The objective of this study was to compare insulin resistance relative to body fat and the associated compensatory responses in 57 healthy children living in Los Angeles, California (14 Caucasians, 15 African-Americans, and 28 Hispanics).
Insulin sensitivity and acute insulin response were determined by intravenous glucose tolerance test. Insulin secretion, hepatic insulin extraction, and insulin clearance were estimated by C-peptide and insulin modeling.
Insulin sensitivity was significantly lower in Hispanics and African-Americans compared with Caucasian children, and acute insulin response was significantly higher in African-American children. No ethnic differences were noted in the first-phase secretion, but second-phase insulin secretion was significantly higher in Hispanic children than in African-American children (200 +/- 53 vs. 289 +/- 41 nmol/min; P = 0.03). The greater acute insulin response in African-Americans, despite lower secretion, was explained by a lower hepatic insulin extraction in African-Americans compared with Hispanics (36.6 +/- 2.9 vs. 47.3 +/- 2.2%; P = 0.0006).
In conclusion, Hispanic and African-American children are more insulin resistant than Caucasian children, but the associated compensatory responses are different across ethnic groups.
"On the other hand, the indexes based on post-hepatic insulin levels were higher than CON and tightly and negatively related to hepatic insulin extraction. From this, it follows that higher OGTT insulin concentrations observed in AI were due to a higher post-hepatic insulin release associated to a lower extraction, proper of insulin–resistant states [33,34]. The reasons for this lower insulin extraction by the liver are still obscure: it may be the interplay of insulin resistance [33,34] and/or glucocorticoid excess, which may also lead to this phenomenon . "
[Show abstract][Hide abstract] ABSTRACT: Insulin-resistance is commonly found in adrenal incidentaloma (AI) patients. However, little is known about beta-cell secretion in AI, because comparisons are difficult, since beta-cell-function varies with altered insulin-sensitivity.
To retrospectively analyze beta-cell function in non-diabetic AI, compared to healthy controls (CON).
AI (n=217, 34%males, 57±1years, body-mass-index:27.7±0.3kg/m(2)) and CON [n=25, 32%males, 56±1years, 26.7±0.8kg/m(2)] with comparable anthropometry (p≥0.31) underwent oral-glucose-tolerance-tests (OGTTs) with glucose, insulin, and C-peptide measurements. 1mg-dexamethasone-suppression-tests were performed in AI. AI were divided according to post-dexamethasone-suppression-test cortisol-thresholds of 1.8 and 5µg/dL into 3subgroups: pDexa<1.8µg/dL, pDexa1.8-5µg/dL and pDexa>5µg/dL. Using mathematical modeling, whole-body insulin-sensitivity [Clamp-like-Index (CLIX)], insulinogenic Index, Disposition Index, Adaptation Index, and hepatic insulin extraction were calculated.
CLIX was lower in AI combined (4.9±0.2mg·kg(-1)·min(-1)), pDexa<1.8µg/dL (4.9±0.3) and pDexa1.8-5µg/dL (4.7±0.3, p<0.04 vs.CON:6.7±0.4). Insulinogenic and Disposition Indexes were 35%-97% higher in AI and each subgroup (p<0.008 vs.CON), whereas C-peptide-derived Adaptation Index, compensating for insulin-resistance, was comparable between AI, subgroups, and CON. Mathematical estimation of insulin-derived (insulinogenic and Disposition) Indexes from associations to insulin-sensitivity in CON revealed that AI-subgroups had ~19%-32% higher insulin-secretion than expectable. These insulin-secretion-index differences negatively (r=-0.45, p<0.001) correlated with hepatic insulin extraction, which was 13-16% lower in AI and subgroups (p<0.003 vs.CON).
AI-patients show insulin-resistance, but adequately adapted insulin secretion with higher insulin concentrations during an OGTT, because of decreased hepatic insulin extraction; this finding affects all AI-patients, regardless of dexamethasone-suppression-test outcome.
PLoS ONE 10/2013; 8(10):e77326. DOI:10.1371/journal.pone.0077326 · 3.23 Impact Factor
"In contrast, lower AIR G and DI represent an inability of the pancreas to secrete enough insulin at a given level of insulin resistance where impaired glucose tolerance may arise (i.e., higher diabetes risk). Indeed, our laboratory has shown both increased AIR G and DI as potential compensatory mechanisms for decreased S I in minority children and adolescents  . "
[Show abstract][Hide abstract] ABSTRACT: Purpose:
It is unclear whether sociocultural and socioeconomic factors are directly linked to type 2 diabetes risk in overweight/obese ethnic minority children and adolescents. This study examines the relationships between sociocultural orientation, household social position, and type 2 diabetes risk in overweight/obese African-American (n = 43) and Latino-American (n = 113) children and adolescents.
Sociocultural orientation was assessed using the Acculturation, Habits, and Interests Multicultural Scale for Adolescents (AHIMSA) questionnaire. Household social position was calculated using the Hollingshead Two-Factor Index of Social Position. Insulin sensitivity (SI), acute insulin response (AIRG) and disposition index (DI) were derived from a frequently sampled intravenous glucose tolerance test (FSIGT). The relationships between AHIMSA subscales (i.e., integration, assimilation, separation, and marginalization), household social position and FSIGT parameters were assessed using multiple linear regression.
For African-Americans, integration (integrating their family's culture with those of mainstream white-American culture) was positively associated with AIRG (β = 0.27 ± 0.09, r = 0.48, P < 0.01) and DI (β = 0.28 ± 0.09, r = 0.55, P < 0.01). For Latino-Americans, household social position was inversely associated with AIRG (β = -0.010 ± 0.004, r = -0.19, P = 0.02) and DI (β = -20.44 ± 7.50, r = -0.27, P < 0.01).
Sociocultural orientation and household social position play distinct and opposing roles in shaping type 2 diabetes risk in African-American and Latino-American children and adolescents.
Journal of obesity 05/2013; 2013:512914. DOI:10.1155/2013/512914
"However, insulin sensitivity during the hyperglycemic clamp was calculated during the last 60 min of the 2-h clamp, whereas first-phase insulin was calculated within the first 10 min after the bolus injection of glucose. This is akin to the minimal model analysis of a single FSIVGTT for acute insulin response to glucose (0–10 min) and insulin sensitivity (modeled at ≥10 min), which was the first proposed and is a very frequently used and popularized method for DI (5,6,40). "
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
To compare β-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcDI).RESEARCH DESIGN AND METHODS
Complete data from hyperglycemic and hyperinsulinemic-euglycemic clamps were available for 330 youth, including 73 normal weight (NW), 168 obese with normal glucose tolerance (OB-NGT), 57 obese with impaired glucose tolerance (OB-IGT), and 32 obese with type 2 diabetes (OB-T2DM). The correlation between hcDI and 2cDI and Bland-Altman analysis of agreement between the two were examined.RESULTSInsulin sensitivity and first-phase insulin from hcDI showed a hyperbolic relationship. The hcDI correlated significantly with 2cDI in the groups combined (r = 0.85, P < 0.001) and within each group separately (r ≥ 62, P < 0.001). Similar to 2cDI, hcDI showed a declining pattern of β-cell function across the glucose-tolerance groups. Overall, hcDI values were 27% greater than 2cDI, due to the hyperglycemic versus euglycemic conditions, reflected in a positive bias with Bland-Altman analysis.CONCLUSIONSβ-Cell function relative to insulin sensitivity could be accurately evaluated from a single hyperglycemic clamp, obviating the need for two separate clamp experiments, when lessening participant burden and reducing research costs are important considerations.
Diabetes care 12/2012; 36(6). DOI:10.2337/dc12-1508 · 8.42 Impact Factor
Akihiro Nishimura, Kaoru Nagasawa, Minoru Okubo, Tetsuro Kobayashi, Yasumichi Mori
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