A controlled trial of the effectiveness of a diabetes education programme in a multi-ethnic community in Glasgow [ISRCT28317455]

BACKGROUND: Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin. Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population. The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes. We then investigated whether this intervention could produce an improvement, and finally whether any improvement was greater than background changes in knowledge in comparison groups. METHODS: A multi-site prospective, randomised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow, Scotland. The intervention consisted of 18 educational sessions in 6 separate programmes. A modified questionnaire was used to measure the knowledge, attitudes, and practice of diabetes before and after intervention. RESULTS: Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes, regarded the disease less seriously, and had a lesser understanding of the relationship between control and complications than the white population. No differences in initial responses were found between those who completed the second assessment and those who did not. The intervention group showed significant improvements in scores for Knowledge (+12.5%); Attitudes toward seriousness (+13.5%), complications (+8.1%), Practice (+20.0%). However there were also changes in the ethnic control group scores; respectively +5.0%, +16.3% (significant P < 0.001), +1.5%, +1.7%. The single white control group also showed some improvements; respectively +12.2%, +12.4% (P = 0.04), +6.0%, +25.0% (P = 0.007), but the differences in improvement between these two control groups were not significant. Overall, the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change (P = 0.36 CI -0.9 to +2.6). CONCLUSION: This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice. However there was no net benefit compared with the control group

Associations between weight change and biomarkers of cardiometabolic risk in South Asians:secondary analyses of the PODOSA trial

Background/Objectives: The association of weight changes with cardiometabolic biomarkers in South Asians has been sparsely studied. Subjects/Methods: We measured cardiometabolic biomarkers at baseline and after 3 years in the Prevention of Diabetes and Obesity in South Asians Trial. We investigated the effect of a lifestyle intervention on biomarkers in the randomized groups. In addition, treating the population as a single cohort, we estimated the association between change in weight and change in biomarkers. Results: Complete data were available at baseline and after 3 years in 151 participants. At 3 years, there was an adjusted mean reduction of 1·44 kg (95% confidence interval (95% CI): 0.18–2.71) in weight and 1.59 cm (95% CI: 0.08–3.09) in waist circumference in the intervention arm as compared with the control arm. There was no clear evidence of difference between the intervention and control arms in change of mean value of any biomarker. As a single cohort, every 1 kg weight reduction during follow-up was associated with a reduction in triglycerides (−1.3%, P=0.048), alanine aminotransferase (−2.5%, P=0.032), gamma-glutamyl transferase (−2.2%, P=0.040), leptin (−6.5%, P&lt;0.0001), insulin (−3.7%, P=0.0005), fasting glucose (−0.8%, P=0.0071), 2-h glucose (−2.3%, P=0.0002) and Homeostatic Model Assessment of insulin resistance (HOMA-IR: −4.5%, P=0.0002). There was no evidence of associations with other lipid measures, tissue plasminogen activator, markers of inflammation or blood pressure. Conclusions: We demonstrate that modest weight decrease in SAs is associated with improvements in markers of total and ectopic fat as well as insulin resistance and glycaemia in South Asians at risk of diabetes. Future trials with more intensive weight change are needed to extend these findings

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings

BackgroundA composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.MethodsWe assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.ResultsThe analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.ConclusionThe GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments

Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight

Abstract Background Cadmium (Cd), lead (Pb) and arsenic (As) are common environmental contaminants that have been associated with lower birthweight. Although some essential metals may mitigate exposure, data are inconsistent. This study sought to evaluate the relationship between toxic metals, nutrient combinations and birthweight among 275 mother-child pairs. Methods Non-essential metals, Cd, Pb, As, and essential metals, iron (Fe), zinc (Zn), selenium (Se), copper (Cu), calcium (Ca), magnesium (Mg), and manganese (Mn) were measured in maternal whole blood obtained during the first trimester using inductively coupled plasma mass spectrometry. Folate concentrations were measured by microbial assay. Birthweight was obtained from medical records. We used quantile regression to evaluate the association between toxic metals and nutrients due to their underlying wedge-shaped relationship. Ordinary linear regression was used to evaluate associations between birth weight and toxic metals. Results After multivariate adjustment, the negative association between Pb or Cd and a combination of Fe, Se, Ca and folate was robust, persistent and dose-dependent (p < 0.05). However, a combination of Zn, Cu, Mn and Mg was positively associated with Pb and Cd levels. While prenatal blood Cd and Pb were also associated with lower birthweight. Fe, Se, Ca and folate did not modify these associations. Conclusion Small sample size and cross-sectional design notwithstanding, the robust and persistent negative associations between some, but not all, nutrient combinations with these ubiquitous environmental contaminants suggest that only some recommended nutrient combinations may mitigate toxic metal exposure in chronically exposed populations. Larger longitudinal studies are required to confirm these findings

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational study

BackgroundThe PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice.MethodsFebrile children and controls were recruited on presentation to hospital in 9 European countries 2016-2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed.FindingsOf 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92-5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07-7.59), Group A streptococcus (OR 2.73, 95% CI 1.13-6.09) and E. coli (OR 2.7, 95% CI 1.02-6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11-0.46), influenza B (OR 0.12, 95% CI 0.02-0.37) and RSV (OR 0.16, 95% CI: 0.06-0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23-0.72) and EBV (OR 0.71, 95% CI 0.56-0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively.InterpretationMost febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics.FundingEU Horizon 2020 grant 668303

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

A Qualitative Exploration of Perceived Medication Adherence Determinants Conducted Among Older Adults with HIV and Type 2 Diabetes Mellitus

Allison P Pack,1 Mary Clare Masters,2 Rachel O’Conor,1 Kenya Alcantara,1 Sophia Svoboda,1 Reneaki Smith,1 Fangyu Yeh,1 Guisselle Wismer,1 Amisha Wallia,2,3 Stacy C Bailey1 1Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 2Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; 3Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Allison P Pack, Division of General Internal Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, Email [email protected]: People living with HIV (PLWH) are at higher risk of developing type 2 diabetes (T2DM). Both chronic conditions require individuals to adhere to medication regimens, yet few studies have sought to explore medication-taking behaviors among individuals with comorbid HIV and T2DM (HIV+T2DM).Objective: This qualitative study sought to: 1) identify and compare perceived determinants of medication adherence for HIV and, separately, for T2DM, and 2) explore how participants prioritize conditions.Methods: Between October 2022 and January 2023, we conducted in-depth interviews with individuals aged 50 or older, living with comorbid HIV+T2DM. Participants were prescribed oral medications to treat their conditions and had recent clinical measures indicating probable challenges with medication adherence. Interviews with consented participants from a large academic health center in the Midwest were conducted remotely. Questions largely drew from the Theoretical Domains Framework (TDF), a widely used implementation science framework. Additional questions explored the prioritization of conditions. Analysis employed the Framework Method and a side-by-side comparison of key determinants of medication adherence by condition.Results: A total of 19 interviews were audio recorded, transcribed, and analyzed. Participants were an average age of 61, mostly male (89.5%), and Non-Hispanic White (47.4%). Although results revealed many commonalities between perceived determinants of medication adherence for HIV and for T2DM, differences relating to two TDF domains were noted: nature of the behavior (taking medications as prescribed), and motivations and goals. Many participants viewed their conditions as equally important, though they suggested T2DM was more difficult to manage, largely due to lifestyle modifications.Conclusion: As individuals with HIV develop chronic conditions, such as T2DM, they may require additional medication adherence support. Attention should be paid to offering support early. Disease perceptions may differ by condition, and as such, one’s motivations to take medication as prescribed may also differ by condition.Keywords: qualitative, HIV, type 2 diabetes, medication adherenc