Low Body Mass Index Individuals Research Articles

Gestational osteoporosis: Myth or true?

Gestational osteoporosis is an existent rare clinical disease presenting with vertebral fractures and is quite often underdiagnosed. Etiology is heterogeneous and risk factors include family history of osteoporosis, low body mass index individuals, women with low physical activity, smoking, failure to achieve maximum bone mass and low level calories nutrition. In our review, we recorded the main hormones and biological markers involved in bone metabolism during pregnancy and breastfeeding period. Regarding imaging methods, ultrasound and magnetic resonance are useful diagnostic tools and MRI can be used as a gold standard when examining hip pain in women who are in the third trimester of pregnancy. Available therapeutic approaches are recorded regarding conservative management and use of medication. The implication of our work is to emphasize the importance of early identification of gestational osteoporosis. Medical specialties dealing with women during pregnancy and postpartum (obstetricians, endocrinologists, orthopedists) should assess the risk factors and be able to make the right diagnosis as early as possible for prognosis optimization.

Lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

e16271 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. We have also shown that there are fewer total cells per area in the tumor region, suggesting a disorganization that may allow more adipose tissue to form in these areas of high BMI patients. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Significant lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.

438 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

An Atypical Form of Diabetes Among Low Body Mass Index Individuals in India

Background: Diabetes among low BMI individuals has been recognized for over 60 years as an entity that is prevalent in low- and middle-income countries (LMICs), and formally classified as Malnutrition-Related Diabetes Mellitus by the World Health Organization (WHO) in 1985. However, the WHO withdrew this category in 1999, citing a lack of supportive evidence. Definitive metabolic characterization of these individuals is therefore essential to establish that this is a distinct form of diabetes. Methods: State-of-the-art, dynamic metabolic studies were used to characterize a group of underweight (BMI 18.3±0.2 kg/m2) Southern Indian individuals with diabetes (“Low BMI Diabetes”; LD) in whom all currently known forms of diabetes were excluded by careful immunogenetic analysis. They were compared with four demographically-matched groups: type 1 diabetes (T1D), type 2 diabetes (T2D), and two groups of non-diabetic subjects who were BMI-matched to LD and T2D. To overcome ‘glucose toxicity‘, all subjects with diabetes underwent correction of hyperglycemia. Insulin secretion was assessed by C-peptide deconvolution, following a mixed-meal tolerance test. Hepatic and peripheral insulin sensitivity were analyzed using tracer-based stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Body composition was measured by Dual Energy Absorptiometry (DEXA) and hepatic and myocellular lipid contents were assessed by 1 H-nuclear-magnetic-resonance-spectroscopy. Findings: Metabolic profiles of LD subjects were distinct from T1D and T2D. Insulin secretion was substantially lower in LD than in T2D, yet higher than in T1D. Although insulin sensitivity varied among LD subjects, they were more insulin sensitive than T2D subjects. Their peripheral insulin sensitivity did not differ from T1D subjects. Endogenous glucose production, a marker of hepatic insulin resistance, was similar in LD compared to T1D subjects, yet lower than in T2D. LD subjects also showed heterogeneity of visceral adipose tissue (VAT) and hepatocellular fat, with VAT averaging higher than T1D subjects, while both were significantly lower than T2D subjects. Additionally, compared to lean-nondiabetic subjects, LD subjects had lower insulin secretion, similar peripheral and hepatic insulin sensitivity, and higher VAT and hepatocellular fat. Interpretation: These studies are the first to demonstrate that low BMI individuals with diabetes in LMICs have a unique metabolic profile. Following correction of glucose toxicity, these individuals are characterized by markedly impaired insulin secretion, variable peripheral insulin sensitivity, and heterogeneity in visceral and hepatocellular triglyceride levels. These findings demonstrate that diabetes among low BMI individuals in LMICs is a distinct entity that warrants further investigation. Funding Information: This study was supported by the Global Diabetes Institute of the Albert Einstein College of Medicine. Declaration of Interests: None declared. Ethics Approval Statement: These comprehensive metabolic studies were performed at the Department of Endocrinology, Christian Medical College (CMC) Vellore, India, in collaboration with the Global Diabetes Institute, Albert Einstein College of Medicine, New York, USA. Approval was obtained from the Institutional Review Boards of both institutions. The objectives of the study were explained to all participants and informed consent was obtained. The study protocol was conducted in accordance to the declaration of Helsinki.

Impact of malnutrition on systemic immune and metabolic profiles in type 2 diabetes

BackgroundWhile obesity and overweight status are firmly established risk factors for Type 2 diabetes mellitus (T2DM), a substantial proportion of diabetic individuals, especially in Africa and Asia, are often underweight or normal weight. However, very little is known about the immunological and metabolic profiles of these individuals.MethodsThis study aimed to assess the relationship between malnutrition and Type 2 diabetes mellitus (T2DM). We examined a variety of analytes associated with the immunological and metabolic profiles of T2DM individuals with low (< 18.5 kg/m2) or normal (18.5–24.9 kg/m2) body mass index (BMI). To this end, we measured plasma levels of HbA1c, glucose, insulin, glucagon, adipocytokines and Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in T2DM individuals with low BMI (LBMI) or normal BMI (NBMI) with small sample size n = 44 in each group.ResultsLBMI individuals exhibited significantly higher levels of HbA1c, random blood glucose, insulin and glucagon compared to NBMI individuals. Similarly, LBMI individuals exhibited significantly higher levels of adiponectin and adipsin and significantly lower levels of leptin in comparison to NBMI individuals. LBMI individuals also exhibited significantly lower levels of the Type 1, Type 2, Type 17, pro-inflammatory and regulatory cytokines in comparison to NBMI individuals. Finally, while the metabolic parameters exhibited a significant negative correlation with BMI, the immunological parameters exhibited a significant positive correlation with BMI.ConclusionsMalnutrition is associated with a significant modulation of glycemic, hormonal and cytokine parameters in T2DM. Hence, the biochemical and immunological profiles of T2DM is significantly influenced by BMI.

Indicators of Sarcopenia: Sex Differences in Competitive Runners Prior to Peak Muscle Mass

Strength, muscle mass, and muscle quality have been observed to be compromised in low body-mass index individuals such as competitive runners, increasing their risk for sarcopenia. The purpose was to compare indices of sarcopenia in young runners to age, height, body-mass, and body-mass index-matched non-runners. Handgrip strength and arm composition from dual-energy x-ray absorptiometry (baseline-T1, T2=5.3±1.4, T3=11.5±0.7 months later) were assessed in 40 non-runners and 40 runners (19.3±0.7 vs. 19.2±1.1 years, 170.7±10.3 vs. 171.1±9.1 cm, 60.2±7.4 vs. 60.2±7.9 kg, 20.6±0.9 vs. 20.5±1.5 kg m-2). The unitless variable of muscle quality, was defined as the sum of right and left maximal handgrip (in kg) divided by the sum of bone-free lean mass of both arms (in kg). Female runners displayed the highest muscle quality (T1=15.3±1.7; T3=15.7±2.0) compared to male runners (T1=13.7±1.4, p < 0.001; T3=14.2±1.6, p < 0.001) and male non-runners (T1=12.4±1.8, p=0.001; T3=13.2±1.6, p < 0.001), while female non-runners (T1=14.6±2.5, p=0.154; T3=15.1 ±2.2, p=0.124) showed higher muscle quality than male non-runners. Higher muscle quality in low-body-mass index females persists over one-year during young-adulthood and while running contributes to whole-body muscle mass accrual, it does not appear to be significantly associated with improvements in the most commonly used upper-body diagnostic indicator of sarcopenia.

Undernutrition is associated with perturbations in T cell-, B cell-, monocyte- and dendritic cell- subsets in latent Mycobacterium tuberculosis infection.

Undernutrition, as described by low body mass index (BMI), is a foremost risk factor for the progression of active Tuberculosis (TB). Undernutrition is also known to impact the baseline frequencies of innate and adaptive immune cells in animal models. To verify whether undernutrition has any influence on the baseline frequencies of immune cells in latent Mycobacterium tuberculosis infection (LTBI), we examined the frequencies of T cell-, B cell, monocyte- and dendritic cell (DC)- subsets in individuals with LTBI and low BMI (LBMI) and contrasted them with LTBI and normal BMI (NBMI) groups. LBMI was characterized by decreased frequencies and absolute cell counts of T cells, B cells and NK cells in comparison with NBMI. LBMI individuals demonstrated significantly enhanced frequencies of naïve and effector CD4+ and CD8+ T cells and significantly decreased frequencies of central memory, effector memory CD4+ and CD8+ T cells and regulatory T cells. Among B cell subsets, LBMI individuals demonstrated significantly diminished frequencies of naïve, immature, classical memory, activated memory, atypical memory and plasma cells. In addition, LBMI individuals showed significantly decreased frequencies of classical monocytes, myeloid DCs and plasmacytoid DCs and significantly increased frequencies of intermediate and non-classical monocytes and myeloid derived suppressor cells. BMI exhibited a positive correlation with B cell and NK cell counts. Our data, therefore, demonstrates that coexistent undernutrition in LTBI is characterized by the occurrence of a significant modulation in the frequency of innate and adaptive immune cell subsets.

Significant neutrophil accumulation, IL-18 deposition, and active inflammasome in tumor regions of human pancreatic ductal adenocarcinoma.

e15754 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients with a body-mass index (BMI) &gt; 27 (obesity, n = 5) and BMI &lt; 22 (normal, n = 5) were incubated with anti-human IL-18 and CD66b antibodies and detected using Alexa Fluor 488-conjugated donkey anti–mouse and Alexa Fluor 594-conjugated goat anti-rabbit secondary antibodies. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of CD66b+ neutrophils and IL-18 in all tissue sections. There is a significantly greater density of CD66b+ neutrophils and IL-18 in the tumor environment when compared to adjacent normal areas and IL-18+ signals appear to be deposited alongside the luminal area in a unique lasso-like pattern. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. There does not appear to be an association between tumor stage and TAN or IL-18 accumulation in the tumor area or the adjacent normal tissue in the tissues. Conclusions: Our data uniquely shows that CD66b+ neutrophils accumulate inside PDAC and this is associated with intra-tumoral active inflammasomes. The novel periductal deposition of IL-18 in the tumor areas may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.

Body Mass Index and Etiology of Intracerebral Hemorrhage

Extremes of body mass index (BMI) are associated with increased incidence of intracerebral hemorrhage (ICH). Because ICH can result from different vessel pathologies, we investigated whether the effect of BMI depends on ICH etiology. We analyzed 384 consecutive ICH cases (188 lobar ICH and 196 deep ICH) and 388 control subjects enrolled between 2004 and 2009 in an ongoing single-center prospective study of primary ICH. ICH was categorized as lobar or deep based on CT imaging at admission. BMI was calculated based on subjects' height and weight at enrollment. We constructed multivariate logistic regression models including BMI and known predictors of ICH occurrence. Analyses were performed separately for lobar and deep ICH subjects versus control subjects. Low BMI (<18.5 kg/m(2)) and very high BMI (>30.0 kg/m(2)) were associated with deep ICH risk (OR, 1.76; P=0.011 and OR, 1.75; P=0.013, respectively), whereas no effect was found for lobar ICH. Furthermore, sex-stratified analyses uncovered that among low BMI individuals, males were at higher ICH risk (OR, 2.85; P=0.041) but females were not (OR, 0.89; P=0.54, respectively). Extremes of BMI are associated with increased risk of deep ICH, but not lobar ICH, suggesting a role for BMI in the vascular pathologies underlying deep ICH, but not in pathologies such as cerebral amyloid angiopathy that cause ICH in the lobar brain regions.

Pressure distribution over the palm region during forward falls on the outstretched hands

Falls on the outstretched hands are the cause of over 90% of wrist fractures, yet little is known about bone loading during this event. We tested how the magnitude and distribution of pressure over the palm region during a forward fall is affected by foam padding (simulating a glove) and arm configuration, and by the faller’s body mass index (BMI) and thickness of soft tissues over the palm region. Thirteen young women with high ( n=7) or low ( n=6) BMI participated in a “torso release experiment” that simulated falling on both outstretched hands with the arm inclined either at 20° or 40° from the vertical. Trials were acquired with and without a 5 mm thick foam pad secured to the palm. Outcome variables were the magnitude and location of peak pressure ( d, θ) with respect to the scaphoid, total impact force, and integrated force applied to three concentric areas, including “danger zone” of 2.5 cm radius centered at the scaphoid. Soft tissue thickness over the palm was measured by ultrasound. The 5 mm foam pad reduced peak pressure, and peak force to the danger zone, by 83% and 13%, respectively. Peak pressure was 77% higher in high BMI when compared with low BMI participants. Soft tissue thickness over the palm correlated positively with distance ( d) ( R=0.79, p=0.001) and force applied outside the danger zone ( R=0.76, p=0.002), but did not correlate with BMI ( R=0.43, p=0.14). The location of peak pressure was shunted 4 mm further from the scaphoid at 20° than that of 40° falls ( d=25 mm (SD 8), θ=−9° (SD 17) in the 20° falls versus d=21 mm (SD 8), θ=−5° (SD 24) in the 40° falls). Peak force to the entire palm was 11% greater in 20° compared with 40° falls. These results indicate that even a 5 mm thick foam layer protects against wrist injury, by attenuating peak pressure over the palm during forward falls. Increased soft tissue thickness shunts force away from the scaphoid. However, soft tissue thickness is not predicted by BMI, and peak pressures are greater in high individuals than that of low BMI individuals. These results contribute to our understanding of the mechanics and prevention of wrist and hand injuries during falls.

Effect of hip protectors, falling angle and body mass index on pressure distribution over the hip during simulated falls

Background We examined how a soft shell hip protector affects the magnitude and distribution of force to the hip during simulated falls, and how the protective effect depends on the fall direction and the amount of soft tissue padding over the hip. Methods Fourteen young women with either high or low body mass index participated in a “pelvis release experiment” that simulated falls resulting in either lateral, anterolateral or posterolateral impact to the pelvis with/without a soft shell hip protector. Outcome variables were the magnitude and location of peak pressure ( d, theta) with respect to the greater trochanter, total impact force, and percent force applied to four defined hip regions. Findings The soft shell hip protector reduced peak pressure by 70%. The effect was two times greater in low than high body mass index individuals. The protector shunted the peak pressure distally along the shaft of the femur ( d = 52 mm (SD 22), theta = −21° (SD 49) in the unpadded trials versus d = 81 mm (SD 23), theta = −10° (SD 35) in the padded trials). Peak force averaged 12% greater in posterolateral and 17% lower in anterolateral than lateral falls. Interpretation Our results indicate that the hip protector we tested had a much stronger protective benefit for low than high body mass index individuals. Next generation protectors might be developed for improved shunting of pressure away from the femur, improved protection during posterolateral falls, and greater force attenuation for low body mass index individuals.

Mefloquine neurotoxicity: A literature review

A literature review revealed that mefloquine neurotoxicity has been demonstrated at both the preclinical and clinical levels, with nausea, dizziness, sleep disturbances, anxiety and psychosis, amongst other adverse neuropsychiatric events, reported in users. Females and individuals of low body mass index (BMI) are at apparent greater risk. Mechanisms of possible neurotoxicity may include binding to neuroreceptors and cholinesterases, inhibition of sarcoendoplasmic reticulum ATPase (SERCA) and interference with cellular Ca(2+) homeostasis, accumulation in the CNS, and reductions in CNS efflux in individuals possessing certain MDR1 polymorphisms. It may be prudent to avoid mefloquine in females and low BMI individuals, and in combination with other potentially neurotoxic agents such as the artemisinin antimalarials.

Human leptin locus (LEP) alleles and BMI in Samoans.

Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3' UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans. The study was designed to detect differences in the proportion of alleles at the six microsatellite markers between two groups of adult Samoans at the extremes of the longitudinal BMI distribution. The 181 unrelated Samoan participants were 25-55 y of age, reported that all four grandparents were Samoan, resided in American Samoa (AS) or Samoa (S) and were without diagnosed hypertension or type 2 diabetes. Initial statistical analysis was based on chi(2) tests of independence between marker allele frequencies and BMI status at each marker. The association of individual alleles with BMI status was tested by aggregating a marker's allelic data into a two-by-two contingency table and applying a two-tailed version of Fisher's exact test, with a Bonferroni correction to account for the multiple testing implicit in the procedure. There were no significant differences in allele frequencies at any of the markers between AS and S, as expected from our prior population genetic analyses. Only the LEP gene 3'-tetranucelotide repeat was associated (P<0.006) with BMI status. The distribution of the marker alleles at the LEP locus was significantly associated with the BMI groups (P<0.01), due to the low frequency of allele 226 in the high BMI group. The same pattern of association was found in sub-group analyses with low BMI individuals from AS and high BMI individuals from S. These findings indicate that the leptin 3'-tetranucleotide repeat is associated with high BMI in adult Samoans, with allele 226 having a low frequency in the high BMI group.