Assimina Galli-Tsinopoulou

Insulin improves clinical status of patients with cystic-fibrosis-related diabetes mellitus.

Cystic‐fibrosis‐related diabetes mellitus is frequently underdiagnosed and associated with deterioration of overall clinical status. The purpose of this prospective study was to investigate the influence of insulin on nutrition, lung function and clinical status of cystic fibrosis patients. For a period of 5y, and at 6‐mo intervals, body mass index, forced expiratory volume in 1 sec, Shwachman score, intravenous glucose tolerance test and first‐phase insulin response were determined in 30 cystic fibrosis patients (age range 10–35 y) with exocrine pancreatic insufficiency. During the study period, six patients (3M and 3F; age range 15–22 y) developed diabetes and required insulin therapy. The decrease of first‐phase insulin response coincided with deterioration of nutritional and clinical status, which improved significantly 6 mo after the institution of insulin.

Long-term prospective study of the effect of ursodeoxycholic acid on cystic fibrosis-related liver disease

Goals To evaluate the efficacy of UDCA in arresting the progression of the early multifocal hepatic lesion to overt CF-related NBC. Background Focal biliary cirrhosis is an early hepatic pathologic change related to the ion transport defect in cystic fibrosis. The factors involved in the progression of focal to nodular biliary cirrhosis are not clear. Ursodeoxycholic—a hydrophilic, nontoxic, choleretic, and hepatoprotective exogenous bile acid—has been reported to be effective in the management of cholestatic liver disease. Study For 10 years at 6-month intervals, 70 individuals with cystic fibrosis (38 men and 32 women; age range, 2–29 years) were examined using hepatosplenomegaly, liver function tests, and ultrasound liver scan. Patients demonstrating evidence of liver involvement at the onset or during the study received ursodeoxycholic acid 20 mg/kg body weight. Results After the administration of ursodeoxycholic acid, the progression of nodular biliary cirrhosis ultrasound changes was arrested, hepatic function was preserved, and no variceal bleeding was observed. No case of focal biliary cirrhosis progressed to nodular biliary cirrhosis. Furthermore, the multifocal, multilobular changes suggestive of focal biliary cirrhosis on ultrasound scan were reversed to normal. Conclusion Ursodeoxycholic acid is effective in improving cholestasis and hepatic dysfunction in nodular biliary cirrhosis and, also, in reversing the early sonography findings suggestive of focal biliary cirrhosis. It is speculated that ursodeoxycholic acid may prove to affect the natural history of cystic fibrosis-related liver disease.

Influence of jejunal morphology changes on exocrine pancreatic function in celiac disease

BACKGROUND Concurrent exocrine pancreatic dysfunction may be one of the factors implicated in malabsorption in untreated celiac disease, as shown by studies on bicarbonate and pancreatic enzyme secretion. The purpose of this study was to evaluate exocrine pancreatic function in relation to jejunal morphology in celiac disease. METHODS Thirty-six patients fulfilling the ESPGHAN criteria for celiac disease, aged 3 to 18 years and 36 control subjects matched for age and sex were investigated. The design of the study included measurement of serum pancreatic isoamylase by a chromogenic method after selective inhibition of sialic isoamylase in the untreated phase in patients consuming a gluten-containing diet and after gluten elimination for a period of 1 year; fecal human elastase activity determined by enzyme-linked immunosorbent assay in patients consuming a gluten-free diet and again after gluten challenge for 6 months; correlation of serum pancreatic isoamylase and fecal elastase to the jejunal morphology, classified by criteria described by Marsch; the enzymes in the control group; and ultrasonography of the pancreas in both groups. RESULTS Enzyme values obtained from celiac disease patients with normal mucosa were significantly higher than those obtained from patients with villous atrophy (p < 0.001) and comparable to those obtained from the control group. Serum pancreatic isoamylase activity increased to normal after gluten elimination, and human elastase activity decreased to values below 200 microg/g of stool after gluten challenge. Enzyme activity was related inversely to the degree of intestinal damage. The echogenicity of the pancreas was normal, regardless of enzyme activity or gut morphology. CONCLUSIONS Exocrine pancreatic function is abnormal in celiac disease when mucosal atrophy is present. Exocrine pancreatic function parameters are associated with the changes of intestinal mucosal morphology in three consecutive phases of the disease.

Insulin resistance and hyperinsulinemia in prepubertal obese children.

BACKGROUND Tissue resistance to insulin has been demonstrated in obese individuals. Pancreatic beta-cells respond to the reduced tissue sensitivity with increased insulin secretion so that glucose homeostasis is maintained. OBJECTIVE The purpose of this prospective study was to investigate the presence of hyperinsulinemia and insulin resistance in obese children and adolescents. SUBJECTS AND METHODS Fasting glucose (FG) and insulin (FI) levels and fasting glucose to insulin ratio (FGIR) were measured in 26 obese prepubertal children and 20 obese adolescents, as compared to 20 non-obese prepupertal children and 20 adolescents with normal body weight. Furthermore, obese children and adolescents underwent an oral glucose tolerance test with measurements of glucose and insulin 2 hours post glucose load. RESULTS In 14/26 (54%) obese prepubertal children and in 16/20 (80%) obese adolescents FI was >24 microU/ml. FGIR was <6 in 23/26 (88%) prepubertal obese children and in all obese adolescents. All non-obese prepubertal children and adolescents had normal FI. However, FGIR was <6 in 6/20 (30%) non-obese prepubertal children and in 15/20 (75%) non-obese adolescents. CONCLUSION Hyperinsulinemia and insulin resistance are already present in prepubertal obese children. As hyperinsulinemia is a potentially reversible condition and the complications related to it may be prevented, early measurements should be undertaken so that obese children lose body weight before the onset of puberty which may enhance the problem of insulin insensitivity.

Adiponectin and Insulin Resistance in Childhood Obesity

Objectives: To measure adiponectin serum levels in Greek children and adolescents and correlate them with body fat and insulin resistance. Patients and Methods: Forty-six obese prepubertal children (19 M, 27 F) and 34 obese adolescents (17 M, 17 F) ages 9.33 ± 1.57 and 13.6 ± 1.42 years, respectively, and 43 matched control individuals were studied. Body mass index standard deviation score and percent body fat were measured by bioelectric impedance analysis. Fasting indices of insulin resistance (HOMA-IR and fasting glucose-to-insulin ratio) were calculated for all participants. Indices of insulin resistance derived from oral glucose tolerance tests were estimated in obese participants. Adiponectin was measured by enzyme-linked immunosorbent assay. Results: (Mean ± SD): Adiponectin serum levels were significantly lower in obese participants than in nonobese participants (8.11 ± 3.80 vs 11.81 ± 4.98 μg/mL, P < 0.001), in obese children than in nonobese children (8.86 ± 3.86 vs 13.08 ± 5.48 μg/mL, P < 0.001), in obese adolescents than in nonobese adolescents (7.04 ± 3.43 vs 10.47 ± 4.10 μg/mL, P = 0.002), and in obese adolescent boys than in obese adolescent girls (5.87 ± 3.52 vs 8.31 ± 3.16 μg/mL, P = 0.042). There were significant correlations between adiponectin and age, body mass index, body mass index standard deviation score, homeostasis model assessment for insulin resistance, and fasting glucose-to-insulin ratio. Adiponectin correlated with percent body fat after adjustment for sex. Adiponectin correlated significantly with several indices of insulin resistance, such as the areas under the curves for glucose and insulin, whole-body insulin sensitivity index, glucose120′, and insulin30′, in obese participants. Conclusions: Adiponectin was significantly lower in obese participants than in nonobese participants in general, and it correlated significantly with fasting indices of insulin resistance and with indices derived from oral glucose tolerance tests. It is worthwhile to further investigate the option of applying a simple measurement of serum adiponectin as a screening tool before applying more time-consuming techniques in young obese individuals.

Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3-like protein 1) are a marker of obesity and insulin resistance in prepubertal children.

YKL-40 (chitinase 3-like protein 1) is a newly recognized protein that is secreted by activated macrophages and neutrophils and expressed in a broad spectrum of inflammatory conditions and cancers. It has also been associated with endothelial dysfunction and diabetes in adults. Its role in childhood obesity has not been evaluated yet. Our aim was to evaluate the associations of serum YKL-40 levels with markers of obesity, inflammation, and insulin resistance in children. Forty-one obese prepubertal children and 41 age- and sex-matched lean controls were included, and serum YKL-40 levels were determined. Body mass index (BMI), blood pressure (BP), body fat percentage, fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) index, whole-body insulin sensitivity index, lipids, white blood cell (WBC) count, C-reactive protein, and fibrinogen levels were also assessed. Obese children had higher YKL-40 levels compared with controls (P = .003). Insulin-resistant individuals showed higher YKL-40 compared with non-insulin-resistant individuals after adjusting for age and BMI (adjusted P = .039). Serum YKL-40 levels were positively correlated with age, BMI, body fat percentage, fasting glucose and insulin, HOMA-IR index, whole-body insulin sensitivity index, systolic BP, mean BP, and WBC count (P < .05). After adjustment for age, sex, BMI, WBC count, and systolic BP, HOMA-IR index remained significantly associated with YKL-40 levels (P < .001). The study suggests that YKL-40 levels are elevated in obese youth and represent a marker of insulin resistance even in childhood. Prospective studies are needed to determine whether children with elevated YKL-40 levels are at higher risk for future cardiovascular disease.

Nutrient intake and anthropometry in children and adolescents with Down syndrome–a preliminary study

Objective: To assess nutrient intake and anthropometrical characteristics of children and adolescents with DS, in Northern Greece. Study design: Cross-sectional study of 34 youngsters with DS. The sample was divided into two age groups, children aged 2–9 years and adolescents aged 10–18 years old. A 3-day food record was used to assess dietary intake. Body weight, height, WHR,% body fat, BMI, FMI, FFMI and z-scores were recorded for each participant. Results: All participants exhibited a high CHO and low fat diet. More than half of the participants reported having five meals daily and the majority exercised twice a week. A great majority was stunted and overweight according to general population growth charts and 22% of the adolescents were also obese. %Body fat, BMI, FMI and FFMI was higher in adolescents. Generally, younger participants presented lower overweight rates and consumed a diet more sufficient in micronutrients; however, WHR was similar in both age-groups, indicating a constant trend in weight distribution of DS patients. Conclusions: Although children with DS are born with a genetic predisposition to become overweight, obesity is actually nurtured throughout childhood when they develop food choices and become more independent.

Osteopenia in Children and Adolescents with Hyperprolactinemia

Three patients with hyperprolactinemia due to pituitary adenomas (two patients) or empty sella (one patient) and osteopenia are described. Their ages at presentation ranged from 8 to 17 years. Each patient was treated with cabergoline. Serum prolactin levels became normal in all patients within one month. Bone density and pubertal stage improved after 12 months of treatment.

Islet autoantibodies and insulin dependent diabetes mellitus in cystic fibrosis.

Cystic fibrosis-related diabetes mellitus (CF-DM) is thought to be secondary to beta-cell destruction by fibrous tissue replacing the exocrine pancreas. The aim of this study was to investigate the hypothesis that other factors may also be responsible. Glutamic acid decarboxylase (GAD) and islet cell (IA-2) antibodies were measured by quantitative ELISA in a group of patients with CF (n=30) in comparison to a group of newly diagnosed DM type 1 (IDDM) patients (n=30) and normal subjects (n=30). GAD antibodies were positive (>32 ng/ml) in 50% of the CF, 93% of the IDDM and 0% of the control group. IA-2 antibodies were detected (>0.9 U/ml) in 40% of the CF, 93% of the IDDM and 0% of the control group. Among the fifteen CF patients with positive GAD and IA-2 antibodies, four already had IDDM and another five abnormally low (<45 mU/l) first phase insulin response (FPIR) indicating a prediabetic state. We conclude that factors other than mechanical may be involved in the development of CFDM. The presence of autoantibodies predicting IDDM supports the hypothesis that CF-DM may have a multifactorial pathogenesis.

Effect of exocrine pancreatic function on resting energy expenditure in cystic fibrosis

Aim: To prove the hypothesis that exocrine pancreatic function determines resting energy expenditure (REE) in cystic fibrosis (CF).