Francisca Eyzaguirre

Insulin resistance markers in children.

The prevalence of obesity among children and adolescents is progressively increasing around the world. One of the important consequences of obesity is the development of insulin resistance (IR). This condition has a multifactorial pathogenesis and is associated with cardiovascular risk, diabetes, hypertension, polycystic-ovary syndrome and a shorter lifespan. IR during childhood may be diagnosed by physical examination or there may be clues in the histories of the patient and his/her family. When IR is suspected, tests on a blood sample (which are more reliable) are recommended. Most of the biochemical markers have been well defined in adults, but appropriate reference data for children are still lacking. Here we discuss the usefulness of various currently known biochemical markers to evaluate insulin sensitivity (homeostatic model assessment, the quantitative insulin sensitivity check index, the oral glucose tolerance test, Matsuda method and the whole-body insulin resistance index), hormones (leptin, adiponectin, resistin, glucocorticoids, the insulin-like growth factor-1-binding protein/growth hormone axis, ghrelin, sex hormone-binding globulin and retinol-binding protein-4) and inflammatory markers (C-reactive protein, IL-6, intercellular adhesion molecule-1, vascular adhesion molecule-1 and E-selectin), which can be used in the diagnosis of IR in children.

Menstrual cycle irregularities and their relationship with HbA1c and insulin dose in adolescents with type 1 diabetes mellitus

OBJECTIVE To evaluate the prevalence and risk factors of menstrual cycle irregularities in adolescents with type 1 diabetes mellitus. DESIGN Prospective diary of menstrual cycle. SETTING Pediatric diabetes clinics and nearby schools. PATIENT(S) Adolescents with type 1 diabetes mellitus treated with multiple daily insulin doses (n = 56) and 56 healthy adolescents. MAIN OUTCOME MEASURE(S) Duration and variability of menstrual cycle. RESULT(S) Duration of the menstrual cycle was 48 ± 39 and 32 ± 7 days in girls with type 1 diabetes mellitus and controls, respectively. Oligomenorrhea (58.9% vs. 19.6%) and amenorrhea (10.7% vs. 1.8%) were more prevalent in girls with type 1 diabetes mellitus than in controls. Oligomenorrhea was observed in 53.3% of the girls with type 1 diabetes mellitus with optimal metabolic control. Girls with an HbA1c level of 7.6% to 8.9% exhibited increased cycle duration, menstrual cycle variability, and prevalence of oligomenorrhea compared with controls. Regression analysis showed that, for each point of increase in HbA1c, the menstrual cycle duration increased by 5.1 days. Cycle variability was associated with a higher daily insulin dose. CONCLUSION(S) Despite optimal metabolic control, a higher prevalence of oligomenorrhea was observed in girls with type 1 diabetes mellitus compared with controls. This is the first report to describe the high variability of the menstrual cycle in type 1 diabetes mellitus. HbA1c and insulin dose are important factors related to menstrual irregularities in type 1 diabetes mellitus.

Bone mass and sex steroids in postmenarcheal adolescents and adult women with Type 1 diabetes mellitus

OBJECTIVE The aim of this study was to compare the bone mass in young adolescents and adult women with Type 1 diabetes mellitus (T1DM) and determine its relationship with sex steroid and sex hormone-binding globulin (SHBG) levels. DESIGN Cross-sectional study. PATIENTS We studied a group of adolescents and adult women with T1DM (n=45) and 50 healthy controls (C) matched by gynecological age and body mass index in a case-control study. Girls with menarche within the last 18-40 months (n=17 T1DM and 32 C) and adult women (age=30.4+1.4 years; n=28 T1DM and 18 C) were recruited. MEASUREMENTS Bone mass was evaluated with a GE Lunar Prodigy densitometer. Sex steroid levels were measured by radioimmunoassay. RESULTS Bone mass was lower in adolescents with T1DM than in control adolescents, but was similar in both groups of postmenarcheal girls after adjusting for age, lean, and fat mass. However, adult T1DM women exhibited lower adjusted and unadjusted (P<.05) Z-femoral neck (-0.2±0.2 vs. 0.4±0.2) and bone mineral content (BMC) (2306±61 vs. 2645±79 g) than adult controls. Adult controls and T1DM adults showed higher whole body BMC than adolescent controls and T1DM adolescents, respectively. Bone mass in T1DM did not correlate with estradiol, free estradiol, testosterone, SHBG, or HbA1c levels. CONCLUSIONS The diminished bone mass observed in adult T1DM women does not appear to be related to sex steroid levels. In young adolescents with T1DM, the observed decrease in bone mass appears to be related to differences in body composition and age.

Prevalence of components of the metabolic syndrome according to birthweight among overweight and obese children and adolescents

Abstract Background/objectives: Extremes of birthweight (BW) have been associated with increased rates of metabolic risks. The objective was to study the prevalence of metabolic risks markers among obese and overweight (OW) subjects according to BW. Subjects/methods: A cross-sectional study was performed in a cohort of 1002 patients (2–18 years, 40.6% male) evaluated for OW or obese subjects in two private clinics. Anthropometrics, fasting lipids, glycemia, and insulin were obtained. Results: Of the subjects, 76.1% were born appropriate for gestational age (AGA), 10.9% small for gestational age (SGA), and 13% large for gestational age (LGA). Children born LGA presented a more severe degree of obesity compared with those born AGA and SGA (p<0.0001). No differences in glycemia, insulin, and lipid levels were detected among the groups. Abnormal glucose was found in 37 subjects: one with type 2 diabetes mellitus (from the previously glucose-intolerant subjects), 10 with glucose intolerance, and 27 with impaired fasting glucose. According to Boney criteria, 6.6% of the patients (6–18 years old) exhibited metabolic syndrome (MS) (69.4% AGA, 12.9% SGA, and 17.7% LGA). Conclusions: Being born LGA represents a higher risk of severe obesity. At this age, the most frequent component of MS was an abnormal lipid profile with low high-density lipoprotein and high triglycerides. Finally, the most frequent finding associated with abnormalities of glucose tolerance was a family history of diabetes. Thus, BW, lipid profile, and family history are mandatory when these patients are evaluated.

Metformin for the Treatment of Hyperandrogenism in Adolescents with Type 1 Diabetes Mellitus

Background: A high prevalence of hyperandrogenism has been reported in women with type 1 diabetes (T1D). Metformin has been used as a therapeutic agent in patients with polycystic ovarian syndrome and in T1D patients without hyperandrogenism. This study sought to determine the effect of metformin on hyperandrogenism and ovarian function in adolescents with T1D. Methods: We recruited 24 girls with T1D. The participants had hyperandrogenism and displayed suboptimal metabolic control. The patients were enrolled in a randomized, double-blind, placebo-controlled trial. One group received metformin (850 mg bid) and the other group received a placebo. Treatment was administered for 9 months. Ovulation, steroids and gonadotropin levels were evaluated. Results: Metformin treatment was associated with decreases in testosterone, free androgen index, androstenedione, 17-OH progesterone and estradiol levels. The girls who were treated with placebo showed stable steroid, gonadotropin and sex hormone-binding globulin levels during the analysis. No differences were observed in the Ferriman-Gallwey scores, ovulation rates, HbA1c levels or daily insulin doses of the girls treated with metformin compared with the placebo group. Conclusion: Treating hyperandrogenic T1D adolescents with metformin significantly decreased the serum androgens compared to the placebo, but metformin therapy did not significantly affect clinical parameters, such as hirsutism, ovulation and metabolic control.

Hipopituitarismo congénito: Experiencia en 23 casos

Congenital hypopituitarism is an uncommon causeof hypophyseal insufficiency. It is less common than growth hormone deficiency, which has anincidence of 1:4.000 to 1:8.000 live newborns. Early diagnosis of this condition is important toprevent impairment of cognitive function, poor growth and alterations in metabolic profile inthese patients.

Pubarquia precoz: Experience in 173 cases

Background: Precocious pubarche (PP), defined as the development of sexual pubic hair before 8 years of age in females and before 9 years in males, is usually a benign condition but it can also be the first sign of an underlying disease. Aim: To analyze the etiology and perform a short term follow up in a cohort ofpatients with PP. Material and methods: A group of 173patients (158 females) consulted for PP with a mean age of 7.4+0.1 years. These patients were followed between 15 to 60 months. Anthropometric measurements, bone age, serum levels of total testosterone, 17 OH progesterone (17 OHP) and dehydroepiandrosterone sulphate (DHEAS) were evaluated. Results: Mean birth weight and length was 3024.1+50.5 g and 48.5+0.3 cm, respectively. Ten percent of children were small for gestational age at birth. Bone age was accelerated by 1.1+0.01 years. One hundred and twelve patients were classified as having idiopathic PP (64.7%; 105 females), 29 as central precocious puberty (16.8%; only females), 16 as exaggerated adrenarche (EA 9.2%; 13 females) and 16 as non classical adrenal hyperplasia (9.2%; 11 females). Conclusions: PP represents a common and usually benign sign. However, 26% of cases had a pathologic underlying condition. Therefore, all children with PP should be evaluated by a pediatric endocrinologist. Low birth weight was not frequent in this cohort and these patients did not show EA .

Polymorphisms in the Interleukin-6 Receptor Gene (Asp358Ala) and Body Mass Index in Chilean Women with Type 1 Diabetes

Introduction. Interleukin-6 receptor (IL6R) has been linked with type 2 diabetes and obesity. The presence of the Asp allele in Asp358Ala of IL6R has been linked with insulin resistance and weight gain. Aim. The aim of this study is to evaluate the frequency and the association of the Asp358Ala in the IL6R gene in Chilean women with type 1 diabetes (T1D) and its relationship with body mass index (BMI). Patients and Methods. One hundred and forty-five patients with T1D (N = 145) and healthy control women (N = 103) were recruited. The polymorphisms were studied with polymerase chain reaction and restriction fragment length polymorphisms. The effect of the polymorphisms on BMI and age of diagnosis was evaluated. Results. A higher frequency of the Asp allele was observed in patients with T1D compared with controls (0.483 vs. 0.364; p < 0.01). The Asp358Asp genotype was more prevalent in the T1D group compared with controls (0.152 vs. 0.097; p < 0.01). T1D patients younger than 19 years had a positive association of BMI–standard deviation scores with the Asp allele (p < 0.05). Finally, lower Glycated Hemoglobin 1c (HbA1c) levels were observed in patients carrying the Asp allele (p < 0.01). Conclusions. T1D in Chilean women appears to be associated with the presence of the Asp allele in IL6R. The IL6R polymorphism (Asp358/Asp) was associated with BMI in T1D patients. This genetic variant could have some role in weight gain in T1D women.