Meta-analysis of the significance of asymptomatic bacteriuria in diabetes.

OBJECTIVE: To evaluate whether asymptomatic bacteriuria (ASB) is more common in patients with diabetes than among control subjects. In addition, we wanted to clarify the clinical significance of ASB in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted a systematic review and meta-analysis of published data since 1966. Twenty-two studies fulfilled the inclusion criteria of the meta-analysis. RESULTS: ASB was present in 439 of 3,579 (12.2%) patients with diabetes and in 121 of 2,702 (4.5%) healthy control subjects. ASB was more common both in patients with type 1 diabetes (odds ratio 3.0 [95% CI 1.1-8.0]) and type 2 diabetes (3.2 [2.0-5.2]) than in control subjects. The point prevalence of ASB was higher in both women (14.2 vs. 5.1%; 2.6 [1.6-4.1]) and men (2.3 vs. 0.8%; 3.7 [1.3-10.2]) as well as in children and adolescents (12.9 vs. 2.7%; 5.4 [2.7-11.0]) with diabetes than in healthy control subjects. Albuminuria was more common in patients with diabetes and ASB than those without ASB (2.9 [1.7-4.8]). History of urinary tract infections was associated with ASB (1.6 [1.1-2.3]). CONCLUSIONS: We were able to show that the prevalence of ASB is higher in all patients with diabetes compared with control subjects. We also found that diabetic subjects with ASB more often had albuminuria and symptomatic urinary tract infections.

Extended family history of diabetes and autoimmune diseases in children with and without type 1 diabetes.

OBJECTIVE: To determine the extended family history of diabetes or autoimmune diseases in families with and without children having type 1 diabetes. RESEARCH DESIGN AND METHODS: Three hundred case families and 381 control families were interviewed using structured questionnaires. RESULTS: The proportion of case children having at least one relative with type 1 diabetes outside the nuclear family was higher than that of control children (50.3 vs. 31.8%, P < 0.001). The proportions of case and control children having relatives with type 2 diabetes or gestational diabetes were similar. Other autoimmune diseases occurred more frequently among the case children (9.7 vs. 1.1%, P < 0.001), in the case nuclear families (22.0 vs. 12.9%, P = 0.002) and in relatives outside the case nuclear family (72.0 vs. 62.2%, P = 0.007). CONCLUSIONS: Type 1 diabetes and autoimmune diseases not only cluster in the nuclear families of children with type 1 diabetes but are also overrepresented in their extended families.

Adolescent manifestations of metabolic syndrome among children born to women with gestational diabetes in a general-population birth cohort.

The association between maternal gestational diabetes (GDM) and manifestations of metabolic syndrome among Caucasian adolescents was studied with data from the population-based Northern Finland 1986 Birth Cohort. This is a longitudinal cohort study from early pregnancy until offspring age 16 years and includes data from a risk group-based GDM screen of pregnant mothers by an oral glucose tolerance test. Metabolic outcomes were compared between the offspring of women with GDM (OGDM; n = 95) and reference group offspring (n = 3,909). The prevalence of overweight was significantly higher in the OGDM group (18.8 vs. 8.4%; P < 0.001) than in the reference group. The median body mass index (20.8 vs. 20.2 kg/m(2), 95% confidence interval (CI) for the percentage difference adjusted for sex: 3.5%, 9.5%), waist circumference (73.3 vs. 71.5 cm, 95% CI: 3.2%, 7.5%), and fasting insulin (10.20 vs. 9.30 milliunits/L, 95% CI: 5.9%, 26.0%) were higher, and homeostatic model assessment-insulin sensitivity (74.7 vs. 82.3, 95% CI: -20.6%, -5.4%) was lower in the OGDM group. These differences were similar after an additional adjustment for birth weight and gestational age. The differences in waist circumference, insulin, and homeostatic model assessment-insulin sensitivity were attenuated but remained statistically significant after additional adjustment for body mass index at 16 years. These findings highlight the importance of prevention strategies among children born to women with GDM.

[Update on current care guidelines. Eating disorders in children and adolescents]. / Lasten ja nuorten syöimishäiriöt.

Eating disorders in childhood and adolescence are considered to involve both somatic and psychological problems. Treatment soon after diagnosis is aimed at correcting the nutritional and somatic status, including psychoeducative guidance and support for the patients and their family. Multi-professional cooperation is needed in the diagnosis and treatment of eating disorders. Once serious undernutrition is corrected, psychotherapy is indicated. Early and active treatment is associated with favourable prognosis.

Lifestyle risk factors for obesity in 7-year-old children.

OBJECTIVE: To evaluate the associates of obesity and overweight in 7-year-old children. DESIGN: Cross-sectional study. SUBJECTS: 855 children out of all 1278 school beginners in the city of Oulu, Northern Finland. METHODS: A questionnaire to be filled in by parents was delivered by the school nurses to 1278 children. The child's eating habits, dietary intake and physical activity patterns were enquired about. There were also questions about the household and parents' level of education and physical activity. Overweight and obesity were defined by BMI according to internationally accepted criteria. The χ(2) test was used to evaluate the significance of the differences between normal and overweight children. Multivariate logistic regression model was used to find the most predictive variables associated with overweight and obesity. The final models are reported using odds ratios (ORs) and their 95% confidence intervals (CI). RESULTS: The number of responders was 855 (66.9%). The prevalence of overweight was 16.7% and that of obesity 4.9%. Fifty-seven percent of the parents who had an overweight or obese child 7-year-old did not recognise their child's overweight. The factors associated with obesity were: mother's obesity (OR 13.04, CI 2.81-60.53), low physical activity (OR 10.95, CI 3.28-36.50), skipping breakfast (OR 10.12, CI 1.81-56.63), habitual overeating (OR 9.35, CI 2.58-33.82), father's overweight (OR 5.89, CI 1.23-28.10) and mother's age over 40 years (OR 2.91, CI 1.09-7.80). CONCLUSION: This cross-sectional study promotes the importance of child's eating behaviour and family's eating patterns. Parents should be helped to recognise their child's overweight, and educational strategies should be targeted at both children and their parents. Avoiding inactivity is essential in preventing obesity in children.

Maternal type 1 and gestational diabetes: postnatal differences in insulin secretion in offspring at preschool age.

BACKGROUND: It is well known that children born to mothers with diabetes in pregnancy are more likely to develop metabolic abnormalities in later life. Most prior studies have not differentiated between offspring of mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) or lack a control group of non-exposed offspring. SUBJECTS: Offspring of T1DM (n = 16), GDM (n = 22) and mothers without diabetes (n = 25) born at Oulu University Hospital. AIM: To assess insulin secretion and insulin resistance in the offspring of T1DM and GDM at preschool age in comparison with offspring of non-diabetic mothers. METHODS: Anthropometric measurements and intravenous glucose tolerance testing were performed. First-phase insulin response (FPIR) and homoeostasis model assessment (HOMA) values were calculated. Pregnancy and birth data were analysed in relation to later metabolic parameters in all three groups using one-way analysis of variance (ANOVA) and analysis of covariance (ANCOVA). RESULTS: At a mean age of 4.9 yr, offspring of T1DM had increased fasting serum insulin concentrations (p = 0.044), FPIR (p = 0.034) and HOMA-B values (p = 0.008) compared with offspring of GDM or with offspring of healthy controls (statistically non-significant). The GDM gained least weight during pregnancy, and when adjusted for maternal weight gain during pregnancy, there were no statistically significant differences between study groups. CONCLUSIONS: Prenatal exposures to maternal type 1 and gestational diabetes may have different effects on postnatal glucose metabolism in the offspring assessed at a mean age close to 5 yr. Maternal weight gain in pregnancy may affect the postnatal glucose metabolism in the offspring.

Basal insulin switch from NPH to glargine in children and adolescents with type 1 diabetes.

BACKGROUND: Insulin glargine is a long-acting insulin analogue increasingly used instead of neutral protamine Hagedorn (NPH) insulin in young subjects with type 1 diabetes. OBJECTIVE: We evaluated the clinical course of diabetes in children and adolescents who were switched from NPH to insulin glargine. METHODS: Between August 2003 and November 2004, a total of 76 subjects were switched to glargine in our clinic, treating 340 children with type 1 diabetes. All the subjects had been receiving insulin NPH, and their serum C-peptide levels had been non-detectable for at least 1 yr. Data were collected retrospectively, and 12-18 months after the change, experiences with glargine were inquired using a questionnaire. Seven subjects (9.2%) discontinued glargine before 12 months, and seven refused to participate. RESULTS: Data for 62 subjects were analyzed. At the switch (0 months), their mean age was 12.7 yr (range 5.1-17.5), mean duration of diabetes was 6.7 yr (range 1.8-14.3), and mean hemoglobin A1c was (HbA1c) 9.2%. Twelve months later (+12 months), the mean HbA1c remained similar (9.2%), the proportion of long-acting insulin was smaller (47.7 vs. 58.1%; p < 0.001), and the daily insulin dose was lower (0.97 vs. 1.05 IU/kg; p < 0.001). The number of injections was lower at +12 months (17.7% with more than five injections vs. 64.5%; p < 0.001). No differences were seen in weight for height or the number of severe hypoglycemias. Most subjects who continued with glargine for > or =12 months considered glargine better than NPH. CONCLUSIONS: A switch to insulin glargine retains a similar glycemic control and does not change the number of severe hypoglycemias.

Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children.

OBJECTIVE: We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland. METHODS: Children with diagnoses commonly associated with mitochondrial diseases were ascertained. Blood DNA from 522 selected children was analyzed for 3243A>G. Children with the mutation were clinically examined. Information on health history before the age of 18 years was collected from previously identified adult patients with 3243A>G. Mutation segregation analysis in buccal epithelial cells was performed in mothers with 3243A>G and their children whose samples were analyzed anonymously. RESULTS: Eighteen children were found to harbor 3243A>G in a population of 97,609. A minimum estimate for the prevalence of 3243A>G was 18.4 in 100,000 (95% confidence interval, 10.9-29.1/100,000). Information on health in childhood was obtained from 37 adult patients with 3243A>G. The first clinical manifestations appearing in childhood were sensorineural hearing impairment, short stature or delayed maturation, migraine, learning difficulties, and exercise intolerance. Mutation analysis from 13 mothers with 3243A>G and their 41 children gave a segregation rate of 0.80. The mothers with heteroplasmy greater than 50% tended to have offspring with lower or equal heteroplasmy, whereas the opposite was true for mothers with heteroplasmy less than or equal to 50% (p = 0.0016). INTERPRETATION: The prevalence of 3243A>G is relatively high in the pediatric population, but the morbidity in children is relatively low. The random genetic drift model may be inappropriate for the transmission of the 3243A>G mutation.

Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]-DOPA positron emission tomography.

Congenital hyperinsulinism of infancy (CHI) is characterized by severe hypoglycemia due to dysregulated insulin secretion, associated with either focal or diffuse pathology of the endocrine pancreas. The focal condition is caused by a paternally inherited mutation in one of the genes encoding the subunits of the beta-cell ATP-sensitive potassium channel (SUR1/ABCC8 or Kir6.2/KCNJ11) and somatic loss of maternal 11p15 alleles within the affected area. Until now, preoperative diagnostics have relied on technically demanding and invasive catheterization techniques. We evaluated the utility of fluorine-18 l-3,4-dihydroxyphenylalanine ([(18)F]-DOPA) positron emission tomography (PET) to identify focal pancreatic lesions in 14 CHI patients, 11 of which carried mutations in the ABCC8 gene (age 1-42 months). To reduce bias in PET image interpretation, quantitative means for evaluation of pancreatic [(18)F]-DOPA uptake were established. Five patients had a visually apparent focal accumulation of [(18)F]-DOPA and standardized uptake value (SUV) >50% higher (mean 1.8-fold) than the maximum SUV of the unaffected part of the pancreas. When these patients were operated on, a focus of 4-5 x 5-8 mm matching with the PET scan was found, and all were normoglycemic after resection of the focus. The remaining nine patients had diffuse accumulation of [(18)F]-DOPA in the pancreas (SUV ratio <1.5). Diffuse histology was verified in four of these, and pancreatic catheterization was consistent with diffuse pathology in four cases. In conclusion, [(18)F]-DOPA PET is a promising noninvasive method for the identification and localization of the focal form of CHI.

Serum androgen levels and testicular structure during pubertal maturation in male subjects with epilepsy.

PURPOSE: To evaluate reproductive endocrine function in boys and young men with epilepsy taking an antiepileptic drug in a population-based, controlled study. METHODS: Seventy patients and 70 controls matched for age and pubertal stage participated in this study. Twenty-eight patients were taking carbamazepine (CBZ); five, lamotrigine (LTG); 12, oxcarbazepine (OXC); and 25, valproate (VPA) as monotherapy for epilepsy. All subjects were examined clinically, and their medical histories were obtained. Serum reproductive hormone and sex hormone-binding globulin concentrations were measured, and testicular ultrasonography was performed. RESULTS: Serum testosterone levels were within the normal range in young male patients with epilepsy. However, the patients taking VPA had high serum androstenedione levels at all pubertal stages. In prepuberty, their serum androstenedione values were already approximately fivefold compared with the values of the controls (8.7 nM; SD, 4.0 vs. 1.8 nM, SD, 1.0; p < 0.0003), and they were elevated in 64% of the VPA-treated patients compared with none of the other patients, p = 0.0006. Serum sex hormone-binding globulin levels were increased, and serum dehydroepiandrosterone sulfate concentrations decreased in the pubertal patients taking CBZ. The mean testicular volumes did not differ between the patients and the controls. CONCLUSIONS: CBZ and VPA, but not LTG and OXC, are associated with changes in serum sex-hormone levels in boys and young men with epilepsy. However, the long-term health consequences of these reproductive endocrine changes during pubertal development remain to be established.

A practice guideline for treatment of eating disorders in children and adolescents.

Eating disorders are diseases of both the body and the psyche. Early treatment focuses on restoration of nutritional status and somatic health, including psycho-educational counselling and support offered to the patient and his/her family. Diagnosis and treatment require a multidisciplinary approach. Psychological factors related to the condition should be assessed. The most severe weight loss should be reversed before psychotherapeutic treatment. Nutritional counselling is recommended, and the benefits of individual and/or family therapy are considered in accordance with the patient's age, development, symptomatology and comorbid psychiatric disorders. Medication is useful in the treatment of bulimia nervosa and certain comorbid symptoms of anorexia nervosa. Early admission to treatment and active therapy are associated with a more favourable prognosis.

Insulin-regulated increase of soluble vascular adhesion protein-1 in diabetes.

Vascular adhesion protein-1 (VAP-1) is one of the molecules on the endothelial cell membrane, which may guide inflammatory cells into atherosclerotic lesions. This dual function molecule may also contribute to the pathogenesis of atherosclerosis and other vasculopathies via its enzymatic activity that oxidizes primary amines to produce their corresponding aldehydes, hydrogen peroxide, and ammonium. Because VAP-1 also exists in a soluble form, we analyzed its potential usefulness as a biomarker to monitor and predict the extent of ongoing atherosclerotic processes. Soluble VAP-1 (sVAP-1) levels were determined from the sera of 136 Finnish men with established coronary heart disease and in 275 controls using sandwich enzyme immunoassays and correlated to multiple risk factors for coronary events. Intriguingly, sVAP-1 showed a statistically significant correlation with diabetes in both cohorts. We then collected patients with type 1 diabetes and observed that sVAP-1 levels were highly elevated when the patients were metabolically compromised. On normalization of their blood glucose and ketone body levels by exogenous insulin, their sVAP-1 concentration rapidly decreased to control levels. Intravenous glucose tolerance and hyperinsulinemic clamp tests further showed that elevation of blood glucose per se did not increase sVAP-1 levels, but rather, sVAP-1 was inversely correlated with circulating insulin concentrations. In conclusion insulin appears to regulate shedding or clearance of VAP-1, and an increase in sVAP-1 because of absolute or relative insulin deficiency may be directly involved in the pathogenesis of diabetic angiopathy.

Lack of physiological suppression of circulating IGFBP-1 in puberty in patients with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the interaction between serum free insulin, insulin-like binding protein (IGFBP)-1 and leptin concentrations during puberty in insulin-dependent diabetes mellitus (IDDM). DESIGN: Adolescent patients with IDDM (n=101, age >9 years, duration >2 years) from the Outpatient Clinic of the Department of Pediatrics at Oulu University Hospital, and non-diabetic controls, were recruited to the study. Free insulin, IGFBP-1, leptin and insulin antibody concentrations were measured from a fasting serum sample. RESULTS: Free insulin concentrations were lower in the patients than in the controls (4.3+/-2.3 mU/l compared with 6.5+/-3.1 mU/l, P<0.001), and there was an inverse correlation between free insulin and fasting blood glucose in the boys with diabetes (r=-0.53, P<0.001), whereas a positive correlation was observed between free insulin and leptin concentrations in the girls with diabetes (r=0.30, P=0.020). The IGFBP-1 concentrations were greater in the patients than in the controls (16.5+/-10.6 microg/l compared with 4.0+/-3.3, P<0.001), and they correlated significantly with blood glucose (r=0.63, P<0.001) and free insulin (r=-0.35, P<0.001). No significant difference was observed in the leptin concentrations between the patients and controls overall, despite greater total body fat in the girls with diabetes compared with the control girls. CONCLUSIONS: Adolescents with IDDM are characterised by morning hypoinsulinaemia and high circulating IGFBP-1 concentrations, which may contribute to insulin resistance and impaired metabolic control during puberty. The mechanism behind the increased total body fat in the postpubertal female patients remains to be determined.

Diabetes and elimination of antipyrine in man: an analysis of 298 patients classified by type of diabetes, age, sex, duration of disease and liver involvement.

UNLABELLED: Effects of diabetes on hepatic drug metabolism in man has not yet been adequately clarified. Two hundred ninety-eight diabetic patients, classified by type of the disease, age, gender, duration of therapy and liver involvement, were investigated. The antipyrine plasma clearance rate and cytochrome P450 content determinations in liver biopsies of subjects with diagnostic liver biopsy were used as indices of hepatic drug metabolising capacity. Drug metabolism was reduced as a function of age. Antipyrine elimination rate was dependent on the type of diabetes (type 1 versus type 2) and gender. Untreated type 1 patients eliminated antipyrine rapidly and insulin treatment normalised antipyrine elimination (clearance rates 89.5 +/- 20.3 versus 58.8 +/- 17.2 ml/min.; P<0.001). Males aged 16-59 years, but not over 60, who responded insufficiently to insulin therapy, had a rapid antipyrine elimination, which could be normalised by readjustment of insulin administration. Women with insufficient glucose control on insulin therapy had antipyrine elimination rate comparable to controls. Among type 2 diabetic patients, women metabolised antipyrine normally, but men over 40 years of age showed a reduced antipyrine metabolism. IN CONCLUSION: Drug metabolism in diabetes is affected by the type of disease, therapy and its effectiveness, and age and gender of the patients. These factors should be taken into account when evaluating overall drug metabolism in diabetic patients. This is especially important when investigating pharmacokinetics of new drugs for diabetic patients at different phases of the disease.

Genetic screening for maternal uniparental disomy of chromosome 7 in prenatal and postnatal growth retardation of unknown cause.

OBJECTIVE: Many short-statured children lack an etiologic explanation for their retarded growth. Recently, uniparental disomy (UPD), the inheritance of both chromosomes of a chromosome pair from only 1 parent, has been associated with short stature for many chromosomes. Silver-Russell syndrome (SRS) represents an extreme syndrome of intrauterine growth retardation (IUGR) and slight dysmorphic signs, and maternal UPD of human chromosome 7 (matUPD7) has been observed in approximately 10% of SRS cases. In addition, matUPD7 has been reported in patients with only slight dysmorphic features and prenatal or postnatal growth retardation. The objectives of this study were to study the role of matUPD7 in growth failure of unknown cause and in cases of SRS, and to evaluate the efficiency of genetic testing for matUPD7 as a diagnostic tool. METHODS: DNA samples were studied from 205 children, 92 girls and 113 boys, with short stature of unknown cause and their parents. The patient cohort included 39 cases of SRS, 91 patients with IUGR and subsequent postnatal short stature, and 75 patients with postnatal growth retardation only. MatUPD7 was screened for by genotyping DNA samples from the patient, mother, and father with 13 chromosome-7-specific polymorphic microsatellite markers. RESULTS: Six (3%) of 205 matUPD7 cases were observed exclusively among 39 (15%) SRS patients studied. Patients with IUGR and/or postnatal growth retardation and with dysmorphic features did not reveal cases of matUPD7. CONCLUSIONS: Our results indicate that matUPD7 cases are predominantly observed among patients meeting the criteria of SRS, and matUPD7 is not a common cause for growth retardation. Genetic screening for cases of matUPD7 among growth-retarded patients should be focused on patients with severe IUGR and features of SRS. In addition, matUPD7 screening is advisable in individuals with cystic fibrosis and other recessive disorders mapped to chromosome 7 who have unusually short stature.