Relation of glomerular filtration to insulin resistance and related risk factors in obese children.

BACKGROUND AND OBJECTIVE: Childhood obesity is associated with later development of significant renal morbidity. We evaluated the impact of the degree of insulin sensitivity on estimated glomerular filtration rate (eGFR) and determined the factors associated with eGFR in obese children. We further tested the relation of eGFR to clinical outcomes such as blood pressure and microalbuminuria. MATERIALS AND METHODS: We evaluated the relation of whole body insulin sensitivity and estimated glomerular filtration rate (eGFR) across the spectrum of obesity in children and adolescents. eGFR was calculated using the iCARE formula, which has been validated in obese children with varying glucose tolerance. RESULTS: 1080 children and adolescents with overweight and obesity (701 females and 379 males) participated. Insulin sensitivity was a strongly negatively associated with (B = -2.72, p < 0.001) eGFR), even after adjustment for potential confounders. Male sex emerged to be significantly associated with eGFR with boys having greater values than girls (B = 18.82, p < 0.001). Age was a positively associated (B = 2.86, p < 0.001) with eGFR. Whole body and hepatic insulin sensitivity decreased across eGFR quartiles. Adjusted eGFR was tightly positively associated with systolic blood pressure (B = 0.09, p = 0.003) and negatively associated with the presence of microalbuminuria (B = -2.18, p = 0.04). CONCLUSIONS: eGFR tends to increase with greater degrees of insulin resistance in children and adolescents representing hyperfiltration and is associated with cardiovascular risk factors. Longitudinal studies are needed to determine the natural history of childhood insulin resistance related hyperfiltration in regards to future kidney disease.

Youth-onset type 2 diabetes in Israel: A national cohort.

BACKGROUND: Prevalence of youth-onset type 2 diabetes (T2D) has increased worldwide, paralleling the rise in pediatric obesity. Occurrence and clinical manifestations vary regionally and demographically. OBJECTIVES: We assessed the incidence, and clinical and demographic manifestations of youth-onset T2D in Israel. METHODS: In a national observational study, demographic, clinical, and laboratory data were collected from the medical records of children and adolescents, aged 10-18 years, diagnosed with T2D between the years 2008 and 2019. RESULTS: The incidence of youth-onset T2D in Israel increased significantly from 0.63/100,000 in 2008 to 3.41/100,000 in 2019. The study cohort comprised 379 individuals (228 girls [59.7%], 221 Jews [58.3%], mean age 14.7 ± 1.9 years); 73.1% had a positive family history of T2D. Mean body mass index (BMI) z-score was 1.96 ± 0.7, higher in Jews than Arabs. High systolic (≥ 130 mmHg) and diastolic blood pressure (≥ 85 mmHg) were observed in 33.7% and 7.8% of patients, respectively; mean glycosylated hemoglobin (A1c) level at diagnosis was 8.8 ± 2.5%. Dyslipidemia, with high triglyceride (>150 mg/dl) and low HDL-c (<40 mg/dl) levels, was found in 45.6% and 56.5%, respectively. Microalbuminuria and retinopathy were documented at diagnosis, 15.2% and 1.9%, respectively) and increased (36.7% and 4.6%, respectively) at follow-up of 2.9 ± 2.1 years. Criteria of metabolic syndrome were met by 224 (62.2%) patients, and fatty liver documented in 65%, mainly Jews. Psychosocial comorbidity was found in 31%. Treatment with metformin (45.6%), insulin (20.6%), and lifestyle modification (18%) improved glycemic control. CONCLUSION: Youth-onset T2D in Israel has increased significantly and presents a unique profile.

The impact of preoperative vitamin administration on skeletal status following sleeve gastrectomy in young and middle-aged women: a randomized controlled trial.

BACKGROUND: The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG). METHODS: Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA). RESULTS: Sixty-two females (median age 29.7 years and median BMI 43.4 kg/m2) were recruited, 87% completed the 12-month follow-up. For the intervention and control arms, significant and similar reductions at 12-months post-surgery were observed in BMD of the hip (-6.8 ± 3.7% vs. -6.0 ± 3.6%; P = 0.646) and of the femoral neck (-7.1 ± 5.8% vs. -7.2 ± 5.5%; P = 0.973). For the intervention compared to the control arm, the 25 hydroxyvitamin D (25(OH)D) increment was greater after 2 months treatment, and vitamin D deficiency rates were lower at 3 and 6-months follow-up (P < 0.016). However, at 12-months postoperative, 25(OH)D values and vitamin D deficiency were comparable between the arms (P > 0.339). Predictors for BMD decline in the total hip were the percentage of excess weight-loss, age>50 years, and lower initial BMI (P ≤ 0.003). CONCLUSIONS: SG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline.

Endothelin-1 levels are decreased in pediatric Type 1 diabetes and negatively correlate with the carotid intima media thickness.

AIMS: Better understanding of the timeline and risk factors for the appearance of complications in pediatric Type-1-diabetes is key for developing prevention strategies. We studied endothelial markers and their determinants in adolescents with Type-1-diabetes at different time points from diagnosis. METHODS: A cross-sectional study of 58 adolescents, mean age 15.0 ± 2.4 years; 20 with recent-onset Type-1-diabetes, 20 with over 7 years of Type-1-diabetes and 18 controls. Clinical and biochemical data were collected. Fingertip arterial reactive hyperemia (EndoPAT) and carotid intima-media-thickness (cIMT) were measured to assess endothelial function and structure. RESULTS: Compared to controls, individuals with prolonged Type-1-diabetes had higher mean cIMT (0.49 ± 0.07 mm vs. 0.43 ± 0.05 mm p = 0.021) and maximal cIMT (0.61 ± 0.08 mm 0.52 ± 0.08 mm, p = 0.025). Endothelin-1 levels were significantly lower in subjects with prolonged Type-1-diabetes (1.2 ± 1.0 pg/ml) compared to controls (3.0 ± 1.7, p = 0.008 pg/ml); they negatively correlated with the mean cIMT (c = - 0.291, p = 0.031) and mean 6 months hemoglobin A1c (c = - 0.301, p = 0.022) and positively correlated with mean c-peptide levels (c = 0.356, p = 0.006) and the weekly exercise time (c = 0.485, p < 0.001). Endothelin-1 levels did not correlate with EndoPAT results. CONCLUSIONS: Our results suggest that the early years after the diagnosis of Type-1-diabetes are an important window for prevention of arterial damage in the pediatric population. The trajectories of relationships of Endothelin-1 with metabolic and vascular measures were opposite from the anticipated, yet consistent. Endothelin-1 related indirectly to adverse measures and directly to favorable measures. Decreased Endothelin-1 levels might reflect early stages in endothelial impairment in Type-1-diabetes, yet its' exact role in the development of complications is yet to be unraveled.

Identifying sources of support and barriers to physical activity in pediatric type 1 diabetes.

OBJECTIVES: Reports suggest that children with type 1 diabetes (T1D) perform less than the recommended daily activity and are less active than their non-diabetic peers. We aimed to: (a) Identify barriers and sources of support for exercise performance in pediatric T1D. (b) Identify strengths and limitations in the exercise-directed education provided by our diabetes team. METHODS: Patients with T1D 5 to 20 years of age were recruited while attending a routine clinic visit. Participants completed a set of questionnaires assessing demographics, health data, barriers, and sources of support for exercise performance and diabetes related exercise education. The clinics' medical staff filled-out a questionnaire assessing the exercise-directed education provided in clinic. RESULTS: Ninety-six subjects were included in this study, mean age 13.7 ± 3.8 years. Median weekly reported exercise time was 3.5 hours. The two most prevalent barriers were fear of hypoglycemia and low fitness, reported by 76% and 51%, respectively. Mean family and social support scores were 4.1 ± 0.7 and 3.3 ± 1.1, respectively (1-5 scale); the latter correlated with the amount of activity performed (cc = 0.360; P < .001). The majority of participants (97%) reported receiving guidance for physical activity, to their satisfaction. Yet, knowledge and implementation were suboptimal. All staff members reported conducting routine exercise-directed teaching, with variations in frequency and content. CONCLUSIONS: Our findings suggest that in order to increase the amount of safely performed exercise in pediatric patients with T1D, fear of hypoglycemia must be addressed. Further efforts should focus on: (a) encouraging active family and social involvement (b) standardization of education.

Impact of Severe Obesity on Cardiovascular Risk Factors in Youth.

OBJECTIVE: To compare cardiovascular risk factor clustering (CVRFC) in severely obese youth with those with lower degrees of obesity. STUDY DESIGN: We divided a childhood obesity clinic derived cohort into the degrees of obesity (class I, II, and III) and added a "class IV" category corresponding to >160% of the 95th centile of body mass index (BMI) for age and sex. In a cross-sectional analysis, we investigated the presence of CVRFC in 2244 participants; in 621 who were followed longitudinally, we investigated the determinants of endpoint CVRFC. RESULTS: Class IV obesity was associated with increased risk for CVRFC compared with overweight (OR = 17.26, P < .001) at a similar magnitude to class III obesity (OR = 17.26, P < .001). Male children were at greater risk for presence of CVRFC (OR = 1.57, P = .03) compared with female children. Adiponectin (OR = 0.90, P < .001) and leptin levels (OR = 0.98, P = .008) were protective, independent of degree of obesity. Baseline class IV obesity was associated with increased risk compared with overweight of having CVRFC at follow-up (OR = 5.76, P = .001), to a similar extent as class III obesity (OR = 5.36, P = .001). Changes in the degree of obesity were significant predictors of CVRFC on follow-up (OR = 1.04, P < .01 per percent BMI change). CONCLUSIONS: The metabolic risk associated with obesity in childhood is conferred prior to reaching class IV obesity. An individualized risk stratification approach in children with severe obesity should be based on presence of complications rather than simple BMI cutoffs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01967849.

Predictors of responses to clinic-based childhood obesity care.

BACKGROUND/OBJECTIVE: Lifestyle modification is the therapy of choice for childhood obesity, yet the response rate is variable and may be affected by genetic factors. We aimed to investigate predictors of poor response to lifestyle modification obesity treatment in children. METHODS: A prospective cohort study of 434 youths (64.5% females) between 4 and 20 years of age undergoing a standard care of lifestyle modification obesity management for 35.9 ± 20.8 months at Yale Childhood Obesity Clinic, USA. The primary outcome was a "poor response," defined as the quintile with the largest increase in BMI Z-score over time. The secondary outcome was the endpoint BMI Z-score. Covariates investigated were sex, baseline pubertal status and degree of obesity, race, biochemical profile, and family history of overweight. A subsample (n = 214) had FTO genotyping (SNP rs8050136) tested. RESULTS: Males (hazard ratio [HR] = 5.35, 95% confidence interval [CI] [3.32-8.61], P < 0.0001) and pubertal adolescents (HR = 2.78, [1.40-5.50], P = 0.003) compared to prepubertal children were more prone to respond poorly. Baseline degree of obesity was associated with relative protection from responding poorly (HR per BMI Z-score unit = 0.32, [0.17-0.61], P = 0.0006). Carriers of the FTO obesity-predisposing allele (AA genotype) were protected from responding poorly compared to non-carriers (CC genotype) (HR = 0.33, [0.12-0.88], P = 0.028). CONCLUSIONS: Boys and pubertal adolescents are more prone to respond poorly to standard obesity care while those with greater baseline degree of obesity and carriers of the FTO obesity-predisposing allele are not.

How are children with HIV faring in Nigeria?--a 7 year retrospective study of children enrolled in HIV care.

BACKGROUND: To review the pediatric care and treatment program at Massey Street Children Hospital, in Lagos, Nigeria a retrospective analysis of medical records focusing on health services, survival and retention in care. METHODS: The analysis covered a cohort of children initiated on antiretroviral therapy (ART) from 2005 to 2011. In this population, pediatric HIV care was defined as initiating ART between ages 0 and 14 years. Treatment initiation and follow-up were according to the Nigerian national guidelines for pediatric ART, which are based on World Health Organization guidelines adapted to our local context. The primary endpoint was mortality measured as cumulative survival. Other outcomes of interest included "loss to follow-up", "transferred out", and "stopped treatment". RESULTS: Mean (SD) age at ART initiation was 51 (39) months in female children and 52 (42) months in male children. After seven years of ART care, 64% of the 660 study children were retained in care and on treatment, 16% were lost to follow-up, 10% were dead, and 9% had discontinued HIV care at this facility for other reasons. World Health Organization disease stage, CD4 count, age, and year of ART initiation were highly predictive of mortality, while anemia at baseline was not statistically significantly associated. CONCLUSIONS: Overall study results suggest a viable pediatric HIV program exists at the study facility. Retention rates were lowest for the earliest cohort of infected children, which implies long-term challenges. Mother-to-child transmission programs need to be dynamic to stem the scourge of pediatric HIV in Nigeria.

A low disposition index in adolescent offspring of mothers with gestational diabetes: a risk marker for the development of impaired glucose tolerance in youth.

AIMS/HYPOTHESIS: With the increase in gestational diabetes mellitus (GDM), there is a growing need to understand the effects of intrauterine glucose exposure on the newborn at birth and later in life. The risk of developing impaired glucose tolerance (IGT) in individuals exposed to diabetes in utero has not been adequately investigated. METHODS: We studied 255 obese adolescents with normal glucose tolerance. All of them were investigated for in utero exposure to GDM and underwent an OGTT, which was repeated after approximately 2.8 years. RESULTS: 210 (82.3%) participants were not exposed to GDM (NGDM group), and 45 (17.7%) were exposed to GDM (EGDM group). In the NGDM group, only 8.6% (n = 18) developed either IGT or type 2 diabetes compared with 31.1% (n = 14) of the EGDM group who developed either IGT or type 2 diabetes (p < 0.001). Exposure to GDM was the most significant predictor of developing IGT or type 2 diabetes (OR 5.75, 95% CI 2.19, 15.07, p < 0.001). At baseline and at follow-up, the EGDM group showed a reduction in beta cell function determined by the oral disposition index (p = 0.03 and p = 0.01, respectively), and, at follow-up, they also displayed a reduction in insulin sensitivity compared with the NGDM group (p = 0.05). CONCLUSIONS/INTERPRETATION: Obese youth exposed in utero to GDM show early inability of the beta cell to compensate adequately in response to decreasing levels of insulin sensitivity.

Nonalcoholic fatty liver disease and type 2 diabetes in obese children.

Nonalcoholic fatty liver disease (NAFLD) is commonly found in adults and adolescents with type 2 diabetes (T2DM). The cause-effect relations of these 2 conditions are complex and it is difficult to decipher whether one drives the other or vice versa. Genetic predispositions, along with obesity, are probably shared culprits of both. NAFLD may precede the diagnosis of diabetes and play a critical role of driving its development by way of increasing hepatic and whole body insulin resistance. On the other hand, T2DM is associated with hyperinsulinemia, a resistance to some of the effects of gut derived peptides and increased systemic free fatty acids, that can all promote hepatic lipid deposition. Thus, each condition may promote the development of the other and their mutual presence creates a vicious cycle. Upon studying this complex interplay from another angle, reduction of liver fat significantly improves glucose metabolism in patients with T2DM highlighting the tight pathophysiological link between them.

An international multidisciplinary consensus on pediatric metabolic dysfunction-associated fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).

Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial.

AIMS/HYPOTHESIS: Bariatric surgery is gaining acceptance as a 'metabolic surgical intervention' for patients with type 2 diabetes. The optimal form of surgery and the mechanism of action of these procedures are much debated. We compared two bariatric procedures for obese patients with type 2 diabetes and evaluated their effects on HbA1c and glucose tolerance. METHODS: We performed a parallel un-blinded randomised trial of Roux-en-Y gastric bypass (RYGB) vs sleeve gastrectomy (SG) in 41 obese patients with type 2 diabetes, who were bariatric surgery candidates attending the obesity clinic. HbA1c, body composition and glucose tolerance were evaluated at baseline, and at 3 and 12 months. RESULTS: Of the 41 patients, 37 completed the follow-up (19 RYGB, 18 SG). Both groups had similar baseline anthropometric and biochemical measures, and showed comparable weight loss and fat:fat-free mass ratio changes at 12 months. A similar normalisation of HbA1c levels was observed as early as 3 months post-surgery (6.37 ± 0.71% vs 6.23 ± 0.69% for RYGB vs SG respectively, p < 0.001 in both groups for baseline vs follow-up). CONCLUSIONS/INTERPRETATION: In this study, RYGB did not have a superior effect in comparison to SG with regard to HbA1c levels or weight loss during 12 months of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT00667706. FUNDING: This work was supported by grant no. 3-000-8480 from the Israel Ministry of Health Chief Scientist, the Stephen Morse Diabetes Research Foundation and by Johnson & Johnson.

Adipose Tissue Insulin Resistance Is Not Associated With Changes in the Degree of Obesity in Children and Adolescents.

CONTEXT: The "carbohydrate-insulin model" claims that adipose tissue insulin sensitivity explains development of obesity via adipocyte energy storage and/or low postprandial metabolic fuel levels. OBJECTIVE: We tested whether adipose tissue insulin sensitivity predicts changes in the degree of obesity over time. METHODS: This secondary analysis of an observational study of youth with obesity included 213 youths at a pediatric weight management clinic. Adipose tissue insulin sensitivity/resistance and whole-body insulin sensitivity were evaluated using oral glucose tolerance test (OGTT)-derived surrogates in the face of changes in the degree of obesity over time. The main outcome measure was change in body mass index (BMI) z score. RESULTS: Mean BMI z change was 0.05 ± 0.28 (range, -1.15 to 1.19), representing a broad distribution of changes in the degree of obesity over a follow-up period of 1.88 ± 1.27 years. Adipose tissue insulin resistance was not associated with changes in the degree of obesity in univariate or multivariate analyses (adjusted for baseline age, BMI z score, sex, ethnicity, and time of follow-up). Low postprandial free fatty acid concentrations or their suppression during the OGTT were not associated with changes in the degree of obesity in univariate or multivariate analyses. Whole-body insulin sensitivity was not associated with changes in the degree of obesity in univariate or multivariate analyses. CONCLUSION: In this secondary analysis, in youth with obesity, adipose tissue insulin resistance is not protective from increases of the degree of obesity and skeletal muscle insulin resistance is not associated with increases of the degree of obesity.The analysis was performed using data derived from NCT00000112 and NCT00536250.

Trabecular Bone Score Preceding and during a 2-Year Follow-Up after Sleeve Gastrectomy: Pitfalls and New Insights.

Bariatric surgery (BS) can have negative effects on bone health. Bone microarchitecture quality evaluation using the trabecular bone score (TBS) has not been described in patients after sleeve gastrectomy (SG). To test the hypothesis that the TBS is clinically useful for this population, we evaluated changes in bone mineral density (BMD) and the TBS in a longitudinal cohort study following SG. The measurements before surgery and after 12 and 24 postoperative months were as follows: weight, height, BMI, waist circumference (WC), BMD and TBS. The results at baseline showed the following: a mean BMI of 43 ± 0.56, TBS of 1.25 ± 0.02, lumbar spine BMD T-score of -0.4 ± 0.93, TBS T-score of -2.30 ± 0.21, significantly lower than BMD-T-score, and associated with a BMD-T-TBS-T gap (T-gap) of -2.05 ± 1.26 (-0.24 ± 0.13). One year after surgery, the TBS had significantly improved (+12.12% ± 1.5), leading to a T-gap of -0.296 ± 0.14, which remained stable at 2 years post-surgery. A correlation analysis revealed a significant negative correlation between the T-gap and WC (r = -0.43 p = 0.004). Our interpretation is that abdominal fat may interfere with image acquisition via increased tissue thickness, leading to a false low TBS at baseline. In conclusion, TBS should be interpreted with caution in patients with obesity and elevated WC. Additionally, we show that after SG, the LS microarchitecture measured using the TBS is partially degraded in up to 25% of patients. Further studies are warranted to assess hip bone microarchitecture changes after bariatric surgery.

Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity.

In youths with obesity, the gut hormone potentiation of insulin secretion - the incretin effect - is blunted. We explored the longitudinal impact of the incretin effect during pubertal transition on ß cell function and insulin sensitivity. Youths with obesity and 2-hour glucose level ≥ 120 mg/dL underwent a 3-hour oral glucose-tolerance test (OGTT) and an isoglycemic i.v. glucose infusion to quantify the incretin effect. After 2 years, 30 of 39 participants had a repeated OGTT and were stratified into 3 tertiles according to the baseline incretin effect. The high-incretin effect group demonstrated a longitudinal increase in ß cell function (disposition index, minimal model [DIMM]), with greater insulin sensitivity at follow-up and stable insulin secretion (φtotal). A lower incretin effect at baseline was associated with higher 1-hour and 2-hour glucose level at follow-up. The high-incretin effect group displayed a greater increase of GLP-17-36 than the moderate- and low-incretin group at baseline, while such a difference did not persist after 2 years. Glucagon suppression was reduced at follow-up in those with low-baseline incretin in respect to the high-incretin group. The incretin effect during pubertal transition affected the longitudinal trajectory of ß cell function and weight in youths with obesity.

Bariatric Surgery in Adolescents with Obesity: Long-Term Perspectives and Potential Alternatives.

BACKGROUND: Severe obesity among adolescent shows a worrisome trend in regard to its increasing prevalence and poses a great challenge for treatment. Conservative measures have modest effects on weight loss, usually fail in achieving a sustainable weight loss and resolution of comorbidities. This has led to greater utilization of bariatric surgery (BS) that offers a fast reduction in body mass index with little perioperative complications. Despite the increasing utilization of BS, data are still insufficient, regarding their long-term outcome in adolescents. We review short- and long-term effects of BS and their implications on bone health and nutritional deficiencies in adolescents. In addition, we discuss possible pharmaceutical alternatives. SUMMARY: BS results in a substantial weight loss of roughly 37% in the first-year post-operation and is superior to conservative measures in resolution of metabolic comorbidities. BS significantly improves health-related quality of life. Longer follow-up (F/U) shows weight regain in 50% of patients. Furthermore, reduced bone mass and nutritional deficiencies were reported in up to 90% of patients. Most recently, alternative to BS became more relevant with approval of GLP-1 analogues use in adolescents. GLP-1 analogues are potent enough to induce moderate clinically meaningful weight loss and improvement of metabolic component. KEY MESSAGES: We conclude that obese adolescents without major obesity-related complications may benefit from pharmacological interventions with lifestyle modification. We advise considering BS as treatment approach in adolescents with severe obesity and major obesity-related complications with proper preoperative preparation and postoperative F/U in excellence centers.

Lack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study.

OBJECTIVE: The carbohydrate-insulin model (CIM) claims that chronic exposure to hyperinsulinemia induced by dietary carbohydrates explains development of obesity via direct effects of insulin and/or low postprandial metabolic fuel levels. We aimed at testing whether indices of hyperinsulinemia and postprandial glucose levels can predict increases in the degree of obesity over time. RESEARCH DESIGN AND METHODS: Children and adolescents with obesity attending a pediatric obesity clinic performed oral glucose tolerance tests (OGTTs) and received standard obesity management. Indices of hyperinsulinemia and insulin secretion were derived from the OGTT and evaluated in the face of changes in the degree of obesity over time. RESULTS: A total of 591 children (217 males and 374 females) participated, and the mean follow-up was 1.86 ± 1.29 years. OGTT-derived area under the curve of insulin, peak insulin, fasting insulin, the insulinogenic index, or insulin at 30 min were not associated with greater changes in the degree of obesity in univariate or multivariate analyses (adjusted for baseline age, BMI z score, sex, and ethnicity). Low postprandial glucose <75 mg/dL was not associated with greater changes in the degree of obesity in univariate or multivariate analyses. In a subsample of 104 participants with a follow-up >4 years, none of these parameters was associated with greater increases in the degree of obesity. CONCLUSIONS: In children and adolescents with obesity, exposure to hyperinsulinemia, greater insulin secretion, or low postprandial glucose is not associated with greater increases in the degree of obesity over 2-4 years. The CIM should be evaluated in children with lower BMI and for longer follow-up periods.

The Relationships of Fibrinogen and C-Reactive Protein With Gait Performance: A 20-Year Longitudinal Study.

Background: Gait speed, a central marker of aging, has been linked to various health outcomes, such as cognitive and physical functions in middle-aged adults. Although long-term systemic low-grade inflammation is considered a mechanism underlying a variety of aging-related risk factors, the longitudinal associations between inflammation markers and gait speed are yet to be fully investigated. Objective: To explore the associations of CRP and fibrinogen levels, measured two decades ago, with gait speed among community dwelling adults, considering the contribution of cardio-metabolic factors and cognition. Methods: Study participants took part in two phases of the of the "Kibbutzim Family Study" (i.e., Phase II, 1999-2000 and Phase III, 2017-2019). Blood samples collected in Phase II (baseline) were used to determine level of inflammatory markers. Gait speed was assessed under single-task (ST) and dual-task (DT) conditions in Phase III. Demographic, anthropometric and clinical data were collected in both phases. Linear regression models were used to assess the adjusted associations of inflammation and gait speed. Results: A total of 373 individuals aged 34-99 (mean 64 ± 13 years) in Phase III were included in the study. Gait speed under ST was negatively associated with baseline levels of fibrinogen (b per standard deviation (SD) = -0.053, p = 0.0007) and CRP (b per SD = -0.043, p = 0.010), after adjusting for baseline and concurrent cardiometabolic risk factors. Accounting for executive functions, associations of fibrinogen with gait under ST were somewhat attenuated, yet associations remained statistically significant (p < 0.05). Associations with CRP were attenuated to the null. In contrast, there were no associations between inflammation markers and gait under DT. Conclusion: Our findings demonstrate that in a sample including younger to older adults, higher systemic inflammatory activity was linked with gait 20 years later, beyond age and cardiometabolic health, and to a certain extent, beyond executive functions. Thus, systemic inflammation may serve as an early marker to identify individuals at risk for gait decline.