ResearchPad - endocrine-disorders https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Estimating the potential impact of behavioral public health interventions nationally while maintaining agreement with global patterns on relative risks]]> https://www.researchpad.co/article/elastic_article_13880 This paper introduces a novel method to evaluate the local impact of behavioral scenarios on disease prevalence and burden with representative individual level data while ensuring that the model is in agreement with the qualitative patterns of global relative risk (RR) estimates. The method is used to estimate the impact of behavioral scenarios on the burden of disease due to ischemic heart disease (IHD) and diabetes in the Turkish adult population.MethodsDisease specific Hierarchical Bayes (HB) models estimate the individual disease probability as a function of behaviors, demographics, socio-economics and other controls, where constraints are specified based on the global RR estimates. The simulator combines the counterfactual disease probability estimates with disability adjusted life year (DALY)-per-prevalent-case estimates and rolls up to the targeted population level, thus reflecting the local joint distribution of exposures. The Global Burden of Disease (GBD) 2016 study meta-analysis results guide the analysis of the Turkish National Health Surveys (2008 to 2016) that contain more than 90 thousand observations.FindingsThe proposed Qualitative Informative HB models do not sacrifice predictive accuracy versus benchmarks (logistic regression and HB models with non-informative and numerical informative priors) while agreeing with the global patterns. In the Turkish adult population, Increasing Physical Activity reduces the DALYs substantially for both IHD by 8.6% (6.4% 11.2%), and Diabetes by 8.1% (5.8% 10.6%), (90% uncertainty intervals). Eliminating Smoking and Second-hand Smoke predominantly decreases the IHD burden 13.1% (10.4% 15.8%) versus Diabetes 2.8% (1.1% 4.6%). Increasing Fruit and Vegetable Consumption, on the other hand, reduces IHD DALYs by 4.1% (2.8% 5.4%) while not improving the Diabetes burden 0.1% (0% 0.1%).ConclusionWhile the national RR estimates are in qualitative agreement with the global patterns, the scenario impact estimates are markedly different than the attributable risk estimates from the GBD analysis and allow evaluation of practical scenarios with multiple behaviors. ]]> <![CDATA[Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study]]> https://www.researchpad.co/article/elastic_article_13877 Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes.MethodsIn this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA.ResultsIn the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27–0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16–3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23–0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis.ConclusionsLow levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes. ]]> <![CDATA[Barriers and facilitating factors in the prevention of diabetes type 2 and gestational diabetes in vulnerable groups: A scoping review]]> https://www.researchpad.co/article/elastic_article_13859 Type 2 diabetes mellitus (T2DM) and gestational diabetes (GDM) are globally on the rise, accompanied by comorbidities and associated health costs. Increased physical activity, healthy nutrition, and weight loss have shown the potential to prevent T2DM/GDM. Despite this, reaching vulnerable groups remains a key challenge. The aim of this scoping review was to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups.MethodsWe conducted a systematic literature search in May 2018, updated in September 2019, in several databases (e.g. PubMed, Embase) to identify barriers and facilitating factors in the prevention of T2DM/GDM in vulnerable groups. Two reviewers independently screened the results. Extracted data was charted, categorized, and summarized.ResultsWe included 125 articles. Ninety-eight studies were extracted, and eight categories of barriers and facilitating factors were formed. The most common categories of barriers were limited knowledge, family/friends, and economic factors, and the most common categories of facilitating factors were family/friends, social support, and knowledge.ConclusionThis scoping review identified various barriers and facilitating factors in vulnerable groups. Preventive interventions should consider these barriers and facilitating factors in developing preventive interventions or in adapting existing ones. ]]> <![CDATA[Health profile of adult special immigrant visa holders arriving from Iraq and Afghanistan to the United States, 2009–2017: A cross-sectional analysis]]> https://www.researchpad.co/article/elastic_article_13850 Between 2,000 and 19,000 Special Immigrant Visa holders (SIVH) from Iraq and Afghanistan have resettled in the United States annually since 2008.Per the Immigration and Nationality Act, SIVH, like other immigrants and refugees, must be examined by a physician before arriving in the US. Results of these overseas examinations are transmitted by the Centers for Disease Control and Prevention (CDC) to US state and local health departments via CDC’s Electronic Disease Notification system (EDN).Increasing provider knowledge about the health conditions most commonly encountered in SIVH as well as any differences in health conditions between SIVH from Iraq and Afghanistan may facilitate diagnostic screening, examination, and referrals to additional healthcare providers in the US.Information about the health of SIV populations is limited and would be beneficial for US clinicians who see SIVH in their clinics.What did the researchers do and find?In this cross-sectional analysis, we analyzed overseas medical exam data in CDC’s EDN for 19,167 SIV Iraqi and Afghan adults who resettled to the United States from April 2009 through December 2017.Among all SIVH, 56.5% were overweight or had obesity, 2.4% reported hypertension, 1.1% reported diabetes, and 19.4% reported current or previous tobacco use.In general, Iraqi SIVH were more likely to have obesity, diabetes, and be current or former smokers than Afghan SIVH.What do these findings mean?State public health agencies and clinicians screening SIVH should consider screening for diabetes among those with risk factors and prompt referral and management of obesity, hypertension, and smoking.Behavioral risk factor counseling and referral to culturally appropriate chronic disease prevention programs can be initiated at screening visits and subsequently reemphasized with primary care providers and other healthcare professionals.Limitations include the inability to obtain all SIVH records, self-reported medical history of NCDs, and underdiagnosis of NCDs such as hypertension and diabetes because formal laboratory testing for NCDs is not used during overseas medical exams. ]]> <![CDATA[Fruit and vegetable consumption in Europe according to gender, educational attainment and regional affiliation—A cross-sectional study in 21 European countries]]> https://www.researchpad.co/article/elastic_article_13846 The purpose of the present study was to examine fruit and vegetable consumption according to gender, educational attainment and regional affiliation in Europe.DesignCross-sectional study.Setting21 European countries.Participants37 672 adults participating in the 7th round of the European Social Survey.Main outcome measuresFruit and vegetable consumption was measured using two single frequency questions. Responses were dichotomized into low (<once a day) and high (≥once a day) consumption. The association between consumption of fruit and vegetables and gender, educational level, regional affiliation was examined using logistic regression analyses.ResultsOverall, females showed increased odds of consuming fruit (OR 1.71 (95%CI:1.62, 1.79) and vegetable (1.59 (1.51, 1.67)) compared to males and high educated participants showed increased odds of consuming fruit (1.53 (1.43, 1.63)) and vegetables (1.86 (1.74, 2.00)) compared to low educated participants. Our results also showed that participants living in Eastern Europe had the lowest odds of consuming fruit and vegetables, whereas participants from Southern- and Northern Europe had the highest odds of consuming fruit and vegetables, respectively. Results from interaction analyses confirmed the positive association between fruit and vegetable consumption and educational level, although for some European regions, decreased odds of fruit and vegetables was observed among medium educated participants compared to those with low education.ConclusionsOverall, the present study showed that being female and having a high education were associated with increased consumption of fruit and vegetables. However, the direction and strength of these relationships depends on regional affiliations. ]]> <![CDATA[Brazilian vegetarians diet quality markers and comparison with the general population: A nationwide cross-sectional study]]> https://www.researchpad.co/article/elastic_article_7851 Vegetarianism is an increasingly common practice worldwide. Despite good evidence from other countries regarding vegetarians’ diet quality, data from the Brazilian population is still scarce.ObjectiveTo characterize the vegetarian Brazilian population and evaluate their diet quality compared to the general Brazilian population.MethodsWe performed a nationwide cross-sectional study using an online self-administered questionnaire, previously validated for the Brazilian population, to evaluate diet quality markers of vegetarians. The invitation to participate in the survey was spread nationwide, aimed at vegetarian communities. Individuals who considered themselves vegetarians and were at least 18 years old were eligible to participate. The results on regular intake and intake adequacy were compared among vegetarians and between genders using the Pearson’s chi-square test. The body mass index (BMI) were analyzed by the Analysis of Variance (ANOVA) followed by Tukey post-hoc test. The Kolmogorov-Smirnov test verified normality. All analyses considered bilateral hypotheses and a significance level of 5% (p <0.05).ResultsBrazilian vegetarians presented better diet quality markers, such as higher regular weekly intake and adequate daily intake of fruits and vegetables, and lower regular intake of soft drinks when compared to the general Brazilian population. Vegetarians also presented a proportionally higher consumption of natural foods and lower consumption of processed foods. Among vegetarians, a higher proportion of vegans showed positive results regarding diet markers analysis, when compared to vegetarians, pesco-vegetarians, and semi-vegetarians.ConclusionsVegetarians showed better results of diet adequacy when compared to the general population in Brazil, and vegans fared better when compared with other vegetarians. Despite the good results found, a large proportion of the participants still did not achieve the fruits and vegetables daily intake, according to the World Health Organization recommendations. ]]> <![CDATA[Life expectancy and survival analysis of patients with diabetes compared to the non diabetic population in Bulgaria]]> https://www.researchpad.co/article/elastic_article_7723 To evaluate the expected life expectancy in patients with diabetes in Bulgaria and to compare it to the expected life expectancy of the non-diabetic population in the country.MethodsIt is a retrospective observational population study on individuals diagnosed with diabetes, compared to the non-diabetic population in Bulgaria for the period 2012–2015. Data from the national diabetes register and national statistical institute were used to construct life-tables with probability of survival with t-test and Chi Square test. Confounder analysis was done by age, sex, and type of diabetes. All-cause mortality and deaths in diabetic patients were analyzed. Kaplan-Meier survival curves were constructed for each age group and a log-rank analysis was conducted.ResultsAverage life expectancy in the non-diabetic population, patients with Type 1 DM and with Type 2 DM is 74.8; 70.96 and 75.19 years, respectively. For 2012–2015 the mortality in the non-diabetic population remained constant and lower (average—1.48%) compared to type-1 DM (5.25%) and Type-2 (4.27%). Relative risk of death in diabetics was higher overall (12%), after the age of 70 before which the relative risk was higher for the non-diabetic population. This was observed as a trend in all analyzed years.ConclusionPatients with type 2 DM have a longer life-expectancy than patients with type-1 DM and overall Diabetics life expectancy equals that of the non-diabetic population, which could suggest improved disease control and its associated complications in Bulgaria. Male diabetics show slightly longer life expectancy than their counterparts in the non-diabetic population, by a marginal gain of 0.6 years for the entire observed period. Life expectancy in diabetic women increased by 1.3 years, which was not observed in the non-diabetic population. Prevalence of diabetes was higher for women. Improved diabetes control may explain this gain in life; however other studies are needed to confirm this. ]]> <![CDATA[Sarcopenia in Endocrine Disorders – The Iceberg or Its Tip?]]> https://www.researchpad.co/article/5bfc7799d5eed0c484f2a96d

Summary

Endocrine myopathies represent disorders of the musculoskeletal system that significantly impair the state of health. Sarcopenia is their pathophysiological common denominator. Recent reports have shown that endocrine disorders, even when subclinical, may also be associated with tendinopathies. It may thus be suggested that both hormones and hormonal disorders have complex actions on the musculoskeletal system and that musculoskeletal endocrinology represents a fascinating research area still awaiting exploration.

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<![CDATA[The natural drug DIAVIT is protective in a type II mouse model of diabetic nephropathy]]> https://www.researchpad.co/article/5c92b34ad5eed0c4843a3d15

There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT). We also investigated the angiogenic and fibrotic pathways involved in the mechanism of action of DIAVIT. Diabetic db/db mice developed hyperglycaemia, albuminuria, and an increased glomerular water permeability; the latter two were prevented by DIAVIT. db/db mice developed fibrotic glomeruli, endothelial insult, and glomerular ultra-structural changes, which were not present in DIAVIT-treated mice. Vascular endothelial growth factor A (VEGF-A) splicing was altered in the db/db kidney cortex, increasing the pro-angiogenic VEGF-A165 relative to the anti-angiogenic VEGF-A165b. This was partially prevented with DIAVIT treatment. Delphinidin, an anthocyanin abundant in DIAVIT, increased the VEGF-A165b expression relative to total VEGF-A165 in cultured podocytes through phosphorylation of the splice factor SRSF6. DIAVIT, in particular delphinidin, alters VEGF-A splicing in type II DN, rescuing the DN phenotype. This study highlights the therapeutic potential of natural drugs in DN through the manipulation of gene splicing and expression.

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<![CDATA[Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis]]> https://www.researchpad.co/article/N07a3560c-fa96-4eb5-821e-9292b7a2bef0

Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze–omic datasets in rare genetic diseases as patient cohorts are inevitably small.

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<![CDATA[Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study]]> https://www.researchpad.co/article/Ndf1a2733-e0b1-4fc7-90ad-b2bfa4368f5f

Introduction

Low levels of vitamin D in pregnancy have been associated with the risk of a variety of pregnancy outcomes. Few studies have investigated vitamin D concentrations throughout pregnancy in healthy women, and most guidelines recommend high vitamin D levels. In the present study, we investigated 25-hydroxyvitamin D concentrations in healthy Caucasian Danish women in relation to season, gestational age and possible vitamin D-linked complications.

Materials and methods

Eight hundred and one healthy Caucasian Danish women with an expected normal pregnancy were recruited among 2147 women attending first trimester screening. Seven blood samplings were planned throughout the pregnancy and delivery period. The 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) concentrations were measured by LC-MS/MS and total 25-hydroxyvitamin D (25(OH)D) were calculated.

Results

A total of 3304 samples from 694 women were available for 25(OH)D measurements. The mean (25th-75th percentiles) concentrations of 25(OH)D, 25(OH)D3, and 25(OH)D2 were 54.6 (38.8–68.6) nmol/L, 52.2 (36.4–66.4) nmol/L, and 2.4 (2.2–2.2) nmol/L, respectively. Season was the strongest predictor of 25(OH)D concentration, with the lowest values observed in winter and spring, where only 42% and 41% of samples, respectively, were above 50 nmol/L. Nearly all women had values below the suggested optimal level of 75 nmol/L, independent of season. 25(OH)D peaked at gestational weeks 21–34. Plasma 25(OH)D2 levels were low in all seasons. Women with complications during pregnancy had higher 25(OH)D (estimated difference 9.8 nmol/L, standard error 2.7, p<0.001) than did women without complications, and women giving birth vaginally had lower 25(OH)D than did those delivering via elective (10.0 nmol/L, standard error 2.1, p<0.001) or emergency cesarean section (6.8 nmol/L, standard error 2.2, p<0.001).

Conclusion

The 25(OH)D concentrations vary with both season and gestational age. Healthy women had lower 25(OH)D concentrations than recommended, without an association with an increased risk of pregnancy complications. Guidelines for vitamin D in pregnancy may require revision.

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<![CDATA[Agreement between cardiovascular disease risk assessment tools: An application to the United Arab Emirates population]]> https://www.researchpad.co/article/N9ca1ffb4-d1e9-4710-8aa8-6eec943148b3

Introduction

Evidence regarding the performance of cardiovascular disease (CVD) risk assessment tools is limited in the United Arab Emirates (UAE). Therefore, we assessed the agreement between various externally validated CVD risk assessment tools in the UAE.

Methods

A secondary analysis of the Abu Dhabi Screening Program for Cardiovascular Risk Markers (AD-SALAMA) data, a large population-based cross-sectional survey conducted in Abu Dhabi, UAE during the period 2009 until 2015, was performed in July 2019. The analysis included 2,621 participants without type 2 Diabetes and without history of cardiovascular diseases. The CVD risk assessment tools included in the analysis were the World Health Organization for Middle East and North Africa Region (WHO-MENA), the systematic coronary risk evaluation for high risk countries (SCORE-H), the pooled cohort risk equations for white (PCRE-W) and African Americans (PCRE-AA), the national cholesterol education program Framingham risk score (FRAM-ATP), and the laboratory Framingham risk score (FRAM-LAB).

Results

The overall concordance coefficient was 0.50. The agreement between SCORE-H and PCRE-W, PCRE-AA, FRAM-LAB, FRAM-ATP and WHO-MENA, were 0.47, 0.39, 0.0.25, 0.42 and 0.18, respectively. PCRE-AA classified the highest proportion of participants into high-risk category of CVD (16.4%), followed by PCRE-W (13.6%), FRAM-LAB (6.9%), SCORE-H (4.5%), FRAM-ATP (2.7%), and WHO-MENA (0.4%).

Conclusions

We found a poor agreement between various externally validated CVD risk assessment tools when applied to a large data collected in the UAE. This poses a challenge to choose any of these tools for clinical decision-making regarding the primary prevention of CVD in the country.

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<![CDATA[Incidence of statin use in older adults with and without cardiovascular disease and diabetes mellitus, January 2008- March 2018]]> https://www.researchpad.co/article/N40ec07ea-30b4-4753-a09f-b8fe9ef6ec46

Background

Data from randomized controlled trials and observational studies on older adults who take statins for primary prevention of atherosclerotic cardiovascular disease are limited. To determine the incidence of statin use in older adults with and without cardiovascular disease (CVD) and/or diabetes (DM), we conducted a descriptive observational study.

Methods

The cohort consisted of health plan members in the NIH Collaboratory Distributed Research Network aged >75 years who had continuous drug and medical benefits for ≥183 days during the study period, January 1, 2008- March 31, 2018. We defined DM and CVD using diagnosis codes, and identified statins using dispensing data. Statin use was considered incident if a member had no evidence of statin exposure in the claims during the previous 183 days, and the use was considered long-term if statins were supplied for ≥180 days. Incidence rates were reported among members with and without CVD and/or diabetes, and stratified by year, sex, and age group.

Results

Among 757,569 eligible members, 109,306 older adults initiated statins and 54,624 became long-term users. Health plan members with CVD had the highest incidence of statin use (143.9 initiators per 1,000 member-years for CVD & DM; 114.5 initiators per 1,000 member-years for CVD & No DM). Among health plan members without CVD, those with DM had rates of statin use that were over two times higher than members without DM (76.1 versus 34.5 initiators per 1,000 member-years, respectively). Statin initiation remained steady throughout 2008–2016, was slightly higher in males, and declined with increasing age.

Conclusion

Incidence of statin use varied by CVD and DM comorbidity, and was lowest among those without CVD. These results highlight the potential clinical equipoise to conduct large pragmatic clinical trials to generate evidence that could be used to inform future blood cholesterol guidelines.

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<![CDATA[Exploring the geography of serious mental illness and type 2 diabetes comorbidity in Illawarra—Shoalhaven, Australia (2010 -2017)]]> https://www.researchpad.co/article/N645ccd00-2b7d-4514-8bd1-1e99a3f678df

Objectives

The primary aim of this study was to describe the geography of serious mental illness (SMI)–type 2 diabetes comorbidity (T2D) in the Illawarra-Shoalhaven region of NSW, Australia. The Secondary objective was to determine the geographic concordance if any, between the comorbidity and the single diagnosis of SMI and diabetes.

Methods

Spatial analytical techniques were applied to clinical data to explore the above objectives. The geographic variation in comorbidity was determined by Moran’s I at the global level and the local clusters of significance were determined by Local Moran’s I and spatial scan statistic. Choropleth hotspot maps and spatial scan statistics were generated to assess the geographic convergence of SMI, diabetes and their comorbidity. Additionally, we used bivariate LISA (Local Indicators of Spatial Association) and multivariate spatial scan to identify coincident areas with higher rates of both SMI and T2D.

Results

The study identified significant geographic variation in the distribution of SMI–T2D comorbidity in Illawarra Shoalhaven. Consistently higher burden of comorbidity was observed in some urban suburbs surrounding the major metropolitan city. Comparison of comorbidity hotspots with the hotspots of single diagnosis SMI and T2D further revealed a geographic concordance of high-risk areas again in the urban areas outside the major metropolitan city.

Conclusion

The identified comorbidity hotspots in our study may serve as a basis for future prioritisation and targeted interventions. Further investigation is required to determine whether contextual environmental factors, such as neighbourhood socioeconomic disadvantage, may be explanatory.

Implications for public health

Ours is the first study to explore the geographic variations in the distribution of SMI and T2D comorbidity. Findings highlight the importance of considering the role of neighbourhood environments in influencing the T2D risk in people with SMI.

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<![CDATA[Executive task-based brain function in children with type 1 diabetes: An observational study]]> https://www.researchpad.co/article/Nd7290b0a-e9f9-4731-9f28-e7228fa093e0

Background

Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.

Methods and findings

Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = −0.36, 95% CI −0.53 to −0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < −0.29, 95% CIs −0.47 to −0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = −0.22, 95% CI −0.41 to −0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI −0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown.

Conclusions

These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

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<![CDATA[Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis]]> https://www.researchpad.co/article/N25fa93a0-706a-4469-9476-c6f8ced4ff6a

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a new class of oral hypoglycemic agents used in the treatment of type 2 diabetes mellitus. They have a positive effect on the progression of chronic kidney disease, but there is a concern that they might cause acute kidney injury (AKI).

Methods and findings

We conducted a systematic review and meta-analysis of the effect of SGLT2is on renal adverse events (AEs) in randomized controlled trials and controlled observational studies. PubMed, EMBASE, Cochrane library, and ClinicalTrials.gov were searched without date restriction until 27 September 2019. Data extraction was performed using a standardized data form, and any discrepancies were resolved by consensus. One hundred and twelve randomized trials (n = 96,722) and 4 observational studies with 5 cohorts (n = 83,934) with a minimum follow-up of 12 weeks that provided information on at least 1 adverse renal outcome (AKI, combined renal AE, or hypovolemia-related events) were included. In 30 trials, 410 serious AEs due to AKI were reported. SGLT2is reduced the odds of suffering AKI by 36% (odds ratio [OR] 0.64 [95% confidence interval (CI) 0.53–0.78], p < 0.001). A total of 1,089 AKI events of any severity (AEs and serious AEs [SAEs]) were published in 41 trials (OR 0.75 [95% CI 0.66–0.84], p < 0.001). Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit on the SAE and AE rate. AEs related to hypovolemia were more commonly reported in SGLT2i-treated patients (OR 1.20 [95% CI 1.10–1.31], p < 0.001). In the observational studies, 777 AKI events were reported. The odds of suffering AKI were reduced in patients receiving SGLT2is (OR 0.40 [95% CI 0.33–0.48], p < 0.001). Limitations of this study are the reliance on nonadjudicated safety endpoints, discrepant inclusion criteria and baseline hypoglycemic therapy between studies, inconsistent definitions of renal AEs and hypovolemia, varying follow-up times in different studies, and a lack of information on the severity of AKI (stages I–III).

Conclusions

SGLT2is reduced the odds of suffering AKI with and without hospitalization in randomized trials and the real-world setting, despite the fact that more AEs related to hypovolemia are reported.

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<![CDATA[Validation of risk factors for recurrence of renal cell carcinoma: Results from a large single-institution series]]> https://www.researchpad.co/article/Ne7ebe4b8-b927-4fd1-a438-3fd04efc5df6

Purpose

To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC).

Materials and methods

We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test.

Results

We identified 873 patients who underwent surgery for RCC between the years 2000–2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265–1.614) and Nuclear grade (HR 2.376, 95% CI 1.734–3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343–5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001).

Conclusions

We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.

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<![CDATA[Association between circulating neuregulin4 levels and diabetes mellitus: A meta-analysis of observational studies]]> https://www.researchpad.co/article/N9558b610-af50-4464-8a85-11a7817968a6

Introduction

Neuregulin 4 (Nrg4) was proven as a brown fat-enriched secreted factor that can regulate glucose and lipid metabolism. However, the association between circulating Nrg4 levels and diabetes mellitus (DM) in human remains unclear. We conducted a meta-analysis to investigate association of circulating Nrg4 with DM.

Methods

Observational studies comparing circulating Nrg4 levels in diabetes patients and health controls were included. Circulating Nrg4, correlation coefficients of clinical indices and circulating Nrg4 were pooled by meta-analysis.

Results

Seven studies were included. The pooled results indicated there were no significant difference in the circulating Nrg4 between diabetes patients and controls (SMD = 0.18, 95%CI = -0.06 to 0.42, P = 0.143). However, diabetes patients had higher circulating Nrg4 than their controls in cross-sectional studies (SMD = 0.55, 95%CI = 0.36 to 0.73, P<0.001). None of the renal function and metabolic syndrome markers were correlated with circulating Nrg4, whereas the HbA1c and BMI were positively correlated (rs = 0.09, 95%CI = 0.03 to 0.16, P = 0.005; rs = 0.20, 95%CI = 0.07 to 0.34, P = 0.003; respectively).

Conclusion

Our findings suggested circulating Nrg4 may play a role in in the development of DM in cross-sectional studies and circulating Nrg4 might be associated with imbalance in glucose metabolism and obesity.

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<![CDATA[Lower plasma insulin levels during overnight closed-loop in school children with type 1 diabetes: Potential advantage? A randomized cross-over trial]]> https://www.researchpad.co/article/5c8c197ad5eed0c484b4d740

Background

Studies have shown that overnight closed-loop insulin delivery can improve glucose control and reduce the risk of hypoglycemia and hence may improve metabolic outcomes and reduce burden for children with type 1 diabetes and their families. However, research so far has not reported insulin levels while comparing closed-loop to open-loop insulin delivery in children. Therefore, in this study we obtained glucose levels as well as plasma insulin levels in children with type 1 diabetes to evaluate the efficacy of a model—based closed-loop algorithm compared to an open-loop administration.

Methods

Fifteen children with type 1 diabetes, 6–12 years, participated in this open-label single center study. We used a randomized cross over design in which we compared overnight closed-loop insulin delivery with sensor augmented pump therapy for two nights in both the hospital and at home (i.e., 1 night in-patient stay and at home per treatment condition). Only during the in-patient stay, hourly plasma insulin and blood glucose levels were assessed and are reported in this paper.

Results

Results of paired sample t-tests revealed that although plasma insulin levels were significantly lower during the closed-loop than in the open-loop (Mean difference 36.51 pmol/l; t(13) = 2.13, p = .03, effect size d = 0.57), blood glucose levels did not vary between conditions (mean difference 0.76 mmol/l; t(13) = 1.24, p = .12, d = 0.37). The administered dose of insulin was significantly lower during the closed-loop compared with the open-loop (mean difference 0.10 UI; t(12) = 2.45, p = .02, d = 0.68).

Conclusions

Lower insulin doses were delivered in the closed-loop, resulting in lower plasma insulin levels, whereby glucose levels were not affected negatively. This suggests that the closed-loop administration is better targeted and hence could be more effective.

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<![CDATA[Hyperkalemia and renin-angiotensin aldosterone system inhibitor therapy in chronic kidney disease: A general practice-based, observational study]]> https://www.researchpad.co/article/5c8acc87d5eed0c48498f966

Data on hyperkalemia frequency among chronic kidney disease (CKD) patients receiving renin-angiotensin aldosterone system inhibitors (RAASis) and its impact on subsequent RAASi treatment are limited. This population-based cohort study sought to assess the incidence of clinically significant hyperkalemia among adult CKD patients who were prescribed a RAASi and the proportion of patients with RAASi medication change after experiencing incident hyperkalemia. We conducted a retrospective, population-based cohort study (1 January 2013–30 June 2017) using Australian national general practice data from the NPS MedicineWise’s MedicineInsight program. The study included adults aged ≥18 years who received ≥1 RAASi prescription during the study period and had CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73m2). Study outcomes included incident clinically significant hyperkalemia (serum potassium >6 mmol/L or a record of hyperkalemia diagnosis) and among patients who experienced incident hyperkalemia, the proportion who had RAASi medication changes (cessation or dose reduction during the 210-day period after the incident hyperkalemia event). Among 20,184 CKD patients with a median follow-up of 3.9 years, 1,992 (9.9%) patients experienced an episode of hyperkalemia. The overall incidence rate was 3.1 (95% CI: 2.9–3.2) per 100 person-years. Rates progressively increased with worsening eGFR (e.g. 3.5-fold increase in patients with eGFR <15 vs. 45–59 ml/min/1.73m2). Among patients who experienced incident hyperkalemia, 46.6% had changes made to their RAASi treatment regimen following the first occurrence of hyperkalemia (discontinuation: 36.6% and dose reduction: 10.0%). In this analysis of adult RAASi users with CKD, hyperkalemia and subsequent RAASi treatment changes were common. Further assessment of strategies for hyperkalemia management and optimal RAASi use among people with CKD are warranted.

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