• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.sup1
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• pp.118-126
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• 2009

The incidence of childhood obesity has increased dramatically. Childhood obesity is an increasing health problem because of its strong associations with chronic health problems in children and adults. These health problems significantly contribute to the development of common chronic diseases in later life, including hypertension, type2 diabetes, hyperinsulinemia, coronary heart disease, and other psychological disorders. So it is an important issue to prevent and treat obesity during childhood and adolescent. Diet and exercise are the cornerstones of treatment for obesity and related complications. For obese children, some clinical trials have shown improvement with diet, exercise, and /or behavioral interventions. Promising interventions for high-risk individuals, such as bariatric surgery and novel pharmacological agents, also require rigorous assessment with attention to long-term patient important outcomes. There are various pharmacological approaches to the treatment of obesity in the adolescent population some of which have FDA approval. In the article we discuss pharmacological approaches to guide the treatment of obesity in the pediatric population, including risks of treatment, monitoring of potential side effects.

• Journal of Yeungnam Medical Science
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• v.14 no.1
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• pp.53-66
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• 1997

Insulin resistance is a prominent feature of diabetic state and has heterogeneous nature. However, the pathogenetic sequence of events leading to the emergence of the defect in insulin action remains controversial. It is well-known that prolonged hyperglycemia and hyperinsulinemia are one of the causes of development of insulin resistance, but both hyperglycemia and hyperinsulinemia stimulate glucose uptake in peripheral tissue. Therefore, it is hypothesized that insulin resistance may be generated by a kind of protective mechanism preventing cellular hypertrophy. In this study, to evaluate whether the acutely increased glucose uptake inhibits further glucose transport stimulated by insulin, insulin sensitivity was measured after preloaded glucose infusion for 2 hours at various conditions in rats. And also, to evaluate the mechanism of decreased insulin sensitivity, insulin receptor binding affinity and glucose transporter 4 (GLUT4) protein of plasma membrane of gastrocnemius muscle were assayed after hyperinsulinemic euglycemic clamp studies. Experimental animals were divided into five groups according to conditions of preloaded glucose infusion: group I, basal insulin ($14{\pm}1.9{\mu}U/ml$) and basal glucose ($75{\pm}0.7mg/dl$), by normal saline infusion; group II, normal insulin ($33{\pm}3.8{\mu}U/ml$) and hyperglycemia ($207{\pm}6.3mg/dl$), by somatostatin and glucose infusion; group III, hyperinsulinemia ($134{\pm}34.8{\mu}U/ml$) and hyperglycemia ($204{\pm}4.6mg/dl$), by glucose infusion; group IV, supramaximal insulin ($5006{\pm}396.1{\mu}U/ml$) and euglycemia ($l00{\pm}2.2mg/dl$), by insulin and glucose infusion; group V, supramaximal insulin ($4813{\pm}687.9{\mu}U/ml$) and hyperglycemia ($233{\pm}3.1mg/dl$), by insulin and glucose infusion. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique. The amounts of preloaded glucose infusion(gm/kg) were $1.88{\pm}0.151$ in group II, $2.69{\pm}0.239$ in group III, $3.54{\pm}0.198$ in group IV, and $4.32{\pm}0.621$ in group V. Disappearance rates of glucose (Rd, mg/kg/min) at steady state of hyperinsulinemic euglycemic clamp studies were $16.9{\pm}3.88$ in group I, $13.5{\pm}1.05$ in group II, $11.2{\pm}1.17$ in group III, $13.2{\pm}2.05$ in group IV, and $10.4{\pm}1.01$ in group V. A negative correlation was observed between amount of preloaded glucose and Rd (r=-0.701, p<0.001) when all studies were combined. Insulin receptor binding affinity and content of GLUT4 were not significantly different in all experimental groups. These results suggest that increased glucose uptake may inhibit further glucose transport and lead to decreased insulin sensitivity.

• Clinical and Experimental Pediatrics
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• v.45 no.6
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• pp.764-772
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• 2002

Purpose : Obesity is closely related to insulin resistance, compensatory hyperinsulinemia and dyslipidemia in adults. We identified the effect of obesity measured by BMI and insulin resistance on dyslipidemia in children and adolescents. Methods : The fasting serum insulin, glucose, total cholesterol, triglyceride, HDL- and LDL-cholesterol were measured and insulin resistance(HOMA-IR) was calculated in 35 children with simple obesity(age :$10.6{\pm}2.8$ years; male 20, female 15; BMI : $27.1{\pm}5.4kg/m^2$). Results : The hypertriglyceridemia(37%), hyperinsulinemia(54%) and HDL-hypocholesterolemia(5.7%) were observed. HOMA-IR was well expressed by fasting insulin. As BMI increased, there was a statistically significant increase in insulin resistance and insulin level in both sexes. BMI was not related with lipid profile in both sexes. Triglyceride was correlated with only insulin level and insulin resistance index in boys. In girls, there was no correlation between triglyceride, HDL-cholesterol and insulin(insulin resistance). Conclusion : These results suggest that hypertriglyceridemia was dependent on insulin resistance in pre-adult males. Monitoring of insulin resistance and those risk factors known to become a part of insulin resistance syndrome should become part of routine medical care for obese children.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.11 no.2
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• pp.150-159
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• 2008

Purpose: To assess the relationship between lifestyle and metabolic syndrome in obese children and adolescents. Methods: We retrospectively reviewed the medical records and laboratory results of 109 subjects (7~15 years of age) who visited our pediatric obesity clinic between January 2004 and December 2007. They completed the parent- and self-report questionnaire developed by the Committee on Nutrition of the Korean Pediatric Society to assess lifestyle. The metabolic syndrome was defined as having 3 or more of the following metabolic risk factors: obesity, hypertension, serum triglycerides ${\geq}$110 mg/dL, HDL-cholesterol ${\leq}$40 mg/dL, fasting glucose ${\geq}$110 mg/dL, and insulin ${\geq}20{\mu}IU/mL$. Results: All subjects had at least 1 risk factor (obesity). Sixty-three percent of subjects had 2 or more risk factors, 32% of subjects had 3 or more risk factors, and 10% had 4 or more metabolic risk factors. Hypertriglyceridemia (36%), hypertension (32%), hyperinsulinemia (24%), and HDL-hypocholesterolemia (20%) were observed. Fasting blood glucose levels were normal in all subjects. Hypertension was significantly associated with an unbalanced diet and hyperinsulinemia was significantly associated with parental obesity (p<0.05). Those who ate after 8 PM were at a risk of hypertension (odds ratio, 2.5; 95% CI, 1.0~6.1). Those who did not have a preference for exercise were at a risk of hyperinsulinemia (odds ratio, 10.4; 95% CI, 2~54.1). Those who watched TV for ${\geq}$3 hours/day were at a risk of metabolic syndrome (odds ratio, 4.8; 95% CI, 1.2∼18.8). Conclusion: Lifestyle, such as eating late, no preference for exercise, and TV watching ${\geq}$3 hours/day, were related to metabolic syndrome in obese children and adolescents.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.1
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• pp.67-76
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• 2002

Objective: To assess the difference of baseline hormonal status and pathophysio logy, and confirm the risk factors for long term complication according to Body Mass Index in women with polycystic ovary syndrome. Materials and Methods: Serum level of LH, FSH, Estradiol, Prolactin, Testosterone, DHEA-S, fasting insulin were measured and 100 gm oral glucose tolerance test and endometrial biopsy were performed in total 75 chronic anovulation patients and 20 normal cycling infertility patients. 95 evaluated patients were divided into 3 groups including patients with chronic anovulation having BMI below 25, BMI beyond 25.1, normal cycling infertility patients, Group 1 (n=39), Group 2 (n=36), Group 3 (n=20), respectively. Statistical analysis was performed respect to relationship between BMI and measured hormone level, sum of glucose level during 100 gm OGTT, insulin resistance using t-test, ANOVA test, Post Hoc test, Mann-Whitney test. p<0.05 was considered as statistically significant. Results: Serum LH level and LH/FSH ratio was significantly higher in Group 1, compared than Group 2 or 3 (p<0.05), BMI and LH, LH/FSH ratio was negatively correlated (r=-0.351, r=-0.318). There was no significant difference according to BMI in FSH, testosterone, estradiol, prolactin, DHEA-S level. Fasting insulin and sum of glucose level during 100 gm OGTT were significantly higher in Group 2 compared than Group 1 or Group 3 (p<0.05), there was no significant difference between Group 1 and Group 3. Insulin resistance was more frequently identified in Group 2 compared than Group 1 (p=0.001). Conclusions: BMI and LH, LH/FSH ratio were negatively correlated, so clinical significance of LH, LH/FSH ratio in diagnosis of PCOS may be attenuated by increasing body weight. Overweight patients with chronic anovulation may be the risk group for developing insulin resistance, hyperinsulinemia, glucose intolerance, later type 2 DM. Hyperinsulinemia may operate mainly in overweight chronic anovulation patients in development of hyperandrogenism.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.1-13
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• 2012

Metabolic syndrome has become quite prevalent within our society. Over the past two decades, the prevalence of metabolic syndrome has sharply increased worldwide and it has become a major public health problem in several countries. It is associated with the global epidemic of obesity and diabetes mellitus and imposes numerous cardiovascular risks. Prostate cancer is the second most common cancer among men, surpassed only by non-melanoma skin cancer. A considerable body of evidence exists suggesting that some components of the metabolic syndrome have been associated with the risk of prostate cancer. These components include obesity, an abdominal fat distribution, and hyperinsulinemia. Androgen deprivation therapy (ADT) is the most widely used therapeutic modality in prostate cancer. It changed the body composition and lipid profile of men with prostate cancer. Androgen deficiency is associated with increased levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, increased production of proinflammatory factors, and increased thickness of the arterial wall and contributes to endothelial dysfunction. The aim of this review is to evaluate the association between metabolic syndrome and prostate cancer and to discuss the implications of androgen deficiency in men with cardiovascular risk factors. A comprehensive literature search was carried out with the use of PubMed from 1980 through 2011, and relevant articles pertinent to metabolic syndrome and prostate cancer are evaluated and discussed.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.185-197
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• 2004

Type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. In vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes (6). To explore the mechanism underlying this effect, we have used the 3T3-Ll adipocytes as a cell type which would represent the periphery, in vivo. Exposure of 3T3-Ll adipocytes to chronic insulin leads to the a 50% loss of insulin-stimulated glucose uptake. Chronic exposure to fibroin blocked, in part, the response to chronic insulin but also increased the sensitivity of control cells to the acute action of insulin. The later effect was most robust at physiological concentrations of insulin. Fibroin did not prevent the insulin-induced down-regulation of the insulin receptor or the tyrosine kinase activity associated with the receptor. Further, fibroin had no affect on the loss in activity of the insulin-sensitive down-stream kinase, Akt. Interestingly, fibroin accelerated glucose metabolism and glycogen turnover independent of insulin action. In addition, fibroin up-regulated GLUT1 which increased its expression at the cell surface and caused the redistribution of GLUT4 to the plasma membrane. Together, these later effects would lead to an improvement in hyperglycemia in vivo which would in turn reduce the need for insulin.

• CELLMED
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• v.4 no.1
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• pp.7.1-7.8
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• 2014

Metabolic effects of ten daily doses of standardized extract of Andrographis paniculata leaves (AP) rich in andrographolide were evaluated in a rat model of type-2 diabetes and in diet induced obese rats. AP was administered per-orally as suspension in 0.3% carboxymethylcellulose at doses of 50, 100 and 200 mg/kg/day for 10 consecutive days. Blood glucose, insulin and lipid profile of rats were measured by using enzyme kits. In addition, effects of such treatments on anti-oxidant enzymes activity and histopathological changes in various organs of diabetic rats were assessed. AP treatments reversed body weight losses and increased plasma insulin level in diabetic rats. The anti-oxidant enzymes activity became normal and histopathological changes observed in pancreas, liver, kidney and spleen of diabetic animals were less severe in extract treated groups. On the other hand, hyperinsulinemia and increased body weight gains observed in high fat or fructose fed rats were less severe in the extract treated groups. These observations revealed therapeutic potentials of the extract for treatments of diabesity associated metabolic disorders, and suggest that the effects of the extract on insulin homeostasis depend on the metabolic status of animals. Activation of cytoprotective mechanisms could be involved in its mode of action.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.3
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• pp.209-214
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• 2002

Objective : To analyze the clinical characteristics of obese infertile women. Material and Method: Height, weight, body mass index, menstrual pattern, glucose, insulin, glucose/insulin ratio, dehydroepiandrosterone sulfate (DHEA-S), testosterone, free testosterone and plasminogen activator inhibitor (PAI-1) of 15 obese infertile women were tested. Results: Of 15 obese infertile women, the number of diabetes mellitus, hyperinsulinemia, and insulin resistance was 2 (13%), 2 (13%), 2 (13%), respectively. The incidence of increased DHEA-S, testosterone, and free testosterone was 7 (47%), 1 (7%), 6 (40%), respectively. Notably, all patients showed increased PAI-1. Conclusions: Obesity is associated with infertility as well as many kinds of health problems. Obesity is closely related to insulin resistance and it also causes hyperandrogenism. Increased PAI-1 is one of the important causes of thrombophilia. Consequently, in the workup of obese infertile patient, many aspects of health problems should be considered.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.116-120
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• 2016

Congenital hyperinsulinism (CHI) is a rare condition that can cause irreversible brain damage during the neonatal period owing to the associated hypoglycemia. Hypoglycemia in CHI occurs secondary to the dysregulation of insulin secretion. CHI has been established as a genetic disorder of islet-cell hyperplasia, associated with a mutation of the ABCC8 or KCNJ11 genes, which encode the sulfonylurea receptor 1 and the inward rectifying potassium channel (Kir6.2) subunit of the ATP-sensitive potassium channel, respectively. We report the case of a female newborn infant who presented with repetitive seizures and episodes of apnea after birth, because of hypoglycemia. Investigations revealed hypoglycemia with hyperinsulinemia, but no ketone bodies, and a low level of free fatty acids. High dose glucose infusion, enteral feeding, and medications could not maintain the patient's serum glucose level. Genetic testing revealed a new variation of ABCC8 mutation. Therefore, we report this case of CHI caused by a novel mutation of ABCC8 in a half-Korean newborn infant with diazoxide-unresponsive hyperinsulinemic hypoglycemia.