Metformin effectiveness and safety in the management of overweight/obese nondiabetic children and adolescents: metabolic benefits of the continuous exposure to metformin at 12 and 24 months

2016 ◽  
Vol 29 (5) ◽  
Author(s):  
Pedro Marques ◽  
Catarina Limbert ◽  
Laura Oliveira ◽  
Maria Inês Santos ◽  
Lurdes Lopes
Keyword(s):  
Insulin Resistance ◽  
Adverse Effects ◽  
Children And Adolescents ◽  
Lifestyle Intervention ◽  
Resistance Index ◽  
Continuous Exposure ◽  
Model Assessment ◽  
Obesity Prevalence ◽  
Insulin Resistant ◽  
Clinical Records

Abstract Introduction: Childhood obesity prevalence is rising and new therapeutical approaches are needed. Metformin is likely beneficial in obese and/or insulin-resistant children/adolescents, but its role in this setting is still unclear. We aimed to evaluate the effectiveness, in terms of weight loss and insulin resistance, and safety of metformin in nondiabetic overweight/obese children and adolescents. Methods: We retrospectively reviewed clinical records of 78 nondiabetic obese/overweight [body mass index (BMI)≥85th/95th percentile for age and sex] children and adolescents. Anthropometric and metabolic outcomes of 39 patients treated with metformin (mean daily dose: 1.3±0.5 g) were analyzed and compared to lifestyle intervention alone at different follow-up times (12 and 24 months). Results: The mean age of the 78 patients was 13.3 years, 41 were females and mean BMI and BMI-SDS were 32.8 kg/m2 and 3.1, respectively. There was a decrease in mean BMI-SDS within each treatment group in all periods, except at 24 months for lifestyle intervention. However, the change in BMI-SDS was not significantly superior in the metformin group when compared to lifestyle intervention. Metformin had greater effectiveness over lifestyle intervention alone in reducing fasting insulin levels and homeostasis model assessment for insulin-resistance index (HOMA-IR) at both 12 and 24 months. Five patients had gastrointestinal adverse effects (12.8%), four requiring dose reduction, but metformin could be resumed in all. Conclusion: Metformin for nondiabetic obese/overweight children and adolescents resulted in a noteworthy insulin resistance improvement, without significant BMI advantage when compared to lifestyle intervention. Metformin metabolic and anthropometric effects appear to be beneficial up to 24 months, without relevant adverse effects, highlighting its potential long-term benefits.

scholarly journals Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity

Life ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 127 ◽  
Author(s):  
Federica Vinciguerra ◽  
Andrea Tumminia ◽  
Roberto Baratta ◽  
Alfredo Ferro ◽  
Salvatore Alaimo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Children And Adolescents ◽  
Metabolic Phenotype ◽  
Sensitivity Index ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Insulin Resistant ◽  
Metabolically Healthy

Obesity represents a major risk factor for metabolic disorders, but some individuals, “metabolically healthy” (MHO), show less clinical evidence of these complications, in contrast to “metabolically unhealthy” (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment–insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

scholarly journals Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

2018 ◽  
Vol 6 (3) ◽  
pp. 511-518 ◽  
Author(s):  
Marko Kostovski ◽  
Viktor Simeonovski ◽  
Kristina Mironska ◽  
Velibor Tasic ◽  
Zoran Gucev
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Plasma Glucose ◽  
Metabolic Profile ◽  
Total Serum ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Obese Children ◽  
Insulin Resistant ◽  
Study Results

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases.AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents.SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged     4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included.  We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test        (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders.RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05).CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

Biochemical predictors of metabolically unhealthy obesity in children and adolescents

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ah Young Cho ◽  
Jung Gi Roh ◽  
Young Suk Shim ◽  
Hae Sang Lee ◽  
Jin Soon Hwang
Keyword(s):  
Insulin Resistance ◽  
Uric Acid ◽  
Children And Adolescents ◽  
Resistance Index ◽  
Serum Levels ◽  
Tolerance Test ◽  
Binary Logistic Regression Analysis ◽  
Oral Glucose ◽  
Model Assessment ◽  
Metabolically Unhealthy Obesity

Abstract Background Children and adolescents with obesity can now be classified according to metabolic profile, as those with metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUO). We aimed to determine the prevalence of MUO and identify its biochemical predictors in pediatric patients with obesity. Methods We evaluated the medical records of 187 boys and girls with obesity. The children were divided into MHO and MUO groups, and anthropometric and biochemical parameters were assessed. Oral glucose tolerance test (OGTT) was used to identify impaired glucose regulation and hyperinsulinism, and binary logistic regression analysis was used to determine predictors of MUO in children with obesity. Results Of the 187 children, MUO was found in 71.7% (n=134) and MHO in 28.3% (n=53); those in the MHO group were younger than those in the MUO group. Blood pressure, triglyceride, total cholesterol, and uric acid levels were significantly higher in the MUO group than in the MHO group. Further, the MUO group exhibited a significantly higher level of insulin resistance (p<0.05) than the MHO group. Serum levels of uric acid and homeostasis model assessment of insulin resistance index (HOMA-IR) were confirmed as biochemical predictors of the MUO phenotype in children with obesity. Conclusions The ratio of MUO in children with obesity was relatively high; further, serum levels of uric acid and HOMA-IR can be used as biochemical predictors of MUO.

scholarly journals Correlation of HOMA-IR with BMI-for-age percentile in children and adolescents from the Soconusco region of Chiapas, Mexico

2019 ◽  
Vol 67 (4) ◽  
pp. 447-450
Author(s):  
Consuelo Chang-Rueda ◽  
Ana Cañas-Urbina ◽  
Karina Trujillo-Murillo ◽  
Marisol Espinoza-Ruiz ◽  
Jorge Feliciano-Díaz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Cross Sectional Study ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
The Body ◽  
Model Assessment ◽  
Obesity Prevalence ◽  
Cross Sectional ◽  
Homeostatic Model Assessment

Introduction: Insulin resistance (IR) is a major risk factor for developing diabetes mellitus type 2 and cardiovascular diseases. In pediatrics, morbidity and mortality associated with these diseases highlights the diagnostic importance of IR for primary care.Objective: To determine Homeostatic Model Assessment Insulin Resistance (HOMA-IR) values and their correlation with BMI-for-age percentile in children and adolescents of the Soconusco region of Chiapas, Mexico.Materials and methods: Cross-sectional study. Overweight and obesity prevalence was determined based on the Body Mass Index (BMI) percentile of 112 children (5-19 years old). Glucose and fasting insulin values were quantified and used for estimation of HOMA-IR.Results: The combined prevalence of obesity and overweight was 66%, with insulin (p=0.010) and HOMA-IR (p=0.015) values higher than those of the normal weight group. The HOMA-IR values correlated positively with age (r=0.636), weight (r=0.569), height (r=0.578) and BMI percentile (r=0.198).Conclusions: In the study population, HOMA-IR has a moderately significant correlation with an increase in BMI percentile.

scholarly journals Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity

2016 ◽  
Vol 47 (6) ◽  
pp. 1718-1726 ◽  
Author(s):  
Oscar L. Llanos ◽  
Panagis Galiatsatos ◽  
Edmarie Guzmán-Vélez ◽  
Susheel P. Patil ◽  
Philip L. Smith ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fasting Glucose ◽  
Sleep Apnoea ◽  
Model Assessment ◽  
Rapid Eye Movement Sleep ◽  
Homeostasis Model Assessment ◽  
Tonsillar Hypertrophy ◽  
Insulin Resistant ◽  
Bariatric Patients ◽  
Respiratory Disturbance

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea.90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) >10 events·h−1, diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, Pcritp) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to Pcritp.Groups with high Pcritp compared to low Pcritp did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high Pcritp group compared to the low Pcritp group (p<0.02). Pcritp correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104–0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196–0.835; p=0.021).Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.

scholarly journals The association between obesity and fluid intelligence impairment is mediated by chronic low-grade inflammation

2014 ◽  
Vol 112 (10) ◽  
pp. 1724-1734 ◽  
Author(s):  
Eirini C. Spyridaki ◽  
Panagiotis Simos ◽  
Pavlina D. Avgoustinaki ◽  
Eirini Dermitzaki ◽  
Maria Venihaki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fluid Intelligence ◽  
Leisure Time Physical Activity ◽  
Resistance Index ◽  
Low Grade ◽  
Model Assessment ◽  
Inverse Association ◽  
Published Evidence ◽  
Activity Measurements ◽  
Low Grade Inflammation

Published evidence suggests that obesity impairs cognition. Development of chronic low-grade inflammation (CLGI) represents the earliest consequence of obesity. The present study investigated the association between obesity and fluid intelligence impairment and assessed the potential mediating role of CLGI and psychological (depression/anxiety symptoms), lifestyle (exercise) and physiological (metabolic dysfunction indices) factors in this association. Clinically healthy participants (n 188), grouped as per BMI, underwent cognitive (General Ability Measure for Adults), psychological (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and activity (Godin leisure-time physical activity) measurements. Biochemical parameters included the following: (a) indices of CLGI (high-sensitivity C-reactive protein, erythrocyte sedimentation rate and fibrinogen); (b) insulin resistance (Homeostasis Model Assessment of Insulin Resistance index); (c) adiposity (plasma adiponectin). An inverse association between elevated BMI and fluid intelligence was observed, with obese participants displaying significantly poorer performance compared with age-matched normal-weight peers. Structural equation modelling results were consistent with a negative impact of obesity on cognition that was mediated by CLGI. The results of the present study support the hypothesis that reduced general cognitive ability is associated with obesity, an adverse effect mainly mediated by obesity-associated activation of innate immunity.

scholarly journals Endotrophin as a novel marker in PCOS and its relation with other adipokines and metabolic parameters: a pilot study

2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Total Testosterone ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Ovary Syndrome ◽  
Significant Difference

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.

scholarly journals Clinical outcome of metformin treatment in patients of acanthosis nigricans with insulin resistance

2017 ◽  
Vol 10 (1) ◽  
pp. 18-23
Author(s):  
Tahmina Akter ◽  
Md. Reza Bin Zaid ◽  
Zeenat Farzana Rahman ◽  
M. Abu Sayeed
Keyword(s):  
Insulin Resistance ◽  
Acanthosis Nigricans ◽  
Controlled Trial ◽  
Treatment Modalities ◽  
Therapeutic Effects ◽  
Model Assessment ◽  
Metformin Therapy ◽  
Insulin Resistant ◽  
Homeostatic Model Assessment ◽  
Anatomic Locations

Background: Acanthosis nigricans (AN) is known to be associated with obesity, insulin resistance (IR) and other systemic morbid conditions. Proper treatment modalities of AN has not been established yet. Metformin may have some therapeutic effects on AN by reducing IR. Objective of the study was to examine the effect of metformin on AN in insulin resistant cases.Methodology and Results: This prospective, controlled trial was conducted in Dermatology OPD of BIRDEM General Hospital, Dhaka from September 2012 to August 2013. All the participants of the study had clinical presentation of AN on different anatomic locations such as neck, axilla, elbow, knuckle and knee and biochemical evidence of IR. Participants were of either sex with age ranging from 18 to 80 years. Any case who had contraindications to metformin therapy were excluded. Severity of AN was examined and assessed by a quantitative scale for measuring acanthosis nigricans. After detecting IR by Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), cases and controls were selected by random sampling method. Randomization was done for metformin in ratio of 2:1. Every third patient was a control. Forty study participants were assigned to receive tablet metformin 500mg thrice daily after meal for three months and twenty control participants were continued on their existing therapy. To maintain a static metabolic status, patients were allowed to remain with their previous diet and lifestyle habit. After 3 months of metformin therapy, improvement was assessed and was compared with control group.Mean age of the participants in case of male: 19.75±2.36 and in case of female: 26.58±9.38, M:F= 1:14, BMI of male: 32.15±4.15 and female: 33.18± 8.05. Mean baseline neck severity score of AN: 3.57 ± 0.78 and after metformin therapy: 2.65 ± 1.02, t-test value: 4.53. Baseline neck texture score of AN: 1.87±0.80, after metformin therapy: 1.25 ± 0.86, ttest value: 3.30. Baseline AN on axilla: 3.05 ± 0.94, after metformin therapy: 2.10 ± 0.98, ttest value: 4.56. Significant improvement of AN was observed clinically on neck and axilla (P<0.005) when compared with control. However, in case of AN on knuckle, elbow and knee, improvement rates were not statistically significant. No side-effect except nausea in 4 patients was reported during study period.Conclusion: Metformin therapy for AN with IR had a significant beneficial effect clinically and was safe and well-tolerated. The effect was more pronounced in neck and axilla.IMC J Med Sci 2016; 10(1): 18-23

scholarly journals Visfatin levels in non-obese, obese, and insulin resistant adolescents

2017 ◽  
Vol 56 (5) ◽  
pp. 291
Author(s):  
Indra Ihsan ◽  
Eka Agustia Rini ◽  
Rismawati Yaswir
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Serum Insulin ◽  
Enzyme Linked Immunosorbent Assay ◽  
Model Assessment ◽  
Fasting Serum ◽  
Obese Adolescents ◽  
Insulin Resistant ◽  
Resistant Group ◽  
Visfatin Level

Background Adipose tissue is not merely a site for energy storage, but is also the largest endocrine organ, secreting various adipocytokines. Plasma visfatin, an adipocytokine predominantly secreted from visceral adipose tissue, has insulin-mimetic effects, and has been closely linked to insulin resistance.Objective To compare plasma visfatin levels between obese and non-obese adolescents, as well as between obese adolecents with and without insulin resistance.Methods This cross-sectional study was conducted in students who attended three senior high schools in Padang. Subjects comprised 28 obese and 28 non-obese adolescents. The age of the subjects ranged from 14-18 years. Obesity criteria were based on body mass index (BMI) measurements. Fasting serum glucose level was measured by glucose hexokinase photometry and serum insulin was measured by chemiluminesence immunoassay. Plasma visfatin was measured by enzyme-linked immunosorbent assay (ELISA). The insulin resistance index was estimated from fasting serum insulin and glucose levels using the homeostatic model assessment for insulin resistance (HOMA-IR). Differences in the variables were tested using independent T-test and Mann-Whitney test, depending on the distribution of the variables.Results The mean plasma visfatin level was significantly higher in the obese than in the control group [2.55 (SD 1.54) vs. 1.61 (SD 0.64) ng/mL, respectively; (P=0.005)]. The insulin resistant group had significantly higher mean plasma visfatin level than the non-resistant group [3.61 (SD 1.59) vs. 1.96 (SD 1.18) ng/mL, respectively; (P=0.004)].Conclusion Obese adolescents with insulin resistance have signifcantly higher plasma visfatin levels compared to those without insulin resistance.

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