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Nutritional and Metabolic Diseases - Top 30 Publications

Gender and age differences in social support and body mass index in adults in Greater Metropolitan Rio de Janeiro, Brazil.

The objective was to investigate gender and age differences in the association between dimensions of social support and body mass index (BMI) in a sample of 1,465 adults (20 to 59 years) in a population-based study in Duque de Caxias, Rio de Janeiro State, Brazil. Anthropometry was conducted by trained evaluators and social support obtained by the Medical Outcomes Study, adapted and validated for the Brazilian population. The analyses were performed with multiple linear regressions, stratified by gender and age bracket, considering the sample's expansion factor and complex design. Obesity prevalence was 28% in women and 16.2% in men. After adjusting for confounders, a negative association was observed between social support and BMI in men 40-49 years of age, and in emotional support/information (β = -2.04), and positive social interaction (β = -2.40). There was a positive association for social support and BMI in men 50-59 years of age in emotional support/information (β = 1.84). The study indicates that social support can protect against obesity in men in some dimensions and age brackets. However, social support does not appear to be a protective factor in women.

Pilot randomized controlled trial of a mindfulness-based group intervention in adolescent girls at risk for type 2 diabetes with depressive symptoms.

(1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance.

Impact of mulberry leaf extract on type 2 diabetes (Mul-DM): A randomized, placebo-controlled pilot study.

Mulberry leaves have been used anecdotally in Asia to treat many disease states, including glucose abnormalities. Animal and human studies illustrate potential benefit of mulberry leaf extract (MLE) in type 2 diabetes mellitus (DM2). The purpose of this study is to evaluate the glycemic and safety effects of MLE in patients with DM2.

Announcement: Community Preventive Services Task Force Recommendation for Team-Based Care for Patients with Type 2 Diabetes.

The Community Preventive Services Task Force recently posted new information on its website: "Diabetes Management: Team-Based Care for Patients with Type 2 Diabetes." The information is available at

Childhood and Adolescent Obesity as a Winnable Battle-Reply.

Genetic Predisposition to Abdominal Obesity and Cardiometabolic Risk-Reply.

Childhood and Adolescent Obesity as a Winnable Battle.

Prevalence of Autoantibodies against 3-DG-Glycated H2A Protein in Type 2 Diabetes.

Advanced glycation end-products (AGEs) have been found to be critically involved in initiation or progression of diabetes secondary complications (nephropathy, retinopathy, neuropathy, and angiopathy). Various hyper-glycating carbonyl compounds such as 3-deoxyglucosone (3-DG) are produced in pathophysiological conditions that form AGEs in high quantity both in vivo and in vitro. In the first stage of this study, we glycated histone H2A protein by 3-DG, and the results showed the formation of various intermediates and AGEs as well as structural changes in the protein. In the second stage, we studied the immunogenicity of native and 3-DG-glycated H2A protein in female rabbits. The modified H2A was highly immunogenic, eliciting high titer immunogen-specific antibodies, while the unmodified form was almost nonimmunogenic. Antibodies against standard carboxymethyllysine (CML) and pentosidine were detected in the immunized female rabbits, which demonstrates the immunogenic nature of AGEs (CML and pentosidine) as well. The results show both structural perturbation and AGEs have the capacity of triggering the immune system due to the generation of neoepitopes that render the molecule immunogenic. This study shows the presence of autoantibodies against 3-DG-modified H2A, CML, and pentosidine in the sera of type 2 diabetes patients having secondary complications. Autoantibodies against damaged H2A and AGEs may be significant in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients or may be used as a marker for early detection of secondary complications in diabetes.

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis.

Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes.Design Systematic review and meta-analysis of randomised trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes.Data collection and analysis Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. Peto's method was used as the primary approach to pool effect estimates from trials, sensitivity analyses were carried out with other statistical approaches, and meta-regression was applied for six prespecified hypotheses to explore heterogeneity. The GRADE approach was used to rate the quality of evidence.Results 189 randomised controlled trials (n=155 145) were included, all of which were at low to moderate risk of bias; 77 reported no events of death and 112 reported 3888 deaths among 151 614 patients. Meta-analysis of 189 trials showed no difference in all cause mortality between incretin drugs versus control (1925/84 136 v 1963/67 478; odds ratio 0.96, 95% confidence interval 0.90 to 1.02, I(2)=0%; risk difference 3 fewer events (95% confidence interval 7 fewer to 1 more) per 1000 patients over five years; moderate quality evidence). Results suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors, but the subgroup hypothesis had low credibility. Sensitivity analyses showed no important differences in the estimates of effects.Conclusions Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

Objective To map the diverse health outcomes associated with serum uric acid (SUA) levels.Design Umbrella review.Data sources Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references.Eligibility criteria Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes.Results 57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10(-6), 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies.Conclusion Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis.

Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor.

Case 17-2017. A 14-Year-Old Boy with Acute Fear of Choking while Swallowing.

Should This Patient Have Weight Loss Surgery?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Obesity is an important public health priority in the United States. One third of U.S. adults are obese and therefore can expect higher rates of diabetes mellitus, other obesity-related comorbidities, and mortality. In 2013, the American Association of Clinical Endocrinologists, the Obesity Society, and the American Society for Metabolic and Bariatric Surgery issued a guideline that recommended weight loss (bariatric) surgery for all patients with a body mass index (BMI) of 40 kg/m2 or higher and for those with a BMI of 35 kg/m2 or greater in the presence of at least 1 obesity-related comorbidity. Among the 3 most commonly performed surgeries, the amount of excess weight reduction ranges from 49% for laparoscopic adjustable gastric banding to 76% for Roux-en-Y gastric bypass. In accredited centers, perioperative mortality averages 0.3%. In this Beyond the Guidelines, 2 experts in obesity management, a bariatric surgeon and a general internist, discuss the role of weight loss surgery versus dietary and lifestyle modification, both in general and for a specific patient who is eligible for surgery. Ethnic and age-related variability in the effects of obesity on mortality, as well as potential long-term benefits and risks of weight loss surgery for patient subgroups, are discussed.

Histologic Remission following Neoadjuvant Immunotherapy in a Patient with Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma.

Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression. Clinical Course Having no evidence of distance metastasis, we decided to initiate off-label use of Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and after receiving six cycles, PET/CT imaging showed regression. The side effects were limited to subclinical autoimmune thyroiditis. After re-operation no evidence of malignancy were found in the resectates of exenteration of the pelvis. Currently the patient is capable of working with only limited symptoms. Conclusion Pembrolizumab offers new treatment options for patients with DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already showed effectiveness in this particular group of patients. The striking and unexpected histo-pathologic results showing full remission should draw attention to the use of Pembrolizumab in neoadjuvant settings.

Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study.

Low bone mineral density (BMD) and osteoporosis remain frequent problems in patients with inflammatory bowel diseases (IBDs). Several guidelines with nonidentical recommendations exist and there is no general agreement regarding the optimal approach for osteoporosis screening in IBD patients. Clinical practice of osteoporosis screening and treatment remains insufficiently investigated.In the year 2014, a chart review of 877 patients included in the Swiss IBD Cohort study was performed to assess details of osteoporosis diagnostics and treatment. BMD measurements, osteoporosis treatment, and IBD medication were recorded.Our chart review revealed 253 dual-energy x-ray absorptiometry (DXA) scans in 877 IBD patients; osteoporosis was prevalent in 20% of tested patients. We identified widely differing osteoporosis screening rates among centers (11%-62%). A multivariate logistic regression analysis identified predictive factors for screening including steroid usage, long disease duration, and perianal disease; even after correction for all risk factors, the study center remained a strong independent predictor (odds ratio 2.3-21 compared to the center with the lowest screening rate). Treatment rates for patients with osteoporosis were suboptimal (55% for calcium, 65% for vitamin D) at the time of chart review. Similarly, a significant fraction of patients with current steroid medication were not treated with vitamin D or calcium (treatment rates 53% for calcium, 58% for vitamin D). For only 29% of patients with osteoporosis bisphosphonate treatment was started. Treatment rates also differed among centers, generally following screening rates. In patients with longitudinal DXA scans, calcium and vitamin D usage was significantly associated with improvement of BMD over time.Our analysis identified inconsistent usage of osteoporosis screening and underuse of osteoporosis treatment in IBD patients. Increasing awareness of osteoporosis as a significant clinical problem in IBD patients might improve patient care.

Impact evaluation of different cash-based intervention modalities on child and maternal nutritional status in Sindh Province, Pakistan, at 6 mo and at 1 y: A cluster randomised controlled trial.

Cash-based interventions (CBIs), offer an interesting opportunity to prevent increases in wasting in humanitarian aid settings. However, questions remain as to the impact of CBIs on nutritional status and, therefore, how to incorporate them into emergency programmes to maximise their success in terms of improved nutritional outcomes. This study evaluated the effects of three different CBI modalities on nutritional outcomes in children under 5 y of age at 6 mo and at 1 y.

Metabolic Effect of 1-Deoxynojirimycin from Mulberry Leaves on db/db Diabetic Mice Using Liquid Chromatography-Mass Spectrometry Based Metabolomics.

Metabolomics was applied to the liquid chromatography-mass spectrometry urinary metabolic profile of type 2 diabetes (T2DM) mice treated with mulberry 1-deoxynojirimycin (DNJ). The serum biochemical indicators related to T2DM like blood glucose, insulin, triglyceride, total cholesterol, nitrogen, malondialdehyde, and creatinine decreased significantly in the treated group. The histopathological changes in liver cells were marked by deformations and disruptions in central area of nuclei in DM mice, whereas DNJ treatment recovered regular liver cells with normal nuclei. Most of the metabolites of T2DM were significantly different from healthy controls in the bulk data generated. The level of 16 metabolites showed that the diabetic group was closer to the healthy group as the DNJ treatment time prolonged. Moreover, DNJ inhibited the activity of glucosidase on glucose, lipid, and amino acid metabolism. Our results showed the mechanism of DNJ treatment of T2DM and could fetch deep insights into the potent metabolite markers of the applied antidiabetic interventions.

Palisaded neutrophilic and granulomatous dermatitis as a novel cause of hypercalcemia: A case report.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is a benign, inflammatory dermatosis with distinct histopathological features often observed in patients with systemic diseases. There were no reports of PNGD without underlying systemic diseases as an underlying cause of hypercalcemia. Herein, we report a case of a 62-year-old man with hypercalcemia due to PNGD, but with no underlying systemic diseases, including tuberculosis, sarcoidosis, or vasculitis.

The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials.

Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies.

Inhibitory Effect of Piceatannol on TNF-α-Mediated Inflammation and Insulin Resistance in 3T3-L1 Adipocytes.

Piceatannol, a bioactive component in grape and blueberry, was examined for its potential in decreasing the inflammatory activities in adipocytes using a cocultured adipocyte and macrophage system, and suppressing tumor necrosis factor-α (TNF-α)-mediated inflammation and the related insulin resistance using a 3T3-L1 adipocyte model. Piceatannol at 10 μM significantly reduced the release of inflammatory cytokines of TNF-α and monocyte chemoattractant protein-1 (MCP-1) by 19 and 31% in the cocultured system, respectively. Pretreatment with piceatannol also inhibited TNF-α-induced expression of interleukin-6 (IL-6) and MCP-1 at both mRNA and protein levels in the 3T3-L1 adipocytes. Piceatannol also partially improved the malfunction of insulin-stimulated glucose uptake, which was reduced by TNF-α in 3T3-L1 adipocytes. Furthermore, the inhibitions were mediated by significant blocking of IκBα phosphorylation and nuclear factor-κB (NF-κB) activation through suppressing nuclear translocation of NF-κB p65 along with c-Jun N-terminal kinase (JNK)-mitogen activated protein kinase (MAPK) activation. In addition, the Akt-dependent forkhead box O1 (FoxO1) signaling pathway was involved in the restoration of insulin-stimulated glucose uptake through suppressing the down-regulation of phosphorylation of Akt and FoxO1 expressions. These results suggested the potential of piceatannol in improving chronic inflammatory condition and insulin sensitivity in obese adipose tissues.

Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity.

Lynch syndrome (LS) is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR) genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS) must be defined. We present an oligonucleotide-directed mutagenesis screen for the identification of pathogenic MSH6 VUS. In the screen, the MSH6 variant of interest is introduced into mouse embryonic stem cells by site-directed mutagenesis. Subsequent selection for MMR-deficient cells using the DNA damaging agent 6-thioguanine (6TG) allows the identification of MMR abrogating VUS because solely MMR-deficient cells survive 6TG exposure. We demonstrate the efficacy of the genetic screen, investigate the phenotype of 26 MSH6 VUS and compare our screening results to clinical data from suspected-LS patients carrying these variant alleles.

Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43's effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS.

Disparities in Diabetes Deaths Among Children and Adolescents - United States, 2000-2014.

Diabetes is a common chronic disease of childhood affecting approximately 200,000 children and adolescents in the United States (1). Children and adolescents with diabetes are at increased risk for death from acute complications of diabetes, including hypoglycemia and diabetic ketoacidosis (2,3); in 2012, CDC reported that during 1968-2009, diabetes mortality among U.S. persons aged ≤19 years declined by 61% (4). CDC observed disparities by race during 1979-2004, with black children and adolescents dying from diabetes at twice the rate of white children and adolescents (5). However, no previous study has examined Hispanic ethnicity. CDC analyzed data from the National Vital Statistics System for deaths among persons aged 1-19 years in the United States during 2000-2014, with diabetes listed as the underlying cause of death overall, and for Hispanic, non-Hispanic white (white), and non-Hispanic black (black) children and adolescents. During 2012-2014, black children and adolescents had the highest diabetes death rate (2.04 per 1 million population), followed by whites (0.92) and Hispanics (0.61). There were no statistically significant changes in diabetes death rates over the study period, but disparities persisted among racial/ethnic groups. Death from diabetes in children and adolescents is potentially preventable through increased awareness of diabetes symptoms (including symptoms of low blood sugar), earlier treatment and education related to diabetes, and management of diabetes ketoacidosis. Continued measures are needed to reduce diabetes mortality in children and understand the cause of racial and ethnic disparities.

Bariatric Surgery or Intensive Medical Therapy for Diabetes after 5 Years.

Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial.

To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes mellitus (T1DM).

Cardiovascular Effects of Antidiabetic Therapies.

Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs, Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin reduces cardiovascular mortality, total mortality and hospitalization by heart failure.

The Way to Closed Loop - Dream and Reality.

An old dream of patients with type 1 diabetes and medical teams alike is a fully automated insulin therapy. Available sensor-augmented insulin-pumps are able to intervene in insulin therapy by reducing the dose. Aim of several studies is to add an algorithm to the interaction of pump and sensor, so that insulin doses can be regulated fully automatically. Totally closed loop systems are currently not yet available for outpatient use. Hybrid closed loop systems have been approved in the US. They can improve the metabolic status of patients with type 1 diabetes. Risks are similar to sensor-augmented insulin-pump therapy. Patients' detailed education will continue to be essential for success.

Diagnostic Approach to Manifestation of Type 1 Diabetes mellitus.

The incidence of type 1 and type 2 diabetes mellitus has been increasing simultaneously. Formerly, these two patients' populations could be differentiated easily, but now, due to the overlapping of both groups, specified diagnostics are necessary. In order to substantiate a suspicion on diabetes, quantifying venous plasma glucose is the gold standard in diagnostics. As a precaution, determination of the HbA1c and OGTT is recommended. It is not necessary to determinate antibodies in every new case of diabetes. In patients with a vague constellation of clinical picture diagnosis can be ensured by findings of uric ketones, BGA, IA-2- and GAD-antibodies and optionally C-peptide. Often T1DM is associated with PGAS. Therefore, once manifestation of diabetes is detected, screening autoimmune disorders is recommended directly and regularly every two years.

Aerobic or Resistance Exercise, or Both, in Dieting Obese Older Adults.

Obesity causes frailty in older adults; however, weight loss might accelerate age-related loss of muscle and bone mass and resultant sarcopenia and osteopenia.