Fasting Plasma Ghrelin Levels Are Negatively Correlated With Insulin Resistance and PAI-1, but Not With Leptin, in Obese Children and Adolescents

Ikezaki, Ayako; Hosoda, Hiroshi; Itō, Keiko; Iwama, Saika; Miura, Noriaki; Matsuoka, Hisafumi; Kondo, Chisato; Kojima, Masayasu; Kangawa, Kenji; Sugihara, Shigetaka

doi:10.2337/diabetes.51.12.3408

Cited by 194 publications

(159 citation statements)

References 24 publications

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“…Fasting insulin levels have been demonstrated to correlate negatively with fasting ghrelin levels in obese and normal -weight subjects in some studies, 10,11 whereas there was no relationship between insulin and ghrelin in other studies. 9 Insulin administration has been shown to decrease ghrelin levels.…”

Section: Introductionmentioning

confidence: 92%

“…Normal weight children had an age-matched BMI below 25 kg/m 2 for adults. Mean age of obese patients was 13.9 years (range 10-16), and of control children 12.3 years (range [10][11][12][13][14][15]. Patients with underlying gastrointestinal disease or endocrine disorders and patients receiving systemic glucocorticoid therapy were excluded from the study.…”

Section: Subjectsmentioning

confidence: 99%

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Regulation of ghrelin is related to estimated insulin sensitivity in obese children

Krohn

Boczan

Otto³

et al. 2006

Int J Obes

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Objective: To investigate whether ghrelin concentrations and their changes during weight loss in obese children are associated with parameters of glucose and insulin metabolism. Design: Total plasma ghrelin, insulin and glucose were measured during oral glucose tolerance testing before and after dietinduced weight loss over 6 weeks. Setting: In-patient rehabilitation program in a pediatric hospital. Participants: Twenty-three obese children (age 10-16 years) and 11 normal weight controls (age 10-15 years). Outcome measures: Changes in ghrelin concentrations during weight loss and correlation analysis of changes in ghrelin and changes in parameters of glucose and insulin metabolism. After data collection, subgroup analysis of obese patients with high, medium and low estimated insulin sensitivity whole-body insulin sensitivity index (WBISI) was performed. Results: Weight loss increased the area under the curve (AUC) of ghrelin by 26% (Po0.001). The increase in ghrelin AUC correlated significantly with improved estimated insulin sensitivity (WBISI) (r ¼ 0.69, Po0.001). The independent predicting effect of WBISI was confirmed in multivariate analysis. In children with low WBISI, ghrelin reached the level of control values after weight loss. In children with high WBISI, ghrelin increased markedly above control levels. Conclusions: Changes in ghrelin are independently associated with changes in glucose and insulin metabolism. The increase in plasma ghrelin above control levels was limited to obese children with high WBISI.

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Section: Introductionmentioning

confidence: 92%

Section: Subjectsmentioning

confidence: 99%

Regulation of ghrelin is related to estimated insulin sensitivity in obese children

Krohn

Boczan

Otto³

et al. 2006

Int J Obes

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“…In contrast to this, other studies reported correlations between ghrelin, adiponectin and leptin levels and insulin resistance. 37,40,41 These differences may be explained by the complexity of interactions, which cannot be figured out in relative moderate-sized study samples. Furthermore, diet composition influences predominately gastrointestinal hormones like ghrelin, while the other hormones are not directly influenced by diet.…”

Section: Ghrelin In Obese Children T Reinehr Et Almentioning

confidence: 98%

“…On the other hand, only weak correlations between fat mass and ghrelin levels were reported. [37][38][39] Probably, there is no direct link between adipose tissue and ghrelin levels but between factors leading to obesity and influencing ghrelin levels. For instance, a high-fat diet decreases ghrelin levels 2,3 and is thought to be one of the causes of obesity.…”

Section: Ghrelin In Obese Children T Reinehr Et Almentioning

confidence: 99%

Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents

et al. 2005

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BACKGROUND: There are conflicting results for ghrelin changes in reduction of overweight. Increasing ghrelin levels in weight reduction are considered to be responsible for compensatory mechanisms that make the reduction of overweight unlikely to be sustained. METHODS:We have analyzed fasting serum ghrelin levels, weighed dietary record and, as biochemical markers of clinically relevant reduction of overweight, leptin, adiponectin and insulin levels and insulin resistance measured by homeostasis model assessment (HOMA) at baseline and after a 1-y outpatient weight reduction program based on a high-carbohydrate and low-fat diet in 37 obese children (median age 10 y). We divided these children into two subgroups according to their degree of weight loss (substantial reduction of overweight: decrease in SDS-BMIZ0.5). Furthermore, we analyzed ghrelin levels in 16 normalweight children. RESULTS: Obese children demonstrated significant (Po0.001) lower ghrelin levels compared to normal-weight children. Daily caloric intake (P ¼ 0.004) and percentage fat content decreased significantly (Po0.001), while percentage carbohydrate content increased significantly (P ¼ 0.003) between baseline and 1-y follow-up in the obese children. The substantial reduction of overweight in 16 children (median SDS-BMI ¼ À0.7) was associated with significant changes in insulin resistance (median decrease of HOMA 27%; P ¼ 0.013), insulin (median decrease 25%, P ¼ 0.036), adiponectin (median increase 15%; P ¼ 0.003), and leptin levels (median decrease 19%; P ¼ 0.023), while there were no significant changes in ghrelin levels (median increase 4%; P ¼ 0.326). In the 21 children without substantial reduction of overweight (median SDS-BMI ¼ À0.3), there were no significant changes in insulin resistance and in insulin, adiponectin, leptin and ghrelin levels. CONCLUSIONS: We conclude that in obese children, low-fat high-carbohydrate diet-induced weight loss does not change ghrelin secretion, but significantly decreases leptin levels, increases adiponectin levels and improves insulin resistance determined by significantly decreased insulin resistance indices as well as lowered serum insulin levels.

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“…Food intake and hyperglycaemia suppress ghrelin secretion [10,11] but it is controversial whether changes in glucose or insulin mediate this effect [10,12]. Several studies have shown ghrelin to be negatively associated with BMI [13][14][15] and insulin [13,15,16].…”

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confidence: 99%

The negative association between plasma ghrelin and IGF-I is modified by obesity, insulin resistance and type 2 diabetes

et al. 2005

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Aims/hypothesis: Ghrelin is a natural growth hormone-releasing peptide thought to be involved in the regulation of energy metabolism. The recent studies concerning the association between ghrelin and insulin-like growth factor-I (IGF-I) concentrations have shown either negative correlation or no correlation at all. The aims of this study were to clarify the association between ghrelin and IGF-I concentrations in a large cohort and to characterize whether obesity, insulin resistance and type 2 diabetes affect this association. Methods: We analysed fasting plasma ghrelin and IGF-I concentrations of 1,004 middleaged subjects of the population-based OPERA study. Insulin resistance was estimated using QUICKI. Results: IGF-I concentrations were negatively associated with ghrelin concentrations in the analysis of all subjects before (β= −0.32, p<0.001) and after adjustments for BMI, insulin levels, sex and age (β=−0.40, p<0.001). The association was particularly strong in males and in the higher BMI tertiles. The degree of association varied in relation to the glycaemic status: no insulin resistance: r 2 =6.5% (p<0.001), insulin resistance without type 2 diabetes: r 2 =21.0% (p< 0.001), type 2 diabetes: r 2 =25.4 (p<0.001). IGF-I levels explained larger proportion (r 2 =9.8%) of the variation in ghrelin concentrations compared to fasting insulin concentration (r 2 =3.0%) and BMI (r 2 =1.5%). Conclusions/ interpretation: There is a negative and independent association between ghrelin and IGF-I concentrations in middleaged subjects. The interaction between IGF-I and ghrelin is modified by obesity, IR and type 2 diabetes. Further studies are warranted to elucidate the role of ghrelin in the development of these states.

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Fasting Plasma Ghrelin Levels Are Negatively Correlated With Insulin Resistance and PAI-1, but Not With Leptin, in Obese Children and Adolescents

Cited by 194 publications

References 24 publications

Regulation of ghrelin is related to estimated insulin sensitivity in obese children

Regulation of ghrelin is related to estimated insulin sensitivity in obese children

Ghrelin levels before and after reduction of overweight due to a low-fat high-carbohydrate diet in obese children and adolescents

The negative association between plasma ghrelin and IGF-I is modified by obesity, insulin resistance and type 2 diabetes

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