Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 14.453
Filter
1.
Sci Rep ; 14(1): 10589, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38719926

ABSTRACT

Maturity Onset Diabetes of the Young (MODY) is a young-onset, monogenic form of diabetes without needing insulin treatment. Diagnostic testing is expensive. To aid decisions on who to test, we aimed to develop a MODY probability calculator for paediatric cases at the time of diabetes diagnosis, when the existing "MODY calculator" cannot be used. Firth logistic regression models were developed on data from 3541 paediatric patients from the Swedish 'Better Diabetes Diagnosis' (BDD) population study (n = 46 (1.3%) MODY (HNF1A, HNF4A, GCK)). Model performance was compared to using islet autoantibody testing. HbA1c, parent with diabetes, and absence of polyuria were significant independent predictors of MODY. The model showed excellent discrimination (c-statistic = 0.963) and calibrated well (Brier score = 0.01). MODY probability > 1.3% (ie. above background prevalence) had similar performance to being negative for all 3 antibodies (positive predictive value (PPV) = 10% v 11% respectively i.e. ~ 1 in 10 positive test rate). Probability > 1.3% and negative for 3 islet autoantibodies narrowed down to 4% of the cohort, and detected 96% of MODY cases (PPV = 31%). This MODY calculator for paediatric patients at time of diabetes diagnosis will help target genetic testing to those most likely to benefit, to get the right diagnosis.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Child , Male , Female , Adolescent , Hepatocyte Nuclear Factor 4/genetics , Hepatocyte Nuclear Factor 1-alpha/genetics , Child, Preschool , Autoantibodies/blood , Autoantibodies/immunology , Glycated Hemoglobin/analysis , Germinal Center Kinases/genetics , Sweden , Glucokinase/genetics
2.
Front Endocrinol (Lausanne) ; 15: 1356131, 2024.
Article in English | MEDLINE | ID: mdl-38711978

ABSTRACT

Objective: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease. Early detection and prevention of DN are important. Retinol-binding protein 4 (RBP4) has been considered as a single diagnostic marker for the detection of renal impairment. However, the results have been inconsistent. The present meta-analysis aimed to determine the diagnostic potential of RBP4 in patients in type 2 diabetes mellitus (T2DM) with DN. Methods: We searched PubMed, Web of Science, Embase, Wanfang and CNKI databases from inception until January 2024. The meta-analysis was performed by Stata version 15.0, and sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were pooled. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was utilized to assess the quality of each included study. In addition, heterogeneity and publication bias were evaluated. Results: Twenty-nine studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.76 [95% confidence interval (CI), 0.71-0.80] and 0.81 (95% CI, 0.76-0.85), respectively. The results showed a pooled PLR of 4.06 (95% CI, 3.16-5.21), NLR of 0.29 (95% CI, 0.24-0.36) and DOR of 13.76 (95% CI, 9.29-20.37). The area under the summarized receiver operating characteristic curve was given a value of 0.85 (95% CI, 0.82-0.88). No obvious publication bias existed in the Deeks' funnel plot asymmetry test. Conclusion: Our findings suggest that RBP4 has a promising diagnostic value with good sensitivity and specificity for patients with T2DM with DN.


Subject(s)
Diabetic Nephropathies , Retinol-Binding Proteins, Plasma , Humans , Diabetic Nephropathies/diagnosis , Retinol-Binding Proteins, Plasma/metabolism , Retinol-Binding Proteins, Plasma/analysis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Biomarkers/blood , Sensitivity and Specificity
3.
Cardiovasc Diabetol ; 23(1): 166, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730425

ABSTRACT

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.


Subject(s)
Antihypertensive Agents , Blood Glucose , Blood Pressure , Diabetes Mellitus, Type 2 , Genetic Predisposition to Disease , Glycemic Control , Guanine Nucleotide Exchange Factors , Polymorphism, Single Nucleotide , Humans , Male , Female , Middle Aged , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , China/epidemiology , Blood Glucose/metabolism , Blood Glucose/drug effects , Aged , Retrospective Studies , Guanine Nucleotide Exchange Factors/genetics , Risk Factors , Treatment Outcome , Glycemic Control/adverse effects , Blood Pressure/drug effects , Blood Pressure/genetics , Asian People/genetics , Diabetic Angiopathies/genetics , Diabetic Angiopathies/diagnosis , Risk Assessment , Phenotype , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Time Factors , Biomarkers/blood , Genetic Association Studies , Hypertension/genetics , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/diagnosis , DNA-Binding Proteins/genetics , East Asian People
4.
Cardiovasc Diabetol ; 23(1): 165, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730445

ABSTRACT

OBJECTIVE: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (ß-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.


Subject(s)
Biomarkers , Blood Glucose , C-Reactive Protein , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Disease Risk Factors , Hyperglycemia , Mendelian Randomization Analysis , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Biomarkers/blood , Hyperglycemia/blood , Hyperglycemia/epidemiology , Hyperglycemia/diagnosis , Hyperglycemia/mortality , Hyperglycemia/genetics , Risk Assessment , Blood Glucose/metabolism , Male , Denmark/epidemiology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/genetics , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/blood , Female , Middle Aged , Incidence , Up-Regulation , Myocardial Ischemia/blood , Myocardial Ischemia/genetics , Myocardial Ischemia/epidemiology , Myocardial Ischemia/diagnosis , Myocardial Ischemia/mortality , Aged , Prognosis , Inflammation Mediators/blood , Genetic Predisposition to Disease , Risk Factors
6.
BMC Cardiovasc Disord ; 24(1): 251, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745157

ABSTRACT

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase , Biomarkers , Coronary Angiography , Coronary Artery Disease , Diabetes Mellitus, Type 2 , Disease Progression , Plaque, Atherosclerotic , Humans , Male , 1-Alkyl-2-acetylglycerophosphocholine Esterase/blood , Female , Middle Aged , Plaque, Atherosclerotic/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Coronary Artery Disease/blood , Coronary Artery Disease/diagnostic imaging , Biomarkers/blood , Aged , Time Factors , Up-Regulation , Case-Control Studies , Risk Factors , Coronary Stenosis/blood , Coronary Stenosis/diagnostic imaging , Prognosis
7.
Endocrinol Diabetes Metab ; 7(3): e00484, 2024 May.
Article in English | MEDLINE | ID: mdl-38739122

ABSTRACT

OBJECTIVE: This study investigates the metabolic differences between normal, prediabetic and diabetic patients with good and poor glycaemic control (GGC and PGC). DESIGN: In this study, 1102 individuals were included, and 50 metabolites were analysed using tandem mass spectrometry. The diabetes diagnosis and treatment standards of the American Diabetes Association (ADA) were used to classify patients. METHODS: The nearest neighbour method was used to match controls and cases in each group on the basis of age, sex and BMI. Factor analysis was used to reduce the number of variables and find influential underlying factors. Finally, Pearson's correlation coefficient was used to check the correlation between both glucose and HbAc1 as independent factors with binary classes. RESULTS: Amino acids such as glycine, serine and proline, and acylcarnitines (AcylCs) such as C16 and C18 showed significant differences between the prediabetes and normal groups. Additionally, several metabolites, including C0, C5, C8 and C16, showed significant differences between the diabetes and normal groups. Moreover, the study found that several metabolites significantly differed between the GGC and PGC diabetes groups, such as C2, C6, C10, C16 and C18. The correlation analysis revealed that glucose and HbA1c levels significantly correlated with several metabolites, including glycine, serine and C16, in both the prediabetes and diabetes groups. Additionally, the correlation analysis showed that HbA1c significantly correlated with several metabolites, such as C2, C5 and C18, in the controlled and uncontrolled diabetes groups. CONCLUSIONS: These findings could help identify new biomarkers or underlying markers for the early detection and management of diabetes.


Subject(s)
Carnitine/analogs & derivatives , Metabolomics , Prediabetic State , Tandem Mass Spectrometry , Humans , Prediabetic State/diagnosis , Prediabetic State/metabolism , Metabolomics/methods , Male , Tandem Mass Spectrometry/methods , Female , Middle Aged , Adult , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/analysis , Blood Glucose/metabolism , Diabetes Mellitus/metabolism , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Aged , Biomarkers/blood , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/diagnosis , Metabolome , Glycemic Control
8.
Sci Rep ; 14(1): 10901, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38740846

ABSTRACT

To investigate the screening and predicting functions of obesity- and lipid-related indices for type 2 diabetes (T2D) in middle-aged and elderly Chinese, as well as the ideal predicted cut-off value. This study's data comes from the 2011 China Health and Retirement Longitudinal Study (CHARLS). A cross-sectional study design was used to investigate the relationship of T2D and 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), visceral adiposity index (VAI), a body shape index (ABSI), body roundness index (BRI), lipid accumulation product (LAP), conicity index (CI), Chinese visceral adiposity index (CVAI), triglyceride- glucose index (TyG index) and its correlation index (TyG-BMI, TyG-WC, TyG-WHtR). The unadjusted and adjusted correlations between 13 indices and T2D were assessed using binary logistic regression analysis. The receiver operating characteristic curve (ROC) was used to determine the usefulness of anthropometric indices for screening for T2D and determining their cut­off value, sensitivity, specificity, and area under the curve (AUC). The study comprised 9488 people aged 45 years or above in total, of whom 4354 (45.89%) were males and 5134 (54.11%) were females. Among them were 716 male cases of T2D (16.44%) and 870 female cases of T2D (16.95%). A total of 13 obesity- and lipid-related indices were independently associated with T2D risk after adjusted for confounding factors (P < 0.05). According to ROC analysis, the TyG index was the best predictor of T2D among males (AUC = 0.780, 95% CI 0.761, 0.799) and females (AUC = 0.782, 95% CI 0.764, 0.799). The AUC values of the 13 indicators were higher than 0.5, indicating that they have predictive values for T2D in middle-aged and elderly Chinese. The 13 obesity- and lipid-related indices can predict the risk of T2D in middle­aged and elderly Chinese. Among 13 indicators, the TyG index is the best predictor of T2D in both males and females. TyG-WC, TyG-BMI, TyG-WHtR, LAP, and CVAI all outperformed BMI, WC, and WHtR in predicting T2D.


Subject(s)
Body Mass Index , Diabetes Mellitus, Type 2 , Obesity , Humans , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Male , Female , Middle Aged , Aged , Obesity/blood , Obesity/diagnosis , China/epidemiology , Cross-Sectional Studies , Waist Circumference , ROC Curve , Lipids/blood , Longitudinal Studies , Risk Factors , East Asian People
9.
BMC Endocr Disord ; 24(1): 60, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711112

ABSTRACT

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.


Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/blood , Blood Glucose/analysis , Blood Glucose Self-Monitoring/methods , Prospective Studies , Point-of-Care Testing , Female , Male , Hospitalization , Insulin/therapeutic use , Insulin/administration & dosage , Hypoglycemic Agents/therapeutic use , Patient Care Team , Adult , Middle Aged , Continuous Glucose Monitoring
10.
Cardiovasc Diabetol ; 23(1): 159, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715052

ABSTRACT

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.


Subject(s)
3-Hydroxybutyric Acid , Aortic Aneurysm , Aortic Dissection , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Aortic Dissection/genetics , Aortic Dissection/epidemiology , Aortic Dissection/etiology , 3-Hydroxybutyric Acid/blood , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Risk Factors , Aortic Aneurysm/genetics , Aortic Aneurysm/epidemiology , Aortic Aneurysm/etiology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Risk Assessment , Protective Factors , Phenotype , Biomarkers/blood , Mediation Analysis
11.
Cardiovasc Diabetol ; 23(1): 157, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715111

ABSTRACT

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. METHODS: Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. RESULTS: A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. CONCLUSIONS: SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.


Subject(s)
Biomarkers , Cerebral Small Vessel Diseases , Mendelian Randomization Analysis , Sodium-Glucose Transporter 1 , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Glucose Transporter 2 , Humans , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 1/genetics , Sodium-Glucose Transporter 1/antagonists & inhibitors , Sodium-Glucose Transporter 1/metabolism , Cerebral Small Vessel Diseases/genetics , Cerebral Small Vessel Diseases/diagnostic imaging , Cerebral Small Vessel Diseases/drug therapy , Cerebral Small Vessel Diseases/blood , Cerebral Small Vessel Diseases/metabolism , Risk Factors , Sodium-Glucose Transporter 2/metabolism , Sodium-Glucose Transporter 2/genetics , Biomarkers/blood , Risk Assessment , Glycated Hemoglobin/metabolism , Pharmacogenomic Variants , Treatment Outcome , Phenotype , Cerebral Hemorrhage/genetics , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/epidemiology , Protective Factors , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Genetic Predisposition to Disease
12.
Croat Med J ; 65(2): 85-92, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38706234

ABSTRACT

AIM: To identify diabetic patients with a potential risk of developing diabetic peripheral neuropathy (DPN) in community pharmacies in Slovakia using a modified Michigan Neuropathy Screening Instrument questionnaire (MNSIq-12). METHODS: This cross-sectional study enrolled 703 patients with type 1 and type 2 diabetes mellitus who had not been diagnosed with DPN. The study took place in selected community pharmacies across Slovakia in October 2019. The MNSIq-12 was administered by pharmacy students, and a Michigan score <1.5 was considered risky. The groups divided based on the Michigan score were compared in terms of duration of diabetes, age, body mass index (BMI), sex, weekly physical activity, level of education, and smoking. RESULTS: The risk of developing DPN was detected in 6.6% of respondents with type 1 diabetes and 13.4% with type 2 diabetes. Patients with both types of diabetes (38.2%; 67.0%) reported fatigue and heaviness in the legs as the most common clinical symptoms that may indicate the development of DPN. Those with a Michigan score <1.5 were older (P<0.0001), had a higher BMI (P<0.0001), a lower level of education (P=0.0020), and were less physically active (P<0.0001). Conclusion Approximately one-eighth of patients with diabetes who visited community pharmacies were potentially at risk for developing DPN. The modified MNSIq-12 was shown to be a simple, time-effective, and non-invasive indicative screening tool that can be applied in the environment of community pharmacies.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Humans , Slovakia/epidemiology , Male , Female , Cross-Sectional Studies , Middle Aged , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Adult , Surveys and Questionnaires , Mass Screening/methods , Pharmacies/statistics & numerical data , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Aged , Risk Factors , Body Mass Index
13.
Diab Vasc Dis Res ; 21(3): 14791641241253540, 2024.
Article in English | MEDLINE | ID: mdl-38710662

ABSTRACT

This case challenges the conventional preference for coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) in patients with diabetes, left main coronary artery disease (LMCAD) and multivessel disease. Current guidelines generally recommend CABG, especially in the context of LMCAD. However, our case involves a male patient with diabetes with LMCAD and extensive multivessel disease who was successfully treated with PCI, demonstrating a favorable outcome. Despite the high-risk profile, including a SYNTAX score of 28, the PCI approach was selected. This decision was supported by evidence suggesting comparable outcomes between PCI and CABG in similar patients. Our case highlights the potential of PCI as not just a viable, but potentially superior alternative in specific high-risk patients with diabetes, contrary to the prevailing belief in favor of CABG for all patients with left main involvement.


Subject(s)
Coronary Artery Bypass , Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Male , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/therapy , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Coronary Artery Disease/complications , Treatment Outcome , Risk Factors , Clinical Decision-Making , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Aged , Coronary Angiography , Patient Selection , Risk Assessment , Middle Aged
14.
Age Ageing ; 53(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38706394

ABSTRACT

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.


Subject(s)
Adiposity , Diabetes Mellitus, Type 2 , Hand Strength , Sarcopenia , Humans , Sarcopenia/epidemiology , Sarcopenia/physiopathology , Sarcopenia/diagnosis , Female , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Male , Aged , Prevalence , Middle Aged , Cross-Sectional Studies , Geriatric Assessment/methods , Predictive Value of Tests , Age Factors , Linear Models
15.
J Am Heart Assoc ; 13(9): e033610, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38700033

ABSTRACT

BACKGROUND: Overweight and obesity represent critical modifiable determinants in the prevention of cardiometabolic disease (CMD). However, the long-term impact of prior overweight/obesity on the risk of CMD in later life remains unclear. We aimed to investigate the association between longitudinal transition of body mass index (BMI) status and incident CMD. METHODS AND RESULTS: This prospective cohort study included 57 493 CMD-free Chinese adults from the Kailuan Study. BMI change patterns were categorized according to the BMI measurements obtained during the 2006 and 2012 surveys. The primary end point was a composite of myocardial infarction, stroke, and type 2 diabetes. Cox regression models were used to evaluate the associations of transitions in BMI with overall CMD events and subtypes, with covariates selected on the basis of the directed acyclic graph. During a median follow-up of 7.62 years, 8412 participants developed CMD. After considering potential confounders, weight gain pattern (hazard ratio [HR], 1.34 [95% CI, 1.23-1.46]), stable overweight/obesity (HR, 2.12 [95% CI, 2.00-2.24]), and past overweight/obesity (HR, 1.73 [95% CI, 1.59-1.89]) were associated with the incidence of CMD. Similar results were observed in cardiometabolic multimorbidity, cardiovascular disease, and type 2 diabetes. Additionally, triglyceride and systolic blood pressure explained 8.05% (95% CI, 5.87-10.22) and 12.10% (95% CI, 9.19-15.02) of the association between past overweight/obesity and incident CMD, respectively. CONCLUSIONS: A history of overweight/obesity was associated with an increased risk of CMD, even in the absence of current BMI abnormalities. These findings emphasize the necessity for future public health guidelines to include preventive interventions for CMD in individuals with past overweight/obesity.


Subject(s)
Body Mass Index , Obesity , Overweight , Humans , Male , China/epidemiology , Female , Middle Aged , Prospective Studies , Obesity/epidemiology , Adult , Incidence , Overweight/epidemiology , Risk Assessment , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Risk Factors , Cardiometabolic Risk Factors
16.
Cardiovasc Diabetol ; 23(1): 153, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702769

ABSTRACT

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) presents a significant healthcare challenge, with considerable economic ramifications. While blood glucose management and long-term metabolic target setting for home care and outpatient treatment follow established procedures, the approach for short-term targets during hospitalization varies due to a lack of clinical consensus. Our study aims to elucidate the impact of pre-hospitalization and intra-hospitalization glycemic indexes on in-hospital survival rates in individuals with T2DM, addressing this notable gap in the current literature. METHODS: In this pilot study involving 120 hospitalized diabetic patients, we used advanced machine learning and classical statistical methods to identify variables for predicting hospitalization outcomes. We first developed a 30-day mortality risk classifier leveraging AdaBoost-FAS, a state-of-the-art ensemble machine learning method for tabular data. We then analyzed the feature relevance to identify the key predictive variables among the glycemic and routine clinical variables the model bases its predictions on. Next, we conducted detailed statistical analyses to shed light on the relationship between such variables and mortality risk. Finally, based on such analyses, we introduced a novel index, the ratio of intra-hospital glycemic variability to pre-hospitalization glycemic mean, to better characterize and stratify the diabetic population. RESULTS: Our findings underscore the importance of personalized approaches to glycemic management during hospitalization. The introduced index, alongside advanced predictive modeling, provides valuable insights for optimizing patient care. In particular, together with in-hospital glycemic variability, it is able to discriminate between patients with higher and lower mortality rates, highlighting the importance of tightly controlling not only pre-hospital but also in-hospital glycemic levels. CONCLUSIONS: Despite the pilot nature and modest sample size, this study marks the beginning of exploration into personalized glycemic control for hospitalized patients with T2DM. Pre-hospital blood glucose levels and related variables derived from it can serve as biomarkers for all-cause mortality during hospitalization.


Subject(s)
Biomarkers , Blood Glucose , Diabetes Mellitus, Type 2 , Hospital Mortality , Machine Learning , Predictive Value of Tests , Humans , Pilot Projects , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Biomarkers/blood , Male , Aged , Female , Middle Aged , Risk Assessment , Risk Factors , Time Factors , Cause of Death , Prognosis , Glycemic Control/mortality , Hospitalization
17.
BMC Public Health ; 24(1): 1033, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38615018

ABSTRACT

BACKGROUND: This study aimed to compare anthropometric indices to predict type 2 diabetes mellitus (T2DM) among first-degree relatives of diabetic patients in the Iranian community. METHODS: In this study, information on 3483 first-degree relatives (FDRs) of diabetic patients was extracted from the database of the Endocrinology and Metabolism Research Center of Isfahan University of Medical Sciences. Overall, 2082 FDRs were included in the analyses. A logistic regression model was used to evaluate the association between anthropometric indices and the odds of having diabetes. Furthermore, a receiver operating characteristic (ROC) curve was applied to estimate the optimal cutoff point based on the sensitivity and specificity of each index. In addition, the indices were compared based on the area under the curve (AUC). RESULTS: The overall prevalence of diabetes was 15.3%. The optimal cutoff points for anthropometric measures among men were 25.09 for body mass index (BMI) (AUC = 0.573), 0.52 for waist-to-height ratio (WHtR) (AUC = 0.648), 0.91 for waist-to-hip ratio (WHR) (AUC = 0.654), 0.08 for a body shape index (ABSI) (AUC = 0.599), 3.92 for body roundness index (BRI) (AUC = 0.648), 27.27 for body adiposity index (BAI) (AUC = 0.590), and 8 for visceral adiposity index (VAI) (AUC = 0.596). The optimal cutoff points for anthropometric indices were 28.75 for BMI (AUC = 0.610), 0.55 for the WHtR (AUC = 0.685), 0.80 for the WHR (AUC = 0.687), 0.07 for the ABSI (AUC = 0.669), 4.34 for the BRI (AUC = 0.685), 39.95 for the BAI (AUC = 0.583), and 6.15 for the VAI (AUC = 0.658). The WHR, WHTR, and BRI were revealed to have fair AUC values and were relatively greater than the other indices for both men and women. Furthermore, in women, the ABSI and VAI also had fair AUCs. However, BMI and the BAI had the lowest AUC values among the indices in both sexes. CONCLUSION: The WHtR, BRI, VAI, and WHR outperformed other anthropometric indices in predicting T2DM in first-degree relatives (FDRs) of diabetic patients. However, further investigations in different populations may need to be implemented to justify their widespread adoption in clinical practice.


Subject(s)
Diabetes Mellitus, Type 2 , Male , Humans , Female , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Iran/epidemiology , Anthropometry , Body Mass Index , Adiposity , Obesity
18.
Front Endocrinol (Lausanne) ; 15: 1253492, 2024.
Article in English | MEDLINE | ID: mdl-38586458

ABSTRACT

Background: Patients with type 2 diabetes are at an increased risk of chronic kidney disease (CKD) hence it is recommended that they receive annual CKD screening. The huge burden of diabetes in Mexico and limited screening resource mean that CKD screening is underperformed. Consequently, patients often have a late diagnosis of CKD. A regional minimal-resource model to support risk-tailored CKD screening in patients with type 2 diabetes has been developed and globally validated. However, population heath and care services between countries within a region are expected to differ. The aim of this study was to evaluate the performance of the model within Mexico and compare this with the performance demonstrated within the Americas in the global validation. Methods: We performed a retrospective observational study with data from primary care (Clinic Specialized in Diabetes Management in Mexico City), tertiary care (Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán) and the Mexican national survey of health and nutrition (ENSANUT-MC 2016). We applied the minimal-resource model across the datasets and evaluated model performance metrics, with the primary interest in the sensitivity and increase in the positive predictive value (PPV) compared to a screen-everyone approach. Results: The model was evaluated on 2510 patients from Mexico (primary care: 1358, tertiary care: 735, ENSANUT-MC: 417). Across the Mexico data, the sensitivity was 0.730 (95% CI: 0.689 - 0.779) and the relative increase in PPV was 61.0% (95% CI: 52.1% - 70.8%). These were not statistically different to the regional performance metrics for the Americas (sensitivity: p=0.964; relative improvement: p=0.132), however considerable variability was observed across the data sources. Conclusion: The minimal-resource model performs consistently in a representative Mexican population sample compared with the Americas regional performance. In primary care settings where screening is underperformed and access to laboratory testing is limited, the model can act as a risk-tailored CKD screening solution, directing screening resources to patients who are at highest risk.


Subject(s)
Diabetes Mellitus, Type 2 , Renal Insufficiency, Chronic , Humans , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Mexico/epidemiology , Glomerular Filtration Rate , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Mass Screening
20.
Sensors (Basel) ; 24(8)2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38676028

ABSTRACT

Diabetes mellitus (DM) is a persistent metabolic disorder associated with the hormone insulin. The two main types of DM are type 1 (T1DM) and type 2 (T2DM). Physical activity plays a crucial role in the therapy of diabetes, benefiting both types of patients. The detection, recognition, and subsequent classification of physical activity based on type and intensity are integral components of DM treatment. The continuous glucose monitoring system (CGMS) signal provides the blood glucose (BG) level, and the combination of CGMS and heart rate (HR) signals are potential targets for detecting relevant physical activity from the BG variation point of view. The main objective of the present research is the developing of an artificial intelligence (AI) algorithm capable of detecting physical activity using these signals. Using multiple recurrent models, the best-achieved performance of the different classifiers is a 0.99 area under the receiver operating characteristic curve. The application of recurrent neural networks (RNNs) is shown to be a powerful and efficient solution for accurate detection and analysis of physical activity in patients with DM. This approach has great potential to improve our understanding of individual activity patterns, thus contributing to a more personalized and effective management of DM.


Subject(s)
Algorithms , Blood Glucose , Exercise , Heart Rate , Neural Networks, Computer , Humans , Exercise/physiology , Heart Rate/physiology , Blood Glucose/analysis , Blood Glucose Self-Monitoring/methods , Male , Diabetes Mellitus/diagnosis , Female , Adult , ROC Curve , Diabetes Mellitus, Type 2/diagnosis , Artificial Intelligence , Diabetes Mellitus, Type 1/physiopathology , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...