, and 90 minutes after ingestion of 75g glucose, using established formula, to estimate whole body insulin sensitivity. Whole body and regional adipose tissue was assessed via DXA, abdominal ultrasound of intra-abdominal and pre-peritoneal adipose depots, circumference measures, and skinfold measures. ANOVA was used to assess mean differences among tertiles of Matsuda Index. Partial correlations were controlled for age and race, then additionally controlled for DXA percent body fat to assess associations of fat distribution independent of overall obesity. Results: ANOVA revealed a higher waist circumference (83.8 ±7.8cm vs. 75.6 ±7.2), waist/hip ratio (0.777 ±0.48 vs. 0.716 ±0.05 ), waist/height ratio (0.524 ±0.028 vs. 0.468 ±0.043), ultrasound intra-abdominal thickness (3.57 ±1.3 vs. 2.48 ±1.1) in the least insulin-sensitive tertile, when compared to the most insulin-sensitive tertile, while age, BMI, and other measures of adiposity were comparable among the three groups. Partial correlations controlled for age and race revealed strong negative relationships between Matsuda Index and measures of upper-body and central adiposity, including waist circumference ( r =-.416, p &lt;0.05), waist/hip ratio ( r = -0.500, p &lt;0.01), waist/height ratio ( r =-0.431, p &lt;0.05), IAAT ( r = -0.412, p &lt;0.05), PPAT ( r =-0.381, p &lt;0.05), but not BMI ( r = -0.173, p =ns) or overall percent fat ( r =-0.132 , p =ns). When further controlled for percent body fat, correlations persisted between Matsuda and waist circumference ( r =-.433, p &lt;0.05), waist/hip ratio ( r =-0.488, p &lt;0.01), waist/height ratio (r= -.470, p &lt;0.01), intra-abdominal fat thickness ( r =-0.394, p &lt;0.05) and pre-peritoneal fat thickness ( r =-0.361, p =0.05). Conclusions: Central and upper-body fat distribution, independent of overall obesity, is strongly associated with metabolic health in young non-diabetic women. These data underscore the clinical utility of central adiposity as an marker of metabolic health.