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Nutritional and Metabolic Diseases - Top 30 Publications

Insulin resistance and reduced metabolic flexibility: cause or consequence of NAFLD?

Whether non-alcoholic fatty liver disease (NAFLD) precedes insulin resistance (IR) or IR preludes/causes NAFLD has been long debated. Recent studies have shown that there are two phenotypes of NAFLD, 'genetic' vs 'metabolic' NAFLD. The former patients are more at risk of hepatocellular carcinoma and chronic liver disease the latter are more IR and at increased risk of type 2 diabetes (T2D). Even if they are not yet diabetics, from a metabolic point of view having NAFLD is equivalent to T2D with reduced peripheral glucose disposal and impaired suppression of hepatic glucose production, but without fasting hyperglycaemia. T2D develops only when hepatic autoregulation is lost and glucose production exceeds the capacity of muscle glucose disposal.In NAFLD adipocytes are resistant to the effect of insulin, lipolysis is increased and excess plasma free fatty acids (FFA) are taken up by other organs (mainly liver) where they are stored as lipid droplets or oxidized. Increased adiposity is associated with worsen severity of both 'genetic' and 'metabolic' NAFLD. FFA oxidative metabolism is increased in NAFLD and not shifted towards glucose during insulin infusion. Although this reduced metabolic flexibility is an early predictor of T2D, it can be seen also as a protective mechanism against excess FFA.In conclusion, IR precedes and causes 'metabolic' NAFLD, but not 'genetic' NAFLD. Reduced metabolic flexibility in NAFLD might be seen as a protective mechanism against FFA overflow, but together with IR remains a strong risk factor for T2D that develops with the worsening of hepatic regulation of glucose production.

Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia.

Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 (glycosylphosphatidylinositol anchor attachment 1) is an essential component of the transamidase complex along with PIGK, PIGS, PIGT, and PIGU (phosphatidylinositol-glycan biosynthesis classes K, S, T, and U, respectively). This complex orchestrates the attachment of the GPI anchor to the C terminus of precursor proteins in the endoplasmic reticulum. Here, we report bi-allelic mutations in GPAA1 in ten individuals from five families. Using whole-exome sequencing, we identified two frameshift mutations (c.981_993del [p.Gln327Hisfs(∗)102] and c.920delG [p.Gly307Alafs(∗)11]), one intronic splicing mutation (c.1164+5C>T), and six missense mutations (c.152C>T [p.Ser51Leu], c.160_161delinsAA [p.Ala54Asn], c.527G>C [p.Trp176Ser], c.869T>C [p.Leu290Pro], c.872T>C [p.Leu291Pro], and c.1165G>C [p.Ala389Pro]). Most individuals presented with global developmental delay, hypotonia, early-onset seizures, cerebellar atrophy, and osteopenia. The splicing mutation was found to decrease GPAA1 mRNA. Moreover, flow-cytometry analysis of five available individual samples showed that several GPI-anchored proteins had decreased cell-surface abundance in leukocytes (FLAER, CD16, and CD59) or fibroblasts (CD73 and CD109). Transduction of fibroblasts with a lentivirus encoding the wild-type protein partially rescued the deficiency of GPI-anchored proteins. These findings highlight the role of the transamidase complex in the development and function of the cerebellum and the skeletal system.

Obesity Often Overstated But Hardly Understood.

Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

Addressing Obesity Must Go Beyond Advising Patients to Eat Healthy and Exercise.

Change in nonhigh-density lipoprotein cholesterol levels in adults with prediabetes.

This study aimed to observe the change in nonhigh-density lipoprotein cholesterol (non-HDL-C) levels and analyzed its related factors in adults with prediabetes (impaired fasting glucose and/or impaired glucose tolerance).This case-controlled study included 56 adults with normal glucose tolerance (NGT) and 74 adults with prediabetes. The cases and controls were age and gender-matched. Anthropometric measurements including height, weight, waist circumference, and blood pressure were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 hours of fasting, and the levels of glucose, insulin, lipids, and uric acid were measured.The levels of non-HDL-C (3.63 ± 0.92 vs 3.27 ± 1.00 mmol/L) were significantly higher in prediabetic subjects than in NGT subjects (P < .05). Non-HDL-C positively correlated with HOMA-IR (r = 0.253, P = .004), triglyceride (r = 0.204, P = .020), and uric acid (r = 0.487, P = .000). After multivariate analysis, uric acid continued to be significantly associated with non-HDL-C (β = 0.006, P = .000).Non-HDL-C is elevated in adults with prediabetes. A relationship between non-HDL-C and uric acid was observed.

Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.

Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system.

The additional benefit of weighted subjective global assessment (SGA) for the predictability of mortality in incident peritoneal dialysis patients: A prospective study.

Although subjective global assessment (SGA) is a widely used tool for nutritional investigation, the scores are dependent on the inspectors' subjective opinions, and there are only few studies that directly assessed the usefulness of SGA and modified SGA in incident peritoneal dialysis (PD) patients. A total of 365 incident PD patients between 2009 and 2015 were enrolled and measured with SGA and calculated using serum albumin and total iron binding capacity (TIBC) levels for weighted SGA. Cox analyses were performed to delineate the association between SGA or weighted SGA and all-cause mortality, and a receiver-operating characteristic was conducted to reveal the additional benefit of weighted SGA on predicting adverse clinical outcomes. The Kaplan-Meier curve showed that the cumulative survival rate in patients with "Good nutrition" (G1) was significantly higher compared to those with "Mild to severe malnutrition" (G2). G2 was significantly associated with an increase in the mortality even after adjusting for several covariates compared with G1. Moreover, a 1-unit increase in weighted SGA was also significantly correlated with mortality after adjustment of the same covariates, while G2 was not significantly associated with an increase in the mortality among young-aged (under 65 years) groups. Meanwhile, a 1-unit increase in weighted SGA was significantly related to an increase in mortality in all the subgroup analyses. Furthermore, the AUCs of weighted SGAs in all groups were significantly increased compared with those of SGA alone. In conclusions, the evaluation of nutritional status based on SGA in incident PD patients might be useful for predicting mortality. However, weighted SGA with serum albumin and TIBC can provide additional predictive power for mortality compared with SGA alone in incident PD patients.

Muscle ultrasound: A useful tool in newborn screening for infantile onset pompe disease.

Our study aimed to evaluate the utility of muscle ultrasound in newborn screening of infantile-onset Pompe disease (IOPD) and to establish a system of severity grading. We retrospectively selected 35 patients with initial low acid alpha-glucosidase (GAA) activity and collected data including muscle ultrasound features, GAA gene mutation, activity/performance, and pathological and laboratory findings. The echogenicity of 6 muscles (the bilateral vastus intermedius, rectus femoris, and sartorius muscles) was compared to that of epimysium on ultrasound and rated either 1 (normal), 2 (mildly increased), or 3 (obviously increased). These grades were used to divide patients into 3 groups. IOPD was present in none of the grade-1 patients, 5 of 9 grade-2 patients, and 5 of 5 grade-3 patients (P < .001). Comparing grade-2 plus grade-3 patients to grade-1 patients, muscle ultrasound detected IOPD with a sensitivity and specificity of 100.0% (95% confidence interval [CI]: 69.2%-100%) and 84.0% (95% CI: 63.9%-95.5%), respectively. The mean number of affected muscles was larger in grade-3 patients than in grade-2 patients (4.2 vs. 2.0, P = .005). Mean alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) levels were differed significantly different between grade-3 and grade-1 patients (P < .001). Because it permits direct visualization of injured muscles, muscle ultrasound can be used to screen for IOPD. Our echogenicity grades of muscle injury also correlate well with serum levels of muscle-injury biochemical markers.

Screen Media Exposure and Obesity in Children and Adolescents.

Obesity is one of the best-documented outcomes of screen media exposure. Many observational studies find relationships between screen media exposure and increased risks of obesity. Randomized controlled trials of reducing screen time in community settings have reduced weight gain in children, demonstrating a cause and effect relationship. Current evidence suggests that screen media exposure leads to obesity in children and adolescents through increased eating while viewing; exposure to high-calorie, low-nutrient food and beverage marketing that influences children's preferences, purchase requests, consumption habits; and reduced sleep duration. Some evidence also suggests promise for using interactive media to improve eating and physical activity behaviors to prevent or reduce obesity. Future interdisciplinary research is needed to examine the effects of newer mobile and other digital media exposures on obesity; to examine the effectiveness of additional interventions to mitigate the adverse effects of media exposures on obesity and possible moderators and mediators of intervention effects; to effectively use digital media interventions to prevent and reduce obesity; and to uncover the mechanisms underlying the causal relationships and interactions between obesity-related outcomes and media content, characteristics, and context.

ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes.

Among adolescents with type 1 diabetes, rapid increases in albumin excretion during puberty precede the development of microalbuminuria and macroalbuminuria, long-term risk factors for renal and cardiovascular disease. We hypothesized that adolescents with high levels of albumin excretion might benefit from angiotensin-converting-enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents.

Growth and Final Height Among Children With Phenylketonuria.

Growth is an important criterion to evaluate health in childhood and adolescence, especially in patients depending on special dietary treatment. Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism. Patients with PKU depend on a special phenylalanine-restricted diet, low in natural protein. The study aimed to evaluate growth, growth rate, and target height in 224 patients with PKU.

Cost-Effectiveness of a Clinical Childhood Obesity Intervention.

To estimate the cost-effectiveness and population impact of the national implementation of the Study of Technology to Accelerate Research (STAR) intervention for childhood obesity.

Intergenerational diabetes and obesity-A cycle to break?

Ronald Ma and Barry Popkin discuss the urgent need and challenges to reduce intergenerational transmission of obesity and diabetes.

Therapeutic Lifestyle Changes for Diabetes Mellitus.

Diabetes mellitus is a common chronic disease affecting approximately 9% of the United States population. Successful management of diabetes demands constant self-management on the part of the patient. The patient has to balance diabetes medications, blood glucose monitoring, food intake, physical activity, and management of diabetes-related acute and chronic complications. The patient is often bombarded with misinformation from friends, relatives, and such sources as the Internet and social media. This article discusses the current recommendations for diabetes self-management education and skills including medical nutrition therapy, physical activity, smoking cessation, and assessment for diabetes distress.

Prediabetes: Beyond the Borderline.

Prediabetes is a complex multifactorial metabolic disorder that extends beyond glucose control. Current studies have found that microvascular disease (neuropathy, nephropathy, and retinopathy), macrovascular disease (stroke, coronary artery disease, and peripheral vascular disease), periodontal disease, cognitive dysfunction, blood pressure changes, obstructive sleep apnea, low testosterone level, fatty liver disease, and cancer are some of conditions that are present with the onset of glycemic dysregulation. The presence of prediabetes increases the risk of developing type 2 diabetes 3-fold to 10-fold. The identification and treatment of prediabetes are imperative to prevent or delay the progression to type 2 diabetes.

Review of 2017 Diabetes Standards of Care.

Diabetes is a complex medical condition that requires evidence-based care. This article discusses the current diabetes screening, diagnostic criteria, and treatment recommendations for patients with type 1 diabetes, type 2 diabetes, gestational diabetes, and prediabetes.

Management of Lipids in Patients with Diabetes.

Abnormal lipids, sometimes referred to as diabetes dyslipidemia, is a common condition in patients with diabetes. With the increasing number of patients with abnormal lipids, especially those with type 2 diabetes, health care practitioners, including nurses, have to properly manage patients with diabetes as well as abnormal lipids. This article examines the pathophysiology of abnormal lipids, the management of abnormal lipids, and the lipid goals for patients with diabetes. Lastly, this article discusses pharmacologic and nonpharmacologic therapies and the role of primary care providers and nurses in the management of abnormal lipids.

Management of Diabetes in Children and Adolescents.

Diabetes is a common chronic illness in children and adolescents. This article will discuss the prevalence, diagnostic criteria, types, treatment, and transition of care into adulthood.

Hypoglycemia in Diabetes.

Hypoglycemia is a common problem in patients with diabetes, and often limits those trying to achieve tight glucose control. Achieving optimal glucose control is necessary to prevent microvascular complications. Hypoglycemia can cause mild disturbances to daily life, but in severe cases can be fatal. Patient education of hypoglycemic medications, risk factors, contributing factors, and prevention strategies should be included in the care plan of patients at risk of developing hypoglycemia.

A Primer on Insulin Pump Therapy for Health Care Providers.

An estimated 1 million people use an insulin pump to manage their diabetes. Few medical professionals understand or feel comfortable caring for people who use an insulin pump. This article will help the medical professional understand the reasons why the insulin pump helps the user to achieve better glycemic control, have more flexibility, and enjoy a better quality of life. Additionally, this article discusses the advantages, disadvantages, candidate selection, contraindications, basic functions, and troubleshooting of the insulin pump.

Insulin Therapy: The Old, the New and the Novel-An Overview.

Since its development, insulin therapy has been a mainstay in the arsenal of every practitioner battling against diabetes. For patients with type 1 diabetes mellitus, insulin is essential for survival, and for those with type 2 diabetes mellitus, as the disease progresses, it may become a necessary addition to treatment. The goal of this article is to discuss insulin therapies that are currently available for use in the management of diabetes, from the old to the new and novel, and briefly discuss insulin use in special populations.

Noninsulin Diabetes Medications.

Pharmacotherapy for diabetes has changed greatly owing to drugs and drug classes available. There are 11 classes of noninsulin diabetes medications available in the United States. With the use of 1 drug alone or in combination with different drugs, it is possible to improve glycemic control in patients with diabetes. Important properties of antidiabetic agents play a role in the choice of that particular medication for individual patients. Prescribing a diabetes medication regimen is based careful assessment of patient needs, and consideration of the medication's efficacy, impact on weight, hypoglycemia risk, potential side effects, cost, and patient preferences.

The How-To for Type 2: An Overview of Diagnosis and Management of Type 2 Diabetes Mellitus.

This article presents an overview of type 2 diabetes diagnosis and management. A brief discussion of epidemiology, including incidence, prevalence, and etiology, provides the basis for the importance of the discussion. The review then proceeds to outline diagnostic criteria and follow-up monitoring guidelines. Recommendations for evidence-based lifestyle measures and current pharmacologic options are addressed. A priority on individualized, holistic care with patient-specified goals and the management of comorbidities is emphasized.

Management of Type 1 Diabetes.

Comprehensive type 1 diabetes management requires understanding of the pathophysiology of disease and the ability to contrast this process with type 2 diabetes. Nurses are often the first contact with patients and must be aware of the advancements in detection, therapies, and signs of complications in these patients. Individuals with type 1 diabetes are at high risk for glycemic complications caused by potentially preventable errors in medication administration, which can be mitigated with appropriate education.

11β-Hydroxysteroid Dehydrogenase Type 1 in Obese Subjects With Type 2 Diabetes Mellitus.

Obesity is one of the most significant contributors to the development of type 2 diabetes mellitus. Tissue-specific glucocorticoids regulated by 11β-hydroxysteroid dehydrogenase enzyme (11β-HSD) type 1 are involved in central obesity and obesity-related comorbidities. Moderate downregulation of 11β-HSD1 can attenuate insulin insensitivity and the impairment of glucose-stimulated insulin secretion. Some of the beneficial effects of 11β-HSD1 inhibition may be mediated, at least in part, through inactivation of tissue-specific glucocorticoid action related to insulin signaling mechanisms, alleviation of abnormal cytokine profile and the improvement of β-cell function. Thus, 11β-HSD1 is a promising target for the treatment and prevention of type 2 diabetes mellitus with obesity.

Association of Bone Metabolic Markers With Diabetic Retinopathy and Diabetic Macular Edema in Elderly Chinese Individuals With Type 2 Diabetes Mellitus.

Diabetic retinopathy (DR) is a common and specific microvascular complication of diabetes. The association of bone metabolic markers with the risk of DR and diabetic macular edema (DME) is unclear.

Cerebral Salt-Wasting Syndrome: Diagnosis by Urine Sodium Excretion.

Cerebral salt-wasting syndrome (CSWS) was initially described over 60 years ago in hyponatremic patients with a cerebral lesion. However, the diagnostic criteria for CSWS have not been fully established. Thus, when hyponatremia is observed in patients with CSWS, they may be misdiagnosed as having the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thus, it is critical to differentiate between these 2 conditions because their treatments are diametrically opposed.

Regional Patterns of Retinal Oxygen Saturation and Microvascular Hemodynamic Parameters Preceding Retinopathy in Patients With Type II Diabetes.

Alterations in retinal oxygen metabolism and retinal microcirculation are signs of impending diabetic retinopathy (DR). However, if specific retinal regions are primarily affected is so far unknown. The purpose of this study was to investigate if retinal oxygen saturation (SO2) and microvascular hemodynamic parameters follow a distinct regional pattern in patients with diabetes but no DR.

Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

Objective To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions.Design An umbrella review of meta-analyses.Data sources PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome.Main outcomes Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes.Data synthesis Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately.Results 156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre-eclampsia, whereas there was no evidence of association with fetal macrosomia.Conclusions Although the associations between adiposity and obstetric and gynaecological outcomes have been extensively studied, only a minority were considered strong and without hints of bias.