Decreased Circulating Levels of Spexin in Obese Children.

CONTEXT: Spexin is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in children. OBJECTIVE: The aim of the current study was to determine the potential role of Spexin in obese children and explore its relationships with various cardiometabolic risk factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study composed of 69 children (51 obese and 18 normal weight; age 15.3 ± 0.26 y). OUTCOME MEASURES: Spexin was measured using a specific enzyme-linked immunosorbent assay. Leptin, total and high-molecular-weight adiponectin, IL-6, high-sensitivity C-reactive protein, glucose, and insulin were also measured. Mann-Whitney U test, Pearson and Spearman rank correlations, logistic regression, and cluster analysis were used for the analysis and interpretation of the data. RESULTS: Spexin levels were significantly lower in obese vs normal-weight children, median(IQR) (0.33 ng/mL [0.27-0.44] vs 0.42 ng/mL [0.33-0.55]; P = .024), but did not correlate with other adipokines and/or insulin and glucose levels. Ordinal categorical variables of Spexin showed a strictly reverse association of obesity with the level of Spexin. Cluster analysis of Spexin and body mass index z score resulted in splitting the participants into normal-weight and obese-weight groups with high accuracy. CONCLUSIONS: Lower circulating levels of Spexin in obese children compared with their normal-weight counterparts and the ability to discriminate obese and normal-weight groups based on Spexin concentration enabled us to suggest a potential role for this novel peptide in childhood obesity. The clinical significance of these findings needs additional investigation.

Effects of fiber supplementation on glycemic excursions and incidence of hypoglycemia in children with type 1 diabetes.

BACKGROUND: Nutritional therapy is an important component of diabetes management. There is data to suggest that fiber content of foods may affect glycemic response. MATERIALS AND METHODS: 10 children, diagnosed with type 1 diabetes, participated. In the first phase of the study, children followed their usual meal plan. In the second phase, subjects followed the same meal plan except that fiber was added to the diet using a powder supplement (wheat dextrin). Data was collected using a continuous glucose monitoring device. The blood glucose excursion level following each meal was compared between the two phases of the study by fitting a repeated measures regression model. The incidence of hypoglycemia was also compared by fitting a logistic regression model. RESULTS: There was no difference in the mean blood glucose excursion after meals or the incidence of hypoglycemia between the two phases. There was a strong negative correlation between the amount of fiber supplemented and the mean maximum post-prandial blood sugar after the lunch and breakfast meals (Spearman rank correlation coefficient = -0.86 lunch and -0.76 breakfast). CONCLUSION: Our study did not show an overall decrease in glucose excursion or incidence of hypoglycemia with fiber supplementation. We did find a strong negative correlation between the amount of fiber added during the supplemental phase and the mean maximum post-prandial blood sugar after the lunch and breakfast meals. We speculate that different types of fiber may have different effects on blood glucose with wheat dextrin having a greater dampening effect.

Effect of vitamin D3 supplementation on serum 25(OH)D, lipids and markers of insulin resistance in obese adolescents: a prospective, randomized, placebo-controlled pilot trial.

BACKGROUND/AIMS: To determine the effect of vitamin D3 supplementation on 25-hydroxyvitamin D [25(OH)D], lipid profile and markers of insulin resistance in obese adolescents. METHODS: In this double-blind, randomized, placebo-controlled trial, 58 obese adolescents (n = 58; 12-18 years of age) received either vitamin D3 (2,000 IU/day) or placebo for 12 weeks. Total 25(OH)D, fasting plasma glucose, insulin and lipid profile were measured at baseline and following supplementation. RESULTS: The trial was completed by 44/58 enrolled participants. At the end of the 12 weeks, total serum 25(OH)D concentrations increased to a modest degree (median 6 ng/ml) in the vitamin D-supplemented group (p < 0.001). Supplementation showed no detectable changes in fasting plasma glucose, insulin, homeostatic model of assessment index (HOMA-IR), lipids and highly sensitive C-reactive protein. CONCLUSIONS: 12 weeks of vitamin D3 supplementation in obese adolescents with 2,000 IU once daily resulted in a modest increase in 25(OH)D concentration in obese adolescents, but did not affect the lipid profile and markers of insulin resistance and inflammation. Further studies with higher doses of vitamin D3 and/or longer duration of supplementation are needed to understand if vitamin D3 supplementation can impact lipid profiles and markers of insulin resistance and inflammation in obese children.

Temporal trends in the diagnosis and management of childhood obesity/overweight in primary care.

OBJECTIVE: To determine the temporal trends in diagnosis and management of pediatric overweight/obesity by primary care providers at a single medical center. PATIENTS: Children 2 to 18 years old undergoing a general medical examination during 3 calendar years (2003, 2006, and 2009). The number of visits for general medical examination were 6390 in 2003, 6646 in 2006, and 7408 in 2009. METHODS: We performed a retrospective review of the electronic medical records for weight related diagnostic and/or management terms and laboratory screening in children with body mass index at or greater than the 85th percentile (n = 1630 in 2003, 1495 in 2006, and 1730 in 2009). RESULTS: There was a significant increase in the diagnosis of obesity among obese children seen in 2009 (53.3%) compared with 2006 (36%, P < .001) and 2003 (24.3%, P < .001). Weight-related counseling was documented in a higher proportion of obese children in 2009 (49.4%) compared with 2006 (34.8%) and 2003 (26.6%). There was a significant increase in counseling regarding screen time in 2009 compared with 2006. A significant increase in screening for nonalcoholic fatty liver disease was also noted (30.5% in 2009 vs 21.9% in 2006, P = .018). CONCLUSIONS: There has been steady improvement in the rates of obesity diagnosis and obesity-related counseling by primary care providers. However, continued efforts to increase awareness of these issues are needed as nearly half of obese children remained undiagnosed and recommended laboratory screening for obesity-related comorbidities was performed in only a third of obese children.

Response to vitamin D3 supplementation in obese and non-obese Caucasian adolescents.

BACKGROUND/AIMS: Vitamin D deficiency is highly prevalent in obese children, and obese children tend to respond poorly to vitamin D supplementation. The objective of the study was to compare the response to vitamin D(3) supplementation (2,000 IU once daily for 12 weeks) between obese and non-obese Caucasian adolescents. METHODS: The study design was open label non-randomized. It was carried out at a single center. Eighteen obese adolescents (aged 12-18 years) and the same number of age-, gender- and season-matched non-obese adolescents received vitamin D(3) (2,000 IU/day) orally for 12 weeks. Total serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone, calcium and phosphorus were measured at baseline and at the end of the 12-week period. RESULTS: The mean baseline 25(OH)D level was higher in the non-obese compared to the obese subjects (mean 28.9 vs. 25.2 ng/ml; p = 0.029). The increment in 25(OH)D levels following vitamin D supplementation was significantly lower in the obese adolescents (mean change 5.8 vs. 9.8 ng/ml; p = 0.019). CONCLUSIONS: Higher doses of vitamin D are required to treat vitamin D deficiency in obese adolescents compared to their non-obese peers.

Relationships between thyroid function and lipid status or insulin resistance in a pediatric population.

BACKGROUND: In adults without thyroid disease, increasing levels of thyroid-stimulating hormone (TSH) within the range of that considered normal have been shown to be associated with increases in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and triglycerides, and with decreases in high-density lipoprotein cholesterol. Serum TSH has also been found to be positively associated with fasting and postload insulin concentrations and negatively associated with insulin sensitivity in euthyroid adults. We hypothesized that such relationships also exist in euthyroid children and adolescents. METHODS: This was a retrospective record review of pediatric outpatients (ages 2-18 years) having measurements of TSH or free thyroxine (T4) and a concurrent lipid panel, fasting glucose, or fasting insulin. Pearson correlation coefficient was used to estimate the correlation between TSH or free T4 and logarithmic transformed lipid, plasma glucose, or insulin levels. Lipid levels, fasting plasma glucose, insulin, and homeostasis model assessment (HOMA) were also compared between subjects with TSH levels in the high normal range (2.5-5 mIU/L) and those with TSH in the low normal range (0.3-2.4 mIU/L). RESULTS: TSH levels were positively correlated with triglyceride levels (r = 0.10, p = 0.001). Conversely, free T4 levels were inversely correlated with triglyceride levels (r = -0.10, p = 0.011). TSH levels were also positively correlated with fasting insulin (r = 0.26, p = 0.002) and with HOMA (r = 0.27, p = 0.001). These associations remained significant after adjustment for age, gender, and body mass index z-score. Children who had TSH levels between 2.5 and 5.0 mIU/L had higher triglycerides (p = 0.003), insulin levels (p = 0.040), and HOMA (p = 0.021) than those having TSH values between 0.3 and 2.4 mIU/L. CONCLUSIONS: In euthyroid children without a history of hypo- or hyperthyroidism, increasing levels of TSH and decreasing levels of free T4 are associated with higher triglyceride levels and elevated markers of insulin resistance. Whether these findings carry implications regarding optimal TSH levels in children at increased risk for cardiovascular disease awaits further study.

Cystic changes in the ovaries of a pre-pubertal girl with Henoch-Schönlein purpura.

Henoch Schönlein Purpura is an IgA mediated vasculitis that is known to be associated with scrotal pathology. However, an association between Henoch Schönlein purpura and ovarian pathology has not been described. We present the case of a girl who developed cystic changes in her ovaries during her course of Henoch Schönlein purpura.

Relationships between 25-hydroxyvitamin D levels and plasma glucose and lipid levels in pediatric outpatients.

OBJECTIVE: To study the relationships between serum vitamin D levels and plasma glucose or lipid levels in children and adolescents. STUDY DESIGN: We conducted a retrospective record review of pediatric outpatients (age, 2-18 years) with simultaneous measurement of 25-hydroxyvitamin D (25[OH] D) and fasting plasma glucose (n = 302) or 25(OH) D and a lipid panel (n = 177). Pearson correlation coefficient was used to estimate the correlation between 25(OH) D and logarithmic transformed plasma glucose or lipid levels. Plasma glucose and lipid levels were compared in subjects with 25(OH) D concentrations greater or less than 30 ng/mL. RESULTS: 25(OH) D levels were inversely correlated with fasting plasma glucose levels (r = -0.20, P < .001). Lower 25(OH) D levels were also associated with lower serum high-density lipoprotein cholesterol (HDL) concentrations (r = 0.41; P < or = .001). The relationship between 25(OH) D levels and fasting glucose and HDL levels did not vary significantly with sex, age, body mass index z-score, or season. Children who were vitamin D insufficient (25[OH] D < or =30 ng/mL) had higher fasting plasma glucose (P = .002) and lower HDL levels (P < .001) than children who were vitamin D sufficient (25[OH] D >30 ng/mL). CONCLUSIONS: Low 25(OH) D levels in children and adolescents are associated with higher plasma glucose and lower HDL concentrations.

Type 2 diabetes mellitus in children and adolescents: where do we stand with drug treatment and behavioral management?

Type 2 diabetes, once considered a disease of adults, is a growing problem in the pediatric population. The emergence of type 2 diabetes in this age group has paralleled the epidemic of childhood obesity. Lifestyle modifications represent first-line therapy for children and adolescents with type 2 diabetes. However, many children and adolescents go on to require treatment with oral medications or insulin for optimal control. A paucity of data exist regarding the optimal treatment regimen for children and adolescents with type 2 diabetes. Further research regarding the treatment of type 2 diabetes in youth is required.

The relationship between 24-hour integrated glucose concentrations and % glycohemoglobin.

OBJECTIVE: Since glycohemoglobin values are widely used clinically as a surrogate for average glucose concentration over an extended period of time, we decided to determine the actual relationship between 24-hour integrated glucose values and percent total glycohemoglobin (%tGHb) in cohorts of people with and without diabetes. RESEARCH DESIGN AND METHODS: In 48 people without known diabetes with known stability of fasting glucose over a 1-year period of time, the calculated 24-hour integrated glucose concentration was compared with their %tGHb. In 15 normal young medical students, the glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb. In 18 people with type 2 diabetes, interstitial glucose concentrations were monitored using the Continuous Glucose Monitoring System (Medtronic MiniMed, Inc., Sylmar, Calif) for 3 days at 20-day intervals over 100 days. %tGHb was performed at 20-day intervals simultaneously. In 29 people with untreated type 2 diabetes, glucose area response was determined from 46 venous blood samples obtained during a 24-hour period and compared with their %tGHb after being on a standardized diet provided to the subjects for at least 5 weeks. The %tGHb and 24-hour profiles were stable. RESULTS: There was an excellent correlation between the mean 24-hour glucose concentration and the %tGHb among subjects with diabetes. The correlation was poor among subjects without diabetes. The relationship was curvilinear when plotted as a single group. Alternatively when data from subjects with or without diabetes were plotted separately, the slopes were identical but the y-intercepts were different. CONCLUSION: The relationship between the mean glucose concentration integrated over an extended period of time and the %tGHb is not linear. The reason for this nonlinearity remains to be determined. This non-linearity needs to be considered in the clinical interpretation of %tGHb (and probably HbA(1c)) in reference to glucose values.

Cannabinoids attenuate capsaicin-evoked hyperalgesia through spinal and peripheral mechanisms.

Previous studies in our laboratory have demonstrated that cannabinoids administered intravenously attenuate the duration of nocifensive behavior and block the development of hyperalgesia produced by intraplantar injection of capsaicin. In the present study, we extended these observations and determined whether cannabinoids attenuate capsaicin-evoked pain and hyperalgesia through spinal and peripheral mechanisms, and whether the antihyperalgesia was receptor mediated. Separate groups of rats were pretreated 7 min before capsaicin with an intrathecal injection of vehicle or the cannabinoid receptor agonist WIN 55,212-2 at doses of 0.1, 1.0 or 10 microg in 10 microl. Although the intrathecal application of WIN 55,212-2 did not alter nocifensive behavior following capsaicin, it produced a dose-dependent decrease in hyperalgesia to heat and mechanical stimuli. Intrathecal pretreatment with the CB1 receptor antagonist SR141716A (10 microg) blocked the antihyperalgesia produced by WIN 55,212-2. The ability of intrathecal administration of WIN 55,212-2 to attenuate hyperalgesia was not due to motor deficits since the highest dose of WIN 55,212-2 did not alter performance on the rota-rod test. To investigate whether cannabinoids attenuated capsaicin-evoked hyperalgesia through peripheral mechanisms, separate groups of rats were pretreated with an intraplantar injection of WIN 55,212-2 at doses of 0.1, 1.0, 10 or 30 microg in 100 microl 5 min before capsaicin. Intraplantar pretreatment with WIN 55,212-2 produced a dose-dependent attenuation of hyperalgesia to heat, but did not attenuate mechanical hyperalgesia or the duration of nocifensive behavior. The inactive enantiomer WIN 55,212-3 did not alter the development of hyperalgesia. SR141716A (100 microg) co-injected with WIN 55,212-2 (30 microg) partially attenuated the effects of WIN 55,212-2 on hyperalgesia to heat. Intraplantar injection of the highest dose of WIN 55,212-2 did not interfere with the development of hyperalgesia following capsaicin injection into the contralateral paw. These data show that cannabinoids possess antihyperalgesic properties at doses that alone do not produce antinociception, and are capable of acting at both spinal and peripheral sites.