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Cardiovascular Diabetology May 2024There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect... (Clinical Trial)
Clinical Trial
BACKGROUND
There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes.
METHODS
This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof.
RESULTS
Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years.
CONCLUSIONS
In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.
Topics: Aged; Female; Humans; Male; Middle Aged; Biomarkers; Blood Glucose; Cause of Death; Chronic Disease; Computed Tomography Angiography; Coronary Angiography; Exercise Test; Glycated Hemoglobin; Prediabetic State; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors
PubMed: 38769562
DOI: 10.1186/s12933-024-02232-z -
World Journal of Diabetes May 2024Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes. Estrogen [17β-estradiol...
BACKGROUND
Visceral obesity is increasingly prevalent among adolescents and young adults and is commonly recognized as a risk factor for type 2 diabetes. Estrogen [17β-estradiol (E2)] is known to offer protection against obesity diverse me-chanisms, while its specific effects on visceral adipose tissue (VAT) remain to be fully elucidated.
AIM
To investigate the impact of E2 on the gene expression profile within VAT of a mouse model of prediabetes.
METHODS
Metabolic parameters were collected, encompassing body weight, weights of visceral and subcutaneous adipose tissues (VAT and SAT), random blood glucose levels, glucose tolerance, insulin tolerance, and overall body composition. The gene expression profiles of VAT were quantified utilizing the Whole Mouse Genome Oligo Microarray and subsequently analyzed through Agilent Feature Extraction software. Functional and pathway analyses were conducted employing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively.
RESULTS
Feeding a high-fat diet (HFD) moderately increased the weights of both VAT and SAT, but this increase was mitigated by the protective effect of endogenous E2. Conversely, ovariectomy (OVX) led to a significant increase in VAT weight and the VAT/SAT weight ratio, and this increase was also reversed with E2 treatment. Notably, OVX diminished the expression of genes involved in lipid metabolism compared to HFD feeding alone, signaling a widespread reduction in lipid metabolic activity, which was completely counteracted by E2 administration. This study provides a comprehensive insight into E2's local and direct protective effects against visceral adiposity in VAT at the gene level.
CONCLUSION
In conclusion, the present study demonstrated that the HFD-induced over-nutritional challenge disrupted the gene expression profile of visceral fat, leading to a universally decreased lipid metabolic status in E2 deficient mice. E2 treatment effectively reversed this condition, shedding light on the mechanistic role and therapeutic potential of E2 in combating visceral obesity.
PubMed: 38766434
DOI: 10.4239/wjd.v15.i5.988 -
Nutrition & Diabetes May 2024Although central adiposity is a well-known risk factor for diabetes, the underlying mechanism remains unclear. The aim of this study was to explore the potential...
AIMS
Although central adiposity is a well-known risk factor for diabetes, the underlying mechanism remains unclear. The aim of this study was to explore the potential mediation role of circulating WBC counts in the association between central adiposity and the risk of diabetes.
MATERIALS AND METHODS
A cross-sectional study was conducted using data from the Fuqing cohort study, which included 6,613 participants aged 35-75 years. Logistic regression analysis and Spearman's rank correlation analysis were used to examine the relationships between waist-to-hip ratio, WBC counts and glycemic status. Both simple and parallel multiple mediation models were used to explore the potential mediation effects of WBCs on the association of waist-to-hip ratio with diabetes.
RESULTS
The study revealed a positive relationship between waist-to-hip ratio and risk of prediabetes (OR = 1.53; 95% CI, 1.35 to 1.74) and diabetes (OR = 2.89; 95% CI, 2.45 to 3.40). Moreover, elevated peripheral WBC counts were associated with both central adiposity and worsening glycemic status (P < 0.05). The mediation analysis with single mediators demonstrated that there is a significant indirect effect of central adiposity on prediabetes risk through total WBC count, neutrophil count, lymphocyte count, and monocyte count; the proportions mediated were 9.92%, 6.98%, 6.07%, and 3.84%, respectively. Additionally, total WBC count, neutrophil count, lymphocyte count, monocyte count and basophil count mediated 11.79%, 11.51%, 6.29%, 4.78%, and 1.76%, respectively, of the association between central adiposity and diabetes. In the parallel multiple mediation model using all five types of WBC as mediators simultaneously, a significant indirect effect (OR = 1.09; 95% CI, 1.06 to 1.14) were observed, with a mediated proportion of 12.77%.
CONCLUSIONS
Central adiposity was independently associated with an elevated risk of diabetes in a Chinese adult population; levels of circulating WBC may contribute to its underlying mechanisms.
Topics: Humans; Middle Aged; Male; Female; Leukocyte Count; Cross-Sectional Studies; Adult; Aged; Obesity, Abdominal; Blood Glucose; Prediabetic State; Waist-Hip Ratio; Risk Factors; China; Cohort Studies; Adiposity
PubMed: 38760348
DOI: 10.1038/s41387-024-00271-9 -
Journal of Diabetes and Its... Jul 2024To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven...
AIM
To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors.
PATIENTS AND METHODS
The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86).
RESULTS
The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus.
CONCLUSION
Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Middle Aged; Carotid Intima-Media Thickness; Male; Female; Adult; Carotid Artery, Common; Aged; Diabetic Angiopathies; Risk Factors; Predictive Value of Tests; Obesity
PubMed: 38759539
DOI: 10.1016/j.jdiacomp.2024.108766 -
Trials May 2024Prediabetes is a highly prevalent condition that heralds an increased risk of progression to type 2 diabetes, along with associated microvascular and macrovascular...
BACKGROUND
Prediabetes is a highly prevalent condition that heralds an increased risk of progression to type 2 diabetes, along with associated microvascular and macrovascular complications. The Diabetes Prevention Program (DPP) is an established effective intervention for diabetes prevention. However, participation in this 12-month lifestyle change program has historically been low. Digital DPPs have emerged as a scalable alternative, accessible asynchronously and recognized by the Centers for Disease Control and Prevention (CDC). Yet, most digital programs still incorporate human coaching, potentially limiting scalability. Furthermore, existing effectiveness results of digital DPPs are primarily derived from per protocol, longitudinal non-randomized studies, or comparisons to control groups that do not represent the standard of care DPP. The potential of an AI-powered DPP as an alternative to the DPP is yet to be investigated. We propose a randomized controlled trial (RCT) to directly compare these two approaches.
METHODS
This open-label, multicenter, non-inferiority RCT will compare the effectiveness of a fully automated AI-powered digital DPP (ai-DPP) with a standard of care human coach-based DPP (h-DPP). A total of 368 participants with elevated body mass index (BMI) and prediabetes will be randomized equally to the ai-DPP (smartphone app and Bluetooth-enabled body weight scale) or h-DPP (referral to a CDC recognized DPP). The primary endpoint, assessed at 12 months, is the achievement of the CDC's benchmark for type 2 diabetes risk reduction, defined as any of the following: at least 5% weight loss, at least 4% weight loss and at least 150 min per week on average of physical activity, or at least a 0.2-point reduction in hemoglobin A1C. Physical activity will be objectively measured using serial actigraphy at baseline and at 1-month intervals throughout the trial. Secondary endpoints, evaluated at 6 and 12 months, will include changes in A1C, weight, physical activity measures, program engagement, and cost-effectiveness. Participants include adults aged 18-75 years with laboratory confirmed prediabetes, a BMI of ≥ 25 kg/m (≥ 23 kg/m for Asians), English proficiency, and smartphone users. This U.S. study is conducted at Johns Hopkins Medicine in Baltimore, MD, and Reading Hospital (Tower Health) in Reading, PA.
DISCUSSION
Prediabetes is a significant public health issue, necessitating scalable interventions for the millions affected. Our pragmatic clinical trial is unique in directly comparing a fully automated AI-powered approach without direct human coach interaction. If proven effective, it could be a scalable, cost-effective strategy. This trial will offer vital insights into both AI and human coach-based behavioral change strategies in real-world clinical settings.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05056376. Registered on September 24, 2021, https://clinicaltrials.gov/study/NCT05056376.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Artificial Intelligence; Mentoring; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Treatment Outcome; Risk Reduction Behavior; Time Factors; Adult; Male; Female; Middle Aged; Mobile Applications
PubMed: 38755706
DOI: 10.1186/s13063-024-08177-8 -
Hypertension (Dallas, Tex. : 1979) Jul 2024Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and...
BACKGROUND
Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals.
METHODS
We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months.
RESULTS
We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; <0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; <0.0001). Prediabetes was found to significantly (<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (<0.0001).
CONCLUSIONS
Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.
Topics: Humans; Metformin; Male; Prediabetic State; Aged; Female; Frailty; Hypertension; Hypoglycemic Agents; Insulin Resistance; Frail Elderly; Aged, 80 and over; Cognitive Dysfunction; Blood Glucose
PubMed: 38752357
DOI: 10.1161/HYPERTENSIONAHA.124.23087 -
The Journal of Clinical Investigation May 2024BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol... (Clinical Trial)
Clinical Trial
BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.
Topics: Humans; Prediabetic State; Male; Female; Diabetes Mellitus, Type 2; Middle Aged; Liver X Receptors; Cholesterol; Aged; Signal Transduction; ATP Binding Cassette Transporter, Subfamily G, Member 1; Monocytes; Risk Factors; ATP Binding Cassette Transporter 1; Aged, 80 and over
PubMed: 38747290
DOI: 10.1172/JCI173278 -
Cardiovascular Diabetology May 2024The relationship between the triglyceride-glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or...
The association between the triglyceride-glucose index and the risk of cardiovascular disease in US population aged ≤ 65 years with prediabetes or diabetes: a population-based study.
BACKGROUND
The relationship between the triglyceride-glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes.
METHODS
We used data from the 2003-2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted.
RESULTS
The study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes.
CONCLUSIONS
A higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients.
Topics: Humans; Prediabetic State; Female; Male; Cardiovascular Diseases; United States; Middle Aged; Blood Glucose; Nutrition Surveys; Risk Assessment; Triglycerides; Biomarkers; Diabetes Mellitus; Prevalence; Adult; Cross-Sectional Studies; Heart Disease Risk Factors; Prognosis; Age Factors; Risk Factors; Predictive Value of Tests
PubMed: 38741118
DOI: 10.1186/s12933-024-02261-8 -
Metabolomics Signature in Prediabetes and Diabetes: Insights From Tandem Mass Spectrometry Analysis.Endocrinology, Diabetes & Metabolism May 2024This study investigates the metabolic differences between normal, prediabetic and diabetic patients with good and poor glycaemic control (GGC and PGC).
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.
Topics: Humans; Prediabetic State; Metabolomics; Male; Tandem Mass Spectrometry; Female; Middle Aged; Adult; Glycated Hemoglobin; Blood Glucose; Diabetes Mellitus; Aged; Biomarkers; Diabetes Mellitus, Type 2; Metabolome; Glycemic Control; Carnitine
PubMed: 38739122
DOI: 10.1002/edm2.484 -
BMC Public Health May 2024This study aimed to explore predictors associated with intermediate (six months) and post-intervention (24 months) increases in daily steps among people with prediabetes... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aimed to explore predictors associated with intermediate (six months) and post-intervention (24 months) increases in daily steps among people with prediabetes or type 2 diabetes participating in a two-year pedometer intervention.
METHODS
A secondary analysis was conducted based on data from people with prediabetes or type 2 diabetes from two intervention arms of the randomised controlled trial Sophia Step Study. Daily steps were measured with an ActiGraph GT1M accelerometer. Participants were divided into two groups based on their response to the intervention: Group 1) ≥ 500 increase in daily steps or Group 2) a decrease or < 500 increase in daily steps. Data from baseline and from six- and 24-month follow-ups were used for analysis. The response groups were used as outcomes in a multiple logistic regression together with baseline predictors including self-efficacy, social support, health-related variables, intervention group, demographics and steps at baseline. Predictors were included in the regression if they had a p-value < 0.2 from bivariate analyses.
RESULTS
In total, 83 participants were included. The mean ± SD age was 65.2 ± 6.8 years and 33% were female. At six months, a lower number of steps at baseline was a significant predictor for increasing ≥ 500 steps per day (OR = 0.82, 95% CI 0.69-0.98). At 24 months, women had 79% lower odds of increasing ≥ 500 steps per day (OR = 0.21, 95% CI 0.05-0.88), compared to men. For every year of increase in age, the odds of increasing ≥ 500 steps per day decreased by 13% (OR = 0.87, 95% CI 0.78-0.97). Also, for every step increase in baseline self-efficacy, measured with the Self-Efficacy for Exercise Scale, the odds of increasing ≥ 500 steps per day increased by 14% (OR = 1.14, 95% CI 1.02-1.27).
CONCLUSIONS
In the Sophia Step Study pedometer intervention, participants with a lower number of steps at baseline, male gender, lower age or higher baseline self-efficacy were more likely to respond to the intervention with a step increase above 500 steps per day. More knowledge is needed about factors that influence response to pedometer interventions.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02374788.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Female; Prediabetic State; Aged; Middle Aged; Walking; Self Efficacy; Accelerometry
PubMed: 38734659
DOI: 10.1186/s12889-024-18766-6