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JMIR Diabetes Jun 2024The COVID-19 pandemic created unprecedented challenges for people with type 2 diabetes (T2D) and prediabetes to access in-person health care support. Primary care teams...
Inequalities in the Ability for People With Type 2 Diabetes and Prediabetes to Adapt to the Reduction in In-Person Health Support and Increased Use of Digital Support During the COVID-19 Pandemic and Beyond: Qualitative Study.
BACKGROUND
The COVID-19 pandemic created unprecedented challenges for people with type 2 diabetes (T2D) and prediabetes to access in-person health care support. Primary care teams accelerated plans to implement digital health technologies (DHTs), such as remote consultations and digital self-management. There is limited evidence about whether there were inequalities in how people with T2D and prediabetes adjusted to these changes.
OBJECTIVE
This study aimed to explore how people with T2D and prediabetes adapted to the reduction in in-person health support and the increased provision of support through DHTs during the COVID-19 pandemic and beyond.
METHODS
A purposive sample of people with T2D and prediabetes was recruited by text message from primary care practices that served low-income areas. Semistructured interviews were conducted by phone or video call, and data were analyzed thematically using a hybrid inductive and deductive approach.
RESULTS
A diverse sample of 30 participants was interviewed. There was a feeling that primary care had become harder to access. Participants responded to the challenge of accessing support by rationing or delaying seeking support or by proactively requesting appointments. Barriers to accessing health care support were associated with issues with using the total triage system, a passive interaction style with health care services, or being diagnosed with prediabetes at the beginning of the pandemic. Some participants were able to adapt to the increased delivery of support through DHTs. Others had lower capacity to use DHTs, which was caused by lower digital skills, fewer financial resources, and a lack of support to use the tools.
CONCLUSIONS
Inequalities in motivation, opportunity, and capacity to engage in health services and DHTs lead to unequal possibilities for people with T2D and prediabetes to self-care and receive care during the COVID-19 pandemic. These issues can be addressed by proactive arrangement of regular checkups by primary care services and improving capacity for people with lower digital skills to engage with DHTs.
PubMed: 38917452
DOI: 10.2196/55201 -
PloS One 2024Hypertension is one of the most common and complicated disorders associated with genetic and environmental risk factors. The angiotensin-converting enzyme (ACE) is...
Hypertension is one of the most common and complicated disorders associated with genetic and environmental risk factors. The angiotensin-converting enzyme (ACE) is important in the renin-angiotensin-system pathway. The gene expression of ACE has been investigated as a possible hypertension marker. This study investigates the association between polymorphisms within the ACE1 and ACE2 genes and hypertension susceptibility in a Jordanian population. The study comprised a total of 200 hypertensive patients and 180 healthy controls. A polymerase chain reaction (PCR) was performed to genotype the candidate polymorphism (rs4646994) of the ACE1gene. The Luminex DNA array technique was used for genotyping SNPs (rs4359, rs4344, rs4341, rs4343, and rs2106809) of the ACE1 and ACE2 genes. Our findings suggest no association between SNPs and hypertension regarding allelic and genotypic frequencies. However, rs4359 was significantly associated with diet (pP = 0.049), know HTN (P = 0.042), and number of years DM (P = 0.003). rs4341 was associated with diet (P = 0.032), peripheral vascular disease (P = 0.005), and chronic kidney disease (p = 0.049). While rs4343 was associated with diet (P = 0.031), diabetes mellitus (P = 0.032), and other medication (P = 0.025). Furthermore, the haplotypes of four SNPs of the ACE1 gene showed no significant association with HTN patients and healthy controls. Our findings indicate no association between the polymorphisms in the ACE gene and the risk of hypertension development in the Jordanian adult population.
Topics: Humans; Hypertension; Jordan; Peptidyl-Dipeptidase A; Male; Female; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Middle Aged; Adult; Case-Control Studies; Angiotensin-Converting Enzyme 2; Gene Frequency; Genotype; Aged
PubMed: 38917192
DOI: 10.1371/journal.pone.0304271 -
PloS One 2024Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been...
OBJECTIVES
Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status.
METHODS
This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing.
RESULTS
There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99).
CONCLUSION
Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls.
Topics: Humans; Cross-Sectional Studies; Periodontitis; Male; Adult; Cystic Fibrosis; Female; Pilot Projects; Diabetes Mellitus; Prevalence; Middle Aged; Diabetes Complications; Young Adult
PubMed: 38917148
DOI: 10.1371/journal.pone.0305975 -
International Journal of... Apr 2024Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep... (Comparative Study)
Comparative Study
BACKGROUND
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), with a high global prevalence and mortality rate. To control the gruesome pathogen, a deep understanding of pathophysiology and host-pathogen interaction is essential for early diagnosis and novel drug development. Cytokines play a crucial role in infection and susceptibility, and their expressions could serve as potential biomarkers to enhance our understanding of Mtb pathophysiology for improved therapeutic approaches. This cross-sectional study investigates the levels of four important T-cell immune-mediated cytokines: interleukins (IL-6 and IL-10), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha in 80 cohort samples, with 20 people in each group.
METHODS
Following proper ethics and patient consent, we collected blood samples and isolated serum from all four groups: TB, type 2 diabetes mellitus (T2DM), type 2 diabetes-TB comorbidity (T2DM + TB), and a healthy individual as a control group (C). Furthermore, cytokine expression was measured in individual serum samples through the enzyme-linked immunosorbent assay method using commercial kits (Diaclone, French). Statistical significance was observed by analyzing triplicate data using t-tests and the one-way ANOVA method with GraphPad Prism 10.
RESULTS
The results showed that all four cytokine levels were higher (P ≤ 0.0001) than the control, especially IL-6, IL-10, and IFN-γ, which were found to be upregulated in T2DM + TB samples (P ≤ 0.0001) than individual TB or T2DM samples.
CONCLUSION
The high levels of cytokines in comorbidity cases raise the risk of insulin resistance and the severity of TB infection. These levels of expression could be used to keep track of the Mtb infection status or severity, aid in early diagnosis as a possible biomarker, and suggest possible treatment plans.
Topics: Humans; Diabetes Mellitus, Type 2; Tuberculosis, Pulmonary; Cross-Sectional Studies; Male; Middle Aged; Female; Adult; Cytokines; Comorbidity; Mycobacterium tuberculosis; Interferon-gamma; Biomarkers; Interleukin-10; Tumor Necrosis Factor-alpha; Interleukin-6; Aged
PubMed: 38916387
DOI: 10.4103/ijmy.ijmy_40_24 -
Journal of Primary Care & Community... 2024Lifestyle interventions can prevent type 2 diabetes (T2D) by successfully inducing behavioral changes (eg, avoiding physical inactivity and sedentariness, increasing...
Hybrid Evaluation of a Lifestyle Change Program to Prevent the Development of Type 2 Diabetes Among Individuals With Prediabetes: Intended and Observed Changes in Intervening Mechanisms.
BACKGROUND
Lifestyle interventions can prevent type 2 diabetes (T2D) by successfully inducing behavioral changes (eg, avoiding physical inactivity and sedentariness, increasing physical activity and/or healthy eating) that reduce body weight and normalize metabolic levels (eg, HbA1c). For interventions to be successful, it is important to influence "behavioral mechanisms" such as self-efficacy, which motivate behavioral changes. Theory-based expectations of how self-efficacy, chronic stress, and mood changed over time were investigated through a group-based behavior change intervention (PREMIT). At 8 intervention sites, PREMIT was offered by trained primary care providers in 18 group-sessions over a period of 36 months, divided into 4 intervention phases. Adherence to the intervention protocol was assessed.
METHOD
Participants (n = 962) with overweight and prediabetes who had achieved ≥8% weight loss during a diet reduction period and completed the intervention were categorized into 3 groups: infrequent, frequent, or very frequent group sessions attendance. The interactions between participation in the group sessions and changes in self-efficacy, stress, and mood were multivariate tested. Intervention sites were regularly asked where and how they deviated from the intervention protocol.
RESULTS
There was no increase in the participants' self-efficacy in any group. However, the level of self-efficacy was maintained among those who attended the group sessions frequently, while it decreased in the other groups. For all participants, chronic stress and the frequency of attending group sessions were inversely related. Significant differences in mood were found for all groups. All intervention centers reported specific activities, additional to intervention protocol, to promote participation in the group sessions.
CONCLUSIONS
The results suggest that the behavioral changes sought by trained primary care providers are related to attendance frequency and follow complex trajectories. The findings also suggest that group-based interventions in naturalistic primary care settings aimed at preventing T2D require formats and strategies that encourage participants to attend group sessions regularly.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Male; Female; Middle Aged; Self Efficacy; Life Style; Aged; Adult; Stress, Psychological; Exercise; Program Evaluation; Affect; Risk Reduction Behavior; Primary Health Care; Overweight
PubMed: 38916158
DOI: 10.1177/21501319241248223 -
Frontiers in Endocrinology 2024Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While... (Review)
Review
Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β-cell apoptosis rates are relatively low in diabetes. Instead, β-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to β-cell failure. The underlying mechanisms driving β-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing β-cell dedifferentiation in T2D. This review explores the proposed drivers of β-cell dedifferentiation leading to β-cell failure, and discusses current interventions capable of reversing this process, thus restoring β-cell identity and function.
Topics: Humans; Insulin-Secreting Cells; Cell Dedifferentiation; Diabetes Mellitus, Type 2; Animals; Cell Differentiation; Apoptosis; Insulin Secretion
PubMed: 38915897
DOI: 10.3389/fendo.2024.1414447 -
Frontiers in Endocrinology 2024Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis...
PURPOSE
Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.
MATERIAL AND METHOD
We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.
RESULT
Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.
CONCLUSION
This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Quantitative Trait Loci; Genetic Predisposition to Disease; Bayes Theorem; Diabetes Mellitus, Type 1; Genomics; Hypoglycemic Agents; Polymorphism, Single Nucleotide
PubMed: 38915894
DOI: 10.3389/fendo.2024.1366290 -
Frontiers in Endocrinology 2024The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or...
OBJECTIVE
The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients.
METHODS
We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model.
RESULTS
For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR.
CONCLUSION
Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.
Topics: Humans; Diabetes Mellitus, Type 2; Glomerular Filtration Rate; Machine Learning; Male; Female; Middle Aged; Aged; Biomarkers; Metabolomics; Carnitine; Cohort Studies; Diabetic Nephropathies
PubMed: 38915893
DOI: 10.3389/fendo.2024.1279034 -
Frontiers in Neurology 2024The objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among...
PURPOSE
The objective of this study was to investigate alterations in functional connectivity density (FCD) mapping and their impact on functional connectivity (FC) among individuals diagnosed with Type 2 diabetes mellitus (T2DM) across different cognitive states. Moreover, the study sought to explore the potential association between aberrant FCD/FC patterns and clinical or cognitive variables.
METHODS
A total of 211 participants were recruited for this study, consisting of 75 healthy controls (HCs), 89 T2DM patients with normal cognitive function (DMCN), and 47 T2DM patients with mild cognitive impairment (DMCI). The study employed FCD analysis to pinpoint brain regions exhibiting significant FCD alterations. Subsequently, these regions showing abnormal FCD served as seeds for FC analysis. Exploratory partial correlations were conducted to explore the relationship between clinical biochemical indicators, neuropsychological test scores, and altered FCD or FC.
RESULTS
The FCD analysis revealed an increased trend in global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD) within the bilateral supramarginal gyrus (SMG) among individuals with DMCN. Additionally, significant lFCD alterations were observed in the right inferior frontal gyrus and left precuneus when comparing DMCN to HCs and DMCI.
CONCLUSION
When comparing individuals with T2DM and healthy controls (HCs), it was revealed that DMCN exhibited significant improvements in FCD. This suggests that the brain may employ specific compensatory mechanisms to maintain normal cognitive function at this stage. Our findings provide a novel perspective on the neural mechanisms involved in cognitive decline associated with T2DM.
PubMed: 38915801
DOI: 10.3389/fneur.2024.1418714 -
BioRxiv : the Preprint Server For... Jun 2024Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep...
Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus that is caused by metabolic toxicity to peripheral axons. We aimed to gain deep mechanistic insight into the disease process using bulk and spatial RNA sequencing on tibial and sural nerves recovered from lower leg amputations in a mostly diabetic population. First, our approach comparing mixed sensory and motor tibial and purely sensory sural nerves shows key pathway differences in affected nerves, with distinct immunological features observed in sural nerves. Second, spatial transcriptomics analysis of sural nerves reveals substantial shifts in endothelial and immune cell types associated with severe axonal loss. We also find clear evidence of neuronal gene transcript changes, like in nerves with axonal loss suggesting perturbed RNA transport into distal sensory axons. This motivated further investigation into neuronal mRNA localization in peripheral nerve axons generating clear evidence of robust localization of mRNAs such as and in human sensory axons. Our work gives new insight into the altered cellular and transcriptomic profiles in human nerves in DPN and highlights the importance of sensory axon mRNA transport as an unappreciated potential contributor to peripheral nerve degeneration.
PubMed: 38915676
DOI: 10.1101/2024.06.15.599167