Gender and race influence metabolic benefits of fitness in children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Increasing obesity and poor cardiovascular fitness (CVF) contribute to higher rates of type 2 diabetes mellitus (T2DM) in children. While the relative contributions of fitness and body fat on development of insulin resistance (IR) in children and adolescents remains unresolved, gender- and race-specific differences likely exist in the degree to which CVF influences IR and risk for T2DM. Better understanding of how gender and race affect interactions between body fat, CVF, and metabolic health would be helpful in designing effective and targeted strategies to reduce obesity-associated disease risk. We evaluated whether metabolic benefits of fitness on reducing inflammation and insulin resistance (IR) are affected by gender and race.</p> <p>Methods</p> <p>This cross-sectional study included 203 healthy children (mean age 12.2 y, 50% male, 46% non-Hispanic white (NHW), 54% racially diverse (RD)). Fasting insulin, glucose, hsCRP, and adiponectin were measured; race was self-reported; cardiovascular fitness (CVF) was evaluated by the Progressive Aerobic Cardiovascular Endurance Run. Associations between inflammation and gender, race, and CVF were evaluated using analysis of covariance. Multivariate regression analysis identified independent predictors of IR.</p> <p>Results</p> <p>Fitness and inflammation were inversely related in both males and females (p < 0.01); this effect was marginally stronger in RD children (p = 0.06) and non-overweight males (p = 0.07). High BMI (p < 0.001), low fitness (p = 0.006), and (female) gender (p = 0.003) were independently associated with higher HOMA-IR. In males, BMI and fitness, but not race independently predicted HOMA-IR. In females, BMI and race, but not fitness independently predicted HOMA-IR.</p> <p>Conclusions</p> <p>In middle school children, the beneficial effects of fitness vary based on gender and race. High CVF has an enhanced anti-inflammatory effect in male and RD children. While BMI is the strongest predictor of IR in the study group as a whole, fitness is a significant predictor of IR only in males, and race is a significant predictor of IR only in females.</p

Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (>/= 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised beta range -0.07 to -0.14; all p </= 0.05). CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes

Inflammatory Adipokines, High Molecular Weight Adiponectin, and Insulin Resistance: A Population-Based Survey in Prepubertal Schoolchildren

BackgroundThe aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.MethodologyWe studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.Principal findingsLeptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (pConclusionsIn prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy

Prenatal Arsenic Exposure Alters Gene Expression in the Adult Liver to a Proinflammatory State Contributing to Accelerated Atherosclerosis

The mechanisms by which environmental toxicants alter developmental processes predisposing individuals to adult onset chronic disease are not well-understood. Transplacental arsenic exposure promotes atherogenesis in apolipoprotein E-knockout (ApoE−/−) mice. Because the liver plays a central role in atherosclerosis, diabetes and metabolic syndrome, we hypothesized that accelerated atherosclerosis may be linked to altered hepatic development. This hypothesis was tested in ApoE−/− mice exposed to 49 ppm arsenic in utero from gestational day (GD) 8 to term. GD18 hepatic arsenic was 1.2 µg/g in dams and 350 ng/g in fetuses. The hepatic transcriptome was evaluated by microarray analysis to assess mRNA and microRNA abundance in control and exposed pups at postnatal day (PND) 1 and PND70. Arsenic exposure altered postnatal developmental trajectory of mRNA and microRNA profiles. We identified an arsenic exposure related 51-gene signature at PND1 and PND70 with several hubs of interaction (Hspa8, IgM and Hnf4a). Gene ontology (GO) annotation analyses indicated that pathways for gluconeogenesis and glycolysis were suppressed in exposed pups at PND1, and pathways for protein export, ribosome, antigen processing and presentation, and complement and coagulation cascades were induced by PND70. Promoter analysis of differentially-expressed transcripts identified enriched transcription factor binding sites and clustering to common regulatory sites. SREBP1 binding sites were identified in about 16% of PND70 differentially-expressed genes. Western blot analysis confirmed changes in the liver at PND70 that included increases of heat shock protein 70 (Hspa8) and active SREBP1. Plasma AST and ALT levels were increased at PND70. These results suggest that transplacental arsenic exposure alters developmental programming in fetal liver, leading to an enduring stress and proinflammatory response postnatally that may contribute to early onset of atherosclerosis. Genes containing SREBP1 binding sites also suggest pathways for diabetes mellitus and rheumatoid arthritis, both diseases that contribute to increased cardiovascular disease in humans

What works for whom in the management of diabetes in people living with dementia: a realist review

Background Dementia and diabetes mellitus are common long-term conditions and co-exist in a large number of older people. People living with dementia (PLWD) may be less able to manage their diabetes, putting them at increased risk of complications such as hypoglycaemia. The aim of this review was to identify key mechanisms within different interventions that are likely to improve diabetes outcomes in PLWD. Methods This is a realist review involving scoping of the literature and stakeholder interviews to develop theoretical explanations of how interventions might work, systematic searches of the evidence to test and develop the theories and their validation with a purposive sample of stakeholders. Twenty-six stakeholders — user/patient representatives, dementia care providers, clinicians specialising in diabetes or dementia and researchers — took part in interviews, and 24 participated in a consensus conference. Results We included 89 papers. Ten focused on PLWD and diabetes, and the remainder related to people with either dementia, diabetes or other long-term conditions. We identified six context-mechanism-outcome configurations which provide an explanatory account of how interventions might work to improve the management of diabetes in PLWD. This includes embedding positive attitudes towards PLWD, person-centred approaches to care planning, developing skills to provide tailored and flexible care, regular contact, family engagement and usability of assistive devices. An overarching contingency emerged concerning the synergy between an intervention strategy, the dementia trajectory and social and environmental factors, especially family involvement. Conclusions Evidence highlighted the need for personalised care, continuity and family-centred approaches, although there was limited evidence that this happens routinely. This review suggests there is a need for a flexible service model that prioritises quality of life, independence and patient and carer priorities. Future research on the management of diabetes in older people with complex health needs, including those with dementia, needs to look at how organisational structures and workforce development can be better aligned to their needs. Trial registration PROSPERO, CRD42015020625. Registered on 18 May 2015

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies