Francisco Pérez-Bravo

Objective vs. Self-Reported Physical Activity and Sedentary Time: Effects of Measurement Method on Relationships with Risk Biomarkers

Purpose Imprecise measurement of physical activity variables might attenuate estimates of the beneficial effects of activity on health-related outcomes. We aimed to compare the cardiometabolic risk factor dose-response relationships for physical activity and sedentary behaviour between accelerometer- and questionnaire-based activity measures. Methods Physical activity and sedentary behaviour were assessed in 317 adults by 7-day accelerometry and International Physical Activity Questionnaire (IPAQ). Fasting blood was taken to determine insulin, glucose, triglyceride and total, LDL and HDL cholesterol concentrations and homeostasis model-estimated insulin resistance (HOMAIR). Waist circumference, BMI, body fat percentage and blood pressure were also measured. Results For both accelerometer-derived sedentary time (<100 counts.min−1) and IPAQ-reported sitting time significant positive (negative for HDL cholesterol) relationships were observed with all measured risk factors – i.e. increased sedentary behaviour was associated with increased risk (all p≤0.01). However, for HOMAIR and insulin the regression coefficients were >50% lower for the IPAQ-reported compared to the accelerometer-derived measure (p<0.0001 for both interactions). The relationships for moderate-to-vigorous physical activity (MVPA) and risk factors were less strong than those observed for sedentary behaviours, but significant negative relationships were observed for both accelerometer and IPAQ MVPA measures with glucose, and insulin and HOMAIR values (all p<0.05). For accelerometer-derived MVPA only, additional negative relationships were seen with triglyceride, total cholesterol and LDL cholesterol concentrations, BMI, waist circumference and percentage body fat, and a positive relationship was evident with HDL cholesterol (p = 0.0002). Regression coefficients for HOMAIR, insulin and triglyceride were 43–50% lower for the IPAQ-reported compared to the accelerometer-derived MVPA measure (all p≤0.01). Conclusion Using the IPAQ to determine sitting time and MVPA reveals some, but not all, relationships between these activity measures and metabolic and vascular disease risk factors. Using this self-report method to quantify activity can therefore underestimate the strength of some relationships with risk factors.

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55±15.05 vs. 33.95±20.40 weeks, P<0.01). In addition, exposure to cows milk and solid foods occurred earlier in the diabetic group than in the control group (15.90±10.95 vs. 21.15 13.65 and 16.85±10.25 vs. 21.20±12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cows milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes

INTRODUCTION It is well established that type 1 diabetes (T1D) is an autoimmune disease. Controversial data exists regarding the differential control of the immune system in T1D patients compared to unaffected individuals. MicroRNAs (miRNAs) are involved in the control of gene expression (by negative regulation of gene expression at post-transcriptional level, by mediating translational repression or degradation of the mRNA targets). Their potential role in T cell activation and autoimmunity is controversial. AIM We investigated the expression profile of miR-21a and miR-93 in PMC samples of 20 T1D patients and 20 healthy controls by means of qPCR in different glucose concentrations (basal, 11 nM and 25 mM), and we analyzed the possible relationship of this expression pattern with autoimmunity. RESULTS MiR-21a was significantly underexpressed in T1D samples (media values expression 0.23 ± 0.05, p < 0.01) compared to controls (values less than 1 indicate a decrease in gene expression). When the PMCs were incubated with glucose 11 mM and 25 mM, miR-21a expression decreased in controls and increased in T1D samples (0.506 ± 0.05, p < 0.04). MiR-93 was underexpressed in T1D patients (0.331 ± 0.05, p < 0.02) compared to control samples. However, when the PBMCs were incubated with glucose, no changes were observed. No association with autoimmunity was observed. CONCLUSION We demonstrated that miRNAs have a differential expression in PBMCs from T1D patients compared to controls, suggesting that these miRNAs or others could be involved in T cell regulation.

Low prevalence of type 2 diabetes despite a high average body mass index in the aymara natives from chile

The aim of this study was to estimate the prevalence of type 2 diabetes mellitus (DM2), impaired glucose tolerance (IGT), and the frequency of dyslipidemia, obesity, and hypertension in the rural Aymara population from Northern Chile. In this cross-sectional study, 196 Aymara adult subjects were characterized with respect to their reported physical activity, fasting plasma glucose levels, insulin concentrations, blood pressures, body mass indexes, and plasma lipid profiles. The participants also underwent a 2-h oral glucose tolerance test. The diagnostic criteria for DM2 and IGT followed those of the World Health Organization. The overall prevalence of DM2 was estimated as 1.5% (95% confidence interval: 0.3--4.5). Overall prevalence of IGT was calculated as 3.6% (1.5--7.3). The occurrence of obesity and dyslipidemia was relatively high in the Aymara population, although the frequency of sedentary habits, and the prevalence of hypertension were low. In conclusion, the prevalence of DM2 in the rural Aymara population living at high altitudes in Northern Chile, was much lower than that of other Amerindian groups that adopted lifestyles from industrialized Western societies. Despite a relatively high prevalence of a body mass index of at least 30 kg/m(2), especially in women (23.5%), high physical activity levels and low plasma-insulin concentrations may have been responsible in part for the low prevalence of DM2 in the Aymara population.

Breast-Feeding and Childhood-Onset Type 1 Diabetes: A pooled analysis of individual participant data from 43 observational studies

OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64–0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75–1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81–1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78–1.00). These associations were all subject to marked heterogeneity (I2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75–0.99), and heterogeneity was reduced (I2 = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

Celiac disease in a Chilean population carrying Amerindian traits.

Background Although clinical manifestations of celiac disease may change throughout life, clinical, histologic, immunologic, and genetic studies show that there are incomplete forms of this condition, making it difficult to define the disease at a given moment. Because there is no information published in the Latin American-Amerindian population, this study was conducted to assess relations between these parameters in Chileans with celiac disease and their first-degree relatives. Methods Sixty-two persons with confirmed celiac disease (mean age, 17.9 ± 5.1 years; 78.3% females) and 126 relatives (mean age, 27.9 ± 17.2 years; 65.1% females) were evaluated. Clinical manifestations, antiendomysial antibodies (EMAs), and human leukocyte antigen (HLA) haplotypes were studied in patients. Additionally, jejunal biopsy specimens were assessed (light microscopy) in EMA-positive (EMA+) relatives. Results Of the patients, 24.1% adhered to a strict gluten-free diet; 26% were oligosymptomatic, and none were malnourished; 45% were EMA+; 13.8% who ingested gluten were EMA-negative (EMA−); one patient consuming a strict gluten-free diet was EMA+. The DQA1*0501 allele was present in the highest frequency (48%, P < 0.0005), whereas combinations of DQ8 were predominant. Of the relatives, 4.8% were EMA+; they had a significantly higher frequency of diarrhea, weight loss, and anorexia (P < 0.03); and all had abnormal histology in biopsy specimens. Conclusions After childhood, celiac disease is oligosymptomatic and is often unrecognized by patients. Disease in 13.8% of patients and in 4.8% relatives appeared as incomplete forms of celiac disease. Predominance of DQ8 HLA haplotypes reflects the genetic Spanish-Mapuche heritage of this population.

Prevalence of Type 2 Diabetes and Obesity in Rural Mapuche Population From Chile

The aim of this study was to estimate the prevalence of Type 2 diabetes, impaired glucose tolerance (IGT), and obesity in the Mapuche natives from rural areas in Chile. This cross-sectional study involved men (n = 95) and women (n = 224) older than 20 y from an aboriginal ethnic group (Mapuches), residing in rural communities from the south of Chile. Prevalence of Type 2 diabetes and IGT was calculated according to the World Health Organization criteria. Data on age, degree of ancestral purity, obesity, and hypertension were also obtained. The prevalence of Type 2 diabetes in rural Mapuche natives was estimated as 3.2% (95% CI: 0.7--9.0) in men and 4.5% (95% CI: 2.2--8.1) in women. The overall prevalence of obesity was 56.1% (95% CI: 50.5--61.6): 40.0% (95% CI: 30.1--40.8) in men and 62.9% (95% CI: 56.3--69.3) in women (P value < 0.001). These data suggest that the prevalence of obesity and Type 2 diabetes has been increasing during recent years in the Mapuche communities. The prevalence estimated in this study is higher than that reported 15 y ago. This suggests an important role of lifestyle changes as a possible explanation for epidemiologic transition.

Leptin Levels and IgF-Binding Proteins in Malnourished Children: Effect of Weight Gain

OBJECTIVES Although it is well known that leptin reflects body fat content in adults, the regulation of leptin levels during childhood malnutrition is poorly understood. Insulin-like growth factor I (IGF-I) and the IGF-binding proteins (IGFBPs) may play important roles in the regulation of body composition. We investigated the relation between leptin, IGF-I, and IGFBPs in children with protein-energy malnutrition (PEM; before and after recovering 10% of their initial body weights) in comparison with well-nourished children. METHODS Fifteen PEM and 16 healthy children were studied on admission and after 10% weight gains in the malnourished group. Leptin was measured with radioimmunoassay, IGF-I and IGFBPs were measured with immunoradiometric assay. RESULTS Patients with PEM had a significantly lower body mass index and percentage of body fat than did the control children. Before weight gain, leptin, IGF-I, and IGFBP-3 were significantly lower and IGFBP-1 was elevated in the malnourished group compared with the control group. Among PEM patients, after 10% weight gains, the levels of leptin, IGF-I, and IGFBP-3 were significantly higher and IGFBP-1 significantly lower compared with the control group. Leptin correlated significantly with IGF-I in the normal children (r(s) = 0.86, P < 0.005). On admission, no correlation was observed between leptin and IGF-I (r(s) = 0.08, P < 0.16) and between leptin and IGFBP-3 (r(s) = 0.02, P < 0.27) in the malnourished group, but those levels improved after 10% recovery of their body weights (r(s) = 0.47, P < 0.002 and r(s) = 0.42, P < 0.005, respectively). In the PEM group, IGF-I correlated significantly with IGFBP-3 when the children gained weight (before: r(s) = 0.006, P < 0.31; after: r(s) = 0.32, P < 0.01). Our study showed results similar to those of anorexia nervosa studies, but the normalization of study variables was obtained in considerable less time for the same weight gain. CONCLUSIONS The main finding of this study was that, after refeeding with only a 10% weight gain, the PEM children normalized their leptin, IGF-I, and IGFBP-3 levels. These results provide evidence that leptin can function as link between this hormonal response and improved nutrition status.

Increasing incidence of type 1 diabetes in population from Santiago of Chile: trends in a period of 18 years (1986–2003)

The aim of this study is to determine the incidence rate of type 1 diabetes in the metropolitan region of Santiago, Chile from 1 January 1986 to 31 December 2003.

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.