Excessive Caloric Intake Research Articles

A journey from microenvironment to macroenvironment: the role of metaflammation and epigenetic changes in cardiorenal disease.

Chronic non-communicable diseases have become a pandemic public problem in the 21st century, causing enormous burden on the economy, health and quality of life of societies. The role of a chronic inflammatory state in the pathogenesis of chronic disease has been more comprehensively recognized by recent findings. The new paradigm ‘metaflammation’ focuses on metabolism-induced (high fat or fructose-based diet or excessive calorie intake) chronic inflammation. There is a close correlation between the increased incidence of chronic kidney disease (CKD) and chronic heart failure with both increased inflammatory marker levels and western-type diet. In this review we describe the concept of metaflammation, its role in the development of CKD and chronic heart disease, the molecular and signalling pathways involved and the therapeutic consequences.

Endoscopy in the bariatric patient

Obesity has become a healthcare problem of epidemic proportions. The etiology is complex and mostly sedentary life style and excessive caloric intake have been implicated. Numerous interventions have been used to treat the disease of obesity. Lifestyle modification along with a combination of healthy diet and exercise are usually first line strategies. This is often not durable in the majority of severely obese individuals. Pharmacotherapy is slightly more effective but recidivism is high once the medication is stopped. Surgical intervention has been shown to be safe, effective and durable. In the last several decades, endoscopic approaches to this disease have become increasingly popular. Endoscopy is an invaluable tool in the armamentarium of any bariatric surgeon or gastroenterologist taking care of bariatric patients. Pre procedural endoscopy remains controversial but is often performed. Post procedural endoscopy is important in identifying various anatomical changes created after these procedures. Endoscopy is increasingly being utilized to manage complications. This requires a thorough knowledge of such normal and altered anatomy in bariatric patients. In this manuscript, the use of endoscopy in the various aspects of the care of the bariatric patient will be reviewed.

Dog owner’s accuracy measuring different volumes of dry dog food using three different measuring devices

Prior research demonstrates significant inaccuracy when repeatedly measuring the same amount of dry dog food using a dry-food measuring cup, bringing into question the accuracy of measuring devices. This study...

Gut-derived GIP activates central Rap1 to impair neural leptin sensitivity during overnutrition.

Nutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone of energy balance. Here, we aimed to identify a physiological signal that arises from excess caloric intake and negatively controls hypothalamic leptin action. We found that deficiency of the gastric inhibitory polypeptide receptor (Gipr) for the gut-derived incretin hormone GIP protected against diet-induced neural leptin resistance. Furthermore, a centrally administered antibody that neutralizes GIPR had remarkable antiobesity effects in diet-induced obese mice, including reduced body weight and adiposity, and a decreased hypothalamic level of SOCS3, an inhibitor of leptin actions. In contrast, centrally administered GIP diminished hypothalamic sensitivity to leptin and increased hypothalamic levels of Socs3. Finally, we show that GIP increased the active form of the small GTPase Rap1 in the brain and that its activation was required for the central actions of GIP. Altogether, our results identify GIPR/Rap1 signaling in the brain as a molecular pathway linking overnutrition to the control of neural leptin actions.

Increased Dietary Inflammatory Index Is Associated with Schizophrenia: Results of a Case-Control Study from Bahrain.

Background: Several studies have indicated that chronic low-grade inflammation is associated with the development of schizophrenia. Given the role of diet in modulating inflammatory markers, excessive caloric intake and increased consumption of pro-inflammatory components such as calorie-dense, nutrient-sparse foods may contribute toward increased rates of schizophrenia. This study aimed to examine the association between dietary inflammation, as measured by the dietary inflammatory index (DII®), and schizophrenia. Methods: A total of 120 cases attending the out-patient department in the Psychiatric Hospital/Bahrain were recruited, along with 120 healthy controls matched on age and sex. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a comprehensive food frequency questionnaire (FFQ). Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, sex, body mass index, education, employment, diabetes, hypertension, and cardiovascular disease with E-DII expressed both as a continuous variable and categorized as quartiles. Results: The mean E-DII score for the entire sample was 1.79 ± 1.52, indicating a generally pro-inflammatory diet. The cases with schizophrenia appeared to have a higher E-DII score compared to controls: 1.99 ± 1.39 vs. 1.60 ± 1.38, respectively (p = 0.009). For every one unit increase in the E-DII score, the odds of having schizophrenia increased by 62% (OR 1.62; 95% CI 1.17–2.26). Similarly, increased risk was observed when the E-DII was used as quartiles, with participants in most pro-inflammatory quartile 4 being nearly 6 times more likely to be schizophrenic than participants in the most anti-inflammatory group quartile 1 (OR 5.96; 1.74–20.38; p-trend = 0.01). Conclusions: The data suggest that a pro-inflammatory diet, as indicated by increasing E-DII score, is associated with schizophrenia. This is the first study to examine the association between the DII and schizophrenia in a Middle Eastern population. Although these results are consistent with findings from research conducted in depression, additional studies are required before generalizing the findings to other populations.

Comprehensive Approaches to Improving Nutrition: Future Prospects.

When it comes to nutrition, nearly everyone has an opinion. In the past, nutrition was considered to be an individual’s responsibility, however, more recently governments have been expected (by some) to share that responsibility by helping to ensure that marketing is responsible, and that food chains offer healthy meal choices in addition to their standard fare, for example. In some countries, governments have gone as far as to remove tax from unprocessed foods or to introduce taxes, such as that imposed on sugary soft drinks in the UK, Mexico, France and Norway. Following on from the sugar tax, chocolate might be next! Is this the answer to our burgeoning calorie intake and increasing poor nutritional status, or is there another approach? In this narrative we will focus on some of the approaches taken by communities and governments to address excess calorie intake and improve nutritional status, as well as some of the conflicts of interest and challenges faced with implementation. It is clear that in order to achieve meaningful change in the quality of nutritional intake and to reduce the long-term prevalence of obesity, a comprehensive approach is required wherein governments and communities work in genuine partnership. To take no or little action will doom much of today’s youth to a poor quality of life in later years, and a shorter life expectancy than their grandparents.

Diet-Induced Rabbit Models for the Study of Metabolic Syndrome.

Simple SummaryIn recent years, obesity and metabolic syndrome (MetS) have become more prevalent owing to increased unhealthy habits and sedentary lifestyles, becoming public health problems. Experimental studies have allowed us to explore the mechanisms underlying the pathophysiological processes related to MetS. Several research protocols can be carried out with minimal staff, maintenance, and resources in animals such as rabbits. High-fat diets enriched with other components, mainly cholesterol and sugars, result in the rapid development of hypercholesterolemia and vascular alterations as a response to dietary manipulation. Furthermore, other experimental models, including transgenic rabbits with altered expression of specific genes, have been used to decrease the duration of experimental studies and increase the response to diet.Obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and excessive caloric intake from processed food rich in fat and sugar. There are several definitions of MetS, but most of them describe it as a cluster of cardiovascular and metabolic alterations such as abdominal obesity, reduced high-density lipoprotein (HDL) and elevated low-density lipoprotein (LDL) cholesterol, elevated triglycerides, glucose intolerance, and hypertension. Diagnosis requires three out of these five criteria to be present. Despite the increasing prevalence of MetS, the understanding of its pathophysiology and relationship with disease is still limited. Indeed, the pathological consequences of MetS components have been reported individually, but investigations that have studied the effect of the combination of MeS components on organ pathological remodeling are almost nonexistent. On the other hand, animal models are a powerful tool in understanding the mechanisms that underlie pathological processes such as MetS. In the first part of the review, we will briefly overview the advantages, disadvantages and pathological manifestations of MetS in porcine, canine, rodent, and rabbit diet-induced experimental models. Then, we will focus on the different dietary regimes that have been used in rabbits to induce MetS by means of high-fat, cholesterol, sucrose or fructose-enriched diets and their effects on physiological systems and organ remodeling. Finally, we will discuss the use of dietary regimes in different transgenic strains and special rabbit breeds.

Can Healthier Food Demand be Linked to Farming Systems’ Sustainability? The Case of the Mediterranean Diet

Promoting healthier diets is strategic to solve the global societal challenge of excessive and unhealthy calorie intake that causes obesity and overweight and is responsible for chronic diseases that burden healthcare systems. The relationship between food and personal health is well established and in recent years it has originated a number of dietary recommendations from the World Health Organisation (WHO) focused on encouraging healthier diets. The environmental impact of food intake and of particular diets is a growing research area. However, neither research nor public policies, in particular, have been able so far to establish a link between promoting healthier diets and their impact on enhancing environmentally healthier farming systems and the sustainability of rural landscapes. This paper addresses this gap by presenting a multidisciplinary literature review which combines evidence from nutrition and health sciences with that from environmental, agrarian and sustainability studies on the impacts of foods and dietary patterns on the environment, ecosystems and rural landscape. This integrate d review, complemented with data analysis, highlights the Mediterranean diet as a healthier dietary pattern whose promotion could be beneficial to recover or maintain the sustainability of Mediterranean rural landscape. Hence, the second part of the paper focus on discussing the role of public policies in enabling the link between enhancing healthier diets and healthier farming systems in order to sustain rural landscapes since these play a key role in the sustainability of Mediterranean rural areas.

The Effect of Diet-Induced and Melanocortin Obesity on Expression of Tryptophan Hydroxylase 2 in the Dorsal Raphe Nucleus and Ventral Tegmental Area in Mice

Serotonin and its signaling pathways are involved in the central regulation of feeding behavior and energy metabolism. The most important role in this regulation is played by dopaminergic neurons of the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) which express tryptophan hydroxylase 2 (TPH2) catalyzing the rate-limiting step in serotonin synthesis. Changes in activity of the serotonin-synthesizing system in the DRN and VTA may significantly contribute to the development of metabolic disorders, including obesity. However, data on TPH2 expression in these brain regions in obesity are unavailable. The aim of this work was to compare immunohistochemically TPH2 expression in the DRN and VTA of C57Bl/6J (a/a) female mice with a diet-induced obesity (DIO) (caused by 8- and 16-week intake of high-calorie food) and C57Bl/6J (Ay/a) agouti mice with genetically predetermined melanocortin obesity. Double immunolabeling demonstrated that in DIO mice with a 16-week high-calorie diet TPH2 expression in the DRN (the main cerebral source of serotonin) decreases while in the VTA increases. In agouti mice, TPH2 expression in the DRN did not change while in the VTA increased. In DIO mice with a 8-week high-calorie diet and in C57Bl/6J (a/a) mice resistant to this diet, TPH2 expression did not change both in the DRN and VTA. Thus, DIO mice kept on a long-term (16 weeks) diet and agouti mice with melanocortin obesity exhibit specific changes in the serotonin synthesis that are lacking in diet-resistant mice. This finding indicates a crucial role of serotonin signaling in the organismal response to excessive caloric intake.

Modifiable factors associated with weight regain after bariatric surgery: a scoping review

Background: Although bariatric surgery is the most effective treatment for severe obesity, weight regain may still occur. While non-modifiable factors associated with weight regain have been explored, modifiable factors responsible for weight regain are understudied. This scoping review aimed to identify modifiable behaviors associated with weight regain after bariatric surgery. Methods: A systematic search was conducted in Medline, Google Scholar, Cochrane, National Collaborating Centre for Methods and Tools (NCCMT) and Practice-based Evidence in Nutrition (PEN) which included articles published between January 1990 and February 2 2017, for studies examining “weight regain” after bariatric surgery. A total of 293 citations were retrieved. Eligible articles must have examined modifiable factors and addressed weight regain, or a long-term post-operative phase in which weight regain may occur. After removing duplicates, 22 studies were included for thematic analysis. Results: Key modifiable factors associated with weight regain were identified and categorized under the following themes: poor dietary adherence (e.g. excessive calorie, carbohydrate, and alcohol intake), maladaptive eating behaviors (e.g. grazing, binging), lack of on-going follow-up with the bariatric team and insufficient physical activity. Conclusions: Health professionals and self-monitoring tools for patients who have undergone bariatric surgery may benefit from these findings to direct their education and interventions to target behavior change.

Macronutrient-Mediated Inflammation and Oxidative Stress: Relevance to Insulin Resistance, Obesity, and Atherogenesis.

The intake of macronutrients as components of a Western dietary pattern leads to oxidative stress and inflammation. Data were largely retrieved from our previous and most recent work. PubMed and Google Scholar were searched for recent articles on the effect of macronutrients/dietary intake on inflammation, insulin resistance, obesity, and atherogenesis. The most relevant, high-quality articles were included in our review. Our previous work has demonstrated the molecular mechanisms of macronutrient-mediated oxidative stress and inflammation. With the induction of inflammation, proinflammatory molecules potentially interfere with insulin signal transduction, thus causing insulin resistance. In addition, other molecules promote atherogenic inflammation. More recently, our work has also shown that certain foods are noninflammatory or anti-inflammatory and thus, do not interfere with insulin signaling. Finally, as obesity is induced by chronic excessive caloric intake, it is characterized by an increase in the expression of proinflammatory molecules, which are induced acutely by a Western diet. Caloric restriction, including fasting, is associated with a reduction in oxidative and inflammatory stress. This review summarizes and attempts to provide an up-to-date profile of the molecular mechanisms involved in macronutrient-mediated oxidative/inflammatory stress and its potential consequences. An understanding of these underlying mechanisms is crucial for making appropriate dietary choices.

311-LB: Gustatory Cortex Response to Sweet Taste Is Positively Correlated with Adiposity

How sweet taste perception promotes excess caloric intake, obesity and diabetes is debated. There is little evidence for altered sweet taste in obesity, and adiposity does not predict sweet liking. However, overweight and obese subjects generally prefer high fat, sweet stimuli. The effect of adiposity on brain responses to sweet taste has not been systematically assessed, particularly in adults. In this ongoing study, 8 normal weight women (BMI 23.4±2.2 kg/m2, age 47±14 y) and 7 women with obesity (BMI 48.8±9.2 kg/m2, age 44±10 y), underwent functional magnetic resonance imaging (fMRI) on a Siemens 3T Magnetom Prisma using 32-channel head coil. fMRI assessed brain responses to 0.40M and 0.10M sucrose sprayed onto the tongue as compared to water (7 sucrose and 17 water trials in each 5:52 min long scan). Two scans were acquired at each concentration, where 0.40M and 0.10M scans alternated and the first scan sucrose concentration was counterbalanced across subjects. Across the whole sample, BOLD activation from [Sucrose (0.40M) > water] was detected (p<0.01, k>10) in gustatory insula, sensorimotor cortex/rolandic operculum, right ventral striatum, and bilateral posterolateral orbital cortex (the latter only in [Sucrose (0.10M) > water]). After including BMI as a covariate, a positive association of BMI and [Sucrose (0.40M) > water] contrast was present in the left gustatory insula area (peak, p<0.005), right rolandic operculum and sensorimotor cortex (ps<0.008). There were no negative correlations between BMI and the [Sucrose (0.40M) > water] contrast. BMI did not correlate with the [Sucrose (0.10M) > water] contrast. These preliminary findings suggest that women with obesity have greater responses in gustatory cortex to sweet taste compared to lean women. This is consistent with reports that overweight and obese subjects generally prefer sweet foods. The data might also suggest that gustatory cortex reactivity is altered by excess adiposity, possibly complicating diet compliance. Disclosure R.V. Considine: None. S.S. Janetsian-Fritz: None. M.D. Picklesimer: None. S.E. Wainscott: None. M. Dzemidzic: None. D.A. Kareken: None. Funding American Diabetes Association (1-18-ICTS-036 to R.V.C.)

Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake

We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean± SE) 31.2± 1.6 years and BMI= 27± 1.5kg/m2. Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2weeks immediately followed by the alternate diet for 2weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508± 106kcal/day; p= 0.0001), with increased consumption of carbohydrate (280± 54kcal/day; p< 0.0001) and fat (230± 53kcal/day; p= 0.0004), but not protein (-2± 12kcal/day; p= 0.85). Weight changes were highly correlated with energy intake (r= 0.8, p< 0.0001), with participants gaining 0.9± 0.3kg (p= 0.009) during the ultra-processed diet and losing 0.9± 0.3kg (p= 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.

Modifiable factors associated with weight regain after bariatric surgery: a scoping review.

Background:Although bariatric surgery is the most effective treatment for severe obesity, weight regain may still occur. While non-modifiable factors associated with weight regain have been explored, modifiable factors responsible for weight regain are understudied. This scoping review aimed to identify modifiable behaviors associated with weight regain after bariatric surgery. Methods:A systematic search was conducted in Medline, Google Scholar, Cochrane, National Collaborating Centre for Methods and Tools (NCCMT) and Practice-based Evidence in Nutrition (PEN) which included articles published between January 1990 and February 2 2017, for studies examining "weight regain" after bariatric surgery. A total of 293 citations were retrieved. Eligible articles must have examined modifiable factors and addressed weight regain, or a long-term post-operative phase in which weight regain may occur.After removing duplicates, 22 studies were included for thematic analysis. Results:Key modifiable factors associated with weight regain were identified and categorized under the following themes: poor dietary adherence (e.g. excessive calorie, carbohydrate, and alcohol intake), maladaptive eating behaviors (e.g. grazing, binging), lack of on-going follow-up with the bariatric team and insufficient physical activity. Conclusions: Health professionals and self-monitoring tools for patients who have undergone bariatric surgery may benefit from these findings to direct their education and interventions to target behavior change.

Risk Factors for Overweight and Obesity among Children and Adolescents in Bangladesh: A Hospital Based Study

Background: Childhood obesity is becoming an epidemic globally as well as in Bangladesh. Although several risk factors are identified for overweight or obesity, limited studies have been done in our country. The objective of this study was to identify the risk factors of overweight and obesity in children and adolescents in Bangladesh.&#x0D; Methodology: It was a cross sectional study done in children, aged 5 to 16 years, attending the Paediatric Endocrine Clinic and Paediatric Outpatient Department, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka over a period of 18 months. Overweight and obese children as well as normal weight children were selected after considering inclusion and exclusion criteria. They were classified as case (overweight/obese) and control (normal weight) according to the Center‘s’ for Disease Control and Prevention age and sex specific growth chart. Among a total of 150 children 100 were cases and 50 were controls.&#x0D; Results: Majority of children in both the groups were male. Among cases 77% were obese and 23% were overweight. Analyzing the risk factors, it was found that first issue had 2.66 times, watching TV &gt;3 hr had 4.47 times, breast feeding &lt;6 month had 4.16 times, daily more caloric intake (approx.) had 17.36 times and maternal BMI &gt;24.9 had 2.70 times increased risk to develop obesity.&#x0D; Conclusion: The first issue, excess television watching, lack of exclusive breast feeding, excess calorie intake and having overweight/obese mother had higher risk to develop overweight or obesity in children and adolescents.&#x0D; Bangladesh J Child Health 2019; VOL 43 (1) :9-14

Nutrition transition – Pattern IV: Leads Bangladeshi youth to the increasing prevalence of overweight and obesity

Fast food and soft drinks consumption leading to excess calorie intake coupled with lack of acceptable physical activity has augmented the prevalence of overweight and obesity among the world population for the past few eras. A cross-sectional study was carried out among 475 youth selected by systematic random sampling attending in 27 established public and private universities and colleges of Bangladesh. The study was aimed to evaluate habitual facts associated with the prevalence of overweight and obesity among Bangladeshi youth. The rates of fast food consumption (once/week) are 50.6%, 43.7%, and 53.3% in overweight, pre-obese and obese-1 respondents accordingly and the rates of soft drinks consumption (4–6 times/week) are 40.5%, 59.2%, and 73.3% respectively for the same subjects. Moreover, approximately 40.8% of the youth went to fast food restaurants at least once per week and 27.2% went regularly (2 times/week). Youth having fast foods 2 times/week, consuming soft drinks 3–4 times/week were more likely to be obese. Besides, obesity epidemic was observed among those who have not the habit of doing physical exercise. This study provides evidence of increasing trend and threat to overweight and obesity for the Bangladeshi youth.

Endurance Exercise Prevents Metabolic Distress-induced Senescence in the Hippocampus.

Metabolic disorder such as obesity and type 2 diabetes caused by excess caloric intake is associated with an increased risk of neurodegenerative diseases. Endurance exercise (EXE) has been suggested to exert neuroprotective effects against the metabolic distress. However, the exact underlying molecular mechanisms responsible for the exercise-induced neuroprotection have not been fully elucidated. In this study, we investigated whether EXE-induced neuroprotection is associated with cellular senescence, neuroinflammation, and oxidative stress using a mouse model of obesity induced by a high-fat/high-fructose diet. C57BL/6 female mice (10 wk old) were randomly divided to three groups: normal chow diet group (CON, n = 11), high-fat diet/high-fructose (HFD/HF) group (n = 11), and high-fat diet/high-fructose + endurance exercise (HFD/HF + EXE) group (n = 11). HFD/HF + EXE mice performed treadmill running exercise for 60 min·d, 5 d·wk for 12 wk. Our data showed that EXE ameliorated HFD/HF-induced weight gain, fasting blood glucose levels, and visceral fat gain. More importantly, HFD/HF diet promoted cellular senescence, whereas EXE reversed it, evidenced by a reduction in the levels of p53, p21, p16, beta-galactosidase (SA-β-gal), and lipofuscin. Furthermore, EXE prevented HFD/HF-induced neuroinflammation (e.g., tumor necrosis factor-α and interleukin-1β) by inhibiting toll-like receptor 2 downstream signaling cascades (e.g., tumor necrosis factor receptor-associated factor 6, c-Jun N-terminal kinase, and c-Jun) in parallel with reduced reactive glial cells. This anti-inflammatory effect of EXE was associated with the reversion of HFD/HF-induced cellular oxidative stress. Our study provides novel evidence that EXE-induced antisenescence against metabolic distress in the hippocampus may be a key neuroprotective mechanism, preventing neuroinflammation and oxidative stress.

Dietary calories and lipids synergistically shape adipose tissue cellularity during postnatal growth

ObjectiveThe susceptibility to abdominal obesity and the metabolic syndrome is determined to a substantial extent during childhood and adolescence, when key adipose tissue characteristics are established. Although the general impact of postnatal nutrition is well known, it is not clear how specific dietary components drive adipose tissue growth and how this relates to the risk of metabolic dysfunction in adulthood. MethodsAdipose tissue growth including cell proliferation was analyzed in juvenile mice upon dietary manipulation with in vivo nucleotide labeling. The proliferative response of progenitors to specific fatty acids was assayed in primary cultures. Long-term metabolic consequences were assessed through transient dietary manipulation post-weaning with a second obesogenic challenge in adulthood. ResultsDietary lipids stimulated adipose tissue progenitor cell proliferation in juvenile mice independently of excess caloric intake and calorie-dependent adipocyte hypertrophy. Excess calories increased mitogenic IGF-1 levels systemically, whereas palmitoleic acid was able to enhance the sensitivity of progenitors to IGF-1, resulting in synergistic stimulation of proliferation. Early transient consumption of excess lipids promoted hyperplastic adipose tissue expansion in response to a second dietary challenge in adulthood and this correlated with abdominal obesity and hyperinsulinemia. ConclusionsDietary lipids and calories differentially and synergistically drive adipose tissue proliferative growth and the programming of the metabolic syndrome in childhood.

Chaos, mitochondria and type 2 diabetes; does type 2 diabetes arise from a metabolic dysrhythmia?

The increasing incidence of type 2 diabetes transcends all cultures, largely due to populations transitioning from traditional diets and manual occupations, to sedentary, calorific lifestyles. Excess calorie intake leads to intramuscular fat accumulation and insulin resistance. Physical inactivity causes underutilization of mitochondria causing dysfunction and inflammation. Both insulin resistance and mitochondrial dysfunction mechanisms are known to be closely related and to antagonise one another, although the precise nature of the relationship has eluded characterization. It is poorly understood why this mutual dysfunction progresses on to clinical diabetes in only some patients, why progression is often stepwise and why diabetes control only weakly predicts future cardiovascular disease in individuals. Clinical prediction in patients is therefore currently unsatisfactory and current linear assumptions require challenging.Cells contain networks of oscillating ionic fluxes. Cellular activity is characterised by complex patterns of fluctuation with sudden transitions between patterns. The non-linear nature of these oscillations is well characterised in neuronal activity, cardiac impulses and more recently mitochondria, but not previously in relation to diabetes. Cells under metabolic stress demonstrate complex fluctuations of mitochondrial distribution, coupling strength and synchronisation resulting in periodic or chaotic oscillations of function, causing accumulation of intracellular fat and excess reactive oxygen species (ROS), which exacerbates insulin resistance. Glucose, insulin and HbA1c in patients are also known to oscillate in complex patterns but the mechanisms and significance are largely unknown.Drawing on existing evidence and models from other diseases, a nonlinear, dynamical hypothesis of diabetes onset and progression is proposed. Insulin receptor pathways and mitochondria are treated as two populations of coupled, phase oscillators. Health or disease states depend on system stability or instability and reflect the balance of substrate supply and energy demand. The implication of this novel mechanism is that diabetes and the complications are not the consequence of a distinct pathological agent or pathway, but more an evolving dysrhythmia of normal cellular energetics systems, resulting from accumulated adverse lifestyle conditions. This hypothesis is proposed with the intention of stimulating research into non-linear dynamical constructs as an alternative to current linear models, to improve risk prediction and trajectory analysis in type 2 diabetes.

Understanding beverage taxation: Perspective on the Philadelphia Beverage Tax's novel approach.

Despite the growing global trend of sugar-sweetened beverage (SSB) taxes for their potential as an untapped source of revenue and as a public health boon, these legislative efforts remain controversial. Multiple articles have reviewed this trend in recent years from modeling of long-term impacts to short-term empirical studies, yet most comprehensive, long-term health impact assessments remain forthcoming. These multi-faceted efficacy studies combined with case-based assessments of the policy process, descriptive pieces highlighting unique features of the policy and reflective perspectives targeting unanswered questions create a comprehensive body of literature to help inform present and future legislative efforts. The passage of the Philadelphia Beverage tax required a mix of political entrepreneurs, timing and context; while uniquely employing a nonpublic health frame, specific earmarking and a broadened scope with the inclusion of diet beverages. This perspective on the Philadelphia Beverage Tax will describe the passage and novel features of the Philadelphia Beverage Tax with a discussion of the ethical questions unique to this case.Significance for public healthThe prevalence of obesity and its related non-communicable diseases has continued its upward trajectory globally, despite our decades-long awareness of this trend. Excess caloric intake is a principle factor for this growing global burden of disease − with overconsumption of liquid calories in the form of sugar-sweetened beverages (SSB) a central component of this imbalance. A relatively recent public health response to reduce SSB consumption and increase revenue for public health spending has been the passage of beverage taxes at the local, state and national levels. However, there are many nuances in the design, passage and goals for these beverage taxes globally. The Philadelphia Beverage Tax’s use of a non-health frame, its specified earmarking and its scope by including diet beverages both allowed for its passage and create unique ethical questions that have yet to be completely addressed by the literature. These ethical considerations in the context of the Philadelphia Beverage Tax’s passage are important for other public health professionals, policy-makers and advocates working towards their own legislative efforts.