Role of fatty acids in the development of insulin resistance and type 2 diabetes mellitus,type 2 diabetes diagnostic criteria ada mp3,m62 update - 2016 Feature


Pathway for the movement of acetyl-CoA units from within the mitochondrion to the cytoplasm.
SLC16A1 protein (also called the monocarboxylic acid transporter 1, MCT1) and transport across the outer mitochondrial membrane involves a voltage-dependent porin transporter.
The synthesis of squalene, from FPP, represents the first cholesterol-specific step in the cholesterol synthesis pathway. This first reaction in this two-step cyclization is catalyzed by the enzyme, squalene epoxidase (also called squalene monooxygenase). As a result, a greater amount of cholesterol is converted to bile acids to maintain a steady level in circulation. Jun-Ling Han, MD, Department of Endocrinology and Metabolism, the 187th Hospital of PLA, No. This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. Correspondence to: Jun-Ling Han, MD, Department of Endocrinology and Metabolism, the 187th Hospital of PLA, No.
Core tip: Type 2 diabetes (T2DM) is believed to be caused by a series of multiple risk factors such as genetic liability, age, overweight or obesity, and an unhealthy lifestyle. INTRODUCTIONAccording to recent estimates by the International Diabetes Federation, there are 382 million people living with diabetes worldwide, and the number is expected to rise to 592 million by 2035[1]. Figure 1 Influence of the intestinal microbiota in promoting gut permeability and insulin resistance. Changes in the intestinal microbiota reduce tight junction proteins of gut epithelial cells and increase gut permeability, thus promoting metabolic endotoxemia and insulin resistance. The intestinal microbiota may play an important role in the onset of type 2 diabetes by influencing body weight, bile acid metabolism, proinflammatory activity, NAFLD and insulin resistance, and modulating gut hormones.
Ja e bem discutida a influencia da dieta e de determinados nutrientes na etiologia da acne.
Em um estudo realizado com pacientes com acne foi observado uma concentracao de zinco serico menor do que nos pacientes sem acne, concluindo que a acne pode ser consequencia de uma deficiencia de zinco. Muitos estudos observaram que na presenca da suplementacao de zinco houve a reducao do Propionobacterium acnes, bacteria envolvida na patologia da acne, e de acidos graxos livres na pele causados pelo excesso de oleosidade, principalmente porque este mineral inibe a lipase da bacteria P. Alem disso, o zinco tem acao anti-inflamatoria na acne, pois e essencial para a enzima antioxidante SOD-1 (superoxido dismutase citosolica), responsavel por reduzir o radical superoxido a peroxido de hidrogenio e oxigenio. O zinco tambem diminui a producao de sebo, um dos principais desencadeadores da acne, inibindo a 5-alfa-redutase enzima, responsavel pela conversao de testosterona em dihidroxitestosterona.
As principais fontes alimentares de zinco sao: ostras, carne vermelha, semente de abobora, amendoim, oleaginosas, graos integrais, e figado de frango. If insulin resistance is such a dominant risk factor in the progression to type II diabetes, it might be useful to have an effective tool for diagnosing it.  In this section I will discuss the various options available for measuring insulin resistance and their efficacy in predicting progression to type II diabetes. Too bad only highly sophisticated metabolic research labs our outfitted with these contraptions.  So unless you volunteer to be a guinea pig at a research facility, it is unlikely that you will have the opportunity to test your insulin resistance with this degree of accuracy.  Your doctor – in case you’re wondering –  probably doesn’t have one stuffed in his clinic closet! Okay, I know, this is just an epidemiological study and, as such, by no means proves that having high A1C causes people to die earlier.  It is entirely possible that some unknown variable is causing both the high A1C and the mortality. As you can see, A1C has a number of issues which make it a less than ideal tool for reliably measuring insulin resistance or predicting progression to diabetes.  Having said that, I do believe that, in general, an A1C  below 5 sustained over time is predictive of good health and indicative of excellent glucose tolerance. The chart below, which I developed from the results of this paper, indicates that, indeed, not all “normal” GTT results are equal. Due to its important role in membrane function, all cells express the enzymes of cholesterol biosynthesis. Pyruvate transport across the inner mitochondrial membrane requires a heterotetrameric transport complex (mitochondrial pyruvate carrier) consisting of the MPC1 gene and MPC2 gene encoded proteins. The HMGCS1 gene is located on chromosome 5p14–p13 and is composed of 12 exons that generate two alternatively spliced mRNAs, both of which encode the same 520 amino acid protein. This is due to the fact that, as depicted in the pathway Figure above, several intermediates in the pathway can be diverted to the production of other biologically relevant molecules. In the second step, this epoxide intermediate is converted to lanosterol through the action of the enzyme lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase). The original designation for these enzymes was ACAT for acyl-CoA: cholesterol acyltranferase. The INSIG1 gene is located on chromosome 7q36 and is composed of 7 exons that generate three alternatively spliced mRNAs encoding three isoforms of Insig-1. In addition to the cleavage-activation of SREBP transcriptional activity, S2P is involved in pathways that regulate cellular responses to endoplasmic reticulum stress, primarily the unfolded protein response, UPR. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
Recently, accumulated evidence has suggested that the intestinal microbiota plays an important role in the pathogenesis of T2DM as a potential novel contributor.
A high-fat diet in mice dramatically increases gut permeability and reduces expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin in intestinal epithelial cells. As principais evidencias mostram que a dieta induz mudancas hormonais relacionadas ao aumento na oleosidade da pele e na homeostase de citocinas, que sao um grupo de moleculas envolvidas no sistema imunologico, fatores estes relacionados no desenvolvimento da acne.
Em individuos suplementados com sulfato de zinco e gluconato de zinco, foi observada uma melhora em relacao a acne severa.
Porem devem ser ingeridos longe de alimentos fontes de ferro e cobre, pois estes minerais diminuem sua biodisponibilidade. Free fatty acids in obesity and type 2 diabetes defining their role in the development of insulin resistance and betacell dysfunction. Homeopathic individualized medicines versus fluoxetine for moderate to severe depression: double-blind, randomized non-inferiority trial.
The MVK gene is located on chromosome 12q24 and is composed of 12 exons that generate three alternatively spliced mRNAs. The IDI1 gene is located on chromosome 10p15.3 and is composed of 7 exons that encode a 284 amino acid protein that is localized to the peroxisomes. The synthesis of squalene is catalyzed by the NADPH-requiring enzyme, farnesyl-diphosphate farnesyltransferase 1 (commonly called squalene synthase).
These 11 different FDFT1-encoded mRNAs collectively synthesize five different isoforms of farnesyl-diphosphate farnesyltransferase 1.
Squalene epoxidase is derived from the SQLE gene which is located on chromosome 8q24.1 and is composed of 12 exons that encode a protein of 574 amino acids. However, this conflicts with the official ACAT enzymes, ACAT1 and ACAT2 which are acetyl-CoA acetyltransferases 1 and 2. The human SREBP-1a protein (1147 amino acids) predominates in the spleen and intestines while the SREBP-1c protein (1123 amino acids) predominates in liver, adipose tissue, and muscle. The INSIG2 gene is located on chromosome 2q14.2 and is composed of 7 exons that encode a 225 amino acid protein. Recent evidence suggests that the intestinal microbiota composition is associated with obesity and T2DM. This review focuses on the underlying role of intestinal microbiota in the pathogenesis of T2DM and the therapeutic potential of modulating gut microbiota in T2DM. T2DM is believed to be caused by a series of multiple risk factors such as genetic liability, age, overweight or obesity, and an unhealthy lifestyle. Antibiotic treatment reduces metabolic endotoxemia in high-fat-fed mice, which is associated with decreased gut permeability, reduced inflammatory markers, and improved metabolic features of diabetes and obesity.
Quando a suplementacao de zinco foi comparada ao uso de antibioticos orais pareceu ser tao eficaz quanto, porem ainda nao sao considerados como a primeira linha de tratamento da acne (CORDAIN, 2005). Ubiratan Cardinalli Adler, UNIFESP (Federal University of SA?o Paulo, Brazil), Av Rouxinol, 1041 cj. Phosphomevalonate kinase is also a peroxisomal enzyme and it is derived from the PMVK gene. The IDI2 gene is located on the same chromosomal region as the IDI1 gene but is composed of only 5 exons and encodes a 227 amino acid protein. Farnesyl diphosphate synthase is derived from the FDPS gene which is located on chromosome1q22 and is composed of 11 exons that generate five alternatively spliced mRNAs that, together, encode three different isoforms of the enzyme.
Lanosterol synthase is derived from the LSS gene which is located on chromosome 21q22.3 and is composed of 25 exons that generate four alternatively spliced mRNAs which together generate three distinct isoforms of the enzyme.
These latter two enzymes are thiolases discussed in the Lipolysis and Fatty Acid Oxidation page. The SREBF2 gene is located on chromosome 22q13 and is composed 23 exons that encode a 1141 amino acid protein.
A major function of PCSK9 is the endosomal degradation of the LDL receptor (LDLR), thereby reducing the recyling of the LDLR to the plasma membrane.
In this review, we provide an overview about the mechanisms underlying the role of intestinal microbiota in the pathogenesis of T2DM. Recently, accumulated evidence has suggested that the intestinal microbiota plays an important role in the pathogenesis of T2DM as a potential novel contributor.The adult human intestine is colonized by about 100 trillion bacteria, which is about 10 times the number of total cells in the human body[3].
The PMVK gene is located on chromosome 1q22 and is composed of 6 exons that encode a 192 amino acid protein. This effect of PCSK9 leads to a reduced ability of the liver to remove IDL and LDL from the blood contributing to the potential for hypercholesterolemia.
There is clear evidence that the intestinal microbiota influences the host through its effect on body weight, bile acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones. Intestinal permeability in human T2DM detected by the 51Cr-EDTA urinary recovery test was significantly increased compared with matched control subjects[38]. 20 sessoes semanalmente – 4 limpezas de pele e as demais sessoes aplicacao dos produtos anti-acne. There is a need for large-scale longitudinal data on treatment utilization and outcomes, stress, emotion, and pain. The potential for the pharmaceutical benefits of the interference in the activity PCSK9 was recognized by a confluence of several studies. Modulating gut microbiota with the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits for improvement in glucose metabolism and insulin resistance in the host.
Modulating gut microbiota composition with prebiotics improves gut permeability, reduces metabolic endotoxemia, lowers inflammation, and alleviates glucose intolerance[39,40].Endocannabinoid systemThe endocannabinoid (eCB) system is now believed to be associated with inflammation and diabetes[41,42]. Patients with a specific form of familial hypercholesterolemia not due to mutations in the LDLR gene were shown to have severe hypercholesterolemia due to mutations in the PCSK9 gene resulting in hyperactivity of the enzyme.
Further studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM. Intestinal microbiota modulate gut eCB expression, which controls gut permeability and plasma LPS levels through the CB1 receptor[43].
Randomized long-term trial of camel milk as an adjunct to insulin therapy in type-1 diabetes.
In addition, it was found that in certain individuals with low serum LDL levels there was an association with the inheritance of nonsense mutations in the PCSK9 gene which result in loss of PCSK9 activity. Further studies may be able to boost the development of new effective therapeutic approaches for T2DM. They also observed similar differences in the gut microbiota of obese compared with lean humans[5]. Changes in the gut microbiota due to prebiotic feeding reduce gut permeability in obese mice. Hypercholesterolemic patients taking another cholesterol-lowering drug while simultaneously utilizing either of these new PCSK9 inhibitors saw further reductions in serum LDL levels of betweeen 55% and 77%. Intestinal microbiota compositional changes have also been investigated in patients with T2DM.
Blocking the CB1 receptor in obese mice also improves gut barrier function by increased distribution and localization of tight junction proteins (ZO-1 and occludin). Researchers have found that the abundance of Firmicutes and Clostridia was significantly reduced, while the relative proportion of Bacteroidetes and Betaproteobacteria was increased in the diabetic group compared with the control group[6]. This demonstrates that the eCB system modulates gut permeability through the distribution and localization of tight junction proteins[44]. Patients are recruited from web sites for patient advocacy and health enhancement programs. However, Zhang et al[7] found that the proportion of Firmicutes and Clostridia were higher in the group of patients with T2DM compared to the normal glucose group.
Bermudez-Silva et al[45] have shown that cannabinoid CB2 receptor activation improves glucose tolerance in rats and that CB1 receptor blockade mimics the effects of CB2 receptor agonists.
Therefore this long-term study was undertaken to assess the efficacy, safety and acceptability of camel milk as an adjunct to insulin therapy in type 1 diabetic patients. FDFT1: farnesyl-diphosphate farnesyltransferase 1 (more commonly called squalene synthase).
Patients in the pre-diabetes and T2DM groups had a significantly increased level of Betaproteobacteria compared with the normal glucose group. The data suggest that the eCB system modulates glucose homeostasis through the interplay of CB1 and CB2 receptors. Methods: In this 2-year randomized clinical parallel design study, 24 patients with type 1 diabetes were enrolled and divided in 2 groups. Qin et al[8] have developed a protocol for a metagenome-wide association study based on deep shotgun sequencing of the gut microbial DNA extracted from fecal samples from Chinese T2DM patients and nondiabetic controls. The changes in CB2 receptor expression are correlated positively with intestinal counts of Lactobacillus supplement and negatively with counts of Clostridium supplement[46].
Group I (n=12) received usual care (ie, diet, exercise, and insulin), and group II (n=12) received 500 mL camel milk in addition to diet, exercise, and insulin. They identified 47 metagenomic linkage groups in the T2DM-associated gene markers from the gut metagenome. Modulation of the intestinal microbiota with specific probiotics has been shown to upregulate CB2 receptor expression in rodents[47].Akkermansia muciniphilaAkkermansia muciniphila (A. Their results showed that patients with T2DM had a moderate degree of gut microbial dysbiosis, a reduction in the abundance of some butyrate-producing bacteria, and an increase in various opportunistic pathogens. Karlsson et al[9] observed significantly higher levels of four Lactobacillus species and significantly lower levels of five Clostridium species in the T2DM group.
Importantly, these changes did not correlate with body mass index (BMI), waist circumference, or waist-to-hip ratio.
Sato et al[10] showed that stool samples of diabetic patients had significantly reduced levels of the Clostridium coccoides group, Atopobium cluster, and Prevotella, and a significantly increased level of total Lactobacillus compared with control subjects. These studies that have aimed to evaluate the association between gut microbiota and diabetes have produced conflicting results. Feeding also promotes intestinal expression of eCBs that control inflammation, gut barrier, and gut hormone secretion.
There may be many factors influencing the results, such as race, eating habits, geographical location, and research methods. This review focuses on the underlying mechanism of intestinal microbiota in the pathogenesis of T2DM, and the therapeutic potential of modulating the gut microbiota in T2DM.INTESTINAL MICROBIOTA AND BODY WEIGHTHumans do not have the enzymes necessary for digestion of many types of plant polysaccharide, such as cellulose, xylans, resistant starch, and inulin[11]. Previous studies have found that between 30% and 60% of pediatric neurology patients have used CAM at some point in their lives.
However, these indigestible carbohydrates can be fermented by intestinal microbes to yield energy and to produce short-chain fatty acids (SCFAs).
The prevalence of ultrasonographic NAFLD in patients with T2DM ranged from 54.11% to 78% in different studies[52]. The role of the intestinal microbiota in the regulation of host body weight and energy homeostasis was revealed primarily in rodents. Bäckhed et al[12] and his colleagues found that conventionally raised mice had 42% more total body fat than germ-free mice (raised in the absence of any microorganisms), even if their daily caloric intake was 29% less than their germ-free counterparts. The first hit is the process of triglyceride accumulation in hepatocytes, while the second hit is responsible for hepatocyte injury, inflammation, and fibrosis through oxidative stress, lipid peroxidation, and proinflammatory cytokines[53,54].
The germ-free mice transplanted with fecal microbiota from conventionally raised animals for 14 d had a 57% increase in their total body fat. Accumulated evidence has suggested that intestinal microbiota may be associated with NAFLD progression.
Bäckhed et al[12] observed that colonization of germ-free mice with normal intestinal microbiota induced insulin resistance and stimulated hepatic lipogenesis.
Germ-free mice transplanted with fecal microbiota from obese donors had a significantly greater increase in total body fat than those colonized with microbiota from lean donors.
Gut microbiota compositional change can increase the amount of TLR ligands delivered to the liver. TLR ligands stimulate Kupffer cells and hepatic macrophages to produce proinflammatory cytokines that can result in insulin resistance and hepatocyte death[55]. Whereas, the effect of vitamin C on conventional photodynamic therapy (PDT) of tumor cells has been documented, the mechanism of vitamin C induced increase in tumor cell response to PDT is unclear.


Once the primary bile acids, such as cholic acid and chenodeoxycholic acid, have reached the intestine, they may be transformed by intestinal microbiota into secondary bile acid species: deoxycholic and lithocholic acids[14].
In addition to TLRs, nucleotide-binding oligomerization domain-like receptors (NLRs) are inflammasome-dependent pathways of proinflammatory cytokine production[56,57]. The most typical secondary bile acid and the most abundant bile acid in biliary bile in humans is deoxycholic acid, which is converted from cholic acid via a 7α-dehydroxylation reaction catalyzed by some species of Clostridium in the large intestine[15]. A meta-analysis to evaluate the effects of probiotic therapy in NAFLD showed that probiotic therapies can improve liver function, lipid metabolism, and insulin resistance in NAFLD patients[59].
Compared with germ-free mice, conventionally raised (CONV-R) mice have significantly lower levels of bile acid in the gallbladder and small intestine, but significantly higher levels of bile acid in the cecum, colon, feces, and serum. A recent randomized clinical trial demonstrated that 4-mo supplementation with probiotics significantly improved fatty liver in children with NAFLD[60].INTESTINAL MICROBIOTA AND GUT HORMONESGLP-1GLP-1 is an incretin secreted from intestinal L cells.
In this report we demonstrate the presence of vitamin C during photo-oxidation of MC540 significantly increases its apoptotic activity in tumor cells. GLP-1 has numerous physiological effects, including stimulation of glucose-dependent insulin secretion, augmentation of β-cell mass, and inhibition of glucagon release, gastric emptying, and food intake[61].
Interestingly, we observed that the presence of vitamin C during photo-oxidation of MC540 only and not its addition to a prior photo-exposed mixture to MC540 is critical for its enhanced sensitivity. Activation of the nuclear farnesoid X receptor (FXR) by the gut microbiota reduce the expression levels of most bile acid synthesis enzymes[16]. In turn, bile acids contribute to suppression of bacterial colonization and growth in the gut because of their strong antimicrobial activity. The altered gut microbiota stimulated production of SCFAs (butyrate) that promoted GLP-1 secretion from L cells to improve the metabolic state. These findings provide impetus to the approach in developing ROS generating small molecule compounds with potent apoptosis inducing activity.
A previous study showed that the primary mechanism underlying the antimicrobial action of bile acids was membrane damage[17]. These data could have implications in the use of vitamin C in photo-sensitizer-mediated reactions with the view to favorably tailoring the cancer cell milieu for efficient apoptotic execution. Only microbial populations able to tolerate physiological concentrations of bile acids can survive in the gut. Prebiotics are non-digestible dietary ingredients that cause specific gut microbial composition changes or stimulate selectively the activity of some microbial species. Feeding with cholic acid induces phylum-level alterations in the composition of the gut microbiota in rats. Many investigations have demonstrated that prebiotics increase release of GLP-1 and improve the metabolic inflammation and insulin resistance induced by a high-fat diet[64-66].GLP-2GLP-2 is co-secreted with GLP-1 and is able to enhance intestinal epithelial proliferation and reduce gut permeability[67]. Many patients are still not discussing their CAM use with their doctors and are using CAM alongside their conventional medicines, thereby increasing the likelihood for potential interactions.
Cholic acid feeding increases significantly the ratio of Firmicutes to Bacteroidetes, which is similar to the changes induced by high-fat feeding[18].Over the past decade, a growing body of evidence has shown that bile acids play an important role in glucose metabolism as signaling molecules and cellular receptor ligands. Changes in mouse gut microbiota with prebiotic ingestion promote a significant release of plasma GLP-2 levels and improve systemic and hepatic inflammation.
One limitation of this study is that our ability to determine between-site differences is limited by the difference in sample size. Electrodermal measures as clinical markers: Jing-point electrical impedance in adolescent women with chronic pelvic pain. Bile acids activate not only FXR but also the membrane-bound, G-protein-coupled receptor (GPCR) 1 (also known as TGR5)[19]. It has been demonstrated that bile acids inhibit the expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase, fructose-1, 6-biphosphatase-1, and glucose-6-phosphatase in vitro via FXR[20]. Besides the roles of GLP-2 in maintaining gut barrier integrity, slowing gastric emptying and intestinal motility, improving nutrient absorption, and enhancing immune function, GLP-2 in central neurons enhances hepatic insulin sensitivity and plays a key role in the control of glucose homeostasis[68].Peptide YYPeptide YY (PYY) is a gastrointestinal hormone secreted from intestinal L cells. PYY has several biological actions including vasoconstriction, inhibition of gastric acid secretion, reduction of pancreatic and intestinal secretion, regulation of appetite and inhibition of gastric motility[69,70].
Consequently, skin electrical measures at Jing points are commonly obtained and interpreted for diagnostic purposes. Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is effective for treatment of obesity and comorbid T2DM. Rats receiving a diet supplemented with oligofructose, oligofructose-enriched inulin or high-molecular-weight inulin demonstrated an increase in portal serum levels of GLP-1 and PYY. Denise Adams, University of Alberta, 1047 RTF Building, University of Alberta, Edmonton, AB, T6G 2E1, Canada. FXR contributes to the maintenance of weight loss and improvement in glucose tolerance following VSG, which are associated with increased circulating bile acids and transition in gut microbiota composition[22].
The objective of this study is to determine whether electrodermal measures at Jing-points are associated with clinical outcomes in adolescents with chronic pelvic pain in a randomized, sham-controlled acupuncture trial.
Activation of TGR5 in enteroendocrine L cells induces glucagon-like peptide (GLP)-1 release, with an improvement in liver and pancreatic function and increased glucose tolerance in obese mice[23]. Dietary-resistant starch is a fermentable fiber that liberates SCFAs through fermentation in the gut. Methods: We recruited 18 adolescent women aged 13 to 22 years of age suffering from chronic pelvic pain and laparoscopically diagnosed with Stage I-III endometriosis. Activation of TGR5 in brown adipose tissue and muscle increases energy expenditure and alleviates diet-induced obesity[24].Fasting serum taurine-conjugated bile acid concentrations are higher in T2DM compared with normoglycemic controls, and intermediate in impaired glucose tolerance. Probiotics are nonpathogenic live microorganisms that may confer health benefits on the host.
However, increases in taurine-conjugated bile acid in patients with T2DM may be related to lower rates of taurine deconjugation that is catalyzed by some bile salt hydrolases enriched in the human gut microbiota[26]. In an animal study, researchers observed that a fermented milk product containing probiotic bacteria significantly delayed the onset of glucose intolerance, hyperglycemia, and hyperinsulinemia in diabetic rats induced by high fructose concentration[73]. Using a Hibiki-7 device, normalized electrical impedance values were obtained at all 24 Jing-points for each treatment session. Bile-acid sequestrants have been used to sequester bile acids in the intestine to increase bile acid synthesis and consequently reduce serum low-density lipoprotein cholesterol. Phase II: CAM research networks in Canada and the US will notify CAM providers of this study, so they may alert patients. Left-right asymmetry and measures for statistical dispersion (standard deviation and Gini coefficient) of Jing-point impedance values were calculated. Parents or legal guardians may self-identify and reply on behalf of patients under 18 year of age if they meet the criteria for Phase I. With a generalized estimating equation method, we evaluated the association between the electrodermal-derived measures and clinical outcomes while accounting for treatment designation and time. The intestinal microbiota is enriched with molecules such as LPS and peptidoglycan that may cause inflammation. Phase III: The methods for phase II were utilized but CAM associations and training organizations were substituted for CAM research networks. Gut microbiota-derived LPS is involved in the onset and development of inflammation and metabolic diseases[32]. The treated animals displayed a significant improvement in fasting blood glucose and oral glucose tolerance.
Elevated plasma LPS concentration in mice induced by high-fat feeding is defined as metabolic endotoxemia.
The enhanced insulin sensitivity was independent of food intake, weight loss, or adiposity. The majority of the cases involved the use of Traditional Chinese Medicine to improve quality of life. Metabolic endotoxemia is induced in mice through continuous subcutaneous infusion of LPS for 4 wk, and fasted glycemia and insulinemia, weight gain and expression of inflammatory cytokines are increased similarly to those in mice fed a high-fat diet. When diet-induced obese and insulin resistant mice were treated with the non-absorbable antibiotics polymyxin B and neomycin, they had a gradual reduction in glycemia, associated with a modified cecal microbiota profile[77].
CD14 knockout mice resist most of the LPS and high-fat diet-induced characteristics of metabolic diseases. Berberine, one of the main ingredients of a Chinese traditional herb used to treat bacterial diarrhea, improves glycemia.
The antimicrobial activity of berberine and its modulation of the gut microbiota may play a role in the antidiabetic effect of this herb[78].
Preliminary analyses indicate that, over time, subjects in the active acupuncture arm were more likely to have reduced left-right asymmetry and statistical dispersion of Jing-point measures compared to subjects in the sham-control arm. The binding of LPS to the complex of mCD14 and TLR4 at the surface of the innate immune cells activates the cascade reaction of inflammation[34,35].
Patients who receive 6 wk intravenous treatment with vancomycin plus gentamicin for infective endocarditis show significant weight gain[79].
Further analyses with multivariable models will be performed to assess whether this difference is statistically significant for each electrodermal measure. These data presented an interesting view of the potential effects of antibiotics on human metabolism.
Therefore, the metabolic endotoxemia induced by LPS derived from the gut microbiota is associated with inflammation and insulin resistance.
Further studies should be performed to investigate the effects of different antibiotics and administration routes on metabolism and T2DM.Fecal microbiota transplantationRecently, a report about fecal microbiota transplantation has aroused strong interest. Fecal microbiota transplantation was testified to be a highly successful therapy for recurrent Clostridium difficile infection[81] This also raised interest in the therapeutic effect of fecal transplantation in metabolic syndrome and T2DM. Patients with metabolic syndrome who received small intestinal infusions of fecal microbiota from allogenic lean donors for 6 wk showed an improvement in peripheral and hepatic insulin sensitivity, along with an increase in butyrate-producing intestinal microbiota[82].CONCLUSIONIntestinal microbiota may play an important role in the pathogenesis of T2DM by influencing body weight, bile-acid metabolism, proinflammatory activity and insulin resistance, and modulation of gut hormones (Figure 2).
Modulating the gut microbiota through the use of probiotics, prebiotics, antibiotics, and fecal microbiota transplantation may have benefits in improving glucose metabolism and insulin resistance in the host. The chiropractic care of children with otitis media: a systematic review of the literature utilizing whole systems research evaluation and meta-synthesis.
Joel Alcantara, International Chiropractic Pediatric Association, 327 N Middletown Rd, Media, PA 19063.
LPS inhibits the synthesis of insulin in isolated rat islets of Langerhans through binding of TLR4 and activation of the NF-κB pathway[83].
We do not know whether the changes in intestinal microbiota directly influence the β cell mass and function of islets in T2DM patients.
Key words were otitis media and related words (ie, acute otitis media, otitis media with effusion, ear infections, etc) AND chiropractic.
Rifaximin, an oral locally acting antibiotic used to treat inflammatory bowel disease, can modulate gut microbiota. A narrative review of the literature was performed and augmented with a meta-synthesis of the literature with a focus on chiropractic management and the application of a whole systems research (WSR) evaluation. What effect of rifaximin can we observe if it is administered to T2DM animal models or patients? Results: Our systematic review revealed 20 articles consisting of 6 case reports, 5 case series, 1 retrospective cohort, 2 prospective cohorts, 2 reviews of the literature, 2 commentaries, 1 survey study and 1 prospective, parallel-group, observer-blinded, randomized feasibility study.
Future studies are required to increase our understanding of the complex interplay between intestinal microbiota and the host with T2DM, and to enable the development of new effective treatments for T2DM. Due to the lack of higher-level research design, a meta-analysis of the literature was not possible. This included the use of otoscopy and tympanogram to provide objective pretreatment and comparative outcome measures.
Eighty-nine percent of respondents reported treating pediatric patients; patients under the age of 17 made up 12% of chiropractic and 20% of both naturopathic and osteopathic patients.
Activator, Gonstead, Toftness, Chiropractic Biophysics, and Diversified Techniques were utilized with an emphasis on the upper cervical spine (the C1 or C2 vertebral bodies). Approximately two-thirds of both osteopaths and naturopaths disagree or strongly disagree that immunizations are safe compared to one-third of chiropractors.
One paper described utilization of cranial technique, 2 papers described a dietary intervention, and 2 papers utilized soft-tissue massage to augment spinal manipulative therapy. Fifteen studies were amenable to the WSR evaluation resulting in a score of 7.06 from a maximum of 11.
The immunizations of most concern to the 3 professions included MMR, varicella, influenza, DPTP, and hepatitis. The most common reasons for concern were related to safety, including that vaccines may contain dangerous ingredients, may produce side effects, and may be linked to future problems such as neurological damage. Conclusion: This systematic review highlights the need for more higher-level research designs in addition to incorporating new methodologies (ie, whole systems research) reflective of the holistic and vitalistic clinical and theoretical framework of chiropractic. The chiropractic care of children with enuresis: a systematic review of the literature utilizing whole systems research evaluation. Significantly more naturopaths advised parents against vaccinations (27%), compared to 10% of chiropractors, and 12% of osteopaths (P=.0002). Joel Alcantara, International Chiropractic Pediatric Association, 327 North Middletown Rd, Media, PA 19063. There was no significant difference between groups for those advising parents in favor of vaccinations (15% C, 14% N, 6% O) (P=.1143). Key words were enuresis, nocturnal enuresis, bedwetting as well as related words AND chiropractic.
A narrative review of the literature was performed and augmented with an evaluation using WSR evaluation. Results: Our systematic review revealed 7 articles meeting the eligibility criteria for review. Four of the 7 papers involve case reports describing the care of children aged 8 to 14 years with primary complaints of nocturnal enuresis.
Spinal manipulative therapy involved the use of Toggle recoil, Sacro-Occipital Technique, Activator Methods, Gonstead Technique, and Diversified Technique to address primarily segmental dysfunctions in the lumbosacral spine. We conducted a systematic review to assess the nature and severity of adverse events associated with pediatric acupuncture.
A large prospective cohort study (N=171) demonstrated improvement in wet nights per week from baseline following 2 weeks of care.
In a randomized clinical trial, within-group comparison of pretreatment and comparative rates of enuresis subjects demonstrated an improvement. However, the study was fraught with research design issues such as randomization and biostatistics. Six of the 7 studies were amenable to WSR evaluation and resulted in a scoring of 7.33 from a maximum possible score of 11 points.
One reviewer screened all articles, while the second reviewed all excluded articles to ensure that no article was inappropriately excluded. Full articles of potentially relevant references were retrieved and assessed by two independent reviewers. The use of Whole Systems Research provides promise in contributing to evidence-based practice and reflects the holistic and vitalistic chiropractic approach to patient care. Results: Seven thousand, two hundred sixty-two potentially relevant articles were identified. Eleven of these studies included adults as the majority of patients; for these studies the age of the patient experiencing the adverse event was never reported. Most of the adverse events that have been identified in children were mild and included pain, bruising, and worsening of symptoms. The few adverse events rated as moderate or serious included one pneumothorax, 2 infections, and 2 cases of complications from needles left in the body. Methods: This study was approved by the Institutional Review Board of Life University (Atlanta, Georgia).
A 26-item questionnaire was sent to 9000 subscribers of an online newsletter from Midwifery Today Magazine. The first domain identified demographics (midwife credentials, age, years in practice, and place of practice). The second domain queried participants regarding their formal and postgraduate training on the subject of chiropractic. The third domain attempted to identify their experience (ie, positive or negative experience) with chiropractic personally and professionally as it pertains to pregnancy and infant care.
The fourth domain asked their opinion about the safety of chiropractic care for pregnant and pediatric patients. The fifth domain surveyed their knowledge regarding the scope of practice of chiropractic for pregnant and pediatric patients. The respondent ranged in age from 41 to 50 years with practice experience ranging from 6 to 10 years. With respect to their training on chiropractic, 31% (n=57) reported receiving formal education (ie, during midwifery education) on the subject of chiropractic.


Fifty-five of the 157 who did not indicated receiving some education on chiropractic through continuing education seminars. With respect to the midwife responders’ experience with chiropractic, 95% (n=176) admitted to making a professional referral to a chiropractor with 73% (n=137) having referred an infant to a chiropractor. Ninety-two percent (n=171) reported being chiropractic patients with another 58% (n=124) presenting their child for chiropractic care.
Over 90% indicated experiencing a positive experience as patients and with their child’s care. All of the respondents perceived chiropractic was safe for pregnant patients, while only 97% considered chiropractic safe for children. An overwhelming majority of the responders (98%) indicated that chiropractors work with birth professionals, while 92% indicated that they were knowledgeable about the role of chiropractic in prenatal care. Lastly, 75% indicated interest in learning more about chiropractic, with 86% wanting more evidence-based practice chiropractic. From the 809 articles reviewed, 18 articles met the full inclusion criteria and proceeded to data extraction. Identified adverse events include local pain or soreness, swelling, mild fevers, and skin rashes.
Thus far, the majority of adverse events reported have been mild with few moderate or serious adverse events occurring in pediatric patients. Total weight and body composition changes in response to weight reduction diets of varied protein content in midlife women.
Age-related changes in body composition for women include loss of lean mass and gains in total weight, fat mass and central fat deposition. There is growing evidence that diets with low-to-moderate carbohydrate and fat content and increased levels of high-quality protein are effective for weight loss.
Greater subjective satiety is reported by subjects following test meals containing whey protein compared to other protein sources. The beneficial effects of whey protein on satiety, thermogenesis, and lean body mass protection suggest that whey may be a preferred protein source for weight loss treatment. The specific aims of this study are to assess weight loss in subjects receiving energy-reduced dietary regimens and to evaluate parameters of weight and body mass change between the 3 treatment groups. Study Design: We are conducting a randomized, controlled pilot feeding study to evaluate the effect of different dietary protein sources on weight loss.
Endpoint measures include body weight and body composition data obtained at baseline and at 8 weeks for dietary treatment. The HP diet and the WP diet produced greater total fat loss and less total lean tissue loss than the CD.
Conclusions: Preliminary data shows that across treatment groups, the high-protein diets conserved lean tissue and promoted reduction of fat tissue. Trials investigating TCM must be conducted with increased methodological rigor to be of value in evaluations. The single included study suggesting that acupuncture may be safe and efficacious in CFS is limited in applicability by the use of sham acupuncture as the control. Integration and interface between naturopaths and conventional rural care: empirical findings from a grass-roots research project. The worsening epidemic of DM in the United States, along with the increasing prevalence of obesity, insulin resistance, and IGT, render the identification of promising interventions for these states a matter of some urgency. Jon Adams, University of Queensland, School of Population Health ,University of Qld, Herston, Queensland, 4006, Australia. While lifestyle interventions based on dietary pattern and physical activity can delay or prevent the onset of diabetes and reduce cardiovascular risk, adherence at the population level is severely limiting. Pharmacotherapy offers promise for diabetes prevention, but with associated high costs, unacceptability to many patients, and potential toxicity. In this context, the potential role of chromium (Cr), an insulin cofactor, in IGT is of great interest.
Proposed, therefore, is a randomized, double-blind, placebo-controlled pilot trial conducted at the Yale Prevention Research Center to investigate the effects of daily Cr for 6 months at 2 dose levels on serum measures of glucose tolerance and on endothelial function in adults with IGT, IFG, and IR. The study is powered to detect a clinically meaningful effect of Cr supplementation at either dose on glucose control, and to compare the two doses for equivalence. The study will investigate effects of Cr on both measures of glucose tolerance (glucose, insulin, OGTT) and brachial artery endothelial function, thus combining serum measures with a physiologic test of Cr effects on the vasculature. The proposed study will generate much needed data regarding the efficacy of Cr in those at risk for type 2 diabetes and offers the promise of guiding practice, as well as directing future study. By contributing to knowledge related to potential diabetes prevention strategies, this study addresses one of the more pressing public health issues in the United States today. Risk to human subjects in this study is a minor increment over minimal due to the administration of nitroglycerin as a control in BARS testing. Secondary outcomes: (4) It will show improved well-being, as measured by elevated melatonin and DHEA. Unlike many relaxation therapies, energy healing requires no participation by the patient, a feature that makes it particularly attractive in the hospital setting, where patients are often anxious, depressed, in pain, or sedated. Despite the increasing use of energy healing, few studies have looked at its benefits and even fewer at its underlying mechanisms of action. In this pilot study, we examined the effects of an energy healing modality known as Reiki on the autonomic nervous system (ANS) and the hypothalamus-pituitary-adrenal (HPA) axis, both of which participate in the stress response and stress-induced pain and disease progression. Subjects rested for 10 min before baseline heart rate and blood pressure were measured and blood was drawn to determine cortisol, ACTH, and DHEA levels, using commercial immunoassay kits.
Subjects then received a 30- to 45-min Reiki or Pretend Reiki session followed immediately by post-session heart rate and blood pressure measurements and at 2h by blood draws. When asked whether they thought they were in the Reiki or Pretend Reiki group, about 70% of the participants reported that they believed that they had received a true Reiki session. This suggests that the beneficial effects of Reiki on physiology, as compared to the Pretend Reiki, cannot be explained solely by the placebo effect.
Issac Amponsah, Faculty of Pharmacy Kwame Nkrumah University of SC, Knust, Kumasi, 233, Ghana. Effects of ultra-low dilutions of sabal serrulata on human prostate cancer growth: mechanistic studies. Hakima Amri, Georgetown University, Basic Science Bldg, 3900 Reservoir Rd NW, Washington, DC 20007.
Finally, serum protein differential expression was carried out using 2-dimensional gel electrophoresis followed by mass spectrometry analysis. Effect of mind-body medicine skills on elements of emotional intelligence in medical students. Yet studies have reported that traits such as altruism and empathy tend to decline throughout medical school training.
In an effort to foster medical student self-awareness and mindfulness, which may improve their EI, Georgetown University School of Medicine (GUSOM) offers an experiential course to undergraduate medical students in mind-body medicine skills. The purpose is to expose students to a variety of mind-body approaches including meditation, imagery, as well as group sharing and listening generously for self-awareness and reflection. The aim of this study was to assess the impact of the Mind Body Medicine Skills (MBS) course on perceived stress, mindfulness, and elements of EI including intrapersonal capacities (attention to feelings, mood repair, clarity of feelings) and interpersonal capacities (perspective-taking, empathetic concern, and personal distress in response to distress in others).
The intervention group (n=30) was comprised of first year medical students who self-selected to participate in this elective. The control group (n=36) included students from the first year class who completed the surveys but did not take the MBS course. Four questionnaires were completed at the start and end of the spring semester by all study participants: the Perceived Stress Scale (PSS), the Mindful Attention Awareness Scale (MAAS), and a survey of EI developed by Stratton et al (2005) comprised of the Trait Meta-Mood Scale and the Interpersonal Reactivity Index. ANCOVA was used to compare the MBS and the control groups at the end of the semester, controlling for beginning scores. Patient perspectives of integrative and primary care management of back and neck paina€”qualitative findings from a randomized clinical trial. These conditions are additionally some of the most common reasons why patients use complementary therapies, often without dialogue with conventional care providers. The focus groups were conducted separately for those in the integrative vs the conventional treatment groups. The interview data were transcribed ad verbatim and analyzed utilizing inductive content analysis technique. Eliane Angst, UCLA Center for Excellence in Pancreatic Diseases, 675 Charles E Young Drive South, Los Angeles, CA 90095. A significant reduction in cell numbers was seen with quercetin concentrations of ~30 AµM and a maximum effect at ~75 AµM.
In MIA PaCa-2 cells a ~65% reduction in cell number was seen with 75 AµM of quercetin after 48 hours.
Starved BxPC-3 cells treated with 75 AµM quercetin showed a ~95% reduction in cell number after 48 hours. Conclusion: These results suggest that quercetin has a potent growth-inhibitory effect in pancreatic cancer cells in vitro. Additional experiments to investigate the underlying mechanism of growth inhibition and animal studies are underway.
Flovanoids may reveal to be potent anticancer drugs found in our daily food, leading to specific diet recommendations.
These can be taken together to qualify as an academic minor in many of the conventional MA or PhD programs, often forming the basis of a thesis or dissertation required for the terminal degree. In the fall of 2009, the university will launch a doctorate of nursing practice with a focus in integrative health and healing.
Georgetown University developed a concentration of CAM within its Masters in Physiology program in 2003. We address the multicultural perspective, comparing data collected in Canada and Europe to those in the United States. The reason for this is that results on the health-promoting effects of spirituality and religiosity cannot easily be transferred from the United States to countries with different cultural and religious backgrounds. Thus, one has to recognize different concepts of spirituality, different attitudes towards its utilization, and objections against the implementation of it in a particular medical system. In Germany, 3 colleagues have founded the Transdisciplinary Working Group on Spirituality and Health, and in Canada the Canadian Research Network on Spirituality and Health has been active for a couple of years. Data and approaches from these different networks will be combined into this symposium.Dr BA?ssing is an associate professor at the University of Witten, Herdeckea€™s Faculty of Medicine, where he directs the research group Spirituality and Health. The effect of a€?acupuncture for losing weighta€? on the level of blood sugar: a survey on the mechanism. Hoda Azizi, Beijing University of Chinese Medicine, 11 Bei San Huan Dong Lu, Beijing, Beijing, 100029, China.
Material and Methods: In this clinical trial study, 66 patients were included in case and control groups.
Blood sugar was examined just before inserting needles and immediately after withdrawal of needles. Conclusion: Our results suggest that the mechanism of acupuncture in losing weight is significantly related to making an increase in BS.
John Balletto, Center for Muscular Therapy, Inc, 545 Pawtucket Avenue, Mailbox 304, Pawtucket, RI 02860-6046.
As with business startups that begin informally and successfully mature into larger enterprises, growth brings new organizational challenges, together with greater visibility and opportunity.
The maturation of massage as a healthcare profession increases the need for a process to formalize the synthesis of massage therapy knowledge from clinical experience and research—to collect what we know and to make such baseline knowledge widely available to practitioners, consumers, and other healthcare stakeholders.
The present paper lays out the motivations and framework for creating massage therapy guidelines that are informed both by research and by clinical experience. It also acts as a report to the massage therapy profession and to other stakeholders about the work of the Best Practices Committee of the Massage Therapy Foundation since 2006. And it has the additional goal of providing a healthcare literature basis for future academic discussions of massage.
The discussion here is based on a definition from the Institute of Medicine and on research into the nature of expertise. Topics addressed include guideline creation, credentialing of complementary and alternative medicine practitioners, definition of competence, and the increasing role of technology (that is, informatics) in managing training and task-necessary competencies. The roles of transparency and a wide and open peer review are emphasized as essential to the usability and credibility of guidelines. Health Canada issues consumer advisories regarding the safety of marketed health products, yet the criteria for issuing advisories have not been evaluated for consistency or objectivity. The Causality Algorithm used by Health Canada was used to rate degree of association between the adverse events (AEs) and the products. The Severity of Adverse Events Scale, developed by the National Cancer Institute, was used to determine the severity of the AEs. Most NHP AWRs were issued based on potential AEs from contamination and adulteration, whereas most of the AWRs for therapeutic drugs were issued due to actual AEs.
Of the 6 NHP AWRs issued for actual AEs, 3 (50%) were unassessable for severity, whereas of the 28 AWRs issued for actual therapeutic drug AEs, 1 (3%) was unassessable for severity. The origin of reports for NHPs tended to be from foreign sources or Health Canada, whereas reports for therapeutic drugs were mostly issued by Health Canada in conjunction with drug manufacturers. The potential of a mistletoe (Viscum album L) extract to alleviate adverse effects of cancer chemotherapy: an in vitro study.
Stephan Baumgartner, University of Bern, Institute of Complementary Medicine KIKOM, Inselspital, Bern, BE, 3010, Switzerland. We investigated the effect of a mistletoe extract on PBMC with and without concomitant treatment with cyclophosphamide and compared viability and replication of normal PBMC with that of a T-cell leukemia cell line. The results motivate further preclinical and clinical investigations of mistletoe extracts as an adjuvant medication in cancer therapy to alleviate side effects of conventional therapy. Stephan Baumgartner, Institute of Complementary Medicine KIKOM, University of Bern, Inselspital, Imhoof-Pavillon, Bern, BE, 3010, Switzerland.
We investigated the potential of a commonly used plant pathogen–system, Arabidopsis thaliana infected with the virulent bacteria Pseudomonas syringae (pv tomato strain DC3000), regarding its response towards a homeopathic treatment. Compared to Bion (a common SAR inducer used as positive control), the magnitude of the treatment effect of Biplantol was about 50%. None of the other tested preparations yielded significant effects in the overall evaluation. The purpose of this study was to determine remedy effects on a common quantitative measure of complexity, the correlation dimension (D2), of human sleep electroencephalography (EEG).
High Hostile subjects increased complexity at C3 and Pz, but decreased complexity at O2 during stage 3 sleep on CC. In the high Anxiety-Sensitive subjects, CC caused significant increases in complexity at Pz and O1 during stage 3 sleep and at C3, C4, and Pz during stage 4 sleep. CC increased complexity significantly at Cz, C4, and O2 during REM sleep in only the high Anxiety-Sensitive subjects. The purpose of the present study was to determine whether or not the objective measure of polysomnographically-recorded all-night sleep recordings can distinguish verum homeopathic remedies from placebo in human subjects.
NV produced more marked effects on increased shifts in sleep stages, with a growth in effects from night 22 to 23. This study examined the effects of olfactory administration of a polycrest homeopathic remedy Sulphur on heart rate variability (HRV).
The Sulphur was given at dilution factors used for preparing 6c, 12c, and 30c potencies (1 potency per session, with potency order randomized), but for each potency, the test solutions were succussed to different degrees (stirred without shaking, 10, 20, or 100 succussions). Homeopathic remedies increase spectral electroencephalographic power during sleep in healthy young adults. The purpose of the present study was to assess the effects of verum vs placebo homeopathic remedies on spectral qEEG measures of polysomnographically-recorded all-night sleep recordings. Evaluating a nonlinear dynamical model for human flourishing: Relationship of PANAS positive-to-negative-affect ratio and global health and well-being. The purpose of the present study was to compare global physical health (GPH) and well-being ratings of young adults whose P:N mood ratios fell above vs below the Losada line.
Despite higher (MCSD) scores in PF, a small sex and age difference between groups, ANCOVAs controlling for MCSD, sex, and age still showed statistical significance of the above PF vs PL group differences. Gurjeet Birdee, Osher Research Center Harvard Medical School, 401 Park Drive, Suite 22-A West, Boston, MA 02215. We identified the prevalence of CAM modalities used and the characteristics of users among the pediatric population.



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