Obesity, Insulin Resistance, Diabetes, and Cardiovascular Risk in Children

Autores: STEINBERGER, Julia; DANIELS Stephen R.

Atherosclerotic cardiovascular disease is the No. 1 killer in the adult population of Western societies, but the pathological processes and risk factors associated with its development have been shown to begin during childhood. Obesity plays a central role in the insulin resistance syndrome, which includes hyperinsulinemia, hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of atherosclerotic cardiovascular disease. The incidence of type 2 diabetes reported in children has increased alarmingly.

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Insulin Resistance and Cardiovascular Disease Risk Factors in Children of Parents With the Insulin Resistance (Metabolic) Syndrome

Autores: PANKOW, James S. et al.

OBJECTIVE— To evaluate whether children of parents with the insulin resistance syndrome (IRS) themselves have greater insulin resistance and unfavorable patterns of cardiovascular disease (CVD) risk factors.

RESEARCH DESIGN AND METHODS— This cross-sectional study included 220 white and 36 black children aged 11–15 years identified through a school-based blood pressure screening program, along with 378 of their parents. Measures of insulin resistance (glucose disposal per minute per kilogram of lean body mass in a euglycemic-hyperinsulinemic clamp [Mlbm] and fasting insulin), adiposity, and other CVD risk factors were compared in children with and without a parental history of IRS, defined according to the National Cholesterol Education Program Adult Treatment Panel III consensus definition.

RESULTS— Compared with children in whom neither parent had IRS, children who had at least one parent with the syndrome had statistically significantly lower meanMlbm (12.1 vs. 13.6 mg _ kg–1 _ min–1; P _ 0.04) and higher fasting insulin (geometric means 99 vs. 76 pmol/l; P _ 0.01) after adjustment for sex, race, age, and Tanner stage. Mean BMI, waist circumference, waist-to-hip ratio, triceps and subscapular skinfolds, and percentage of body fat were also significantly higher in children of an affected parent, but there were no significant differences in lipid or blood pressure levels between the two groups.

CONCLUSIONS— Insulin resistance and obesity may be the earliest manifestations of IRS in children with a parental history of the syndrome.

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Insulin resistance and triglyceride/HDLc index are associated with coronary artery disease

Autores: BERTOLUCI, Marcelo C et al.

Abstract

Background: Insulin-resistance is associated with cardiovascular disease but it is not used as a marker for disease in clinical practice.

Aims: To study the association between the homeostatic model assessment (HOMA-IR) and triglyceride/HDLc ratio (TG/HDLc) with the presence of coronary artery disease in patients submitted to cardiac catheterization.

Methods: In a cross-sectional study, 131 patients (57.0 ± 10 years-old, 51.5% men) underwent clinical, laboratory and angiographic evaluation and were classified as No CAD (absence of coronary artery disease) or CAD (stenosis of more than 30% in at least one major coronary artery).

Results: Prevalence of coronary artery disease was 56.7%. HOMA-IR and TG/HDLc index were higher in the CAD vs No CAD group, respectively: HOMA-IR: 3.19 (1.70-5.62) vs. 2.33 (1.44-4.06), p = 0.015 and TG/HDLc: 3.20 (2.38-5.59) vs. 2.80 (1.98-4.59) p = 0.045) - median (p25-75). After a ROC curve analysis, cut-off values were selected based on the best positive predictive value for each variable: HOMA-IR = 6.0, TG/HDLc = 8.5 and [HOMA-IR×TG/HDLc] = 28. Positive predictive value for coronary artery disease for HOMA-IR>6.0 was 82.6%, for TG/HDLc>8.5 was 85.7% and for [HOMA-IR×TG/HDLc]>28 was 88.0%. Adjusted relative risk (age, gender, diabetes, body mass index, systolic blood pressure) for the presence of coronary artery disease was: for HOMA-IR>6.0, 1.47 (95.CI: 1.06-2.04, p = 0.027), for TG/HDLc>8.5, 1.46 (95% CI:1.07-1.98), p = 0.015) and for [HOMA-IR × TG/HDLc] >28, 1.64 (95%CI: 1.28-2.09), p < 0.001).

Conclusions: Increased HOMA-IR, TG/HDLc and their product are positively associated with angiographic coronary artery disease, and may be useful for risk stratification as a high-specificity test for coronary artery disease.

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Large effects on body mass index and insulin resistance of fat mass and obesity associated gene (FTO) variants in patients with polycystic ovary syndrome (PCOS)

Autores: TAN, Susanne et al.

Background: The polycystic ovary syndrome (PCOS), a common endocrine disorder in women of child-bearing age, mainly characterised by chronic anovulation and hyperandrogenism, is often associated with insulin resistance (IR) and obesity. Its etiology and the role of IR and obesity in PCOS are not fully understood. We examined the influence of validated genetic variants conferring susceptibility to obesity and/or type 2 diabetes mellitus (T2DM) on metabolic and PCOS-specific traits in patients with PCOS.

Methods: We conducted an association study in 386 patients with PCOS (defined by the Rotterdam-criteria) using single nucleotide polymorphisms (SNPs) in or in proximity to the fat mass and obesity associated gene (FTO), insulin-induced gene-2 (INSIG2), transcription factor 7-like 2 gene (TCF7L2) and melanocortin 4 receptor gene (MC4R). To compare the effect of FTO obesity risk alleles on BMI in patients with PCOS to unselected females of the same age range we genotyped 1,971 females from the population-based KORA-S4 study (Kooperative Gesundheitsforschung im Raum Augsburg, Survey 4).

Results: The FTO risk allele was associated with IR traits and measures of increased body weight. In addition, the TCF7L2 SNP was associated with body weight traits. For the SNPs in the vicinity of INSIG2 and MC4R and for the other examined phenotypes there was no evidence for an association. In PCOS the observed per risk allele effect of FTO intron 1 SNP rs9939609 on BMI was +1.56 kg/m2, whereas it was +0.46 kg/m2 in females of the same age range from the general population as shown previously.

Conclusion: The stronger effect on body weight of the FTO SNP in PCOS might well have implications for the etiology of the disease.

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Hiperandrogenismo e pele: Síndrome do Ovário Policístico e Resistência Periférica à Insulina

Autores: YARAK, Samira et al.

RESUMO: A síndrome do ovário policístico é distúrbio endócrino feminino, extremamente comum na idade reprodutiva. Caracteriza-se por anormalidades menstruais, hiperandrogenismo e/ou hiperandrogenemia. A principal alteração na fisiopatologia é desconhecida. Entretanto, parece que a resistência à insulina, o hiperandrogenismo e a alteração na dinâmica das gonadotropinas são os mais importantes mecanismos fisiopatológicos envolvidos. As características clínicas mais freqüentes da síndrome do ovário policístico estão relacionadas com a unidade pilossebácea, como hirsutismo, acne, seborréia e alopecia. Desse modo, o dermatologista pode ser responsável pelo diagnóstico precoce da síndrome, evitando o retardo na instituição de medidas terapêutico-preventivas. Atualmente, as drogas recomendadas para as manifestações cutâneas da síndrome do ovário policístico são os contraceptivos orais conjugados, antiandrógenos e sensibilizantes de insulina e, além disso, é geralmente recomendada a modificação no estilo de vida. Trata-se de artigo de revisão sobre diagnóstico, fisiopatologia e tratamento da síndrome do ovário policístico. Os autores enfatizam que o conhecimento da fisiopatologia dessa síndrome, principalmente pelos dermatologistas, é fundamental para seu tratamento preventivo, nas diferentes fases da vida da mulher.

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Doenças associadas à Resistência à Insulina, Hiperinsulinemia, não incluídas na Síndrome Metabólica

Autores: CAVALHEIRA, José BC ; SAAD, Mário JA.

RESUMO: Nos últimos anos, no Brasil e em países do mundo desenvolvido, a obesidade se tornou um problema de saúde pública mais importante que a desnutrição. Com o aumento de prevalência de obesidade, identificou-se que, além do DM2 e da síndrome metabólica, outras entidades clínicas também estavam associadas à resistência à insulina. Nesta revisão, abordaremos algumas destas alterações, com destaque para a doença hepática gordurosa não alcoólica, mas incluindo também a SOP, a hiperuricemia, a doença renal crônica, a insuficiência cardíaca, alterações cognitivas e câncer.

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Role of Intestinal Epithelial Cells in Immune Effects Mediated by Gram-Positive Probiotic Bacteria: Involvement of Toll-Like Receptors

Autores: VINDEROLA, Gabriel ; MATAR, Chantal ; PERDIGON, Gabriela.

RESUMO

The mechanisms by which probiotic bacteria exert their effects on the immune system are not completely understood, but the epithelium may be a crucial player in the orchestration of the effects induced. In a previous work, we observed that some orally administered strains of lactic acid bacteria (LAB) increased the number of immunoglobulin A (IgA)-producing cells in the small intestine without a concomitant increase in the CD4_T-cell population, indicating that some LAB strains induce clonal expansion only of B cells triggered to produce IgA. The present work aimed to study the cytokines induced by the interaction of probiotic LAB with murine intestinal epithelial cells (IEC) in healthy animals. We focused our investigation mainly on the secretion of interleukin 6 (IL-6) necessary for the clonal expansion of B cells previously observed with probiotic bacteria. The role of Toll-like receptors (TLRs) in such interaction was also addressed. The cytokines released by primary cultures of IEC in animals fed with Lactobacillus casei CRL 431 or Lactobacillus helveticus R389 were determined. Cytokines were also determined in the supernatants of primary cultures of IEC of unfed animals challenged with different concentrations of viable or nonviable lactobacilli and Escherichia coli, previously blocked or not with anti-TLR2 and anti-TLR4. We concluded that the small intestine is the place where a major distinction would occur between probiotic LAB and pathogens. This distinction comprises the type of cytokines released and the magnitude of the response, cutting across the line that separates IL-6 necessary for B-cell differentiation, which was the case with probiotic lactobacilli, from inflammatory levels of IL-6 for pathogens.

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REVIEW ARTICLE: THE ROLE OF BUTYRATE ON COLONIC FUNCTION

Autores: Hamen, HM. et al.

O butirato, um ácido graxo de cadeia curta (AGCC), é o principal produto final da fermentação de fibras alimentares pela microbiota intestinal. É considerado uma importante fonte energética para as células epiteliais intestinais e propicia a manutenção da homeostase colônica.

Nessa revisão são descritas as considerações atuais sobre a bioatividade do butirato, enfatizando os efeitos e possíveis mecanismos de ação relacionados à função do cólon humano.

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