Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Whole-Body and Hepatic Insulin Resistance in Obese Children

Background

Insulin resistance may be assessed as whole body or hepatic.

Objective

To study factors associated with both types of insulin resistance.

Methods

Cross-sectional study of 182 obese children. Somatometric measurements were registered, and the following three adiposity indexes were compared: BMI, waist-to-height ratio and visceral adiposity. Whole-body insulin resistance was evaluated using HOMA-IR, with 2.5 as the cut-off point. Hepatic insulin resistance was considered for IGFBP-1 level quartiles 1 to 3 (<6.67 ng/ml). We determined metabolite and hormone levels and performed a liver ultrasound.

Results

The majority, 73.1%, of obese children had whole-body insulin resistance and hepatic insulin resistance, while 7% did not have either type. HOMA-IR was negatively associated with IGFBP-1 and positively associated with BMI, triglycerides, leptin and mother''s BMI. Girls had increased HOMA-IR. IGFBP-1 was negatively associated with waist-to-height ratio, age, leptin, HOMA-IR and IGF-I. We did not find HOMA-IR or IGFBP-1 associated with fatty liver.

Conclusion

In school-aged children, BMI is the best metric to predict whole-body insulin resistance, and waist-to-height ratio is the best predictor of hepatic insulin resistance, indicating that central obesity is important for hepatic insulin resistance. The reciprocal negative association of IGFBP-1 and HOMA-IR may represent a strong interaction of the physiological processes of both whole-body and hepatic insulin resistance.     

Metabolic Signatures of Cultured Human Adipocytes from Metabolically Healthy versus Unhealthy Obese Individuals

Background and Aims

Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO) can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.

Methods

10 insulin-resistant (IR) vs. 10 insulin-sensitive (IS) non-diabetic morbidly obese (BMI >40 kg/m²) Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.

Results/Interpretation

Among others, aspartate was reduced intracellularly to one third (p = 0.0039) in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO''s and MHO''s adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs) were lower in MUHO''s extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA) metabolism was found: 15(S)-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014), AA (1.5-fold; p = 0.0055) and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033) were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.

Conclusion/Interpretation

We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.     

Sympathovagal Imbalance Contributes to Prehypertension Status and Cardiovascular Risks Attributed by Insulin Resistance,Inflammation, Dyslipidemia and Oxidative Stress in First Degree Relatives of Type 2 Diabetics

Background

Though cardiovascular (CV) risks are reported in first-degree relatives (FDR) of type 2 diabetics, the pathophysiological mechanisms contributing to these risks are not known. We investigated the association of sympathovagal imbalance (SVI) with CV risks in these subjects.

Subjects and Methods

Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate-pressure product (RPP), spectral indices of heart rate variability (HRV), autonomic function tests, insulin resistance (HOMA-IR), lipid profile, inflammatory markers, oxidative stress (OS) marker, rennin, thyroid profile and serum electrolytes were measured and analyzed in subjects of study group (FDR of type 2 diabetics, n = 72) and control group (subjects with no family history of diabetes, n = 104).

Results

BMI, BP, BHR, HOMA-IR, lipid profile, inflammatory and OS markers, renin, LF-HF (ratio of low-frequency to high-frequency power of HRV, a sensitive marker of SVI) were significantly increased (p<0.0001) in study group compared to the control group. SVI in study group was due to concomitant sympathetic activation and vagal inhibition. There was significant correlation and independent contribution of markers of insulin resistance, dyslipidemia, inflammation and OS to LF-HF ratio. Multiple-regression analysis demonstrated an independent contribution of LF-HF ratio to prehypertension status (standardized beta 0.415, p<0.001) and bivariate logistic-regression showed significant prediction (OR 2.40, CI 1.128–5.326, p = 0.002) of LF-HF ratio of HRV to increased RPP, the marker of CV risk, in study group.

Conclusion

SVI in FDR of type 2 diabetics occurs due to sympathetic activation and vagal withdrawal. The SVI contributes to prehypertension status and CV risks caused by insulin resistance, dyslipidemia, inflammation and oxidative stress in FDR of type 2 diabetics.     

Associations between Serum Apelin-12 Levels and Obesity-Related Markers in Chinese Children

Objective

To investigate possible correlations between apelin-12 levels and obesity in children in China and associations between apelin-12 and obesity-related markers, including lipids, insulin sensitivity and insulin resistance index (HOMA-IR).

Methods

Forty-eight obese and forty non-obese age- and gender-matched Chinese children were enrolled between June 2008 and June 2009. Mean age was 10.42±2.03 and 10.86±2.23 years in obesity and control groups, respectively. Main outcome measures were apelin-12, BMI, lipids, glucose and insulin. HOMA-IR was calculated for all subjects.

Results

All obesity group subjects had significantly higher total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), insulin levels and HOMA-IR (all P<0.05). In separate analyses, obese girls had significantly higher LDL-C, insulin and HOMA-IR than controls, and obese boys had significantly higher TC, TG, insulin and HOMA-IR than controls (all P<0.05). Apelin-12 levels were significantly higher in obese girls compared to controls (P = 0.024), and correlated positively with TG in all obese subjects. Among obese girls, apelin-12 levels correlated positively with TG, insulin and HOMA-IR after adjusting for age and BMI. In all boys (obese and controls) apelin-12 was positively associated with fasting plasma glucose (FPG). No significant correlations were found in either group between apelin-12 levels and other characteristics after adjusting for age, sex, and BMI.

Conclusions

Apelin-12 levels are significantly higher in obese vs. non-obese girls in China and correlate significantly with obesity-related markers insulin, HOMA-IR, and TG. Increased apelin-12 levels may be involved in the pathological mechanism of childhood obesity.     

MR Quantification of Total Liver Fat in Patients with Impaired Glucose Tolerance and Healthy Subjects

Objective

To explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects.

Materials and Methods

56 subjects were enrolled and each of them underwent upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated.

Results

For all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group.

Conclusions

People with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus.     

Serum 25-Hydroxyvitamin D and Insulin Resistance in Apparently Healthy Adolescents

Purpose

Vitamin D deficiency is a common condition that is associated with diabetes and insulin resistance. However, the association between vitamin D and insulin resistance has not been fully studied, especially in the general adolescent population. Therefore, we assessed the association between serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance among apparently healthy Korean adolescents.

Methods

A total of 260 (135 male and 125 female) adolescents in a rural high school were assessed for serum 25(OH)D, fasting plasma glucose, and insulin. All of the participants were aged 15 to 16 years old, and without known hypertension or diabetes. Serum 25(OH)D was analyzed both as a continuous and categorical variable in association with insulin resistance. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Increased insulin resistance was operationally defined as a HOMA-IR value higher than the sex-specific 75th percentile.

Results

In male adolescents, every 10 ng/ml decrease in 25(OH)D level was associated with a 0.25 unit increase in HOMA-IR (p = 0.003) after adjusting for age and BMI. Compared to those in the highest quartile, male adolescents in the lowest 25(OH)D quartile were at significantly higher risk for insulin resistance: unadjusted odds ratio 4.06 (95% CI, 1.26 to 13.07); age and BMI adjusted odds ratio 3.59 (95% CI, 1.03 to 12.57). However, 25(OH)D level, either in continuous or categorical measure, was not significantly associated with insulin resistance among female adolescents.

Conclusions

This study suggests that serum 25(OH)D level may be inversely associated with insulin resistance in healthy male adolescents.     

Serum Glycine Is Associated with Regional Body Fat and Insulin Resistance in Functionally-Limited Older Adults

Background

Metabolic profiling may provide insight into biologic mechanisms related to age-related increases in regional adiposity and insulin resistance.

Objectives

The objectives of the current study were to characterize the association between mid-thigh intermuscular and subcutaneous adipose tissue (IMAT, SCAT, respectively) and, abdominal adiposity with the serum metabolite profile, to identify significant metabolites as further associated with the homeostasis model assessment of insulin resistance (HOMA-IR), and, to develop a HOMA-IR associated metabolite predictor set representative of regional adiposity, in 73 functionally-limited (short physical performance battery ≤10; SPPB) older adults (age range, 70–85 y).

Methods

Fasting levels of 181 total metabolites, including amino acids, fatty acids and acylcarnitines were measured with use of an untargeted mass spectrometry-based metabolomic approach. Multivariable-adjusted linear regression was used in all analyses.

Results

Thirty-two, seven and one metabolite(s) were found to be associated with IMAT, abdominal adiposity and, SCAT, respectively, including the amino acid glycine, which was positively associated with SCAT and, negatively associated with both IMAT and abdominal adiposity. Glycine and four metabolites found to be significantly associated with regional adiposity were additionally associated with HOMA-IR. Separate stepwise regression models identified glycine as a HOMA-IR associated marker of both IMAT (model R² = 0.51, p<0.0001) and abdominal adiposity (model R² = 0.41, p<0.0001).

Conclusion

Our findings for a positive association between glycine with SCAT but, a negative association between glycine with IMAT and abdominal adiposity supports the hypothesis that SCAT metabolic processes are different from that found in other fat depots. In addition, because of the significant associations found between glycine with HOMA-IR, IMAT, SCAT and abdominal adiposity, our results suggest glycine as a serum biomarker of both insulin sensitivity and regional fat mass in functionally-limited older adults.     

Comparison of the Metabolic Syndrome Risk in Valproate-Treated Patients with Epilepsy and the General Population in Estonia

Background

No study has explored the risk of metabolic syndrome (MS) in patients with epilepsy treated with valproate (VPA) at the population level. The aim of this study was to compare the risk of MS in VPA-treated patients in Estonia to the risk in the general population.

Methods

This study involved 118 patients with epilepsy (63 men, 55 women) who received VPA monotherapy. MS was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Data were compared with the results of a population-based study of the prevalence of MS in the same geographic region (N = 493; 213 men, 280 women).

Results

In the multiple logistic regression analysis, after adjustment for age and sex, the risk of MS in VPA-treated patients was not increased compared to the control subjects (odds ratio [OR] = 1.00; 95% confidence interval [CI], 0.59–1.68). VPA-treated patients had higher serum insulin concentrations than control subjects, independent of body mass index (BMI). A positive association was found between MS development and BMI (OR = 1.47; 95% CI, 1.25–1.73) in VPA-treated patients, but there were no associations with the VPA dosage or the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. In control subjects, BMI and HOMA-IR had similar predictive abilities for MS occurrence. In VPA-treated patients, the predictive ability of the HOMA-IR index was significantly lower than that of BMI, with areas under the receiver operating characteristic curves of 0.808 and 0.897 (P = 0.05), respectively.

Conclusions

The risk of MS is not increased among VPA-treated patients with epilepsy in Estonia compared to the general population. The HOMA-IR index likely has a lower predictive ability for MS in VPA-treated patients compared to its predictive ability in the general population.     

Serum Liver Fatty Acid Binding Protein Levels Correlate Positively with Obesity and Insulin Resistance in Chinese Young Adults

Background

Liver fatty acid–binding protein (FABP1) plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old.

Methodology and Principal Findings

Cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR) and by the insulin sensitivity index (S_i) derived from Bergman’s minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001) and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001). Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary S_i (OR = 1.868 per SD unit, 95% CI [1.035–3.373], p = 0.038) after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001). Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels.

Conclusions and Significance

Serum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.     

Food Marketing towards Children: Brand Logo Recognition,Food-Related Behavior and BMI among 3–13-Year-Olds in a South Indian Town

Objectives

To assess exposure to marketing of unhealthy food products and its relation to food related behavior and BMI in children aged 3–13, from different socioeconomic backgrounds in a south Indian town.

Methods

Child-parent pairs (n = 306) were recruited at pediatric clinics. Exposure to food marketing was assessed by a digital logo recognition test. Children matched 18 logos of unhealthy food (high in fat/sugar/salt) featured in promotion material from the food industry to pictures of corresponding products. Children''s nutritional knowledge, food preferences, purchase requests, eating behavior and socioeconomic characteristics were assessed by a digital game and parental questionnaires. Anthropometric measurements were recorded.

Results

Recognition rates for the brand logos ranged from 30% to 80%. Logo recognition ability increased with age (p<0.001) and socioeconomic level (p<0.001 comparing children in the highest and lowest of three socioeconomic groups). Adjusted for gender, age and socioeconomic group, logo recognition was associated with higher BMI (p = 0.022) and nutritional knowledge (p<0.001) but not to unhealthy food preferences or purchase requests.

Conclusions

Children from higher socioeconomic groups in the region had higher brand logo recognition ability and are possibly exposed to more food marketing. The study did not lend support to a link between exposure to marketing and poor eating behavior, distorted nutritional knowledge or increased purchase requests. The correlation between logo recognition and BMI warrants further investigation on food marketing towards children and its potential role in the increasing burden of non-communicable diseases in this part of India.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Olive (Olea europaea L.) Leaf Polyphenols Improve Insulin Sensitivity in Middle-Aged Overweight Men: A Randomized,Placebo-Controlled,Crossover Trial

Background

Olive plant leaves (Olea europaea L.) have been used for centuries in folk medicine to treat diabetes, but there are very limited data examining the effects of olive polyphenols on glucose homeostasis in humans.

Objective

To assess the effects of supplementation with olive leaf polyphenols (51.1 mg oleuropein, 9.7 mg hydroxytyrosol per day) on insulin action and cardiovascular risk factors in middle-aged overweight men.

Design

Randomized, double-blinded, placebo-controlled, crossover trial in New Zealand. 46 participants (aged 46.4±5.5 years and BMI 28.0±2.0 kg/m²) were randomized to receive capsules with olive leaf extract (OLE) or placebo for 12 weeks, crossing over to other treatment after a 6-week washout. Primary outcome was insulin sensitivity (Matsuda method). Secondary outcomes included glucose and insulin profiles, cytokines, lipid profile, body composition, 24-hour ambulatory blood pressure, and carotid intima-media thickness.

Results

Treatment evaluations were based on the intention-to-treat principle. All participants took >96% of prescribed capsules. OLE supplementation was associated with a 15% improvement in insulin sensitivity (p = 0.024) compared to placebo. There was also a 28% improvement in pancreatic β-cell responsiveness (p = 0.013). OLE supplementation also led to increased fasting interleukin-6 (p = 0.014), IGFBP-1 (p = 0.024), and IGFBP-2 (p = 0.015) concentrations. There were however, no effects on interleukin-8, TNF-α, ultra-sensitive CRP, lipid profile, ambulatory blood pressure, body composition, carotid intima-media thickness, or liver function.

Conclusions

Supplementation with olive leaf polyphenols for 12 weeks significantly improved insulin sensitivity and pancreatic β-cell secretory capacity in overweight middle-aged men at risk of developing the metabolic syndrome.

Trial Registration

Australian New Zealand Clinical Trials Registry #336317.     

An Interaction between a FNDC5 Variant and Obesity Modulates Glucose Metabolism in a Chinese Han Population

Background

To investigate the impact of common variants of FNDC5 on type 2 diabetes and clinical traits related to glucose metabolism in a large Chinese population sample.

Methods

Three tagging single nucleotide polymorphisms within the region of the FNDC5 gene were selected and genotyped in 6822 participants. Detailed clinical investigations and biochemistry measurements were carried out in all of the participants. Subjects without diabetes were classified into normal weight and overweight/obese subgroups according to body mass index (BMI).

Results

None of the SNPs were associated with either the risk of type 2 diabetes in all of the participants or with any of the clinical quantitative traits in the controls with normal glucose regulation. Subgroup analysis showed that in controls with normal weight (BMI <25 kg/m²), the rs16835198 major allele G was significantly associated with fasting insulin levels, and that each additional copy of the allele resulted in a 0.0178 mU/L increment of the values (p = 0.046). Moreover, after adjusting for confounding variables, there were trends towards correlation of rs16835198 with HOMA-insulin resistance (HOMA-IR) (p = 0.057) and low-density lipoprotein cholesterol (LDL-C) levels (p = 0.083). In overweight/obese subjects (BMI ≥25 Kg/m²), we noted rs16835198 showed trends towards association with fasting insulin (p = 0.057) and HOMA-IR levels (p = 0.091), both of which declined with additional copies of the major allele G. Moreover, rs16835198 was significantly associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 0.013), and HOMA-β cell function (p = 0.028) in the overweight/obese subjects. Finally, we observed a significant interaction between BMI-rs16835198 and fasting insulin levels in the control group (p = 0.003).

Conclusions

Our data indicate that the effect of the common FNDC5 SNP rs16835198 on fasting insulin was significantly modified by BMI in the Chinese Han population.     

Insulin Sensitivity from Preschool to School Age in Patients with Severe Obesity

Background

Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age.

Research design and methods

Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); β-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test.

Results

After a median follow-up of 2.23 (1–4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8–11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R² = 0.309; p = 0.002; β = −0.556), ISSI-2 (R² = 0.465; p<0.0001; β = −0.682), and BMI z-score (R² = 0.246; p = 0.008; 0.496), respectively.

Conclusions

In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.     

General Practitioners Can Evaluate the Material,Social and Health Dimensions of Patient Social Status

Objective

To identify which physician and patient characteristics are associated with physicians'' estimation of their patient social status.

Design

Cross-sectional multicentric survey.

Setting

Fourty-seven primary care private offices in Western Switzerland.

Participants

Random sample of 2030 patients ≥16, who encountered a general practitioner (GP) between September 2010 and February 2011.

Main measures

Primary outcome: patient social status perceived by GPs, using the MacArthur Scale of Subjective Social Status, ranging from the bottom (0) to the top (10) of the social scale.Secondary outcome: Difference between GP''s evaluation and patient''s own evaluation of their social status. Potential patient correlates: material and social deprivation using the DiPCare-Q, health status using the EQ-5D, sources of income, and level of education. GP characteristics: opinion regarding patients'' deprivation and its influence on health and care.

Results

To evaluate patient social status, GPs considered the material, social, and health aspects of deprivation, along with education level, and amount and type of income. GPs declaring a frequent reflexive consideration of their own prejudice towards deprived patients, gave a higher estimation of patients'' social status (+1.0, p = 0.002). Choosing a less costly treatment for deprived patients was associated with a lower estimation (−0.7, p = 0.002). GP''s evaluation of patient social status was 0.5 point higher than the patient''s own estimate (p<0.0001).

Conclusions

GPs can perceive the various dimensions of patient social status, although heterogeneously, according partly to their own characteristics. Compared to patients'' own evaluation, GPs overestimate patient social status.     

Metabolite Profiling Identifies Candidate Markers Reflecting the Clinical Adaptations Associated with Roux-en-Y Gastric Bypass Surgery

Background

Roux-en-Y gastric bypass (RYGB) surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data.

Methodology and Principal Findings

Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2±1.7). Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172) of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05), including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9) and obese/diabetic (n = 5) groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2), nervonic (C24:1) acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI) and estimates for insulin resistance (HOMA-IR). Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = −0.55).

Conclusions

Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.     

The Systemic Immune Network in Recent Onset Type 1 Diabetes: Central Role of Interleukin-1 Receptor Antagonist (DIATOR Trial)

Background

The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.

Methods and Findings

All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18–39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25–0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.

Conclusions

In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.

Trial registration

ClinicalTrials.gov registration number: {"type":"clinical-trial","attrs":{"text":"NCT00974740","term_id":"NCT00974740"}}NCT00974740     

Risk of Obstructive Sleep Apnea with Daytime Sleepiness Is Associated with Liver Damage in Non-Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease

Background

A high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.

Aims

To determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.

Methods

We considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m², and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.

Results

In NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).

Conclusions

A proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.