Nutritional modulation of insulin resistance

Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts

Clinical problems caused by obesity

Over the past few decades the incidence of obesity has doubled worldwide and current estimates classify more than 1.5 billion adults as overweight and at least 500 million of them as clinically obese, with body mass index (BMI) over 25 kg/m2 and 30 kg/m2, respectively. Obesity prevalence rates are steadily rising in the majority of the modern Western societies, as well as in the developing world. Moreover, alarming trends of weight gain are reported for children and adolescents, undermining the present and future health status of the pediatric population. To highlight the related threat to public health, the World Health Organization has declared obesity a global epidemic, also stressing that it remains an under-recognized problem of the public health agenda

Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice

Although most of the proposed beneficial effects of fiber consumption have been attributed to viscous and gel-forming properties of soluble fiber, it is mainly insoluble cereal fiber and whole grains that are strongly associated with reduced diabetes risk in prospective cohort studies, indicating that other unknown mechanisms are likely to be involved. We performed a long-term study investigating potential protective effects of adding soluble guar fiber (10% w/w) vs. insoluble cereal fiber (10% w/w) to an isoenergetic and macronutrient matched high-fat diet in obesity-prone C57BL/6J mice. After 45 weeks, mice fed soluble vs. insoluble fiber showed both significantly increased body weight (41.8±3.0 vs. 33.6±1.5 g, P=.03) and elevated markers of insulin resistance. In mice fed soluble fiber, energy loss via the feces was significantly lower and colonic fermentation with production of short chain fatty acids (SCFA) was markedly increased. Gene expression analysis in white adipose tissue showed significantly increased levels of the fatty acid target G-protein coupled receptor-40 in soluble fiber-fed mice. Liver gene expression in the insoluble fiber group showed a pattern consistent with increased fatty acid oxidation. The present results show that soluble vs insoluble dietary fiber added to a high-fat, Western-style diet differently affected body weight and estimates of insulin sensitivity in obesity-prone mice. Soluble fiber intake with increased SCFA production significantly contributed to digested energy, thereby potentially outweighing the well known short-term beneficial effects of soluble fiber consumption

Obesity : novel and unusual predisposing factors

To tackle the complexity of the global obesity epidemic, it is important to consider the many predisposing factors that underlie progressive and sustained weight gain. Some of the biological drivers for weight gain following initial weight loss include persistent changes in appetite hormones [including ghrelin and postprandial plasma peptide YY (PYY)], and ‘persistent metabolic adaptation’. However, many factors within our busy, stressful modern-day environment seem to conspire towards promotion of weight gain. These include the effects of sleep deprivation on appetite regulation, and the effects of modern-day technology on ‘attention competition’. These factors, combined with cultural and societal factors can result in a ‘mindless’ attitude regarding eating-related behaviour that is likely to predispose to weight gain. In addition to the external environment, our internal environment within the gut has also changed radically within the last few decades, resulting from changes in fibre intake, and increased ingestion of highly refined, sterilised and processed foods. Although contentious, these dietary changes have implications for our gut microbiota, and possible downstream effects on control of appetite and metabolism. In this brief review, we consider some of the novel predisposing factors for weight gain within our modern-day 21st century environments (both external and internal), and explore how legal terminology can help to conceptualise the numerous factors that contribute towards weight gain, and, ultimately the global obesity epidemic

Multiple roles of glyoxalase 1-mediated suppression of methylglyoxal glycation in cancer biology—involvement in tumour suppression, tumour growth, multidrug resistance and target for chemotherapy

Glyoxalase 1 (Glo1) is part of the glyoxalase system in the cytoplasm of all human cells. It catalyses the glutathione-dependent removal of the endogenous reactive dicarbonyl metabolite, methylglyoxal (MG). MG is formed mainly as a side product of anaerobic glycolysis. It modifies protein and DNA to form mainly hydroimidazolone MG-H1 and imidazopurinone MGdG adducts, respectively. Abnormal accumulation of MG, dicarbonyl stress, increases adduct levels which may induce apoptosis and replication catastrophe. In the non-malignant state, Glo1 is a tumour suppressor protein and small molecule inducers of Glo1 expression may find use in cancer prevention. Increased Glo1 expression is permissive for growth of tumours with high glycolytic activity and is thereby a biomarker of tumour growth. High Glo1 expression is a cause of multi-drug resistance. It is produced by over-activation of the Nrf2 pathway and GLO1 amplification. Glo1 inhibitors are antitumour agents, inducing apoptosis and necrosis, and anoikis. Tumour stem cells and tumours with high flux of MG formation and Glo1 expression are sensitive to Glo1 inhibitor therapy. It is likely that MG-induced cell death contributes to the mechanism of action of current antitumour agents. Common refractory tumours have high prevalence of Glo1 overexpression for which Glo1 inhibitors may improve therapy

The health benefits of dietary fibre

Background: Dietary fibre consists of non-digestible forms of carbohydrate, usually as polysaccharides that originate from plant-based foods. Over recent decades, our diet within Westernised societies has changed radically from that of our hominid ancestors, with implications for our co-evolved gut microbiota. This includes increased ingestion of ultra-processed foods that are typically impoverished of dietary fibre, and associated reduction in the intake of fibre-replete plant-based foods. Over recent decades, there has been a transformation in our understanding of the health benefits of dietary fibre. Objective: To explore the current medical literature on the health benefits of dietary fibre, with a focus on overall metabolic health. Data Sources: We performed a narrative review, based on relevant articles written in English from a PubMed search, using the terms ‘dietary fibre and metabolic health’. Results: In the Western world, our diets are impoverished of fibre. Dietary fibre intake associates with overall metabolic health (through key pathways that include insulin sensitivity) and a variety of other pathologies that include cardiovascular disease, colonic health, gut motility and risk for colorectal carcinoma. Dietary fibre intake also correlates with mortality. The gut microflora functions as an important mediator of the beneficial effects of dietary fibre, including the regulation of appetite, metabolic processes and chronic inflammatory pathways. Conclusions: Multiple factors contribute to our fibre-impoverished modern diet. Given the plethora of scientific evidence that corroborate the multiple and varied health benefits of dietary fibre, and the risks associated with a diet that lacks fibre, the optimization of fibre within our diets represents an important public health strategy to improve both metabolic and overall health. If implemented successfully, this strategy would likely result in substantial future health benefits for the population. View Full-Tex

A randomised controlled trial of the impact of structured written and verbal advice by community pharmacists on improving hypertension education and control in patients with high blood pressure

Purpose: This study was aimed to determine whether structured written and verbal education provided to patients by community pharmacists about high blood pressure (BP) and its treatment would be (a) better retained and (b) be associated with improved BP control as compared to patients receiving verbal advice only. Methods: The study was designed as a randomised controlled trial and was conducted in the West Midlands, UK, between January 2014 and June 2014. The primary outcome measures were differences in systolic and diastolic BP from baseline and retention of information about high BP assessed with a questionnaire at 2-, 4- and 26-week follow-up points. Results: A total of 64 adults were included in the study. At the week 26 follow-up, compared to participants in the control group, there was a significant improvement in the knowledge of intervention participants about the risks associated with high BP (p < 0.001) and awareness about potential adverse effects of the new BP medicine (p < 0.001). Similarly, there was a greater and more significant reduction in systolic BP in favour of the intervention group 8 mmHg (95% CI 2.1–13.3 p = 0.009) compared to 6 mmHg (95% CI 0.6–11.7 p = 0.02) in the control group at the week 4 follow-up. However, this greater effect of an intervention on BP was not sustained at the 26-week follow-up. For diastolic BP, there was no added effect of the intervention. Conclusion: This randomised controlled trial suggests that although written advice provided by community pharmacists in comparison to verbal advice was more effective in improving knowledge and understanding of patients about hypertension and its treatment, it did not lead to better blood pressure control

Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

Objective: To study the association of vaspin with glucose metabolism. Design: Cross-sectional and intervention study. Subjects and methods: The association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10). Results: Neither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009). Conclusion: Our results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

Human amylase gene copy number variation as a determinant of metabolic state

Introduction Humans have multiple genes encoding amylase that are broadly divided into salivary (AMY1) and pancreatic (AMY2) genes. They exhibit some of the greatest copy numbers of any human gene, an expansion possibly driven by increased dietary starch intake. Within the population, amylase gene copy number is highly variable and there is evidence of an inverse association between AMY1 copy number and BMI. Areas covered We examine the evidence for the link between AMY1 and BMI, its potential mechanisms, and the metabolic effects of salivary and pancreatic amylase, both in the gastrointestinal tract and the blood. Expert commentary Salivary amylase may influence postprandial ‘cephalic phase’ insulin release, which improves glucose tolerance, while serum amylase may have insulin-sensitizing properties. This could explain the favorable metabolic status associated with higher AMY1 copy number. The association with BMI is harder to explain and is potentially mediated by increased flux of undigested starch into the ileum, with resultant effects on short-chain fatty acids (SCFAs), changes in gut microbiota and effects on appetite and energy expenditure in those with low copy number. Future research on the role of amylase as a determinant of metabolic health and BMI may lead to novel therapies to target obesity