Relatively Low ß-Cell Responsiveness Contributes to the Association of BMI with Circulating Glucose Concentrations Measured under Free-Living Conditions among Pregnant African American Women.

BACKGROUND: Body mass index (BMI, in kg/m(2)) is positively associated with plasma glucose in late pregnancy and with risk of adverse obstetric outcomes. Much of the existing research uses single-clinic measures of plasma glucose, which may not accurately reflect circulating glucose under free-living conditions. Furthermore, little is known about circulating glucose concentrations of African American women, who tend to have poorer diet quality and a greater risk of obstetric complications. OBJECTIVE: The objective of the study was to test the hypothesis that the positive association of BMI in early pregnancy with third-trimester circulating glucose concentrations measured under free-living conditions among African American women would be at least partially attributable to lower ß-cell insulin secretion relative to insulin sensitivity [i.e., lower disposition index (DI)]. METHODS: Using a prospective, observational design, 40 pregnant African American women (mean ± SD age: 23.1 ± 4.0 y; mean ± SD BMI: 28.4 ± 7.5) wore continuous glucose monitors and accelerometers for 3 d at 32-35 wk of gestation and concurrently maintained a food diary to report their self-selected meals. The DI was derived from a 75-g oral glucose tolerance test. Linear regression modeling was used to calculate the association of BMI with the 24-h glucose (GLUC24h) and 2-h (GLUC2hPP) postprandial glucose areas under the curve and with the percentage of time the glucose concentrations were >120 mg/dL. RESULTS: The positive associations between BMI and GLUC24h (standardized ß = 0.36, P = 0.03) and the percentage of time glucose concentrations were >120 mg/dL (standardized ß = 0.40, P = 0.02) were independent of total carbohydrate intake and physical activity and were attenuated when DI was added to the model. The positive association of BMI with GLUC2hPP was attenuated when DI was added to the model, and DI itself was independently associated with GLUC2hPP after self-selected breakfast and dinner (standardized ß = -0.33 and -0.42, respectively; P = 0.01). CONCLUSIONS: The association of BMI with high circulating glucose in free-living pregnant African American women is at least partially attributable to lower ß-cell responsiveness.

Association of late-night carbohydrate intake with glucose tolerance among pregnant African American women.

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy.

Associations of total and undercarboxylated osteocalcin with peripheral and hepatic insulin sensitivity and ß-cell function in overweight adults.

CONTEXT: Animal studies indicate that osteocalcin (OC), particularly the undercarboxylated isoform (unOC), affects insulin sensitivity and secretion, but definitive data from humans are lacking. OBJECTIVE: The objectives of the study were to determine whether total OC and unOC are independently associated with insulin sensitivity and ß-cell response in overweight/obese adults; whether glucose tolerance status affects these associations; and whether the associations are independent of bone formation, as reflected in procollagen type 1 amino propeptide (P1NP). DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study conducted at a university research center involving 63 overweight/obese adults with normal (n = 39) or impaired fasting glucose (IFG; n = 24). MAIN OUTCOME MEASURES: Serum concentrations of total/undercarboxylated OC and P1NP were assessed by RIA; insulin sensitivity was determined by iv glucose tolerance test (S(I)-IVGTT), liquid meal test (S(I) meal), and homeostasis model assessment of insulin resistance; ß-cell response to glucose [basal ß-cell response to glucose; dynamic ß-cell response to glucose; static ß-cell response to glucose; and total ß-cell response to glucose] was derived using C-peptide modeling of meal test data; and intraabdominal adipose tissue was measured using computed tomography scanning. RESULTS: Multiple linear regression, adjusting for intraabdominal adipose tissue and P1NP, revealed that total OC was positively associated with S(I)-iv glucose tolerance test (P < .01) in the total sample. OC was not associated with S(I) meal or homeostasis model assessment of insulin resistance. In participants with IFG, unOC was positively associated with static ß-cell response to glucose and total ß-cell response to glucose (P < .05), independent of insulin sensitivity. CONCLUSIONS: In overweight/obese individuals, total OC may be associated with skeletal muscle but not hepatic insulin sensitivity. unOC is uniquely associated with ß-cell function only in individuals with IFG. Further research is needed to probe the causal inference of these relationships and to determine whether indirect nutrient sensing pathways underlie these associations.

Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.

OBJECTIVE: Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects ß-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. DESIGN: In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. PATIENTS: Thirty women with PCOS. MEASUREMENTS: ß-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. RESULTS: Paired t-test indicated that the lower-CHO diet induced significant decreases in basal ß-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') ß-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). CONCLUSIONS: In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.

A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves ß-cell function in individuals with impaired fasting glucose.

The objective was to examine the effects of diet macronutrient composition on insulin sensitivity, fasting glucose, and ß-cell response to glucose. Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL) and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass index, 32.5 ± 4.2 kg/m(2)) men and women. For 8 weeks, participants were provided with eucaloric diets, either higher carbohydrate/lower fat (55% carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39). Insulin sensitivity and ß-cell response to glucose (basal, dynamic [PhiD], and static) were calculated by mathematical modeling using glucose, insulin, and C-peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG. After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this pattern was not observed among NGT. Within IFG, fasting glucose at baseline and the change in fasting glucose over the intervention were inversely associated with baseline PhiD (-0.40, P < .05) and the change in PhiD (-0.42, P < .05), respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and lower fasting glucose and greater glucose-stimulated insulin secretion in individuals with IFG. If confirmed, these results may have an impact on dietary recommendations for overweight individuals with and without IFG.

Race differences in the association of oxidative stress with insulin sensitivity in African- and European-American women.

Excessive metabolism of glucose and/or fatty acids may impair insulin signaling by increasing oxidative stress. The objective of this study was to examine the association between insulin sensitivity and protein carbonyls, a systemic marker of oxidative stress, in healthy, nondiabetic women, and to determine if the relationship differed with race. Subjects were 25 African-Americans (AA, BMI 28.4 ± 6.2 kg/m(2), range 18.8-42.6 kg/m(2); age 33.1 ± 13.5 years, range 18-58 years) and 28 European-Americans (EA, BMI 26.2 ± 5.9 kg/m(2), range 18.7-48.4 kg/m(2); age 31.6 ± 12.4 years, range 19-58 years). Insulin sensitivity was determined using an intravenous glucose tolerance test incorporating [6,6-(2)H(2)]-glucose, and a two-compartment mathematical model. Multiple linear regression results indicated that insulin sensitivity was inversely associated with protein carbonyls in AA (standardized regression coefficient -0.47, P < 0.05) but not EA (0.01, P = 0.945), after adjusting for %body fat. In contrast, %body fat was significantly and positively associated with insulin sensitivity in EA (-0.54, P < 0.01) but not AA (-0.24, P = 0.196). Protein carbonyls were associated with free fatty acids (FFA) in AA (r = 0.58, P < 0.01) but not EA (r = -0.11, P = 0.59). When subjects were divided based on median levels of fasting glucose and FFA, those with higher glucose/FFA concentrations had a significantly greater concentration of circulating protein carbonyls compared to those with lower glucose/FFA concentrations (P < 0.05). These results suggest that oxidative stress independently contributes to insulin sensitivity among AA women. Further, this association in AA may be mediated by circulating FFA and/or glucose.

Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women.

Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (S(I)) among African Americans (AA) compared with European Americans (EA). Whole-body S(I) represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic S(I). The purpose of this study was to examine specific indexes of S(I) among AA and EA women to determine whether lower whole-body S(I) in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal S(I) and Hepatic S(I) were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-(2)H(2)]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal S(I) and Hepatic S(I) were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body S(I) among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic S(I), AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk.

Dietary macronutrient composition affects ß cell responsiveness but not insulin sensitivity.

BACKGROUND: Altering dietary carbohydrate or fat content may have chronic effects on insulin secretion and sensitivity, which may vary with individual metabolic phenotype. OBJECTIVE: The objective was to evaluate the contribution of tightly controlled diets differing in carbohydrate and fat content for 8 wk to insulin sensitivity and ß cell responsiveness and whether effects of diet would vary with race, free-living diet, or insulin response. DESIGN: Healthy overweight men and women (36 European Americans, 33 African Americans) were provided with food for 8 wk and received either a eucaloric standard diet (55% carbohydrate, 27% fat) or a eucaloric reduced-carbohydrate (RedCHO)/higher-fat diet (43% carbohydrate, 39% fat). Insulin sensitivity and ß cell responsiveness were assessed at baseline and 8 wk by using a liquid meal tolerance test. RESULTS: Insulin sensitivity did not change with diet (P = 0.1601). Static ß cell response to glucose (ФS) was 28.5% lower after the RedCHO/higher-fat diet. Subgroup analyses indicated that lower ФS with the RedCHO/higher-fat diet occurred primarily among African Americans. A significant inverse association was observed for change in glucose area under the curve compared with change in ФS. CONCLUSIONS: Consumption of a eucaloric 43% carbohydrate/39% fat diet for 8 wk resulted in down-regulation of ß cell responsiveness, which was influenced by baseline phenotypic characteristics. Further study is needed to probe the potential cause-and-effect relation between change in ФS and change in glucose tolerance. This trial is registered at clinicaltrials.gov as NCT00726908.

Higher maternal gestational glucose concentration is associated with lower offspring insulin sensitivity and altered beta-cell function.

CONTEXT: Intrauterine exposure to elevated glucose concentrations may be a mediating factor in prenatal programming of offspring diabetes risk. However, studies examining the effects of maternal glucose concentration on measures of insulin sensitivity and ß-cell response in prepubertal children are limited. OBJECTIVE: We tested the hypothesis that maternal gestational glucose concentration would be inversely associated with children's insulin sensitivity independent of adiposity and positively associated with children's ß-cell response independent of adiposity and insulin sensitivity. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 21 children aged 5-10 yr in a clinical research setting. OUTCOMES MEASURED: Children's insulin sensitivity index and basal, static, dynamic, and total ß-cell response to glucose were determined by mathematical modeling using insulin, glucose, and C-peptide values after a liquid meal tolerance test. Children's percent body fat was determined by dual-energy x-ray absorptiometry. Maternal gestational glucose concentration for the target pregnancy was determined after a 50-g, 1-h oral glucose challenge test at 24-28 wk gestation. RESULTS: Maternal glucose concentration was significantly, inversely associated with children's insulin sensitivity, independent of percent fat and ethnicity (P <0.05). A significant, positive association was observed for maternal glucose concentration with static ß-cell response, independent of percent fat and insulin sensitivity (P < 0.05). CONCLUSIONS: Maternal gestational glucose concentration was significantly associated with offspring insulin sensitivity and ß-cell response independent of adiposity. These results suggest that maternal glucose may program the fetus both at the pancreas and at the level of insulin target tissues such as skeletal muscle and liver.

Age-related changes in insulin sensitivity and ß-cell function among European-American and African-American women.

Type 2 diabetes (T2D) is more prevalent among African-American (AA) than European-American (EA) women for reasons that are unknown. Ethnic differences in physiological processes related to insulin sensitivity (S(I)) and secretion, and age-related changes in these processes, may play a role. The purpose of this study was to identify ethnicity- and age-related differences in S(I) and ß-cell responsivity among AA and EA females, and to determine whether these differences are independent of body composition and fat distribution. Healthy, normoglycemic females aged 7-12 years (n = 62), 18-32 years (n = 57), and 40-70 years (n = 49) were recruited for entry into this study. Following an overnight fast, S(I), intravenous glucose tolerance (Kg), acute C-peptide secretion (X0), and basal, first-phase, second-phase, and total ß-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively) were measured by an intravenous glucose tolerance test. Total % body fat was assessed by dual-energy X-ray absorptiometry, and intra-abdominal adiposity (IAAT) by computed tomography. Main effects of age group and ethnicity were measured with analysis of covariance, adjusting for % fat, IAAT, and S(I) as indicated. AA had lower S(I), and higher Kg, X0, Phi1, and Phi(TOT) (P < 0.05), which remained after adjustment for % fat and IAAT. Greater X0, Phi1, and Phi(TOT) among AA were independent of S(I). Advancing age was associated with greater Phi2 among both EA and AA. To conclude, inherent ethnic differences in ß-cell function exist independently of adiposity and S(I). Future research should examine whether ethnic differences in ß-cell physiology contribute to disparities in T2D risk.

Incidence, relevance and response for Ralsfonia respiratory infections.

BACKGROUND: Cases of Ralstonia colonization/infection occasionally reported by hospitals has generated increased interest in an organism previously little known to most clinicians. Our goal was to determine the incidence of respiratory colonizations and infections involving Ralstonia and the association of mechanical ventilation (limited to reports on respiratory-related occurrences in the U.S.A.) and propose a decision chart to assist response. METHODS: We performed a secondary analysis of published clinical reports of Ralstonia to determine the potential risks for respiratory colonization and infection in the USA and if being on mechanical ventilation (MV) had an influence on colonization and conversion to infection (symptomatic). RESULTS: The odds of developing colonization with Ralstonia were eight times higher and the likelihood of developing infection with Ralstonia was twelve times higher in those mechanically ventilated compared to those not mechanically ventilated. CONCLUSIONS: Our results suggest that individuals who are currently on mechanical ventilation and are Ralstonia culture-positive have an increased risk for colonization and may have increased propensity to the development of infection (two decision trees for approaching diagnosis and therapy included).

Adiposity and ß-cell function: relationships differ with ethnicity and age.

The prevalence of type 2 diabetes is higher among African Americans (AA) vs. European Americans (EA), is highest at middle age, and is related to obesity. This study was conducted to test the hypothesis that the association of adiposity (percent body fat (%fat)) with indexes of insulin sensitivity (S(I)) and ß-cell function would differ with ethnicity and age. Subjects were 168 healthy, normoglycemic AA and EA girls and women aged 7-12 years, 18-32 years, and 40-70 years. An intravenous glucose tolerance test (IVGTT) was used to assess indexes of insulin secretion and action: S(I), acute C-peptide secretion (X0); basal, first-phase, second-phase, and total ß-cell responsivity to glucose (PhiB, Phi1, Phi2, and Phi(TOT), respectively); and the disposition index (DI = S(I) × Phi(TOT)). %Fat was assessed with dual energy X-ray absorptiometrys. Adiposity was significantly associated with S(I) among EA (-0.57, P < 0.001) but not AA (-0.20, P = 0.09). Adiposity appeared stimulatory to ß-cell function in the two groups of younger subjects and in EA, but inhibitory in postmenopausal women, particularly AA postmenopausal women. Among AA postmenopausal women, %fat was inversely associated with Phi1 (r = -0.57, P < 0.05) and Phi(TOT) (r = -0.68, P < 0.01). These results suggest that the impact of adiposity on insulin secretion and action differs with age and ethnicity.

Entero-insular axis and postprandial insulin differences in African American and European American children.

BACKGROUND: African Americans have a greater insulin response after glucose challenge than do European Americans. Factors underlying this response are unknown. OBJECTIVE: We determined the insulin, C-peptide, and incretin responses to a mixed macronutrient meal in African American and European American children. We hypothesized that 1) African Americans would have greater postprandial insulin and C-peptide responses, 2) African Americans would have higher incretin responses, and 3) the greater beta cell response among African Americans would be explained by greater incretin responses. DESIGN: Subjects were 34 African American and 18 European American children. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured after the subjects consumed a liquid mixed meal. Insulin, C-peptide, and incretin responses were derived from the area under the curve (AUC) for minutes 0-30 (early response) and minutes 30-180 (late response) after meal ingestion. RESULTS: The early insulin response was higher in African American (14,565 +/- 6840 pmol/L x 30 min) than in European American (7450 +/- 4077 pmol/L x 30 min; P < 0.01) children. Early C-peptide AUC did not differ by ethnicity (African Americans: 34.8 +/- 12.5; European Americans: 28.6 +/- 12.5 nmol/L x 30 min; P = 0.10). Early and late GLP-1 responses were lower in African Americans than in European Americans: 108.1 +/- 56.4 compared with 160.5 +/- 90.8 pmol/L x 30 min and 509.4 +/- 286.9 compared with 781.9 +/- 483.4 pmol/L x 150 min, respectively (P < 0.05 for both). The GIP response did not differ between groups. CONCLUSIONS: The greater early insulin response in African Americans than in European Americans is not due to differences in circulating GLP-1 or GIP and may be due to lesser insulin clearance. Further research is needed to determine the physiologic implications of lower GLP-1 among African Americans.

Stethoscopes: what are we hearing?

This paper develops an objective methodology to test the audio quality of stethoscopes, classifies stethoscopes into five functional categories, and compares the audio performance of each of the five categories. These categories, based on the manufacturer's recommended use, are basic assessment, cardiology, disposable, high-end cardiology, and physical assessment. The classification into categories is based on the intended performance of the stethoscopes as provided by the manufacturers. After developing the procedures and running more than 500 tests, the stethoscope with the least amount of loss over the spectrum was chosen from each of the five categories; the five were then compared to one another. Thirty-nine stethoscopes from 11 manufacturers were used in this study. The objective test methodology allows for side-by-side comparison of stethoscopes from various manufacturers that is independent of the manufacturer's published test results.

An evaluation of 2 new devices for nasal high-flow gas therapy.

BACKGROUND: The traditional nasal cannula with bubble humidifier is limited to a maximum flow of 6 L/min to minimize the risk of complications. We conducted a bench study of 2 new Food and Drug Administration-approved nasal cannula/humidifier products designed to deliver at flows> 6 L/min. METHODS: Using a digital psychrometer we measured the relative humidity and temperature of delivered gas from each device, at 5 L/min increments over the specified functional high-flow range. RESULTS: The Salter Labs unit achieved 72.5-78.7% relative humidity (5-15 L/min range) at ambient temperature (21-23 degrees C). The Vapotherm device achieved 99.9% relative humidity at a temperature setting of 37 degrees C (5-40 L/min). CONCLUSIONS: Both devices meet minimum humidification standards and offer practical new treatment options. The patient-selection criteria are primarily the severity of the patient's condition and cost.

Contribution of insulin secretion and clearance to glucose-induced insulin concentration in african-american and caucasian children.

Relative to Caucasians (C), African-American (AA) children and adults have lower indices of insulin sensitivity (S(i)) and a higher acute insulin response to glucose (AIR(g)). Among AA children, AIR(g) is greater than that which would be predicted based on lower S(i). The objectives of the present study were 1) to determine whether insulin secretory parameters differ in AA vs. C children and adolescents using C-peptide modeling, 2) to determine whether hepatic insulin extraction differs with ethnicity/race using the C-peptide to insulin molar ratio, and 3) to determine whether the relatively greater AIR(g) among African-Americans is due to greater insulin secretion or lesser clearance. Subjects (n = 76) were AA and C children (mean age, approximately 11 yr). A 3-h tolbutamide-modified iv glucose tolerance test and minimal modeling were used to determine S(i) and AIR(g). First phase C-peptide/insulin secretion and basal, first, and second phase beta-cell sensitivity to glucose were determined using C-peptide modeling with standard kinetic parameters developed in adults. The incremental C-peptide to insulin molar ratio over the 3-h test period, an index of hepatic insulin extraction, was calculated with the trapezoidal method. S(i) was lower and AIR(g) was higher in AA vs. C children. First phase C-peptide/insulin secretion and first phase beta-cell sensitivity to glucose were approximately 2-fold greater in AA vs. C children (P < 0.001); there were no between-group differences in basal or second phase beta-cell sensitivity to glucose. Hepatic insulin extraction was lower in AA vs. C (3.77 +/- 1.78% vs. 5.99 +/- 2.18%; P < 0.001). Multiple linear regression modeling indicated that first phase C-peptide/insulin secretion and hepatic insulin extraction contributed independently to AIR(g); however, it was only first phase C-peptide/insulin secretion that explained the significant independent contribution of ethnicity/race to AIR(g) after adjusting for S(i). The results of this study suggest that greater AIR(g) among AA is due to both greater insulin secretion and lesser hepatic insulin extraction, and that AIR(g) above that predicted based on lower S(i) is due to greater insulin secretion. The insulin secretion data await verification that the kinetic parameters used apply to children and AA.