Reconstruction of the interosseous talocalcaneal ligament using allograft for subtalar joint stabilization is effective.

PURPOSE: The aim of this study was to assess the biomechanical effects of subtalar ligament injury and reconstruction on stability of the subtalar joint in all three spatial planes. METHODS: Fifteen fresh frozen cadaveric legs were used, with transfixed tibiotalar joints to isolate motion to the subtalar joint. An arthrometer fixed to the lateral aspect of the calcaneus measured angular displacement in all three spatial planes on the inversion and eversion stress tests. Stress manoeuvres were tested with the intact joint, and then repeated after sequentially sectioning the inferior extensor retinaculum (IER), cervical ligament (CL), interosseous talocalcaneal ligament (ITCL), arthroscopic graft reconstruction of the ITCL, and sectioning of the calcaneo-fibular ligament (CFL). RESULTS: Sectioning the ITCL significantly increased angular displacement upon inversion and eversion in the coronal and sagittal planes. Reconstruction of the ITCL significantly improved angular stability against eversion in the axial and sagittal planes, and against inversion in the axial and coronal planes, at the zero time point after reconstruction. After sectioning the CFL, resistance to eversion decreased significantly in all three planes. CONCLUSION: Progressive injury of ligamentous stabilisers, particularly the ITCL, led to increasing angular displacement of the subtalar joint measured with the inversion and eversion stress tests, used in clinical practice. Reconstruction of the ITCL using tendon graft significantly stabilised the subtalar joint in the axial and sagittal planes against eversion and in the axial and coronal planes against inversion, immediately after surgery.

Results of Anatomical Arthroscopic Repair of Anterior Talofibular Ligament in Chronic Lateral Ankle Instability Patients.

BACKGROUND: To assess the clinical and functional outcomes of all-inside arthroscopic anatomical repair of anterior talofibular ligament (ATFL) for management of chronic lateral ankle instability (CLAI) in a considerable number of patients during medium-term follow-up. METHODS: A retrospective analytic study was performed on 100 patients with CLAI who presented between August 2015 and July 2020 (average age: 32.9 years; range: 16-54 years). All-inside arthroscopic ATFL direct repair was performed in all patients through 2 portals only with fixation using 2 knotless anchors. Associated intraarticular lesions were treated in the same procedure. Outcomes were assessed with pre- and postoperative visual analog scale (VAS), the ankle-hindfoot score of the American Orthopaedic Foot & Ankle Society (AOFAS), and the Karlsson Ankle Functional Score (KAFS). RESULTS: All patients were followed for 24-48 months. At the final follow-up, ankle pain had improved significantly. Both the ankle anterior drawer test and the ankle varus stress tests were negative. There was no loss of ankle range of motion compared with preoperative measures, and all patients returned to normal gait. The mean VAS score decreased to 0.39 ± 0.63, the AOFAS score increased to 95.17 ± 4.7, and the KAFS score increased to 95 ± 4.07. All the follow-up indexes significantly improved compared to those before surgery. CONCLUSION: At minimum 24-month follow-up, the all-inside arthroscopic ATFL repair used to treat CLAI was found to restore ankle stability and yield good clinical outcomes with a relatively low complication rate. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Anatomic Arthroscopic Graft Reconstruction of the Interosseous Talocalcaneal Ligament for Subtalar Instability.

Instabilities of the subtalar joint are commonly overlooked or mismanaged, and chronic instability is a debilitating condition leading to premature joint degeneration. Several methods of treatment have been described, mainly screw fixation, arthrodesis, or ligament reconstruction. Most studies describe open methods for ligament reconstruction. We describe an original technique for "all-inside" arthroscopic graft reconstruction of the interosseous talocalcaneal ligament for subtalar instability.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain.

A common variant in the MTNR1b gene is associated with increased risk of impaired fasting glucose (IFG) in youth with obesity.

OBJECTIVE: To explore the role of MTNR1B rs10830963 and G6PC2 rs560887 variants in the pathogenesis of impaired fasting glucose (IFG) in obese adolescents. METHODS: A total of 346 Caucasians, 218 African-Americans, and 217 Hispanics obese children and adolescents underwent an oral glucose tolerance test (OGTT) and 518 underwent the evaluation of insulin secretion by the oral minimal model (OMM). Also, 274 subjects underwent a second OGTT after 3.0 ± 2.1 years. RESULTS: The MTNR1B rs10830963 variant was associated with higher fasting glucose levels and lower dynamic beta-cell response in Caucasians and Hispanics (P < 0.05) and conferred an increased risk of showing IFG to Caucasians (P = 0.05), African-Americans (P = 0.0066), and Hispanics (P = 0.024). Despite the association between the G6PC2 rs560887 and higher fasting glucose levels (P < 0.05), there was no association between this variant and IFG at baseline or at follow-up (all P > 0.10). CONCLUSIONS: It has been shown for the first time in obese youth that the MTNR1B variant is associated with an increased risk of IFG.

Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance.

OBJECTIVE: Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. METHODS: Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. RESULTS: Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. CONCLUSIONS: Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating.

Glucose effectiveness in obese children: relation to degree of obesity and dysglycemia.

OBJECTIVE: Impaired glucose effectiveness (GE) plays a role in the deterioration of glucose metabolism. Our aim was to validate a surrogate of GE derived from an oral glucose tolerance test (OGTT) and to assess the impact of degrees of obesity and of glucose tolerance on it. RESEARCH DESIGN AND METHODS: The OGTT-derived surrogate of GE (oGE) was validated in obese adolescents who underwent an OGTT and an intravenous glucose tolerance test (IVGTT). We then evaluated anthropometric determinants of the oGE and its impact on the dynamics of glucose tolerance in a cohort of children with varying degrees of obesity. RESULTS: The correlation of oGE and IVGTT-derived GE in 98 obese adolescents was r = 0.35 (P < 0.001) as a whole and r = 0.51 (P < 0.001) in subjects with normal glucose tolerance. In a cohort of 1,418 children, the adjusted GE was associated with increasing obesity (P < 0.001 for each category of obesity). Quartiles of oGE and the oral disposition index were associated with 2-h glucose levels (P < 0.001 for both). Among 421 nondiabetic obese subjects (276 subjects with normal glucose tolerance/145 subjects with impaired glucose tolerance who repeated their OGTT after a mean time of 28 ± 16 months), oGE changes were tightly associated with weight (r = 0.83, P < 0.001) and waist circumference changes (r = 0.67, P < 0.001). Baseline oGE and changes in oGE over time emerged as significant predictors of the change in 2-h glucose levels (standardized B = -0.76 and B = -0.98 respectively, P < 0.001 for both). CONCLUSIONS: The oGE is associated with the degree of and changes in weight and waist circumference and is an independent predictor of glucose tolerance dynamics.

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.

Co-occurrence of risk alleles in or near genes modulating insulin secretion predisposes obese youth to prediabetes.

OBJECTIVE: Paralleling the rise of pediatric obesity, the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) is increasing among youth. In this study, we asked whether the co-occurrence of risk alleles in or near five genes modulating insulin secretion (TCF7L2 rs7903146, IGF2BP2 rs4402960, CDKAL1 rs7754840, HHEX rs1111875, and HNF1A rs1169288) is associated with a higher risk of IGT/T2D in obese children and adolescents. RESEARCH DESIGN AND METHODS: We studied 714 obese subjects (290 boys and 424 girls; mean age 13.6 ± 3.1 years; mean z score BMI 2.2 ± 0.4) and evaluated the insulin secretion by using the oral minimal model and, in a subgroup of 37 subjects, the hyperglycemic clamp. Also, 203 subjects were followed up for a mean of 2.1 years. RESULTS: We observed that the increase of risk alleles was associated with a progressive worsening of insulin secretion (P < 0.001) mainly due to an impairment of the dynamic phase of insulin secretion (P = 0.004); the higher the number of the risk alleles, the higher the chance of progression from normal glucose tolerance (NGT) to IGT/T2D (P = 0.022). Also, for those who were IGT at baseline, a higher risk score was associated with a lower odds to revert to NGT (P = 0.026). CONCLUSIONS: Obese children and adolescents developing IGT/T2D have a higher genetic predisposition than those who do not show these diseases, and this predisposition is mainly related to gene variants modulating the early phase of insulin secretion. Although these data are very interesting, they need to be replicated in other cohorts.

Polycystic ovary syndrome in adolescence: impaired glucose tolerance occurs across the spectrum of BMI.

CONTEXT: Polycystic ovary syndrome (PCOS) is a chronic condition with metabolic manifestations spanning the reproductive years. OBJECTIVE: We sought to examine glucose metabolism, irrespective of the presence of obesity in a cohort of adolescent girls with PCOS. DESIGN: One hundred adolescents were assessed for PCOS in a multi-specialty adolescent PCOS program. PCOS was diagnosed by Androgen Excess Society criteria. Oral glucose tolerance testing (OGTT), homeostatic model assessment of insulin resistance, and androgen and lipid profiles were performed for those meeting criteria. RESULTS: Sixty-six adolescents (mean age 15.8 ± 0.2 yrs, range 13.0-18.6) had confirmed PCOS, and were eligible for inclusion in our analysis. Abnormal glucose metabolism was present in 12 of 66 (18.2%) subjects: 2 (3.0%) impaired fasting glucose, 10 (15.2%) impaired glucose tolerance (IGT), and 1 (1.5%) type 2 diabetes. IGT was the most common abnormality, occurring with equal frequency in obese (OB, mean body mass index (BMI) 36.9 ± 0.8 kg/m(2) ) and non-obese (NOB, mean BMI 24.5 ± 0.6 kg/m(2) ) adolescents (p = 0.3). In a subgroup analysis, NOB adolescents with IGT (NOB-IGT) had similar mean 2-h insulin, high density lipoprotein, C-reactive protein, and testosterone levels to the OB cohort despite marked differences in BMI (p < 0.001) and % body fat (p = 0.002). However, the NOB-IGT group had a lower mean fasting insulin level than the OB cohort (p = 0.04). CONCLUSION: Abnormal glucose metabolism is highly prevalent in adolescents with PCOS. In particular, IGT occurs across the spectrum of BMI. A screening OGTT should be considered for adolescents diagnosed with PCOS, independently of their BMI.

Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth.

OBJECTIVE: We used fast-gradient magnetic resonance imaging (MRI) to determine the longitudinal associations between the hepatic fat content (HFF), glucose homeostasis, and a biomarker of hepatocellular apoptosis in obese youth. RESEARCH DESIGN AND METHODS: Baseline and longitudinal liver and abdominal MRI were performed with an oral glucose tolerance test in 76 obese youth followed for an average of 1.9 years. Cytokeratin-18 (CK-18) was measured at baseline and follow-up as a biomarker of hepatic apoptosis. The relationship between baseline HFF and metabolic parameters and circulating levels of CK-18 at follow-up were assessed using a bivariate correlation. RESULTS: At baseline, 38% had hepatic steatosis based on %HFF ≥5.5% with alterations in indices of insulin sensitivity and secretion. At follow-up, BMI increased in both groups and baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group. Baseline HFF correlated with 2-h glucose (r = 0.38, P = 0.001), whole-body insulin sensitivity (r = -0.405, P = 0.001), adiponectin (r = -0.44, P < 0.001), CK-18 levels, (r = 0.63, P < 0.001), and disposition index (r = -0.272, P = 0.021) at follow-up. In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity. CONCLUSIONS: In obese youth, the phenotype of MRI-measured hepatic steatosis is persistent. Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.

Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance.

OBJECTIVE: Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT). METHODS: We therefore conducted a 4-month double-blind clinical trial in 28 obese [mean body mass index (BMI): 40.3 +/- 5.7 kg/m(2)], insulin-resistant [homeostasis model assessment - insulin resistance: 7.6 +/- 2.8 and whole body insulin sensitivity index (WBISI): 1.5 +/- 0.7] adolescents (age 15.0 +/- 1.3 yr) randomized to MET (n = 15, dose 1500 mg daily) or placebo (n = 13). RESULTS: The treatment with MET was well tolerated. MET treatment was associated with a decreased BMI (p = 0.02) as well as with a reduction in subcutaneous fat (p = 0.03), particularly the deep subcutaneous fat (p = 0.04) as assessed by magnetic resonance imaging. Postintervention, the MET group had a 35% improvement in insulin sensitivity (WBISI) compared with the placebo group (p = 0.008). However, significance was lost with adjustments for differences in baseline insulin sensitivity (p = 0.09). While there was no change in inflammatory cytokines or lipid parameters, cardiovascular function as assessed by heart rate recovery after exercise improved with MET and worsened in placebo (p = 0.03). CONCLUSION: Short-term use of MET is well tolerated by obese children with NGT and has a beneficial effect on BMI and autonomic control of the heart as well as a trend toward improved insulin sensitivity. Thus, long-term treatment with MET may provide a means to ameliorate the cardio-metabolic consequences of adolescent obesity.