As humans evolved, perhaps the two strongest selection determinants of survival were a robust immune response able to clear bacterial, viral, and parasitic infection and an ability to efficiently store nutrients to survive times when food sources were scarce. These traits are not mutually exclusive. It is now apparent that critical proteins necessary for regulating energy metabolism, such as peroxisome proliferator-activated receptors, Toll-like receptors, and fatty acid-binding proteins, also act as links between nutrient metabolism and inflammatory pathway activation in immune cells. Obesity in humans is a symptom of energy imbalance: the scale has been tipped such that energy intake exceeds energy output and may be a result, in part, of evolutionary selection toward a phenotype characterized by efficient energy storage. As discussed in this review, obesity is a state of low-grade, chronic inflammation that promotes the development of insulin resistance and diabetes. Ironically, the formation of systemic and/or local, tissue-specific insulin resistance upon inflammatory cell activation may actually be a protective mechanism that co-evolved to repartition energy sources within the body during times of stress during infection. However, the point has been reached where a once beneficial adaptive trait has become detrimental to the health of the individual and an immense public health and economic burden. This article reviews the complex relationship between obesity, insulin resistance/diabetes, and inflammation, and although the liver, brain, pancreas, muscle, and other tissues are relevant, we focus specifically on how the obese adipose microenvironment can promote immune cell influx and sustain damaging inflammation that can lead to the onset of insulin resistance and diabetes. Finally, we address how substrate metabolism may regulate the immune response and discuss how fuel uptake and metabolism may be a targetable approach to limit or abrogate obesity-induced inflammation.

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The inflammation highway: metabolism accelerates inflammatory traffic in obesity

Background
Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts.

Objectives
To assess the efficacy of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

Search methods
We searched CENTRAL, MEDLINE and EMBASE for relevant randomized controlled trials published between 1966 to 2007.

Selection criteria
Women receiving at least one year of alendronate, for postmenopausal osteoporosis, were compared to those receiving placebo and/or concurrent calcium/vitamin D. The outcome was fracture incidence.

Data collection and analysis
We undertook study selection and data abstraction in duplicate. We performed meta-analysis of fracture outcomes using relative risks and a > 15% relative change was considered clinically important. We assessed study quality through reporting of allocation concealment, blinding and withdrawals.

Main results
Eleven trials representing 12,068 women were included in the review.

Relative (RRR) and absolute (ARR) risk reductions for the 10 mg dose were as follows. For vertebral fractures, a significant 45% RRR was found (RR 0.55, 95% CI 0.45 to 0.67). This was significant for both primary prevention, with 45% RRR (RR 0.55, 95% CI 0.38 to 0.80) and 2% ARR, and secondary prevention with 45% RRR (RR 0.55, 95% CI 0.43 to 0.69) and 6% ARR. For non-vertebral fractures, a significant 16% RRR was found (RR 0.84, 95% CI 0.74 to 0.94). This was significant for secondary prevention, with 23% RRR (RR 0.77, 95% CI 0.64 to 0.92) and 2% ARR, but not for primary prevention (RR 0.89, 95% CI 0.76 to 1.04). There was a significant 40% RRR in hip fractures (RR 0.60, 95% CI 0.40 to 0.92), but only secondary prevention was significant with 53% RRR (RR 0.47, 95% CI 0.26 to 0.85) and 1% ARR. The only significance found for wrist was in secondary prevention, with a 50% RRR (RR 0.50 95% CI 0.34 to 0.73) and 2% ARR.

For adverse events, we found no statistically significant differences in any included study. However, observational data raise concerns regarding potential risk for upper gastrointestinal injury and, less commonly, osteonecrosis of the jaw.

Authors' conclusions
At 10 mg per day, both clinically important and statistically significant reductions in vertebral, non-vertebral, hip and wrist fractures were observed for secondary prevention ('gold' level evidence, www.cochranemsk.org). We found no statistically significant results for primary prevention, with the exception of vertebral fractures, for which the reduction was clinically important ('gold' level evidence).

Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women

Sex differences in healthy human heart rate variability: A meta-analysis.

Studying the links between dietary patterns and obesity is especially relevant for Middle-Eastern populations because of their high prevalence of a particular type of obesity, the so-called Middle-Eastern pattern, and their diets' unique characteristics. Therefore, we wondered if major dietary patterns are related to the prevalence of general obesity and central adiposity among Iranian women. In this cross-sectional study of 486 women aged 40-60 y, usual dietary intakes were evaluated using a FFQ and anthropometric measurements. By the use of factor analysis, we extracted 3 major dietary patterns: healthy dietary pattern, western dietary pattern, and Iranian dietary pattern. Individuals in the upper category of the healthy pattern score were less likely to be generally (OR = 0.28; 95% CI = 0.14-0.53) and centrally obese (OR = 0.30; 95% CI = 0.16-0.55), whereas those in the upper quintile of western pattern had greater odds (for general obesity: 2.73; 95% CI = 1.46-5.08 and for central obesity: 5.74; 95% CI =2.99-10.99). Controlling for potential confounders attenuated the associations, but even after adjusting for energy intake, the associations were significant for both general and central obesity. Although the Iranian dietary pattern and general obesity were not significantly associated, subjects in the highest quintile had greater odds of being centrally obese, either before (OR = 2.15; 95% CI = 1.18-3.90) or after (OR = 2.08; 95% CI = 1.09-3.65) control for confounders. This study indicates significant associations among major dietary patterns, general obesity, and central adiposity in a Middle-Eastern country. Further prospective investigations are required to confirm such associations.

Major Dietary Patterns in Relation to General Obesity and Central Adiposity among Iranian Women

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO₂, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO₂ exposure was associated with lower levels of FEV₁ (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁ (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.

https://erj.ersjournals.com/content/erj/45/1/38.full.pdf

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis

Background Obese people have a higher prevalence of cardiovascular disease, but the mechanism of this result remains obscure. The purpose of this study was to prove heart rate variability (HRV) response at rest and during stimuli in these persons. Methods The subjects were 41 healthy persons (19 men, 22 women) ranging in age from 20 to 65 years. HRV was measured at rest and at given stresses with noise and standing. Results Higher levels of fat mass, percentage fat content, and waist/hip ratio were significantly associated with lower low frequency (LF) (r = -0.34, r = -0.43; P .05). Conclusion Although there was no significant HRV response to stimuli, root mean square of successive differences (which reflects parasympathetic acivity) and low frequency (which mainly reflects sympathetic activity) were negatively correlated with fat mass, fat percentage, and waist-to-hip ratio at rest in obese persons. These results mean obesity can change cardiac autonomic nervous response, meaning that the mechanism by which obesity increases cardiac mortality would be explained, at least partially.

Heart rate variability and obesity indices: emphasis on the response to noise and standing.

The presence of metabolic syndrome in children and adolescents represents a high-risk state that conveys an increased risk of metabolic disease (1,2). The importance of the role of dietary patterns cannot be overemphasized because of the relation to metabolic disease. Although previous studies show that some dietary patterns are related to the risk of the metabolic syndrome (3–6), these studies focus on adults and were rarely conducted on children or adolescents in a nationally based survey. Therefore, the aim of this study was to identify dietary patterns and to examine the association between dietary patterns and the metabolic syndrome in Korean adolescents. Although studies on the Korean population may yield unique results primarily due to the ethnic homogeneity inherent to the Korean population with very little genetic diversity, the results tend to be applicable to other countries as well.

The 2001 Korean National Health and Nutrition Survey, a cross-sectional and nationally representative survey, was conducted from November to December 2001. A stratified, multistage, probability sampling design was used, with selection made from sampling units. Weights indicating the probability of being sampled were assigned to each participant, which enabled the results to represent the entire Korean population.

A total of 12,441 individuals participated in the Health Interview Survey, which included a 24-h dietary intake recall. …

https://care.diabetesjournals.org/content/diacare/30/7/1904.full.pdf

Dietary Patterns and the Metabolic Syndrome in Korean Adolescents: 2001 Korean National Health and Nutrition Survey

The association between abdominal fat distribution and inflammatory markers is currently a subject of debate Here, we delineate the relationship between white blood cell (WBC) counts and abdominal fat distribution in female obese adolescents A total of 102 female obese adolescent subjects were analyzed Anthropometry, WBC count, blood pressure, fasting plasma glucose, lipid profiles, and fasting insulin concentrations were measured Subcutaneous adipose tissue (SAT) and visceral adipose tissue areas were calculated using computed tomography Mean values of waist circumference (P < 05), total adipose tissue (TAT) (P < 01), and SAT (P < 01) were significantly higher in the group with the higher WBC count The WBC count was positively related to body mass index, waist circumference, and TAT and SAT areas after adjustment for age and metabolic risk factors (P < 01) Among the WBC components, neutrophils were positively associated with body mass index (P < 01), waist circumference (P < 01), and TAT (P < 05) The WBC count escalated with a graded increase in TAT or SAT (P for trend < 01) Our findings collectively indicate that the WBC count is positively related to abdominal adiposity in female obese adolescents Moreover, this relationship is more distinguishable with subcutaneous than visceral adiposity

White blood cell count and abdominal fat distribution in female obese adolescents.

Inflammation and thrombogenesis have been suggested as possible causes for cardiovascular events in patients suffering from metabolic syndrome (MS). The primary objective of this study was to determine the relationship between red blood cell (RBC) or white blood cell (WBC) subtypes and MS. The secondary objective was to reveal any gender differences inherent to this association. Body mass index (BMI), blood pressure, serum high-density lipoprotein cholesterol, triglycerides, and glucose were measured. The numbers of WBC subtypes and RBCs were determined in healthy adults. In male subjects, the numbers of total leukocytes, neutrophils, and lymphocytes was elevated in the MS patients (P<0.05). In the male subjects, the numbers of total leukocytes, neutrophils, and lymphocytes were elevated in accordance with the metabolic component count (P<0.05). RBC, monocyte, eosinophil, and basophil counts did not differ in accordance with metabolic component counts (r = 0.406, r = 0.304, r = 0.366; P<0.05). In the female subjects, we determined there to be no differences in the numbers of RBC and WBC subtypes in the MS patients, in accordance with metabolic component counts. The numbers of total leukocytes, neutrophils, and lymphocytes were elevated in the male MS subjects in this study, and these counts increased in accordance with the metabolic component counts. In the female subjects in this study, we determined there to be no association between RBC and WBC subtype counts with MS.

https://www.jstage.jst.go.jp/article/endocrj/53/1/53_1_133/_pdf

Association of metabolic syndrome with white blood cell subtype and red blood cells.

We examined the association between heart rate variability (HRV) and survival duration to evaluate the usefulness of HRV as a prognostic factor for hospice cancer patients. In terminally ill cancer patients who visited the Hospice clinic, we checked demographic data, Karnofsky performance scale (KPS), HRV, dyspnea, anorexia, as well as fasting blood glucose and total cholesterol. After following up their duration of survival, we examined meaningful prognostic factors for predicting life expectancy through the survival analysis. A total of 68 patients were included in final analysis. As KPS was lower, or when combined with dyspnea or anorexia, the survival duration was much shorter. HRV parameters except heart rate were all impaired in most patients. In particular, the group with mean heart rate of 100 or more beats per minute and the group with standard deviations of normal-to-normal R-R intervals (SDNN) of 21.3 ms (75 percentile) or less showed significantly shorter survival duration. The final multivariate analysis adjusting for age, gender, fasting blood glucose, and total cholesterol showed that KPS, dyspnea, anorexia, and SDNN were significant prognostic factors in survival duration. For the first time, we report that SDNN is a prognostic factor in terminal cancer patients.

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Jeong A Kim

Papers

Heart rate variability and obesity indices: emphasis on the response to noise and standing.

Dietary Patterns and the Metabolic Syndrome in Korean Adolescents: 2001 Korean National Health and Nutrition Survey

White blood cell count and abdominal fat distribution in female obese adolescents.

Association of metabolic syndrome with white blood cell subtype and red blood cells.

Heart Rate Variability and Length of Survival in Hospice Cancer Patients