Normal Glucose Tolerance Participants Research Articles

Defective Visceral Adipose Tissue Adaptation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a complex obstetric condition affecting localized glucose metabolism, resulting in systemic metabolic dysfunction. This cross-sectional study aimed to explore visceral adipose tissue (VAT) as an integral contributor to GDM, focusing on elucidating the specific contribution of obesity and GDM pathology to maternal outcomes. Fifty-six nulliparous pregnant women were recruited, including normal glucose tolerant (NGT) (n = 30) and GDM (n = 26) participants. Participants were subgrouped as nonobese (BMI <30 kg/m2) or obese (BMI ≥30 kg/m2). Metabolic markers in circulation, VAT, and placenta were determined. Morphological analysis of VAT and immunoblotting of the insulin signaling cascade were performed. GDM participants demonstrated hyperinsulinemia and elevated homeostatic model assessment for insulin resistance (HOMA-IR) scores relative to NGT participants. The GDM-obese subgroup had significant VAT adipocyte hypoplasia relative to NGT-nonobese tissue. GDM-obese VAT had significantly lower insulin receptor substrate (IRS)-2 expression, with elevated ser312 phosphorylation of IRS-1, relative to NGT-nonobese. GDM-obese participants had significantly elevated circulating leptin levels and placental adipsin secretion, while GDM-nonobese participants had elevated circulating adipsin levels with reduced placental adiponectin secretion. These findings suggest that GDM-obese pregnancy is specifically characterized by inadequate VAT remodeling and dysfunctional molecular signaling, which contribute to insulin resistance and hinder metabolic health.

L-ergothioneine reduces mitochondrial-driven NLRP3 activation in gestational diabetes mellitus

BackgroundMaternal hyperglycaemia has a significant impact on placental metabolism and mitochondrial function. The NLRP3 inflammasome is responsive to endogenous signals of mitochondrial dysfunction. We tested our hypothesis that mitochondrial dysfunction orchestrates activation of the NLRP3 inflammasome and contributes to inflammation in gestational diabetes mellitus (GDM). MethodsFasting blood, omental and placental tissue were collected on the day of caesarean section from nulliparous women with normal glucose tolerant (NGT) (n = 30) and GDM (n = 27) pregnancies. Cell-free mitochondrial DNA (cf-mtDNA) copy number was quantified by real-time PCR. M1-like (CD14+CD86+CD206-) and M2-like (CD14+CD86+CD206+) macrophage populations were characterized by flow cytometry. Immunoblotting for protein expression of NLRP3, ASC and caspase-1 was performed in maternal BMI and age-matched tissue samples. IL-1β and IL-18 were measured by multiplex ELISA. Placental explants from GDM participants were cultured for 24 h with 1 mM L-ergothioneine (antioxidant) and 1 µM MCC950 (NLRP3 inhibitor). ResultsCf-mtDNA copy numbers were significantly higher in GDM compared to NGT participants (p = 0.002). Placental populations of CD14+ (p = 0.02) and CD14+CD86+CD206- (p = 0.03) macrophages produced significantly increased levels of mitochondrial superoxide in GDM compared to NGT participants. Placental production of IL-18 (p = 0.04) was significantly increased in GDM. This increase in placental IL-18 was attenuated by treatment with 1 µM MCC950 (p = 0.0005), and 1 mM L-ergothioneine (p = 0.007). ConclusionPlacental inflammation is significantly increased in women with GDM. Furthermore, this increase may be initiated by elevated production of mitochondrial superoxide by macrophage subpopulations and orchestrated by the NLRP3 inflammasome. The mitochondrial antioxidant, L-ergothioneine, ameliorates NLRP3-induced placental inflammation in GDM, identifying a potential therapeutic role.

Variability, Mean, and Baseline Values of Metabolic Parameters in Predicting Risk of Type 2 Diabetes.

The effect of baseline (B) and alteration of metabolic parameters (MPs), including plasma glucose (PG) testing, insulin resistance surrogates, and lipid profile and their mutual interactions on the development of type 2 diabetes mellitus (T2DM), has not been investigated systematically. To access the association of the past variability (V), past mean (M), and B values of various MPs and their mutual interaction with the risk of T2DM. A community-based, longitudinal analysis was conducted using the Korean Genome and Epidemiology Study comprising 3829 nondiabetic participants with completed MPs measurements during 3 biannually visits who were followed over the next 10 years. Outcomes included the incidence of T2DM during follow-up. Among predictors, PG concentrations measured during the oral glucose tolerance test were the most prominent T2DM determinants, in which the M of the average value of fasting PG (FPG), 1-hour, and 2-hour PGs had the strongest discriminative power (hazard ratios and 95% CI for an increment of SD: 3.00 (2.5-3.26), AUC: 0.82). The M values of MPs were superior to their B and V values in predicting T2DM, especially among postload PGs. Various mutual interactions between indices and among MPs were found. The most consistent interactants were the M values of high-density lipoprotein cholesterol and the M and V values of FPG. The findings were similar in normal glucose tolerance participants and were confirmed by sensitivity analyses. Postload PG, past alteration of measurements, and mutual interactions among indices of MPs are important risk factors for T2DM development.

The mean of fasting, 1-h, and 2-h plasma glucose levels is superior to each separate index in predicting diabetes

AimsThe fasting, 1-h, and 2-h plasma glucose (PG) levels during oral glucose tolerance test represent different glucose metabolic functions. We examined whether averaging these PG indices (GLUM0.60.120) results in a better predictor of future type 2 diabetes (T2DM). Methods7533 participants were followed up biannually for 12 years. Hazard ratios (HRs), area under the curve (AUC) of the receiver-operating characteristic, and the net reclassification index (NRI) for T2DM were calculated to compare the discriminative ability of GLUM0.60.120 versus other PG indices. ResultsThe adjusted HRs and 95% confidence intervals for an increase in SD of GLUM0.60.120 was 2.50 (2.36–2.65) and 1.88 (1.73–2.04) in T2DM-free and normal glucose tolerance (NGT) participants, respectively. The AUC of GLUM0.60.120 was higher than that of fasting PG, 1-h, and 2-h PG values for T2DM-free (0.79 versus 0.67, 0.77, and 0.73) and NGT (0.73 versus 0.65, 0.72, and 0.61). The model using GLUM0.60.120 improved the classification of the models with fasting PG, 1-h, and 2-h PG values (NRI: 0.369, 0.272, and 0.282 for T2DM-free and 0.249, 0.131, and 0.351 for NGT participants with all p < 0.001). ConclusionsThe mean of fasting, 1-h, and 2-h PG levels predicts future T2DM better than each index.

Serum Metrnl Level is Correlated with Insulin Resistance, But Not with β-Cell Function in Type 2 Diabetics.

BackgroundMetrnl is a novel identified adipomyokine which might have therapeutic potential for metabolic and inflammatory diseases, including type 2 diabetes mellitus. We aimed to explore the associations of circulating Metrnl level with β-cell function and insulin resistance (IR) and further explore the possible correlation between Metrnl and another adipomyokine named irisin in patients diagnosed type 2 diabetes.Material/MethodsOur study recruited 59 participants with type 2 diabetes and 30 normal glucose tolerance (NGT) participants. We used enzyme-linked immunosorbent assay (ELISA) to measure serum levels of Metrnl and irisin. The associations of Metrnl level with indexes of β-cell function and IR and irisin level were analyzed by multiple linear regression analysis or spearman correlation analysis.ResultsCompared with NGT participants, serum Metrnl level was elevated in participants with type 2 diabetes: 210.30 pg/mL (range 105.94–323.91 pg/mL) versus 132.02 pg/mL (range 104.93–195.92 pg/mL). Metrnl level did not show significant correlation with β-cell function-related indicators, but positively correlated with HOMA2-IR and negatively correlated with HOMA2-%S after controlling multiple covariates in participants with type 2 diabetes. Metrnl level was also not associated with obesity-related indicators (body mass index, waist circumference, body fat percentage, and visceral adipose tissue area) in the type 2 diabetes group. In addition, the correlation between Metrnl and irisin level was also not present (r=−0.159, P=0.229) in type 2 diabetes group.ConclusionsSerum Metrnl level was associated with IR, but not with β-cell function in participants with diagnosed type 2 diabetes.

Association of serum CMPF level with fatty acid metabolism and obesity in community population

Objective To detect the serum level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), a significant metabolite of fish oil, in subjects with normal glucose tolerance (NGT) in local communities, and to investigate the association of CMPF with fatty acid metabolism. Methods A total of 272 NGT participants from screening for diabetes in Shanghai in 2013 were enrolled. Anthropometric measurements, biochemical evaluation, and questionnaire interview were performed for all the participants. The participants were divided into normal weight group [body mass index (BMI)≤23.9 kg/m2,n=143]and overweight/obesity group (BMI≥24 kg/m2,n=129). The serum CMPF concentrations were determined using an enzyme-linked immunosorbent assay. Results Serum CMPF level in overweight/obesity group was lower than that in normal weight group [96.50(46.11, 169.56)μmol/L vs 153.20(83.16, 282.97)μmol /L, P<0.05]. The serum CMPF level was negatively correlated with BMI (r=-0.256, P<0.01), triglycerides (r=-0.175, P=0.004), and free fatty acid (r=-0.126, P=0.041) according to bivariate correlation analyses. A multivariate stepwise linear regression analysis showed that the serum CMPF level was independently associated with BMI, triglycerides, free fatty acid, and HbA1C. A logistic regression analysis showed that the CMPF was a protective factor against obesity (OR=0.324, 95%CI 0.158, 0.664). Conclusion Serum CMPF level is reduced in overweight/obese subjects. CMPF is beneficial to lipid metabolism. Key words: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid; Obesity; Triglycerides; Free fatty acids

Postprandial glucose-lowering effect of premeal consumption of protein-enriched, dietary fiber-fortified bar in individuals with type 2 diabetes mellitus or normal glucose tolerance.

Aims/IntroductionProtein preload improves postprandial glycemia by stimulating secretion of insulin and incretin hormones. However, it requires a large dose of protein to produce a significant effect. The present study was carried out to investigate the postprandial glucose‐lowering effect of a premeal protein‐enriched, dietary fiber‐fortified bar (PFB), which contains moderate amounts of protein, in individuals with type 2 diabetes mellitus or normal glucose tolerance (NGT).Materials and MethodsThe participants (15 type 2 diabetes mellitus and 15 NGT) were randomly assigned to either a premeal or postmeal PFB group and underwent two mixed meal tolerance tests, 1 week apart in reverse order. Plasma levels of glucose, insulin, glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide were measured.ResultsDuring the mixed meal tolerance tests, the incremental area under the curve from 0 to 180 min of plasma glucose levels was lower with premeal PFB than with postmeal PFB in the type 2 diabetes mellitus (14,723 ± 1,310 mg min/dL vs 19,642 ± 1,367 mg min/dL; P = 0.0002) and NGT participants (3,943 ± 416 mg min/dL vs 4,827 ± 520 mg min/dL, P = 0.0296). In the type 2 diabetes mellitus participants, insulinogenic index and the incremental area under the curve from 0 to 180 min of plasma total glucagon‐like peptide‐1 levels were higher with premeal PFB than with postmeal PFB, but not in the NGT participants. There was no difference in postprandial glucose‐dependent insulinotropic polypeptide levels between premeal and postmeal PFB in both groups.ConclusionsAcute administration of premeal PFB decreased postprandial glucose excursion in both type 2 diabetes mellitus and NGT participants. In the type 2 diabetes mellitus participants, premeal PFB augmented the early‐phase insulin secretion, possibly through enhancing glucagon‐like peptide‐1 secretion.

Increased secreted frizzled-related protein 4 and ficolin-3 levels in gestational diabetes mellitus women.

By biochemical and epidemiological similarity with type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) has some overlap between prediction markers and risk factors of T2DM. The present study aimed to establish that secreted frizzled-related protein 4 (SFRP4) and ficolin-3 levels, which have been linked to insulin resistance and the development of T2DM, are elevated in GDM women. A longitudinal prospective cohort study of 86 GDM and 273 normal glucose tolerant (NGT) pregnant women was performed. The clinical parameters, lipid profiles, and serum SFRP4 and ficolin-3 levels were tested during the early and late second-trimester and third-trimester of pregnancy. Both SFRP4 and ficolin-3 levels were significantly higher in GDM women as compared to the NGT participants at three test points (p < 0.01). Spearman's correlation analysis showed that serum SFRP4 levels were significantly positively correlated with ficolin-3 during the early and late second-trimester and third-trimester of pregnancy. The elevated SFRP4 and ficolin-3 concentrations at 16-18 weeks gestation significantly associated with GDM were conformed using binary logistic regression analysis after controlling for other variables [odds ratios (OR) with 95% confidence intervals (CI) for SFRP4: 2.84 (1.78-4.53), p < 0.01; for ficolin-3: 2.45 (1.55-3.88), p < 0.01]. In Conclusions, increased SFRP4 and ficolin-3 levels are significantly associated with GDM development and might be important risk factors for this pregnancy complication.

Women with prior gestational diabetes mellitus and prediabetes are characterised by a decreased incretin effect.

We investigated whether a reduced incretin effect, as observed in patients with type 2 diabetes, can be detected in high-risk individuals, such as women with prior gestational diabetes mellitus (pGDM). In this cross-sectional study, 102 women without diabetes with pGDM and 15 control participants without pGDM and with normal glucose tolerance (NGT) underwent a 4h 75g OGTT and an isoglycaemic i.v. glucose infusion (IIGI). Women with pGDM were classified as having NGT or prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Insulin sensitivity was assessed using the Matsuda index and HOMA2-IR and the incretin effect was calculated from insulin responses during the study (100%×[AUCinsulin,OGTT-AUCinsulin,IIGI]/AUCinsulin,OGTT). Sixty-three of the 102 women with pGDM (62%) had prediabetes (median [interquartile range]: age, 38.3 [6.5] years; BMI, 32.1 [5.8] kg/m2) and 39 women (38%) had NGT (age, 39.5 [5.6] years; BMI, 31.0 [6.7] kg/m2). Control participants (n=15) were not significantly different from the pGDM group with regards to age (39.2 [7.4] years) and BMI (28.8 [9.2] kg/m2). Compared with women with NGT and control participants, women with prediabetes had lower insulin sensitivity, as measured by the Matsuda index (3.0 [2.4] vs 5.0 [2.6] vs 1.5 [1.8], respectively; p<0.001). The incretin effect was 55.3% [27.8], 73.8% [19.0] and 76.7% [24.6] in women with prediabetes, women with normal glucose tolerance and control participants, respectively (p<0.01). Prediabetes was highly prevalent in women with pGDM, and alterations in the incretin effect were detected in this group before the development of type 2 diabetes. clinicaltrialsregister.eu 2012-001371-37-DK.

Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance.

Evidence has shown that endoplasmic reticulum (ER) stress was involved in the progression to type 2 diabetes mellitus (T2DM) and development of insulin resistance. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel secreted protein upregulated by ER stress. This study aimed to assess serum level of MANF in normal glucose tolerance (NGT) participants and newly diagnosed prediabetic and T2DM patients. A total of 257 participants with NGT, newly diagnosed prediabetes or T2DM were recruited from Yinchao and Hangtian communities of Chengdu, Sichuan, China. Serum MANF level was quantified by enzyme-linked immunosorbent assay (ELISA). The mean age for the 257 participants (147 females) was 62±8 years (range 44-78): 71 with NGT, 115 with newly diagnosed prediabetes and 71 with T2DM. Mean serum MANF level was significantly higher with newly diagnosed prediabetes and T2DM than NGT (2.89±1.09 and 3.03±1.73 vs 2.13±1.37 ng/mL, both p<0.001). MANF level was not correlated with insulin sensitivity indexes (homeostasis model assessment for insulin resistance [HOMA-IR], Matsuda Index and quantitative insulin sensitivity check index [QUICKI]) for NGT and T2DM participants but was correlated with such indexes for prediabetes patients. We concluded that serum MANF level was higher in patients with newly diagnosed prediabetes and T2DM than in NGT controls. MANF appears to be associated with Matsuda Index, QUICKI and HOMA-IR in prediabetes patients.

Adipose Insulin Resistance in Obese Adolescents Across the Spectrum of Glucose Tolerance.

Adipocytes represent an important insulin-responsive tissue taking an active part in glucose metabolism. This study sought to assess adipose tissue insulin resistance (IR) across the spectrum of glucose tolerance and to test its relation with free fatty acid (FFA) suppression during an oral glucose tolerance test (OGTT). A cross-sectional analysis of a pediatric clinic-derived cohort of obese adolescents. Participants age 7-20 y with a body mass index that exceeded the 95th percentile for their age and sex. A standard oral glucose tolerance test. The adipose tissue insulin resistance index (calculated as the product of fasting insulin and FFA concentrations) (Adipose IR) and the area under curve of FFAs during the OGTT were compared between glucose tolerance categories. A total of 962 obese children and adolescents participated in this study. Adipose IR significantly increased across glucose tolerance categories (P for trend < .001). Within the normal glucose tolerance participants, an increase in adipose IR was observed related to an increase in 2-hr glucose levels. In a subsample of participants who underwent abdominal imaging for determination of lipid partitioning (n = 115), a tight relation of visceral fat (r = 0.34; P < .001) and the visceral/sc fat ratio (r = 0.55; P < .001) with the Adipose IR index was evident. Greater area under the curve FFAs (lower FFA suppression) during the OGTT was evident with worsening glucose tolerance (P for trend < .001). Glucose tolerance category, degree of obesity (body mass index-z score), IL-6, and low adiponectin emerged as significant predictors of the Adipose IR. Adipose IR is associated with reduced suppression of FFAs during the OGTT and with an altered adipocytokine profile. The negative relation with insulin secretion deserves further longitudinal investigation in the context of deteriorating glucose tolerance.

Association of the ACTN3 R577X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle.

A common polymorphism (R577X) in the α-actinin (ACTN) 3 gene, which leads to complete deficiency of a functional protein in skeletal muscle, could directly influence metabolism in the context of health and disease. Therefore, we tested the hypothesis that states of glucose tolerance are associated with the ACTN3 R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured muscle-specific α-actinin 2 and 3 mRNA and protein abundance in skeletal muscle biopsies. Furthermore, we investigated the protein abundance of the myosin heavy chain isoforms and the components of the mitochondrial electron transport chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX genotype was higher in T2D patients, genotype distribution was unrelated to metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein abundance was unchanged between NGT and T2D participants. Protein abundance of mitochondrial complexes II and IV was related to genotype and glucose tolerance status. Gene expression of sarcomeric z-disk proteins was increased in skeletal muscle from NGT participants with the ACTN3 577XX genotype. While genetic variation in ACTN3 does not influence metabolic control, genotype does appear to influence gene expression of other sarcomeric proteins, which could contribute to the functional properties of skeletal muscle and the fatigue-resistant phenotype associated with the R577X polymorphism.

Sestrin 3 regulation in type 2 diabetic patients and its influence on metabolism and differentiation in skeletal muscle

In mammals, the sestrin family is composed of three stress-responsive genes. Ablation of sestrin in Drosophila attenuates longevity, which is accompanied by increased S6K phosphorylation and decreased AMPK phosphorylation. Nevertheless, the metabolic role of sestrins in mammals is not comprehensively understood. We characterized the expression of individual sestrin family members and determined their role in vastus lateralis muscle biopsies from participants with normal glucose tolerance (NGT) or type 2 diabetes (T2D). Expression of sestrin 1 or sestrin 2 mRNA was unaltered between the NGT and T2D participants. Conversely, sestrin 3 mRNA was increased in T2D patients and correlated with fasting plasma glucose, 2-h postprandial plasma glucose and HbA1c. A trend for increased sestrin 3 protein was observed in T2D patients. In human primary myotubes, sestrin 3 mRNA increased during differentiation, and this response was unaltered in T2D-derived myotubes. Long-term treatment of myotubes with insulin or AICAR decreased sestrin 3 mRNA. Exposure of myotubes to the reactive oxygen species H2O2 increased mRNA expression of sestrin 1 and 2, whereas sestrin 3 was unaltered. siRNA-mediated silencing of sestrin 3 in myotubes was without effect on insulin-stimulated glucose incorporation into glycogen or AICAR-stimulated palmitate oxidation. These results provide evidence against sestrin 3 in the direct control of glucose or lipid metabolism in human skeletal muscle. However, siRNA-mediated sestrin 3 gene silencing in myotubes increased myostatin expression. Collectively, our results indicate sestrin 3 is upregulated in T2D and could influence skeletal muscle differentiation without altering glucose and lipid metabolism.

Eosinophil inversely associates with type 2 diabetes and insulin resistance in Chinese adults.

ContextLimited population-based study focused on relationship between eosinophil and type 2 diabetes (T2D).ObjectivesWe aimed to evaluate the relationship between peripheral eosinophil percentage and glucose metabolism and insulin resistance in a large sample size of Chinese population aged 40 and older.Design and MethodsA cross-sectional study was performed among 9,111 Chinese adults including 3,561 men and 5,550 women. The glucose metabolism status was confirmed by 75-g oral glucose tolerance test. Homeostasis model assessment of insulin resistance index and serum insulin levels were used to evaluate insulin resistance. Homeostasis model assessment-B was used to evaluate β cell function.ResultsThe average age of participants was 58.5 years. The prevalence of T2D decreased across the tertiles of eosinophil percentage (21.3%, 18.2% and 16.9%, P<0.0001). Each one tertile increase of eosinophil percentage inversely associated with risk of T2D when referred not only to normal glucose tolerance (NGT) (odds ratio (OR) 0.81, 95% CI 0.76–0.87, P< 0.0001), but also to impaired glucose regulation (OR 0.89, 95% CI 0.83–0.97, P = 0.006), respectively, after adjustment for the confounding factors. Compared with the first tertile, the third tertile of eosinophil percentage associated with a 23% decrease of insulin resistance in NGT participants after full adjustments (P = 0.005). Each 1-standard deviation of increment of eosinophil percentage associated with a 37% decrease of insulin resistance (P = 0.005).ConclusionsHigher peripheral eosinophil percentage was associated with decreased risk of T2D. The inverse relation to insulin resistance was detected in NGT participants.

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

We tested the hypothesis that the reversibility of insulin resistance and diabetes observed after biliopancreatic diversion (BPD) is related to changes in circadian rhythms of gastrointestinal hormones. Ten morbidly obese participants, five with normal glucose tolerance (NGT) and five with type 2 diabetes, were studied before and within 2 weeks after BPD. Within-day variations in glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1) levels were assessed using a single cosinor model. Insulin sensitivity was assessed by euglycaemic-hyperinsulinaemic clamp. Basal GLP1 relative amplitude (amplitude/mesor x 100) was 25.82-4.06% in NGT; it increased to 41.38-4.32% after BPD but was unchanged in diabetic patients. GLP1 and GIP mesor were shifted in time after surgery in diabetic patients but not in NGT participants. After BPD, the GLP1 AUC significantly increased from 775 +/- 94 to 846 +/- 161 pmol l(-1) min in NGT, whereas GIP AUC decreased significantly from 1,373 +/- 565 to 513 +/- 186 pmol l(-1) min in diabetic patients. Two-way ANOVA showed a strong influence of BPD on both GIP (p = 0.010) and GLP1 AUCs (p = 0.033), which was potentiated by the presence of diabetes, particularly for GIP (BPD x diabetes, p = 0.003). Insulin sensitivity was markedly improved (p < 0.01) in NGT (from 9.14 +/- 3.63 to 36.04 +/- 8.55 micromol [kg fat-free mass](-1) min(-1)) and diabetic patients (from 9.49 +/- 3.56 to 38.57 +/- 4.62 micromol [kg fat-free mass](-1) min(-1)). An incretin circadian rhythm was shown for the first time in morbid obesity. The effect of BPD on the 24 h pattern of incretin differed between NGT and diabetic patients. GLP1 secretion impairment was reversed in NGT and could not be overcome by surgery in diabetes. On the other hand, GIP secretion was blunted after the operation only in diabetic patients, suggesting a role in insulin resistance and diabetes.

Association of total and central adiposity measures with fasting insulin in a biracial population of young adults with normal glucose tolerance: the CARDIA study.

To determine the association of computed tomography (CT)-measured visceral adipose tissue (AT) and other measures of adiposity with fasting insulin in a biracial (African American and Caucasian) study population of young adults. The study population consisted of 251 young adults with normal glucose tolerance (NGT), ages 28-40 years, who were volunteers from the Birmingham, Alabama, and Oakland, California centers of the Coronary Artery Risk Development in Young Adults (CARDIA) study. In regression models with total adiposity measures (body mass index or dual-energy X-ray absorptiometry-measured percent fat), visceral AT (measured as a cross-sectional area in cm2) was generally a stronger predictor of insulin than overall adiposity in all race/gender groups (partial correlation coefficients ranging from 0.31 to 0.47) except for black men, in whom the associations were nonsignificant. Partial correlation coefficients between waist circumference and insulin, controlling for percent fat, were nearly identical to those between visceral AT and insulin in women and in white men. Analyses performed on 2060 NGT CARDIA subjects who were not in this study of visceral AT showed significant correlations of waist circumference with insulin in all race/gender groups, including black men, and that black men in the visceral AT study group were significantly leaner than other black male CARDIA subjects. We conclude that visceral AT was associated with fasting insulin in NGT participants in three of the four race/gender groups (black men excepted) and that waist circumference was a good surrogate for visceral AT in examining associations of central adiposity with fasting insulin.