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Nature Communications Sep 2023Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to... (Clinical Trial)
Clinical Trial
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
Topics: Humans; Cytokines; Gastrointestinal Microbiome; Hyperglycemia; Microbiota; Prediabetic State
PubMed: 37666816
DOI: 10.1038/s41467-023-41042-x -
MMW Fortschritte Der Medizin Oct 2023
Topics: Humans; Vitamin B 12; Prediabetic State
PubMed: 37759026
DOI: 10.1007/s15006-023-3019-4 -
The Lancet. Diabetes & Endocrinology Jan 2024Statins reduce LDL cholesterol and cardiovascular events among those with or without diabetes but have been reported to increase new-onset diabetes. The CLEAR Outcomes... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Statins reduce LDL cholesterol and cardiovascular events among those with or without diabetes but have been reported to increase new-onset diabetes. The CLEAR Outcomes trial demonstrated that bempedoic acid reduced the risk of major adverse cardiovascular events among statin-intolerant patients at high cardiovascular risk. In this prespecified analysis, our dual aims were to evaluate the cardiovascular benefits of bempedoic acid, an ATP-citrate lyase inhibitor, in individuals with diabetes, and to evaluate the risk of new-onset diabetes and HbA among those without diabetes in the CLEAR Outcomes trial.
METHODS
CLEAR Outcomes was a randomised, double-blind, placebo-controlled trial conducted across 1250 primary care and outpatient sites in 32 countries. Patients with or without cardiovascular disease who were unwilling or unable to take guideline-recommended doses of statins and an LDL cholesterol of 2·59 mmol/L or more were randomly assigned (1:1) in a double-blinded manner to either bempedoic acid 180 mg once per day or placebo. In this prespecified analysis, the efficacy endpoint was a time-to-event analysis of four-component major adverse cardiovascular event (MACE-4), which is the composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularisation, using the intention-to-treat population stratified by baseline glycaemia status. The prespecified analysis of risk of new-onset diabetes and HbA increase was evaluated in patients without diabetes at baseline. The CLEAR Outcomes trial was completed on Nov 7, 2022, and is registered with ClinicalTrials.gov (NCT02993406).
FINDINGS
Between Dec 22, 2016, and Nov 7, 2022, 13 970 patients were screened and randomly assigned; 6373 (45·6%) with diabetes, 5796 (41·5%) with prediabetes, and 1801 (12·9%) with normoglycaemia. Over a median of 3·4 years follow up, patients with diabetes had significant relative and absolute cardiovascular risk reductions in MACE-4 endpoints with bempedoic acid (HR 0·83; 95% CI 0·72-0·95; absolute risk reduction of 2·4%) compared to placebo, with no statistical evidence of effect modification across glycaemic strata (interaction p=0·42). The proportion of patients who developed new-onset diabetes were similar between the bempedoic acid and placebo groups, with 429 of 3848 (11·1%) with bempedoic acid versus 433 of 3749 (11·5%) with placebo (HR 0·95; 95% CI 0·83-1·09). HbA concentrations at month 12 and the end of the study were similar between randomised groups in patients who had prediabetes and normoglycaemia. Placebo-corrected LDL cholesterol concentrations and high-sensitivity C-reactive protein at 6 months were reduced in each glycaemic stratum (diabetes, prediabtes, and normoglycaemia) for patients randomly assigned to bempedoic acid (all p<0·001).
INTERPRETATION
Among patients with diabetes, bempedoic acid reduces LDL cholesterol and high-sensitivity C-reactive protein and risk of cardiovascular events. Patients without diabetes had no increase in new-onset diabetes or worsening HbA with bempedoic acid. The efficacy and cardiometabolic safety profile of bempedoic acid makes it a clinical option for those with and without diabetes.
FUNDING
Esperion Therapeutics.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Prediabetic State; C-Reactive Protein; Treatment Outcome; Diabetes Mellitus; Cardiovascular Diseases; Double-Blind Method
PubMed: 38061370
DOI: 10.1016/S2213-8587(23)00316-9 -
Cardiovascular Diabetology Feb 2024The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship...
The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005-2018.
BACKGROUND
The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes.
METHODS
This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005-2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG.
RESULTS
During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P < 0.001). Multivariate Cox regression analyses indicated that, compared to the 1st quartile, the 4th quartile was associated with higher all-cause mortality (model 1: HR = 0.89, 95% CI 0.74-10.7, P = 0.226; model 2: HR = 1.24, 95% CI 1.03-1.49, P = 0.026; model 3: HR = 1.30, 95% CI 1.08-1.57, P = 0.006). The 3rd quartile was associated with lower cardiovascular mortality than quartile 1 (model 1: HR = 0.47, 95% CI 0.32-0.69, P < 0.001; model 2: HR = 0.66, 95% CI 0.45-0.96, P = 0.032; model 3: HR = 0.68, 95% CI 0.46-0.99, P = 0.049). There was a U-shaped association between SHR and all-cause mortality and an L-shaped association between SHR and cardiovascular mortality, with inflection points of SHR for poor prognosis of 0.87 and 0.93, respectively.
CONCLUSION
SHR is related to all-cause and cardiovascular mortality in patients with diabetes or prediabetes. SHR may have predictive value in those patients.
Topics: Humans; Prediabetic State; Nutrition Surveys; Prognosis; Diabetes Mellitus; Hyperglycemia; Cardiovascular Diseases
PubMed: 38419029
DOI: 10.1186/s12933-024-02172-8 -
Diabetes Care Nov 2023
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Glucose; Incidence; Randomized Controlled Trials as Topic; Phenotype; Life Style
PubMed: 37890107
DOI: 10.2337/dci23-0052 -
Metabolism: Clinical and Experimental Sep 2023The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among...
Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States.
BACKGROUND
The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among individuals with pre-diabetes (PreD) and metabolically healthy and metabolically unhealthy individuals without T2D are not known. Our aim was to assess prevalence and mortality of NAFLD among these four groups.
METHODS
The Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) with mortality data (follow up to 2019) via linkage to the National Death Index was utilized. NAFLD was defined by ultrasound and absence of other liver diseases and excess alcohol use. Pre-D was defined as fasting plasma glucose values of 100-125 mg/dL and/or HbA1c level between 5.7 %-6.4 % in the absence of established diagnosis of T2D. Metabolically healthy (MH) was defined if all of the following criteria were absent: waist circumference of ≥102 cm (men) or ≥ 88 cm (women) or BMI of ≥30; blood pressure (BP) ≥ 130/85 mmHg or using BP-lowering medication; triglyceride level ≥ 150 mg/dL or using lipid-lowering medication; lipoprotein cholesterol level of <40 mg/dL (men) or < 50 mg/dL (women); homeostasis model assessment of insulin resistance (HOMA-IR) score ≥ 2.5; C-reactive protein (CRP) level of >2 mg/L; Pre-D and T2D. Metabolically unhealthy (MU) individuals were defined as the presence of any component of metabolic syndrome but not having Pre-D and T2D. Competing risk analyses of cause-specific mortality were performed.
FINDINGS
11,231 adults (20-74y) were included: mean age 43.4 years; 43.9 % male; 75.4 % white, 10.8 % Black, and 5.4 % Mexican American, 18.9 % NAFLD, 7.8 % T2D; 24.7 % PreD; 44.3 % MU; and 23.3 % in MH individuals. In multivariable adjusted logistic model, as compared to MH individuals, the highest risk of having NAFLD were in T2D individuals (Odd Ratio [OR] = 10.88 [95 % confidence interval: 7.33-16.16]), followed by Pre-D (OR = 4.19 [3.02-5.81]), and MU (OR = 3.36 [2.39-4.71]). During a median follow up of 26.7 years (21.2-28.7 years), 3982 died. NAFLD subjects had significantly higher age-adjusted mortality than non-NAFLD (32.7 % vs. 28.7 %, p < .001). Among subjects with NAFLD, the highest age-standardized cumulative mortality was observed among those with T2D (41.3 %), followed by with Pre-D (35.1 %), MU subjects (30.0 %), and MH subjects (21.9 %) (pairwise p-values<.04 vs. MH). Multivariable adjusted cox models showed that NAFLD with T2D had a higher risk of all-causes and cardiac-specific deaths (Hazard Ratio [HR] = 4.71 [2.23-9.96] and HR = 20.01 [3.00-133.61]), followed by NAFLD with Pre-D (HR = 2.91 [1.41-6.02] and HR = 10.35 [1.57-68.08]) and metabolically unhealthy NAFLD (HR = 2.59 [1.26-5.33] and HR = 6.74 [0.99-46.03]) compared to metabolically healthy NAFLD. In addition to older age, independent predictors of mortality among NAFLD with T2D included high CRP, CVD, CKD, high FIB-4, and active smoking. Similarly, among NAFLD with PreD, high CRP, CKD, CVD, hypertension, and active smoking were associated with mortality. Finally, CVD and active smoking were predictors of mortality among metabolically unhealthy NAFLD, and active smoking was the only mortality risk among metabolically healthy NAFLD subjects.
INTERPRETATION
Metabolic abnormality impacts both prevalence and outcomes of subjects with NAFLD.
Topics: Adult; Humans; Male; Female; United States; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2; Nutrition Surveys; Prediabetic State; Hypertension; Body Mass Index; Renal Insufficiency, Chronic; Risk Factors
PubMed: 37380016
DOI: 10.1016/j.metabol.2023.155642 -
Journal of Internal Medicine Nov 2023Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this...
BACKGROUND
Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF.
OBJECTIVE
To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF.
METHODS
We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference.
RESULTS
The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF.
CONCLUSIONS/INTERPRETATION
The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.
Topics: Humans; Prediabetic State; Atrial Fibrillation; Diabetes Mellitus, Type 2; Cohort Studies; Blood Glucose; Risk Factors
PubMed: 37387643
DOI: 10.1111/joim.13688 -
Journal of Diabetes Jul 2023To estimate secular trends and disease burden of diabetes and prediabetes among Chinese adults.
BACKGROUND
To estimate secular trends and disease burden of diabetes and prediabetes among Chinese adults.
METHODS
Three population-based surveys were performed among Chinese adults in Shanghai in 2002-2003 (n = 12 302), 2009 (n = 7414), and 2017 (n = 18 960). Diabetes and prediabetes were defined using the 1999 World Health Organization (WHO) criteria. Cochran-Armitage trend test was used to examine the trends in prevalence, awareness, and glycemic control status. Disability adjusted life years (DALYs) were estimated to evaluate the disease burden of diabetes-related complications using the population attribution fraction approach based on published data.
RESULTS
The age-adjusted prevalence of diabetes increased during the 15-year period (p for trend <.001) and reached 23.0% (95% CI: 22.1 ~ 24.0%) in men and 15.7% (95% CI: 15.1 ~ 16.4%) among women in 2017. The prevalence of impaired glucose tolerance peaked in 2009, whereas that of impaired fasting glucose increased continuously (p for trend <.001). The awareness of diabetes was found to increase and the glycemic control rates decreased over the three surveys. The estimated DALYs of diabetes complications were found to have increased rapidly due to the increasing prevalence of diabetes and the decreasing glycemic control rates.
CONCLUSIONS
Prediabetes and diabetes affect a considerable proportion of Chinese adults in Shanghai. Our results highlight the necessary to strengthen the community healthcare system in China to guarantee extensive management of diabetes and prediabetes.
Topics: Male; Adult; Female; Humans; Prediabetic State; Prevalence; East Asian People; China; Diabetes Mellitus; Cost of Illness
PubMed: 37203303
DOI: 10.1111/1753-0407.13391 -
Diabetes & Metabolism Journal Sep 2023In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with... (Review)
Review
In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.
Topics: Adult; Humans; Asian People; Dyslipidemias; Prediabetic State; Republic of Korea; Societies, Medical; Diabetes Mellitus
PubMed: 37793979
DOI: 10.4093/dmj.2023.0282 -
Pediatrics Oct 2023Carbohydrate restriction is increasingly popular as a weight loss strategy and for achieving better glycemic control in people with diabetes, including type 1 and type 2...
Carbohydrate restriction is increasingly popular as a weight loss strategy and for achieving better glycemic control in people with diabetes, including type 1 and type 2 diabetes. However, evidence to support low-carbohydrate diets in youth (children and adolescents 2-18 years of age) with obesity or diabetes is limited. There are no guidelines for restricting dietary carbohydrate consumption to reduce risk for diabetes or improve diabetes outcomes in youth. Thus, there is a need to provide practical recommendations for pediatricians regarding the use of low-carbohydrate diets in patients who elect to follow these diets, including those with type 1 diabetes and for patients with obesity, prediabetes, and type 2 diabetes. This clinical report will: Provide background on current dietary patterns in youth, describe how moderate-, low-, and very low-carbohydrate diets differ, and review safety concerns associated with the use of these dietary patternsReview the physiologic rationale for carbohydrate reduction in youth with type 1 diabetes and for youth with obesity, prediabetes, and type 2 diabetesReview the evidence for low-carbohydrate diets in the management of youth with type 1 diabetesReview the evidence for low-carbohydrate diets in the management of youth with obesity, prediabetes, and type 2 diabetesProvide practical information for pediatricians counseling families and youth on carbohydrate recommendations for type 1 diabetes and for obesity, prediabetes, and type 2 diabetes.
Topics: Adolescent; Humans; Child; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Prediabetic State; Diet, Carbohydrate-Restricted; Obesity; Dietary Carbohydrates
PubMed: 37718964
DOI: 10.1542/peds.2023-063755