Obesity Attenuates the Contribution of African Admixture to the Insulin Secretory Profile in Peripubertal Children: A Longitudinal Analysis

The pubertal transition has been identified as a time of risk for development of type 2 diabetes, particularly among vulnerable groups, such as African Americans (AAs). Documented ethnic differences in insulin secretory dynamics may predispose overweight AA adolescents to risk for type 2 diabetes. The objectives of this longitudinal study were to quantify insulin secretion and clearance in a cohort of 90 AA and European American (EA) children over the pubertal transition and to explore the association of genetic factors and adiposity with repeated measures of insulin secretion and clearance during this critical period. Insulin sensitivity was determined by intravenous glucose tolerance test (IVGTT) and minimal modeling; insulin secretion and clearance by C‐peptide modeling; genetic ancestry by admixture analysis. Mixed‐model longitudinal analysis indicated that African genetic admixture (AfADM) was independently and positively associated with first‐phase insulin secretion within the entire group (P < 0.001), and among lean children (P < 0.01). When examined within pubertal stage, this relationship became significant at Tanner stage 3. Total body fat was a significant determinant of first‐phase insulin secretion overall and among obese children (P < 0.001). Total body fat, but not AfADM, was associated with insulin clearance (P < 0.001). In conclusion, genetic factors, as reflected in AfADM, may explain greater first‐phase insulin secretion among peripubertal AA vs. EA; however, the influence of genetic factors is superseded by adiposity. The pubertal transition may affect the development of the β‐cell response to glucose in a manner that differs with ethnic/genetic background.     

β‐Cell Function and Insulin Sensitivity in Adolescents From an OGTT

Given the increase in the incidence of insulin resistance, obesity, and type 2 diabetes in children and adolescents, it would be of paramount importance to assess quantitative indices of insulin secretion and action during a physiological perturbation, such as a meal or an oral glucose‐tolerance test (OGTT). A minimal model method is proposed to measure quantitative indices of insulin secretion and action in adolescents from an oral test. A 7 h, 21‐sample OGTT was performed in 11 adolescents. The C‐peptide minimal model was identified on C‐peptide and glucose data to quantify indices of β‐cell function: static φ_s and dynamic φ_d responsivity to glucose from which total responsivity φ was also measured. The glucose minimal model was identified on glucose and insulin data to estimate insulin sensitivity, S_I, which was compared to a reference measure, S_I^ref, provided by a tracer method. Disposition indices, which adjust insulin secretion for insulin action, were then calculated. Indices of β‐cell function were φ_s = 51.35 ± 8.89 × 10^?9min^?1, φ_d = 1,392 ± 258 × 10^?9, and φ = 82.09 ± 17.70 × 10^?9min^?1. Insulin sensitivity was S_I = 14.19 ± 2.73 × 10^?4, not significantly different from S_I^ref = 14.96 ± 3.04 × 10^?4 dl/kg·min per µU/ml, and well correlated: r = 0.98, P < 0.0001, thus indicating that S_I can be accurately measured from an oral test. Disposition indices were DI_s = 1,040 ± 201 × 10^?14 dl/kg/min² per pmol/l, DI_d = 33,178 ± 10,720 × 10^?14 dl/kg/min per pmol/l, DI = 1,844 ± 522 × 10^?14 dl/kg/min² per pmol/l. Virtually the same minimal model assessment was obtained with a reduced 3 h, 9‐sample protocol. OGTT interpreted with C‐peptide and glucose minimal model has the potential to provide novel insight regarding the regulation of glucose metabolism in adolescents, and to evaluate the effect of obesity and interventions such as diet and exercise.     

Greater Omentectomy Improves Insulin Sensitivity in Nonobese Dogs

Visceral adiposity is strongly associated with insulin resistance; however, little evidence directly demonstrates that visceral fat per se impairs insulin action. Here, we examine the effects of the surgical removal of the greater omentum and its occupying visceral fat, an omentectomy (OM), on insulin sensitivity (S_I) and β‐cell function in nonobese dogs. Thirteen male mongrel dogs were used in this research study; animals were randomly assigned to surgical treatment with either OM (n = 7), or sham‐surgery (SHAM) (n = 6). OM failed to generate measurable changes in body weight (+2%; P = 0.1), or subcutaneous adiposity (+3%; P = 0.83) as assessed by magnetic resonance imaging (MRI). The removal of the greater omentum did not significantly reduce total visceral adipose volume (?7.3 ± 6.4%; P = 0.29); although primary analysis showed a trend for OM to increase S_I when compared to sham operated animals (P = 0.078), further statistical analysis revealed that this minor reduction in visceral fat alleviated insulin resistance by augmenting S_I of the periphery (+67.7 ± 35.2%; P = 0.03), as determined by the euglycemic‐hyperinsulinemic clamp. Insulin secretory response during the hyperglycemic step clamp was not directly influenced by omental fat removal (presurgery 6.82 ± 1.4 vs. postsurgery: 6.7 ± 1.2 pmol/l/mg/dl, P = 0.9). These findings provide new evidence for the deleterious role of visceral fat in insulin resistance, and suggest that a greater OM procedure may effectively improve insulin sensitivity.     

Interaction of FTO and physical activity level on adiposity in African-American and European-American adults: the ARIC study

Physical inactivity accentuates the association of variants in the FTO locus with obesity‐related traits but evidence is largely lacking in non‐European populations. Here we tested the hypothesis that physical activity (PA) modifies the association of the FTO single‐nucleotide polymorphism (SNP) rs9939609 with adiposity traits in 2,656 African Americans (AA) (1,626 women and 1,030 men) and 9,867 European Americans (EA) (5,286 women and 4,581 men) aged 45–66 years in the Atherosclerosis Risk in Communities (ARIC) study. Individuals in the lowest quintile of the sport activity index of the Baecke questionnaire were categorized as low PA. Baseline BMI, waist circumference (WC), and skinfold measures were dependent variables in regression models testing the additive effect of the SNP, low PA, and their interaction, adjusting for age, alcohol use, cigarette use, educational attainment, and percent European ancestry in AA adults, stratified by sex and race/ethnicity. rs9939609 was associated with adiposity in all groups other than AA women. The SNP × PA interaction was significant in AA men (P ≤ 0.002 for all traits) and EA men (P ≤ 0.04 for all traits). For each additional copy of the A (risk) allele, WC in AA men was higher in those with low PA (β_lowPA: 5.1 cm, 95% confidence interval (CI): 2.6–7.5) than high PA (β_highPA: 0.7 cm, 95% CI: ?0.4 to 1.9); P (interaction) = 0.002). The interaction effect was not observed in EA or AA women. FTO SNP × PA interactions on adiposity were observed for AA as well as EA men. Differences by sex require further examination.     

Associations of Free Fatty Acids With Insulin Secretion and Action Among African‐American and European‐American Girls and Women

Ethnic differences in insulin secretion and action between African Americans (AAs) and European Americans (EAs) may influence mobilization of free fatty acids (FFAs). We tested the hypotheses that FFA concentrations would be associated with measures of insulin secretion and action before and during a glucose challenge test. Subjects were 48 prepubertal girls, 60 premenopausal women, and 46 postmenopausal women. Fasting insulin (insulin₀), the acute insulin response to glucose (AIR_g), the insulin sensitivity index (S_I), basal and nadir FFA (FFA₀, FFA_nadir), and nadir time (TIME_nadir) were determined during an intravenous glucose tolerance test (IVGTT). Stepwise multiple linear regression (MLR) analysis was conducted to identify associations of FFA₀, FFA_nadir, and TIME_nadir with ethnicity, age group, insulin measures, indexes of body composition from dual‐energy X‐ray absorptiometry, and measures of fat distribution from computed tomography scan. In this population, insulin₀ and AIR_g were higher among AAs vs. EAs, whereas S_I was lower, independent of age group. MLR analyses indicated that FFA₀ was best predicted by lean tissue mass (LTM), leg fat mass, ethnicity (lower in AAs), S_I, and insulin₀. FFA_nadir was best predicted by FFA₀, age group, and intra‐abdominal adipose tissue (IAAT). TIME_nadir was best predicted by leg fat mass, AIR_g, and S_I. In conclusion, indexes of insulin secretion and action were associated with FFA dynamics in healthy girls and women. Lower FFA₀ among AAs was independent of insulin₀ and S_I. Whether lower FFA₀ is associated with substrate oxidation or risk for obesity remains to be determined.     

Glucose Metabolism and Diet Predict Changes in Adiposity and Fat Distribution in Weight‐reduced Women

Among obesity‐prone individuals, metabolic state may interact with diet in determining body composition. We tested the hypotheses that, among 103 weight‐reduced women over 1 year, (i) insulin sensitivity would be positively associated with change in %fat; (ii) this association would be modulated by dietary glycemic load (GL); and (iii) changes in fat distribution would be related to indexes of glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and postchallenge insulin and glucose, and glucose tolerance were assessed during intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution were examined using dual‐energy X‐ray absorptiometry and computed tomography. Dietary GL was assessed on 67 women using food records. On average, women showed a +5.3 ± 3.0% change in %fat over 1 year, with the magnitude of this change being greater in relatively insulin sensitive women (+6.0 ± 0.4%, mean ± s.e.m.) than in relatively insulin resistant women (+4.4 ± 0.4 kg; P < 0.05). Women who were relatively insulin sensitive and who consumed a higher GL diet showed a +6.8 ± 0.7% change in %fat, which was greater than those who were less insulin sensitive, regardless of diet (P < 0.05), but did not differ from women who were relatively insulin sensitive and who consumed a lower GL diet (P = 0.105). Changes in intra‐abdominal and deep subcutaneous abdominal fat were inversely associated with the postchallenge decline in serum glucose. In conclusion, greater insulin sensitivity may predispose to adiposity among weight reduced women, an effect that may be ameliorated by a lower GL diet. The potential association between indexes of glucose disposal and changes in fat distribution warrants further study.     

Fat Distribution,Aerobic Fitness,Blood Lipids,and Insulin Sensitivity in African‐American and European‐American Women

The purpose of this study was to determine independent relationships of intra‐abdominal adipose tissue (IAAT), leg fat, and aerobic fitness with blood lipids and insulin sensitivity (S_i) in European‐American (EA) and African‐American (AA) premenopausal women. Ninety‐three EA and ninety‐four AA with BMI between 27 and 30 kg/m² had IAAT by computed tomography, total fat and leg fat by dual‐energy X‐ray absorptiometry, aerobic fitness by a graded exercise test, African admixture (AFADM) by ancestry informative markers, blood lipids by the Ektachem DT system, and S_i by glucose tolerance test. Independent of age, aerobic fitness, AFADM, and leg fat, IAAT was positively related to low‐density lipoprotein–cholesterol (LDL‐C), cholesterol‐high‐density lipoprotein (HDL) ratio, triglycerides (TGs), and fasting insulin (standardized β varying 0.16–0.34) and negatively related to HDL‐cholesterol (HDL‐C) and S_i (standardized β ?0.15 and ?0.25, respectively). In contrast, independent of age, aerobic fitness, AFADM, and IAAT, leg fat was negatively related to total cholesterol, LDL‐C, cholesterol‐HDL ratio, TGs, and fasting insulin (standardized β varying ?0.15 to ?0.21) and positively related to HDL‐C and S_i (standardized β 0.16 and 0.23). Age was not independently related to worsening of any blood lipid but was related to increased S_i (standardized β for S_i 0.25, insulin ?0.31). With the exception of total cholesterol and LDL‐C, aerobic fitness was independently related to worsened blood lipid profile and increased S_i (standardized β varying 0.17 to ?0.21). Maintenance of favorable fat distribution and aerobic fitness may be important strategies for healthy aging, at least in premenopausal EA and AA women.     

Ethnic Differences in Self‐reported and Measured Obesit

As use of self‐reported data to classify obesity continues, ethnic differences in reporting errors remain unclear. The objective of this study is to elucidate misreporting disparities between African Americans (AAs) and European Americans (EAs). The Pennington Center Longitudinal Study (PCLS) is an ongoing investigation of environmental, behavioral, and biological factors associated with obesity, diabetes, and other common diseases. Self‐reported and measured height and weight were collected during initial screening for eligibility in various studies by telephone and clinic visits. All ethnicity‐sex groups (15,656 adults aged 18–65 years, 53% obese, 34% AA, 37% men) misreported heights and weights increasingly as measured values increased (P < 0.0001). More AA vs. EA women (P < 0.001) misreported height and weight, but more EA vs. AA men misreported their weight (P < 0.02). Obesity was underestimated more in AA vs. EA women (self‐reported ? measured prevalence = ?4.0% (AA) vs. ?2.6% (EA), P < 0.0001), but less in AA vs. EA men (?3.2% (AA) vs. ?4.2% (EA), P < 0.0001)). With measured obesity prevalence equalized at 53% in all groups, the self‐reported obesity prevalence in women was 50.4% (AA) vs. 49.6% (EA), and in men 49.8% (AA) vs. 47.3 (EA). Underestimation in women was ?2.6% (AA) vs. ?3.4% (EA); in men it was ?3.2% (AA) vs. ?5.7% (EA), P < 0.003. Self‐reported height and weight portend underestimation of obesity prevalence and the effect varies by ethnicity and gender. However, comparisons depend on the true prevalence within ethnicity‐gender groups. After controlling for obesity prevalence, disparity in underestimation was greater in EA than in AA men (P < 0.003) but not women.     

Age-related changes in insulin sensitivity and β-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 β-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 β-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 β-cell function exist independently of adiposity and S(I). Future research should examine whether ethnic differences in β-cell physiology contribute to disparities in T2D risk.     

Variant in the 3′ Region of the IκBα Gene Associated With Insulin Resistance in Hispanic Americans: The IRAS Family Study

The IKKβ/NF‐κB pathway is known to play an important role in inflammatory response and has also recently been implicated in the process of insulin resistance. We hypothesized that one or more variants in the IκBα gene (NFKBIA) or surrounding untranslated regions would be associated with insulin sensitivity (S_I) in Hispanic‐American families. We tested for association between 25 single‐nucleotide polymorphisms (SNPs) in and near NFKBIA and S_I in 981 individuals in 90 Hispanic‐American families from the Insulin Resistance Atherosclerosis (IRAS) Family Study. SNP rs1951276 in the 3′ flanking region of NFKBIA was associated with S_I in the San Antonio (SA) sample after adjusting for age, gender, and admixture (uncorrected P = 1.69 × 10^?5; conservative Bonferroni correction P = 3.38 × 10^?4). Subjects with at least one A allele for NFKBIA rs1951276 had ～29% lower S_I compared to individuals homozygous for the G allele in the SA sample. Although not statistically significant, the effect was in the same direction in the San Luis Valley (SLV) sample alone (P = 0.348) and was significant in the combined SA and SLV samples (P = 5.37 × 10^?4; presence of A allele associated with ～20% lower S_I). In SA, when adjusted for subcutaneous adipose tissue area (SAT, cm²), the association was modestly attenuated (P = 1.25 × 10^?3), but the association remained highly significant after adjustment for visceral adipose tissue area (VAT, cm²; P = 4.41 × 10^?6). These results provide corroborating evidence that the NF‐κB/IKKβ pathway may mediate obesity‐induced insulin resistance in humans.     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Racial Differences in Relative Skeletal Muscle Mass Loss During Diet‐Induced Weight Loss in Women

Objective

It is unclear whether there are race‐specific differences in the maintenance of skeletal muscle during energy restriction. Changes in relative skeletal muscle index (RSMI; limb lean tissue divided by height squared) were compared following (1) diet alone, (2) diet + aerobic training, or (3) diet + resistance training.

Methods

Overweight, sedentary African American (AA; n = 72) and European American (EA; n = 68) women were provided an 800‐kcal/d diet to reduce BMI < 25 kg/m². Regional fat‐free mass was measured with dual‐energy x‐ray absorptiometry. Steady‐state VO₂ and heart rate responses during walking were measured.

Results

AA women had greater RSMI and preserved RSMI during diet alone, while RSMI was significantly reduced among EA women (EA women –3.6% vs. AA women + 1.1%; P < 0.05). Diet + resistance training subjects retained RSMI (EA women + 0.2% vs. AA women + 1.4%; P = 50.05), whereas diet + aerobic training subjects decreased RSMI (EA women –1.4% vs. AA women –1.5%; P < 0.05). Maintenance of RSMI was related to delta walking ease and economy.

Conclusions

Compared with AA women, EA women are less muscular and lose more muscle during weight loss without resistance training. During diet‐induced weight loss, resistance training preserves skeletal muscle, especially among premenopausal EA women. Maintenance of muscle during weight loss associates with better ease and economy of walking.

     

Relationship of Intramyocellular Lipid to Insulin Sensitivity May Differ With Ethnicity in Healthy Girls and Women

The prevalence of type 2 diabetes is greater among African Americans (AA) vs. European Americans (EA), independent of obesity and lifestyle. We tested the hypothesis that intramyocellular lipid (IMCL) or extramycellular lipid (EMCL) would be associated with insulin sensitivity among healthy young women, and that the associations would differ with ethnic background. We also explored the hypothesis that adipokines and estradiol would be associated with muscle lipid content. Participants were 57 healthy, normoglycemic, women and girls mean age 26 (±10) years; mean BMI 27.3 (±4.8) kg/m²; 32 AA, 25 EA. Soleus IMCL and EMCL were assessed with ¹H magnetic resonance spectroscopy (MRS); insulin sensitivity with an insulin‐modified frequently sampled intravenous glucose tolerance test and minimal modeling; body composition with dual‐energy X‐ray absorptiometry; and intra‐abdominal adipose tissue (IAAT) with computed tomography. Adiponectin, leptin, and estradiol were assessed in fasting sera. Analyses indicated that EMCL, but not IMCL, was greater in AA vs. EA (2.55 ± 0.16 vs. 1.98 ± 0.18 arbitrary units, respectively, P < 0.05; adjusted for total body fat). IMCL was associated with insulin sensitivity in EA (r = ?0.54, P < 0.05, adjusted for total fat, IAAT, and age), but not AA (r = 0.16, P = 0.424). IMCL was inversely associated with adiponectin (r = ?0.31, P < 0.05, adjusted for ethnicity, age, total fat, and IAAT). In conclusion, IMCL was a significant determinant of insulin sensitivity among healthy, young, EA but not AA women. Further research is needed to determine whether the component lipids of IMCL (e.g., diacylglycerol (DAG) or ceramide) are associated with insulin sensitivity in an ethnicity specific manner.     

Both Subcutaneous and Visceral Adipose Tissue Correlate Highly with Insulin Resistance in African Americans

Objective: The contribution of visceral adipose tissue (VAT) to insulin resistance is well‐established; however, the role of subcutaneous abdominal adipose tissue (SAT) in insulin resistance remains controversial. Sex may determine which of these two components of abdominal obesity is more strongly related to insulin resistance and its consequences. The aim of this study was to determine whether both VAT and SAT contribute to insulin resistance in African Americans and to examine the effects of sex on this relationship. Research Methods and Procedures: This was a cross‐sectional study of 78 nondiabetic African‐American volunteers (44 men, 35 women; age 33.8 ± 7.3 years; BMI 30.9 ± 7.4 kg/m²). VAT and SAT volumes were measured using serial computerized tomography slices from the dome of the diaphragm to the iliac crest. The insulin sensitivity index (S_I) was determined from the minimal model using data obtained from the frequently sampled intravenous glucose tolerance test. Results: In men, both VAT and SAT were negatively correlated with S_I (r for both correlations = ?0.57; p < 0.01). In women, the correlation coefficient between VAT and S_I was ?0.50 (p < 0.01) and between SAT and S_I was ?0.67 (p < 0.01). In women, the correlation coefficient for S_I with SAT was significantly greater than the correlation coefficient with VAT (p = 0.02). Discussion: Both SAT and VAT are strongly correlated with insulin resistance in African Americans. For African‐American women, SAT may have a greater effect than VAT on insulin resistance.     

Racial Differences in Insulin Resistance and Mid‐Thigh Fat Deposition in Postmenopausal Women

Objective: To determine whether racial differences in insulin resistance between African American (AA) and white women exist in postmenopausal women and whether they are related to physical fitness and/or obesity. Research Methods and Procedures: We studied 35 obese AA (n = 9) and white (n = 26) women of comparable maximal oxygen consumption, obesity, and age. Total body fat was measured by DXA. Abdominal and mid‐thigh low‐density lean tissue (a marker of intramuscular fat) were determined with computed tomography. Glucose utilization (M) was measured during the last 30 minutes of a 3‐hour hyperinsulinemic‐euglycemic clamp. Insulin sensitivity was estimated from the relationship of M to the concentration of insulin during the last 30 minutes of the clamp. Results: The percentage of fat and total body fat mass were similar between AA and white women, whereas fat‐free mass was higher in African American women. Visceral adipose tissue was not different between groups, but subcutaneous abdominal fat was 17% higher in the AA than in the white women. AA women had an 18% greater mid‐thigh muscle area (p < 0.01) and a 34% greater mid‐thigh low‐density lean tissue area than the white women. Fasting glucose concentrations were not different, but fasting insulin concentrations were 29% higher in AA women. Glucose utilization was 60% lower in the AA women because of a lower non‐oxidative glucose disposal. Insulin sensitivity was 46% lower in the AA women. Discussion: AA postmenopausal women have more mid‐thigh intramuscular fat, lower glucose utilization, and are less insulin sensitive than white women despite comparable fitness and relative body fat levels.     

β‐Amino acids containing peptides and click‐cyclized peptide as β‐turn mimics: a comparative study with ‘conventional’ lactam‐ and disulfide‐bridged hexapeptides

The increasing interest in click chemistry and its use to stabilize turn structures led us to compare the propensity for β‐turn stabilization of different analogs designed as mimics of the β‐turn structure found in tendamistat. The β‐turn conformation of linear β‐amino acid‐containing peptides and triazole‐cyclized analogs were compared to ‘conventional’ lactam‐ and disulfide‐bridged hexapeptide analogs. Their 3D structures and their propensity to fold in β‐turns in solution, and for those not structured in solution in the presence of α‐amylase, were analyzed by NMR spectroscopy and by restrained molecular dynamics with energy minimization. The linear tetrapeptide Ac‐Ser‐Trp‐Arg‐Tyr‐NH₂ and both the amide bond‐cyclized, c[Pro‐Ser‐Trp‐Arg‐Tyr‐D ‐Ala] and the disulfide‐bridged, Ac‐c[Cys‐Ser‐Trp‐Arg‐Tyr‐Cys]‐NH₂ hexapeptides adopt dominantly in solution a β‐turn conformation closely related to the one observed in tendamistat. On the contrary, the β‐amino acid‐containing peptides such as Ac‐(R)‐β³‐hSer‐(S)‐Trp‐(S)‐β³‐hArg‐(S)‐β³‐hTyr‐NH₂, and the triazole cyclic peptide, c[Lys‐Ser‐Trp‐Arg‐Tyr‐βtA]‐NH₂, both specifically designed to mimic this β‐turn, do not adopt stable structures in solution and do not show any characteristics of β‐turn conformation. However, these unstructured peptides specifically interact in the active site of α‐amylase, as shown by TrNOESY and saturation transfer difference NMR experiments performed in the presence of the enzyme, and are displaced by acarbose, a specific α‐amylase inhibitor. Thus, in contrast to amide‐cyclized or disulfide‐bridged hexapeptides, β‐amino acid‐containing peptides and click‐cyclized peptides may not be regarded as β‐turn stabilizers, but can be considered as potential β‐turn inducers. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Differential Effects of Abdominal Adipose Tissue Distribution on Insulin Sensitivity in Black and White South African Women

Black South African women are more insulin resistant than BMI‐matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal‐weight (BMI 18–25 kg/m²) and obese (BMI > 30 kg/m²) black and white premenopausal South African women underwent the following measurements: body composition (dual‐energy X‐ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S_I, frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 ± 0.8 vs. 9.5 ± 0.8 and 3.0 ± 0.8 vs. 6.0 ± 0.8 × 10^?5/min/(pmol/l), for normal‐weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S_I correlated with deep and superficial SAT in both black (R = ?0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = ?0.554, P = 0.005 and R = ?0.546, P = 0.004), but with VAT in white women only (R = ?0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.     

Racial Differences in Insulin Secretion and Sensitivity in Prepubertal Children: Role of Physical Fitness and Physical Activity

Objective: To investigate in prepubertal children whether physical fitness and/or physical activity are: 1) associated with insulin secretion and sensitivity and 2) account for racial differences in insulin secretion and sensitivity. Research Methods and Procedures: Subjects included 34 African American and 34 white nondiabetic children aged 5 to 11 years. Data were divided into two sets according to the availability of VO_2max and physical activity data. Body composition was measured by dual‐energy X‐ray absorptiometry. Subcutaneous abdominal adipose tissue and intra‐abdominal adipose tissue were examined by computed tomography. Insulin sensitivity (S_I) and acute insulin response (AIR) were determined by a frequently sampled intravenous glucose tolerance test. An all‐out, progressive treadmill exercise test was used for measuring VO_2max. Physical activity data were collected by questionnaire. Results: African American children had lower S_I and higher AIR than white children, after adjusting for total body fat mass. African Americans reported higher levels of physical activity (hours/wk) than whites, but had a lower VO_2max. In multiple linear regression analysis, hours/wk of activity and hours/wk of vigorous activity, but not moderate activity, were independently related to S_I and AIR after adjusting for race, total body fat mass or fat distribution, and total lean tissue mass. VO_2max was not related to AIR, and was inversely related to S_I, after adjusting for body composition. Race remained significantly associated with both S_I and AIR, even after adjusting for body composition, fat distribution, and hours/wk of activity or hours/wk of vigorous activity. Discussion: In summary, overall physical activity and, especially, vigorous activity were associated with insulin secretion and sensitivity. However, neither physical activity nor VO_2max explained the racial difference in insulin secretion (higher in African Americans) and sensitivity (lower in African Americans). Thus, racial (African American to white) differences in aspects of insulin action seem to be due to factors other than body composition, fat distribution, cardiovascular fitness, and amount of physical activity.     

Resistance training conserves fat-free mass and resting energy expenditure following weight loss

Objective: To determine what effect diet‐induced ～12 kg weight loss in combination with exercise training has on body composition and resting energy expenditure (REE) in premenopausal African‐American (AA) and European‐American (EA) women. Methods and Procedures: This study was a longitudinal, randomized weight loss clinical intervention, with either aerobic (AT), resistance (RT), or no exercise training (NT). Forty‐eight AA and forty‐six EA premenopausal overweight (BMI between 27 and 30) women underwent weight loss to a BMI <25. Body composition (densitometry), REE (indirect calorimetry), maximal oxygen uptake (VO₂max), and muscular strength (isometric elbow flexion) were evaluated when subjects were in energy balance. Results: AA women lost less fat‐free mass (FFM, P ≤ 0.05) (47.0 ± 4.6 to 46.9 ± 5.0 kg) than EA women (46.4 ± 4.9 to 45.2 ± 4.6 kg). Regardless of race, RT maintained FFM (P ≤ 0.05) following weight loss (46.9 ± 5.2 to 47.2 ± 5.0 kg) whereas AT (45.4 ± 4.2 to 44.4 ± 4.1 kg) and NT (47.9 ± 4.7 to 46.4 ± 5.1 kg) decreased FFM (P ≤ 0.05). Both AT and NT decreased in REE with weight loss but RT did not. Significant time by group interactions (all P ≤ 0.05) for strength indicated that RT maintained strength and AT did not. Discussion: AA women lost less FFM than EA women during equivalent weight losses. However, following weight loss in both AA and EA, RT conserved FFM, REE, and strength fitness when compared to women who AT or did not train.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.