DISEASE:MESH:D003924
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Publication
Journal: Journal of Diabetes Investigation
February/21/2022
Abstract
Aims: To assess the association between vitamin D and diabetic foot (DF) in patients with type 2 diabetes mellitus (T2DM), in order to summarize clinical evidence in the prevention and treatment of DF.
Materials and methods: Between January 2012 and December 2019, a total of 1721 hospitalized patients with T2DM were continuously enrolled in West China Hospital, Sichuan University, which were divided into DF and non-DF groups according to whether with DF, and divided into four subgroups according to admission season. We compared 25-OH-Vitamin D levels between groups and subgroups, and discussed independent risk factors for the occurrence of DF.
Results: The vitamin D insufficiency and deficiency rate were higher in the DF group (77.51%) than in the non-DF group (59.2%). The 25-OH-Vitamin D levels were lower in the DF group (35.80 nmol/L) than in the non-DF group (45.48 nmol/l) (P<0.001). Patients with poor glycemic control had lower 25-OH-Vitamin D levels (P=0.01). The 25-OH-Vitamin D levels were lower in winter and spring. In the same season, the 25-OH-Vitamin D levels of patients with DF were still lower (P<0.001). The 25-OH-Vitamin D levels of patients with Wagner grades 0 to 5 showed a downward trend(P=0.114). The 25-OH-Vitamin D was independently associated with the DF (P<0.001, OR=0.986).
Conclusions: The low serum vitamin D level was significantly associated with a higher prevalence of DF among Chinese T2DM patients. Although vitamin D levels vary seasonally, patients with DF were always at higher risk of bearing vitamin D insufficiency and deficiency.
Keywords: 25-OH-Vitamin D; diabetic foot; inflammation; seasonal fluctuation; type 2 diabetes; vitamin D deficiency; vitamin D supplementation.
Publication
Journal: Clinical Medicine
February/21/2022
Abstract
Obesity is a modifiable risk factor in the development of type 2 diabetes mellitus (T2DM), with the prevalence of both increasing worldwide. This trend is associated with increasing mortality, cardiovascular risk and healthcare costs. An individual's weight will be determined by complex physiological, psychological and societal factors. Assessment by a skilled multidisciplinary team will help identify these factors and will also support screening for secondary causes, assessing cardiovascular risk and identifying sequelae of obesity.A range of treatment options are available for people with obesity and T2DM, including low-calorie diets, medications and bariatric surgery. People should be carefully counselled and personalised care plans developed. Bariatric surgery is an under-utilised resource in this context.Obesity should also be considered when choosing medical therapy for T2DM. Common diabetes medications may lead to weight gain whereas others (such as glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors) support weight loss.Bariatric surgery improves obesity-related complications and all-cause mortality. Diabetes remission is possible after surgery and is recommended by National Institute for Health and Care Excellence in individuals with a body mass index of >35 kg/m2 and recent onset T2DM.
Keywords: GLP-1; bariatrics; diabetes; obesity; total diet replacement.
Publication
Journal: Clinical Medicine
February/21/2022
Abstract
Diabetes mellitus is a common condition which all clinicians will encounter in their clinical practice. The most common form is type 2 diabetes followed by type 1 diabetes. However, there are many other atypical forms of diabetes which are important for a clinician to consider as it can impact on the diagnosis and their management.This article focuses on maturity onset diabetes of the young (MODY), latent autoimmune diabetes in adults (LADA), ketosis-prone diabetes and other secondary forms of diabetes such as pancreatic cancer and haemochromatosis. We briefly describe the key clinical features of these forms of diabetes and their investigations and treatment.
Keywords: LADA; MODY; atypical; diabetes; uncommon.
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Publication
Journal: Frontiers in Physiology
February/20/2022
Abstract
Objectives: Insulin resistance (IR) has been shown to play important role in the pathogenesis of type 2 diabetes mellitus (T2DM). There is an intricate interplay between IR, dyslipidemia, and serum uric acid (SUA) in people with and without diabetes. Physical activity has a positive impact on insulin sensitivity in insulin-resistant populations. However, the effect of different intensities of physical activity on insulin levels under different lipid indices and SUA levels is unclear.
Methods: To explore the association between physical activity and insulin, we enrolled 12,982 participants aged above 18 years from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2018. Next, we conducted multivariate logistic regression analyses, generated fitted smoothing curves, and visualized the data using generalized additive models.
Results: Increased intensities of physical activity can significantly reduce insulin levels. The association between physical activity and insulin persisted even after adjusting for confounding factors, with β value (95% CI) = -17.10 (-21.64, -12.56) in moderate group, β value (95% CI) = -28.60 (-33.08, -24.11) in high group, respectively. High-intensity physical activity significantly lowered insulin levels in the lower and higher SUA tertiles, and three tertiles of LDL-c, HDL-c, and TG. Moreover, the link between physical activity and insulin was stronger in male individuals.
Conclusion: This study shows that physical activity can significantly lower insulin levels, and high-intensity physical activity still has additional potential benefits for insulin levels, even in the condition of dyslipidemia and hyperuricemia.
Keywords: NHANES; SUA; insulin; lipids; physical activity.
Publication
Journal: Frontiers in Pharmacology
February/20/2022
Abstract
Background: Type 2 diabetes mellitus (T2DM) complicated with dyslipidaemia is associated with a high risk of cardiovascular diseases. The Jiangtang Tiaozhi (JTTZ) recipe is a Chinese herbal formula that has been used to regulate the blood glucose and lipid levels for many years. Interestingly, a previous study has demonstrated its efficacy; however, the associated mechanism remains unclear. We hypothesised that the therapeutic effect of the JTTZ on patients with T2DM may be mediated by the modulation of metabolites secreted by the gut microbiota. This study aims to examine this mechanism. Methods and analysis: This study is a randomised, positive drug parallel-controlled, open-label clinical trial in patients with T2DM and dyslipidaemia. A total of 96 patients will be recruited and randomly assigned to treatment with JTTZ or metformin for 12 weeks. The primary outcome will be the rates of effectively regulated blood glucose and lipid levels (measured with the levels of glycated haemoglobin, fasting plasma glucose, 2-h plasma glucose, triglyceride, and low-density lipoprotein cholesterol). The secondary outcomes will be the changes in body weight, body mass index, and waist circumference and Traditional Chinese Medicine symptom scores. In addition, 16S rRNA gene sequencing will be performed on the gut microbiota obtained from faeces, and metabolomics analysis will be performed based on blood and gut microbiota samples. Intention-to-treat, per-protocol analysis and safety analysis will be performed. Clinical trial registration number: https://clinicaltrials.gov/ct2/show/NCT04623567.
Keywords: Jiangtang Tiaozhi recipe; clinical trial protocol; dyslipidaemia; herbal medicine; type 2 diabetes.
Publication
Journal: Endocrine Journal
February/20/2022
Abstract
Evidence about the relationship between Helicobacter pylori (Hp) infection and type 2 diabetes mellitus (T2DM) is inconsistent and contradictory. This study attempted to investigate this association in the middle-aged and elderly Chinese population and analyze the joint effects of Hp infection and some risk factors on T2DM. Following a cross-sectional design, participants were recruited from the First Affiliated Hospital of Anhui Medical University in Hefei City, China. Hp status was measured using a 14C urea breath test. A total of 1,288 participants, including 90 diabetic patients and 1,198 nondiabetic subjects, were recruited in the current study. The participants with T2DM had a greater prevalence of Hp infection than participants without T2DM (26.67% versus 18.11%, p = 0.045). Furthermore, we found that Hp infection was closely associated with an incremental risk of T2DM [odds ratio (OR) = 1.77, 95% confidence intervals (CI): 1.04-3.00] after adjustment for potential confounders. In addition, we observed that the participants who were Hp-positive and ≥60 years old (OR = 9.16, 95% CI: 3.29-25.52), Hp-positive and obese (OR = 3.35, 95% CI: 1.57-7.14) or Hp-positive and hypertensive (OR = 6.10, 95% CI: 3.10-12.01) had a significantly higher risk for T2DM than those who were Hp-negative and ≤50 years old, Hp-negative and nonobese or Hp-negative and nonhypertensive. These findings imply that Hp infection is associated with an increased risk of T2DM in the middle-aged and elderly Chinese population. The association could be further elevated by the combination of Hp infection and some traditional risk factors.
Keywords: Helicobacter pylori (Hp); Joint effects; Type 2 diabetes mellitus (T2DM).
Publication
Journal: F1000Research
February/20/2022
Abstract
Introduction: Self-management (SM) interventions are complex interventions and one of the main components of high-quality chronic disease care for which the incorporation of the perspectives of patients and their informal caregivers is crucial. We aim to identify, appraise and synthesise the evidence exploring patients' and caregivers' perspectives on SM interventions. More precisely, we aim to 1) describe how they value the importance of outcomes of SM interventions, and 2) identify the factors that might impact on acceptability and feasibility of SM interventions based on their preferences and experiences. Methods and analysis: We will conduct four mixed-methods overviews as part of COMPAR-EU, a European Union (EU) funded project aimed to identify the most effective and cost-effective SM interventions for chronic obstructive pulmonary disease (COPD), heart failure (HF), obesity, and type 2 diabetes mellitus (T2DM). We will search in MEDLINE, CINAHL, and PsycINFO for systematic reviews of studies addressing patients' preferences on outcomes, or their experiences with SM alongside their disease trajectory or with SM interventions, published in English. Selection of studies and data extraction will be conducted in pairs. We will assess the overlap of studies and methodological quality. We will follow a three-step synthesis process: 1) narrative synthesis for quantitative evidence, 2) thematic synthesis for qualitative evidence, and 3) integration of findings in the interpretation phase. Additionally, we will consult on the relevance of findings with patients and their caregivers. Systematic review registration: PROSPERO CRD42019117867.
Keywords: Chronic Diseases; Mixed-Methods Research; Outcomes; Patient Preferences; Self-Management; Systematic Review.
Publication
Journal: Journal Francais d'Ophtalmologie
February/20/2022
Abstract
Purpose: To assess foveal and parafoveal retinal and choroidal microvascular changes using optical coherence tomography angiography (OCTA) and changes in retinal vessel caliber in pregnant women with gestational diabetes mellitus (GDM), non-pregnant female patients with type 2 diabetes mellitus (DM2), and healthy pregnant female subjects.
Methods: The study was conducted cross-sectionally and composed of three age-matched groups: 32 near-term pregnant women with GDM (GDM group), 32 non-pregnant female patients with a recent diagnosis of DM2 (DM2 group), and 32 healthy near-term pregnant female subjects. Vessel density (VD) and vessel diameter were the main outcomes. Detailed ophthalmic examinations were performed for each participant, including swept-source OCTA measurements consisting of superficial, deep, outer retinal and choroidal vessel density.
Results: The average VD values in the central fovea of the superficial and deep retina were significantly lower in the GDM group (P=0.001 for both, between the three groups), whereas the mean VD in the parafoveal nasal sector of the deep retina was significantly lower in the DM2 group (P=0.008, between the three groups). There were no significant differences in the foveal or parafoveal VD measurements of the outer retina and choriocapillaris (P>0.05 for all). There were statistically significant differences in the retinal venous diameter and arterial vein ratio in the GDM and DM2 groups compared to the control group (P=0.001 for all).
Conclusion: The microvascular density changes seen on OCTA images of pregnant women with GDM are remarkable. These changes in retinal vessels appeared to occur rapidly after the onset of the metabolic impairment or might be the reflection of previous insulin resistance as well, as in recent diabetes. Our results also suggest that these changes may be more significant in a GDM pregnant woman than in a pregnant, established diabetic patient.
Keywords: Densités des vaisseaux; Diabète sucré de type 2; Diabète sucré gestationnel; Diamètre du vaisseau; Gestational diabetes mellitus; OCTA à source balayée; Swept-source OCTA; Type 2 diabetes mellitus; Vessel density; Vessel diameter.
Publication
Journal: Diabetes, Obesity and Metabolism
February/20/2022
Abstract
Aims: Evaluate the immunogenicity of LY2963016 insulin glargine (LY IGlar) versus originator Lantus® insulin glargine (IGlar) in Chinese patients with Type 1 or Type 2 diabetes mellitus (T1DM or T2DM).
Materials and methods: ABES and ABET are prospective, randomized, active control, open label, Phase III studies, enrolled Chinese patients with T1DM (N=272) and T2DM (N=536), respectively. Immunogenicity was evaluated by comparing the proportion of patients with detectable anti-insulin glargine antibodies and median antibody levels (percent binding) between the treatment groups. The incidence of anti-insulin antibodies and treatment-emergent antibody response (TEAR) were compared using the Fisher's exact test or Pearson's Chi-square test. Levels of anti-insulin antibodies were compared using the Wilcoxon rank sum test. We also evaluated the relationship between antibody formation or TEAR and clinical outcomes using analysis of covariance, negative binomial regression, or partial correlations.
Results: There were no significant treatment differences in the incidence of detectable anti-insulin antibodies, median antibody levels or TEAR, overall or at week 24 with last observation carried forward, and median antibody levels were low (<5%) after 24 weeks of treatment, in patients with T1DM or T2DM. Levels of anti-insulin antibodies and developing TEAR were not associated with efficacy (HbA1c, insulin dose [U/kg/day] and hypoglycemia) or safety outcomes.
Conclusions: The immunogenicity profiles of LY IGlar and IGlar are similar, with low levels of anti-insulin antibodies observed for both insulins. No association was observed between antibody levels or TEAR status and clinical outcomes. This article is protected by copyright. All rights reserved.
Publication
Journal: Frontiers in Cardiovascular Medicine
February/20/2022
Abstract
Background: Few studies have answered the guiding significance of individual components of the Framingham risk score (FRS) to the risk of cardiovascular disease (CVD) after antihypertensive treatment. This study on the systolic blood pressure intervention trial (SPRINT) and the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD-BP) aimed to reveal previously undetected association patterns between individual components of the FRS and heterogeneity of treatment effects (HTEs) of intensive blood pressure control.
Methods: A self-organizing map (SOM) methodology was applied to identify CVD-risk-specific subgroups in the SPRINT (n = 8,773), and the trained SOM was utilized directly in 4,495 patients from the ACCORD. The primary endpoints were myocardial infarction (MI), non-myocardial infarction acute coronary syndrome (non-MI ACS), stroke, heart failure (HF), death from CVD causes, and a primary composite cardiovascular outcome. Cox proportional hazards models were then used to explore the potential heterogeneous response to intensive SBP control.
Results: We identified four SOM-based subgroups with distinct individual components of FRS profiles and the CVD risk. For individuals with type 2 diabetes mellitus (T2DM) in the ACCORD or without diabetes in the SPRINT, subgroup I characterized by male with the lowest concentrations for total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol measures, experienced the highest risk for major CVD. Conversely, subgroup III characterized by a female with the highest values for these measures represented as the lowest CVD risk. Furthermore, subgroup II, with the highest systolic blood pressure (SBP) and no antihypertensive agent use at baseline, had a significantly greater frequency of non-MI ACS under intensive BP control, the number needed to harm (NNH) was 84.24 to cause 1 non-MI ACS [absolute risk reduction (ARR) = -1.19%; 95% CI: -2.08, -0.29%] in the SPRINT [hazard ratio (HR) = 3.62; 95% CI: 1.33, 9.81; P = 0.012], and the NNH of was 43.19 to cause 1 non-MI ACS (ARR = -2.32%; 95% CI: -4.63, 0.00%) in the ACCORD (HR = 1.81; 95% CI: 1.01-3.25; P = 0.046). Finally, subgroup IV characterized by mostly younger patients with antihypertensive medication use and smoking history represented the lowest risk for stroke, HF, and relatively low risk for death from CVD causes and primary composite CVD outcome in SPRINT, however, except stroke, a low risk for others were not observed in ACCORD.
Conclusion: Similar findings in patients with hypertensive with T2DM or without diabetes by multivariate subgrouping suggested that the individual components of the FRS could enrich or improve CVD risk assessment. Further research was required to clarify the potential mechanism.
Keywords: ACCORD; SPRINT; cardiovascular diseases; framingham risk score; heterogeneous treatment effects; self-organizing map.
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Publication
Journal: Frontiers in Pharmacology
February/20/2022
Abstract
The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial evidenced the potential of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of patients with diabetes and cardiovascular disease. Recent evidences have shown the benefits of the SGLT2 inhibitor empagliflozin on improving liver steatosis and fibrosis in patients with T2DM. Metabolomic studies have been shown to be very useful to improve the understanding of liver pathophysiology during the development and progression of metabolic hepatic diseases, and because the effects of empagliflozin and of other SGLT2 inhibitors on the complete metabolic profile of the liver has never been analysed before, we decided to study the impact on the liver of male Zucker diabetic fatty (ZDF) rats of a treatment for 6 weeks with empagliflozin using an untargeted metabolomics approach, with the purpose to help to clarify the benefits of the use of empagliflozin at hepatic level. We found that empagliflozin is able to change the hepatic lipidome towards a protective profile, through an increase of monounsaturated and polyunsaturated glycerides, phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylinositols and lysophosphatidylcholines. Empagliflozin also induces a decrease in the levels of the markers of inflammation IL-6, chemerin and chemerin receptor in the liver. Our results provide new evidences regarding the molecular pathways through which empagliflozin could exert hepatoprotector beneficial effects in T2DM.
Keywords: diabetes; empagliflozin; inflammation; liver; metabolome.
Publication
Journal: Frontiers in Public Health
February/20/2022
Abstract
Introduction: Type 2 Diabetes Mellitus is a modern-day epidemic and dementia has been declared as a global challenge. It is, therefore, worthwhile to investigate the effect that Diabetes has on cognition. Although effective screening is routinely carried out for various complications of Diabetes, its effect on Higher Mental Functions is often overlooked.
Methodology: A cross-sectional analytical study to assess Cognitive Impairment was carried out on 800 participants, 400 diabetics and 400 non-diabetics attending a tertiary care center. The Addenbrooke's Cognitive Examination- III was used, which is a validated, highly sensitive tool having a maximum score of 100. Patients with a score < /= 82 were considered to have impaired Cognition. Statistical analysis was done using SPSSv.21. Suitable statistical tests like Mann-Whitney U, t-test, ROC curve and Logistic regression analysis were done.
Results: Cognitive Impairment was present in 63.8% of the diabetics when compared to only 10.8% in the non-diabetics, with an Odds Ratio-8.78 (CI-4.47-17.22). The total ACE score in diabetics [median-82 (IQR-4), mean rank-270.06] was less compared to the non-diabetic patients [median- 85 (IQR-3), mean rank-530.94] (U = 27822, p-0.001). Attention, Memory, Language, and Visuospatial domains were significantly lower in the diabetics compared to the non-diabetics. However, the fluency domain was not affected. Hypertension and the presence of macrovascular diseases were significantly associated with Cognitive Impairment (p < 0.005). Those with Cognitive dysfunction also had higher mean RBS values and longer duration of Diabetes (p-0.001). The cut-off value for RBS (to distinguish people with and without Cognitive Impairment) from ROC curve was 142.5 (AUC = 0.834, Youden's Index-0.586, p-0.001) and for duration of Diabetes was 7.5 years (AUC = 0.847, Youden's Index-0.529, p-0.001).
Conclusion: This paper highlights that Cognitive Impairment exists in a very high proportion of diabetic patients in Kerala. So, it is important that we do an early assessment of cognitive function in diabetes patients and manage them prudently. Early interventions may prove to be beneficial in the long run, considering the burden of diabetes and cognitive dysfunction associated with the disease.
Keywords: ACE-3; cognitive dysfunction; cognitive impairment; diabetes; high blood glucose.
Publication
Journal: BioMed Research International
February/20/2022
Abstract
Background: Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade inflammation, showing an increasing trend. The infiltration of immune cells into adipose tissue has been shown to be an important pathogenic cause of T2DM. The purpose of this study is to use the relevant database to identify some abnormally expressed or dysfunctional genes related to diabetes from the perspective of immune infiltration.
Methods: Weighted gene coexpression network analysis (WGCNA) was employed to systematically identify the coexpressed gene modules and hub genes associated with T2DM development based on a microarray dataset (GSE23561) from the Gene Expression Omnibus (GEO) database. The key genes in modules highly related to clinical features were calculated and screened by using R software, and their participation in T2DM was determined by gene enrichment analysis. The mRNA levels of CSF1R, H2AFV, LCK, and TLR9 in pre-T2DM mice and normal wild-type mice were detected by WGCNA screening and real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
Results: We constructed 14 coexpressed gene modules, and the brown module was shown to be significantly related to T2DM. Through verification of the protein-protein interaction (PPI) network, four upregulated hub genes, CSF1R, H2AFV, LCK, and TLR9, were screened from the brown module and successfully distinguishedT2DM patients from healthy people. These hub genes may be used as biomarkers and important indicators for patient diagnosis. Enrichment analysis showed that these hub genes were highly associated with IL-6-related inflammatory metabolism, immune regulation, and immune cell infiltration. Finally, we verified the hub genes CSF1R, LCK, and TLR9 in a T2DM animal model and found that their mRNA levels were significantly higher in animals with T2DM than in control group mice (NC).
Conclusions: In summary, our results suggest that these hub genes (CSF1R, LCK, and TLR9) can serve as biomarkers and immunotherapeutic targets for T2DM.
Publication
Journal: Frontiers in Public Health
February/20/2022
Abstract
The coexistence of raised blood pressure (BP) in people with type 2 diabetes mellitus (T2DM) is a major contributor to the development and progression of both macrovascular and microvascular complications. The aim of our study was to determine the prevalence of uncontrolled BP and its associated factors in persons with T2DM in a district in Kerala.
Methods: The study was conducted in Ernakulam district in Kerala, and a total of 3,092 individuals with T2DM were enrolled after obtaining consent. Those with a BP "above or equal to 140 mmHg" and/or "above or equal to 90 mmHg" were thus considered to have uncontrolled BP. If the BP was equal or >140 and/or 90 mmHg, a repeat reading was taken after 30 min and the average of the two was considered. Basic demographic details were enquired along with electronic measurement of BP, HbA1c estimation and screening for diabetic retinopathy, peripheral arterial disease (PAD), and peripheral neuropathy. Quantitative and qualitative variables were expressed as mean (SD) and proportions, respectively. The model for determinants of uncontrolled BP was developed adjusting for age, gender, education, duration of diabetes, occupation, body mass index (BMI) and clustering effect.
Results: The mean age of the study population was 59.51 ± 9.84 years. The mean duration of T2DM was found to be 11.3 ± 6.64 years. The proportion of uncontrolled HTN adjusted for clustering was 60% (95% CI 58 and 62%). Among them, only one in two persons (53.3%) had a history of hypertension. Age >60 years [adjusted odds ratio (aOR) 1.48, 95% CI 1.24, 1.76; p < 0.001], unemployment (aOR 1.33, 95% CI 1.01, 1.75; p < 0.01), duration of diabetes > 11 years (aOR 1.42, 95% CI 1.19, 1.68; p < 0.001), and BMI ≥23 (aOR 1.33, 95% CI 1.10, 1.59; p < 0.002) were found to be independent determinants of high BP levels when adjusted for the aforementioned variables, gender, education, and cluster effect. The association between complications, such as peripheral neuropathy, PAD, and retinopathy showed a higher risk among those with uncontrolled BP. Retinopathy was 1.35 times more (95% CI 1.02, 1.7, p < 0.03), PAD was 1.6 times more (95% CI 1.2, 2.07, p < 0.001), and peripheral neuropathy was 1.5 (95% CI 1.14, 1.9, p < 0.003) times more compared to their counterparts.
Conclusion: Target BP levels were far from being achieved in a good majority of the persons with T2DM. To reduce further macrovascular and microvascular events among people with T2DM, effective awareness and more stringent screening measures need to be employed in this population.
Keywords: blood pressure; coexistent disease; diabetes complications; diabetic neuropathies; diabetic retinopathy; peripheral arterial disease; type 2 diabetes mellitus.
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Publication
Journal: Clinical Medicine Insights: Endocrinology and Diabetes
February/20/2022
Abstract
Sulfonylureas (SUs) are one of the commonly prescribed oral anti-hyperglycemic agents (AHA) in low- and middle-income countries (LMICs), either in combination with metformin therapy or alone. However, concern about cardiovascular safety has limited the use of SUs in the management of type 2 diabetes mellitus (T2DM). Additionally, lack of uniformity in the national and international guidelines regarding the positioning of SUs in the management of diabetes has also been reported. The objective of this review was to assess the various national and international guidelines on diabetes management and understand the recommendations specific to SUs in various scenarios. A total of 33 national and international guidelines on the management of T2DM published in English were evaluated. These guidelines have considered the latest evidence and suggest the use of certain second-generation SUs as second-line therapy or in combination with other AHAs in select population and specific scenarios. Identification of the appropriate population, classification based on underlying risk, thorough assessment of the comorbid conditions, and a step-wise approach for the selection of appropriate SUs is essential for the effective management of T2DM. Additionally, cost-to-benefit ratio should be considered, particularly in LMICs, and SUs could continue to play an important role in such settings.
Keywords: Sulfonylureas; national and international guidelines; type 2 diabetes.
Publication
Journal: Frontiers in Endocrinology
February/20/2022
Abstract
Mounting evidence indicates that gut microbiome may be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). However, there is no consensus on whether there is a causal link between gut microbiome and T2DM risk. In the present study, the Mendelian randomization (MR) analysis was performed to investigate whether gut microbiome was causally linked to T2DM risk. The single nucleotide polymorphisms (SNPs) that were significantly related to exposure from published available genome-wide association study (GWAS) were selected as instrumental variables (IVs). The robust methods including inverse variance weighting (IVW), MR Egger, and weighted median were conducted to infer the causal links. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression were used to test whether there was horizontal pleiotropy and identify outlier SNPs. The estimates of IVW suggested that Streptococcaceae (odds ratio (OR) = 1.17, 95% confidence interval (CI), 1.04-1.31, p = 0.009) was associated with higher risk of T2DM in European population. In Asian population, the MR IVW estimates revealed that there was a causal link between Acidaminococcaceae and T2DM risk (OR = 1.17, 95% CI, 1.04-1.31, p = 0.008). There was no evidence of notable heterogeneity and horizontal pleiotropy. However, after false discovery rate (FDR) correction, the causal link between gut microbiome and T2DM was absent (FDR, p > 0.05). In summary, using genetic instruments, this study does not find evidence of association between the 28 gut microbiome families and T2DM risk. However, Streptococcaceae and Acidaminococcaceae may have a borderline positive correlation with T2DM risk.
Keywords: Mendelian randomization; causality; gut microbiome; mechanism; type 2 diabetes mellitus.
Publication
Journal: Environmental Research
February/20/2022
Abstract
Background: Experimental studies have shown the diabetogenic potential of inorganic arsenic (iAs); however, the epidemiological evidence is still inconclusive. This could be explained by differences in exposure, metabolism efficiency, nutritional and genetic factors.
Objective: To evaluate the association between type 2 diabetes mellitus (T2DM) prevalence with arsenic exposure and metabolism, considering one-carbon metabolism nutrient intake and arsenite methyltransferase (AS3MT) polymorphisms.
Methods: From healthy controls of a case control study for female breast cancer in northern Mexico, 227 self-reported diabetic women were age-matched with 454 non-diabetics. Participants were interviewed about dietary, sociodemographic and clinical characteristics. Urinary iAs metabolites were determined by HPLC-ICP-MS, methylation efficiency parameters were calculated, and AS3MT c.860 T > C and c.529-56G > C genotypes were determined. Unconditional logistic regression models were used to evaluate associations.
Results: Total arsenic in urine (TAs) ranged from 0.73 to 248.12 μg/L with a median of 10.48 μg/L. In unadjusted analysis, TAs (μg/g) was significantly higher in cases than controls, but not when expressed as TAs (μg/L). Cases had significantly lower urinary monomethylarsonic acid percentage (%MMA), first methylation ratio (FMR), creatinine, and choline and selenium intakes. In multi-adjusted models and in women without HTA history T2DM showed significant positive associations with %iAs and FMR, respectively, and a significant negative association with %DMA. In participants with HTA history there was a marginal positive association (p = 0.08) between T2DM and TAs concentrations (μg/g) without other significant associations.
Conclusions: Our results support an association between T2DM prevalence and iAs metabolism but not with urinary arsenic levels. However, elucidation of the interplay among iAs metabolism, T2DM and HTA merit further studies.
Keywords: Arsenic metabolism; Creatinine; Nutrients; Polymorphisms; Type 2 diabetes mellitus.
Publication
Journal: Drugs of Today
February/20/2022
Abstract
Dapagliflozin is an oral agent for type 2 diabetes mellitus (T2DM) belonging to the sodium/glucose cotransporter 2 inhibitor (SGLT2-I) class of antihyperglycemic medications. In clinical trials, dapagliflozin has also been shown to reduce cardiovascular and major renal events. In the DAPA-CKD trial, dapagliflozin significantly reduced the composite renal outcome in patients with chronic kidney disease (CKD). Dapagliflozin represents a new pharmacologic option for reducing CKD progression in patients with and without diabetes.
Keywords: Chronic kidney disease; Dapagliflozin; Diabetes; Nephropathy; Renal disorders; Sodium/glucose cotransporter 2 (SGLT2) inhibitors.
Publication
Journal: Asia Pacific Allergy
February/20/2022
Abstract
Aim The aim of the study is to assess the risk of acidosis in diabetic advanced chronic kidney disease (CKD) patients on and off metformin. Methods This retrospective descriptive study was conducted in the nephrology department in The Kidney Centre Post Graduate Training Institute (TKC PGTI) Karachi from February to April 2020. We reviewed the records of all patients over 18 years old who visited the nephrology outpatient department in three months in 2020 (from February 2020 to April 2020), who had CKD (stage 2-5), are not on dialysis, and had type 2 diabetes. These were divided into two groups: those on metformin for more than one year and those not on metformin. We looked at hospitalizations due to acidosis in the previous one-year period. Results A total of 524 CKD patients had diabetes; out of those, 268 patients were on metformin, and 256 were not on metformin. The male vs. female distribution was 52.1% vs. 47.9%. A total of 114 (21.8%) patients required admission in the previous one-year period, and only 12 hospitalized patients had acidosis, seven (58.3%) were on metformin, and five (41.7%) were not on metformin, which was statistically insignificant. Conclusion Biguanides, especially metformin, is a known oral hypoglycemic drug used for decades to treat type 2 diabetes mellitus (DM). Metformin use is related to a rare but serious adverse event, metformin-associated lactic acidosis (MALA), especially in renal failure patients. In our study, metformin use in CKD diabetic patients did not result in more admissions due to acidosis than non-metformin users.
Keywords: chronic kidney disease; diabetes mellitis; metabolic acidosis; metformin; metformin associated lactic acidosis.
Publication
Journal: Internal Medicine Journal
February/20/2022
Abstract
Examination of the oral cavity can identify clinical signs indicative of underlying systemic disease. Key features to examine include the general appearance and number of the teeth, signs of inflammation of the mucosa or gingival tissues including bleeding of the gums and redness, swelling or hyperplasia. Additionally, the tongue should be assessed for any ulceration or discolouration and the presence of excessive build-up (coating). Cardiovascular disease and diabetes, together known as cardiometabolic disease have an impact on oral health. Similarly, oral health conditions, such as gum disease (periodontitis) and dryness of the mouth (xerostomia), are associated with an increased risk for both cardiovascular disease and type 2 diabetes mellitus. The aim of this narrative review is to outline both the impact of periodontitis and xerostomia on cardiometabolic disease and the impact of cardiometabolic health on these oral health conditions. Key features of periodontitis and xerostomia will be provided along with a brief discussion of current concepts in early prevention and management of these oral health conditions. The biological mechanisms linking cardiometabolic disease and periodontitis will be outlined and the evidence supporting the association between cardiometabolic disease and oral health conditions will be presented together with an identification of areas where further research is indicated. Last, guidance for general practitioners to assess and support early diagnosis and management of oral health conditions by raising awareness of the relationship between oral health and cardiometabolic disease, providing simple oral health advice and referring to a dental practitioner will be presented.
Keywords: cardiovascular disease; diabetes; gingivitis; periodontitis; tooth loss; xerostomia.
Publication
Journal: BMJ Open Diabetes Research and Care
February/20/2022
Abstract
Introduction: We quantified the proportion and the absolute number of deaths attributable to type 2 diabetes mellitus (T2DM) in Latin America and the Caribbean (LAC) using an estimation approach.
Research design and methods: We combined T2DM prevalence estimates from the NCD Risk Factor Collaboration, relative risks between T2DM and all-cause mortality from a meta-analysis of cohorts in LAC, and death rates from the Global Burden of Disease Study 2019. We estimated population-attributable fractions (PAFs) and computed the absolute number of attributable deaths in 1990 and 2019 by multiplying the PAFs by the total deaths in each country, year, sex, and 5-year age group.
Results: Between 1985 and 2014 in LAC, the proportion of all-cause mortality attributable to T2DM increased from 12.2% to 16.9% in men and from 14.5% to 19.3% in women. In 2019, the absolute number of deaths attributable to T2DM was 349 787 in men and 330 414 in women. The highest death rates (deaths per 100 000 people) in 2019 were in Saint Kitts and Nevis (325 in men, 229 in women), Guyana (313 in men, 272 in women), and Haiti (269 in men, 265 in women).
Conclusions: A substantial burden of all deaths is attributed to T2DM in LAC. To decrease the mortality attributable to T2DM in LAC, policies are needed to strengthen early diagnosis and management, along with the prevention of complications.
Keywords: population health; risk assessment.
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Publication
Journal: Frontiers in Cardiovascular Medicine
February/20/2022
Abstract
Background: Insulin resistance (IR) plays a key role in the development of type 2 diabetes mellitus (T2DM) and is one of its most important characteristics. Previous studies have shown that IR and T2DM were independent risk factors for a variety of cardiovascular and cerebrovascular diseases. However, there are few studies on the relationship between IR and aortic dissection (AD). The goal of this research was to find evidence that IR promotes the occurrence of AD.
Methods: Through the statistical analysis, we determined the proportion of glycosylated hemoglobin (HbA1c) abnormalities (HbA1c > 5.7) in people with acute thoracic aortic dissection (ATAD) and compared the difference of messenger RNA (mRNA) and protein expression of GluT1 in the thoracic aorta of normal people and those with ATAD to find evidence that IR is a causative factor in AD. The mouse model of IR and AD and the IR model of human aortic vascular smooth muscle cells (HA-VSMC) were established. Real time-PCR (RT-PCR) and Western blotting were used to study the mRNA and protein expression. Hematoxylin and eosin (H&E), Masson, and elastic fiber staining, and immunofluorescence were used to study the morphological structure.
Results: The proportion of HbA1c abnormalities in patients with ATAD was 59.37%, and the mRNA and protein expression of GluT1 were significantly lower than that in normal people. Fasting glucose concentration (FGC), serum insulin concentration (SIC), and the homeostasis model assessment of insulin resistance (HOMA-IR) of mice was obviously increased in the high-fat diet group and the protein expressions of Glut1 and GluT4 were reduced, indicating that the mouse IR model was successfully established. The incidence of AD was different between the two groups (IR: 13/14, Ctrl: 6/14), and the protein expression of MMP2, MMP9, and OPN were upregulated and SM22 and α-SMA were downregulated in mice. The expressions of mRNA and protein of GluT1 and SM22 in HA-VSMCs with IR were reduced and OPN was increased.
Conclusion: Combined results of clinical findings, mouse models, and cell experiments show that IR induced the phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to synthetic, which contributes to the occurrence of AD. It provides a basis for further research on the specific mechanism of how IR results in AD and a new approach for the prevention and treatment of AD.
Keywords: aortic dissection; insulin resistance; phenotypic switch; promotes; vascular smooth muscle cells.
Publication
Journal: Frontiers in Pharmacology
February/20/2022
Abstract
Aims: Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors play a key role in the treatment of type 2 diabetes mellitus. This meta-analysis aims to evaluate the efficacy and safety of their combination, emphatically focusing on the effects of treatment duration and add-on drugs. Methods: Seven databases were searched until June 2021 for randomized controlled trials with a duration of at least 12 weeks, evaluating the effects of combination therapy with glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors. Results: A total of eight eligible articles were included, pooling data retrieved from 1895 patients with type 2 diabetes mellitus. Compared to monotherapy, combination therapy resulted in a greater reduction in glycated haemoglobin (HbA1c), body weight, fasting plasma glucose (FPG), 2 h postprandial glucose (2 h PG), systolic blood pressure (SBP), body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C). The decrease in HbA1c, body weight and FPG was maintained for more than 1 year, but these effects gradually regressed over time. The risk for hypoglycaemia was significantly increased with combination therapy. In addition, drug discontinuation, diarrhoea, injection-site-related events, nausea, vomiting and genital infections were more likely to occur in combination therapy. Conclusion: Glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor combination therapy showed superior effects on reducing HbA1c, body weight, FPG, 2 h PG, SBP, BMI and LDL-C, without major safety issues, when compared with monotherapy in patients with type 2 diabetes mellitus.
Keywords: combination therapy; glucagon-like peptide-1 receptor agonists; meta-analysis; sodium-glucose co-transporter-2 inhibitors; type 2 diabetes mellitus.
Publication
Journal: Midwifery
February/20/2022
Abstract
Background: Gestational diabetes mellitus is associated with higher risk for developing type 2 diabetes. Breastfeeding is protective against the development of type 2 diabetes after gestational diabetes. There are no data regarding the effect of breastfeeding on the development of recurrent gestational diabetes.
Objective: Investigate the relationship of previous breastfeeding duration and intensity with the recurrence of gestational diabetes, and second pregnancy glucose tolerance test results.
Methods: We conducted a questionnaire-based pilot cohort study, enrolling 210 women during a subsequent second pregnancy, after a gestational diabetes-affected first pregnancy. Models for length and intensity of breastfeeding as predictors of the oral glucose tolerance test and for diagnosis of gestational diabetes in second pregnancy were fitted and then adjusted for possible confounders.
Results: Recurrent gestational diabetes rate in the study cohort was 70% (n = 146). In a fully adjusted model high intensity breastfeeding was associated with a lower 2-hour glucose level on the oral glucose tolerance test (by 0.66 mmol/L, 95% CI [0.15-1.17]; p = 0.01) and breastfeeding greater than six months with a lower 1-hour glucose on the oral glucose tolerance test (by 0.67 mmol/L, 95% CI [0.16-1.19]; p = 0.01), compared to women who breastfed less intensively or for a shorter duration respectively. There was an 18% reduction in the risk of gestational diabetes if a woman breastfed for more than six months (RR 0.82, 95% CI [0.69-0.98]; p = 0.03). The association was attenuated in the fully adjusted model (RR 0.89, 95% CI [0.78-1.02]; p = 0.09).
Conclusions and implications for practice: We found the risk of recurrent gestational diabetes was reduced by both increased duration and intensity of breastfeeding. Antenatal lactation education should be embedded into care pathways for women diagnosed with gestational diabetes.
Keywords: Breastfeeding; Cardiovascular disease; Diabetes; Gestational diabetes mellitus; Lactation; Pregnancy; Type 2 diabetes mellitus.
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