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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 -
Nutrients Apr 2024This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with... (Observational Study)
Observational Study
This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (β = -2.3, SE = 1.0, = 0.03) in D-GLYC, while a later last EO predicted a higher GV (β = 1.5, SE = 0.6, = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (β = 0.9, SE = 0.4, = 0.02) and GV (β = 0.4, SE = 0.2, = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.
Topics: Humans; Pilot Projects; Male; Female; Prediabetic State; Diabetes Mellitus, Type 2; Blood Glucose; Adult; Middle Aged; Meals; Diet; Feeding Behavior; Dietary Carbohydrates; Aged
PubMed: 38732543
DOI: 10.3390/nu16091295 -
Nutrients Apr 2024Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of... (Randomized Controlled Trial)
Randomized Controlled Trial
Validation of Nutritional Approaches to Modulate Cardiovascular and Diabetic Risk Factors in Patients with Hypertriglyceridemia or Prediabetes-The MoKaRi II Randomized Controlled Study.
Hypertriglyceridemia and diabetes mellitus type 2 are among the most important metabolic diseases globally. Diet plays a vital role in the development and progression of both clinical pictures. For the 10-week randomized, controlled, intervention study, 67 subjects with elevated plasma triglyceride (TG) concentrations (≥1.7 mmol/L) and 69 subjects with elevated fasting glucose concentrations (≥5.6 < 7.0 mmol/L) were recruited. The intervention groups received specially developed, individualized menu plans and regular counseling sessions to lower (A) TG or (B) fasting glucose and glycated hemoglobin A1c as well as other cardiovascular and diabetic risk factors. The hypertriglyceridemia intervention group was further supplemented with fish oil (3.5 g/d eicosapentaenoic acid + docosahexaenoic acid). The two control groups maintained a typical Western diet. Blood samples were taken every 2 weeks, and anthropometric data were collected. A follow-up examination was conducted after another 10 weeks. In both intervention groups, there were comparable significant reductions in blood lipids, glucose metabolism, and anthropometric parameters. These results were, with a few exceptions, significantly more pronounced in the intervention groups than in the corresponding control groups (comparison of percentage change from baseline). In particular, body weight was reduced by 7.4% (6.4 kg) and 7.5% (5.9 kg), low-density lipoprotein cholesterol concentrations by 19.8% (0.8 mmol/L) and 13.0% (0.5 mmol/L), TG concentrations by 18.2% (0.3 mmol/L) and 13.0% (0.2 mmol/L), and homeostatic model assessment for insulin resistance by 31.8% (1.1) and 26.4% (0.9) ( < 0.05) in the hypertriglyceridemia and prediabetes intervention groups, respectively. Some of these changes were maintained until follow-up. In patients with elevated TG or fasting glucose, implementing individualized menu plans in combination with regular counseling sessions over 10 weeks led to a significant improvement in cardiovascular and diabetic risk factors.
Topics: Humans; Prediabetic State; Hypertriglyceridemia; Male; Female; Middle Aged; Blood Glucose; Diabetes Mellitus, Type 2; Triglycerides; Heart Disease Risk Factors; Adult; Cardiovascular Diseases; Glycated Hemoglobin; Risk Factors; Dietary Supplements; Fish Oils; Aged
PubMed: 38732508
DOI: 10.3390/nu16091261 -
BMC Endocrine Disorders May 2024The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may...
BACKGROUND
The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status.
METHODS
Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors.
RESULTS
Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19-1.58) for all-cause mortality and 1.63 (95% CI, 1.29-2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03-1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08-2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively.
CONCLUSIONS
The findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR's fluctuations over time should be further focused.
Topics: Humans; Prediabetic State; Male; Cardiovascular Diseases; Female; Neutrophils; Prospective Studies; Middle Aged; Lymphocytes; United States; Adult; Diabetes Mellitus; Follow-Up Studies; Prognosis; Nutrition Surveys; Cause of Death; Aged; Leukocyte Count
PubMed: 38730476
DOI: 10.1186/s12902-024-01592-7 -
PloS One 2024Rates of prediabetes, which can lead to type 2 diabetes, are increasing worldwide. Interventions for prediabetes mainly focus on lifestyle changes to diet and exercise.... (Review)
Review
BACKGROUND
Rates of prediabetes, which can lead to type 2 diabetes, are increasing worldwide. Interventions for prediabetes mainly focus on lifestyle changes to diet and exercise. While these interventions are effective, they are often delivered face-to-face, which may pose a barrier to those with limited access to healthcare. Given the evidence for digital interventions addressing other noncommunicable diseases, these may also be effective for prediabetes self-management. The aim of this scoping review was to assess the breadth of evidence around digital interventions for prediabetes self-management.
METHODS
We developed a targeted search strategy and relevant studies were identified through searches conducted in four bibliographic databases (Medline, Embase, PsycInfo, and Scopus). Published studies were eligible if they included a digital intervention to support adults aged 18+ with prediabetes self-management. Titles and abstracts were first screened for relevance by one researcher. Full texts of selected records were assessed against the review criteria independently by two researchers for inclusion in the final analysis.
RESULTS
Twenty-nine studies were included, of which nine were randomised controlled trials. Most efficacy studies reported significant changes in at least one primary and/or secondary outcome, including participants' glycaemic control, weight loss and/or physical activity levels. About one-third of studies reported mixed outcomes or early significant outcomes that were not sustained at long-term follow-up. Interventions varied in length, digital modalities, and complexity. Delivery formats included text messages, mobile apps, virtually accessible dietitians/health coaches, online peer groups, and web-based platforms. Approximately half of studies assessed participant engagement/acceptability outcomes.
CONCLUSION
Whilst the evidence here suggests that digital interventions to support prediabetes self-management are acceptable and have the potential to reduce one's risk of progression to type 2 diabetes, more research is needed to understand which interventions, and which components specifically, have the greatest reach to diverse populations, are most effective at promoting user engagement, and are most effective in the longer term.
Topics: Humans; Prediabetic State; Self-Management; Diabetes Mellitus, Type 2; Exercise; Telemedicine
PubMed: 38728296
DOI: 10.1371/journal.pone.0303074 -
BMC Cardiovascular Disorders May 2024Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation....
BACKGROUND
Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes.
MATERIALS AND METHODS
A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0.
RESULTS
Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively).
CONCLUSION
The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.
Topics: Humans; Male; Polymorphism, Single Nucleotide; Middle Aged; Female; Case-Control Studies; Kazakhstan; Genetic Predisposition to Disease; Risk Factors; PPAR gamma; Aged; Phenotype; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Risk Assessment; Genetic Association Studies; X-ray Repair Cross Complementing Protein 1; Heart Diseases; Autonomic Nervous System Diseases; Adult; Diabetic Neuropathies; Autonomic Nervous System; Genetic Markers; alpha-Synuclein
PubMed: 38724937
DOI: 10.1186/s12872-024-03912-0 -
Diabetes Research and Clinical Practice Jun 2024To assess the effects of non-diabetic hyperglycaemia (NDH, also known as pre-diabetes), including the impact of the NHS Diabetes Prevention Programme (NHS DPP), on...
Prediabetes, participation in the English National Health Service Diabetes Prevention Programme, and associations with COVID-19-related mortality: A whole population study.
AIMS
To assess the effects of non-diabetic hyperglycaemia (NDH, also known as pre-diabetes), including the impact of the NHS Diabetes Prevention Programme (NHS DPP), on COVID-19-related mortality during the pandemic.
METHODS
This study included all 61,438,225 individuals registered with General Practices in England and alive on 1st March 2020. We assessed COVID-19-related mortality in the 2,290,280(3.7 %) individuals with diagnosed NDH between March 2020 and February 2022 compared to those without diagnosed NDH or diabetes using Cox regression to adjust for demographic factors and cardiovascular comorbidities. Individuals with diagnosed NDH were further sub-categorised based on their contact with the NHS DPP (N = 376,590). Analyses were stratified by age (years) (<50, 50-69 and ≥ 70).
RESULTS
There were 158,070 COVID-19 deaths; 17,280(11 %) for people with diagnosed NDH. The adjusted hazard ratio (HR) was 0.95(0.93-0.96),p < 0.001 for those with diagnosed NDH compared to those without diagnosed diabetes or NDH. By age (years), HRs were, 2.53(2.23-2.88),p < 0.001 for < 50, 1.29(1.24-1.35),p < 0.001 for 50-69 and 0.87(0.85-0.89),p < 0.001 for ≥ 70. NHS DPP attendance was associated with lower COVID-19 mortality with a dose-response relationship with engagement.
CONCLUSIONS
Younger people with diagnosed NDH were at higher relative risk of COVID-19 mortality. Attendance at the NHS DPP was associated with significantly lower COVID-19-related mortality.
Topics: Humans; COVID-19; Middle Aged; Male; Female; Aged; England; Prediabetic State; SARS-CoV-2; State Medicine; Adult
PubMed: 38723673
DOI: 10.1016/j.diabres.2024.111692