Open research questions in Diabetes, Cardiovascular Risks, and Lipoproteins

What the literature leaves open

• The study faced challenges in terms of missing values for independent variables, which were addressed using predictive mean matching. The study had to balance the need for a large sample size with the potential for selection bias due to case deletion. The study had to account for the cross-sectional design and the potential for reverse causality.

  Gender-specific age inflection points for hypertension, elevated fasting blood glucose, and dyslipidemia in a Northern Chinese cohort: a comorbidity-based analysis · 2026 · DOI

• There is a lack of understanding of the gender-specific age inflection points for hypertension, elevated fasting blood glucose, and dyslipidemia. Prior studies have not examined the relationships between these conditions using a comorbidity-based analysis. There is a need for a gender-comorbidity dual-dimension inflection point atlas for these conditions.

  Gender-specific age inflection points for hypertension, elevated fasting blood glucose, and dyslipidemia in a Northern Chinese cohort: a comorbidity-based analysis · 2026 · DOI

• Further research is needed to understand the drivers of the divergent trends in CKM syndrome burden across countries, - Studies should investigate the impact of different risk factors on CKM syndrome burden, - Research should focus on developing effective interventions to reduce the burden of CKM syndrome

  National divergence in cardio-kidney-metabolic syndrome burden and implications for health policy: a global burden of disease analysis with projections to 2050 · 2026 · DOI

• Comparative studies on long-term trends of the three core components of Cardio-Kidney-Metabolic syndrome across major countries are still limited. The study aims to fill this gap by analyzing age-standardized disability-adjusted life year rates of IHD, DKD, and NAFLD attributable to high fasting plasma glucose from 1990 to 2021.

  National divergence in cardio-kidney-metabolic syndrome burden and implications for health policy: a global burden of disease analysis with projections to 2050 · 2026 · DOI

• Further studies are needed to refine cardiovascular risk stratification beyond body mass index (BMI) alone. Longitudinal analyses are needed to examine the association between metabolic-obesity phenotypes and subclinical carotid atherosclerosis across age groups.

  Metabolically unhealthy normal weight is associated with subclinical carotid atherosclerosis: cross-sectional and longitudinal evidence from a Chinese health examination cohort · 2026 · DOI

• The relative cardiovascular risk associated with excess adiposity and metabolic dysfunction remains uncertain, particularly when the two are dissociated. Longitudinal analyses and age-group specific comparisons are lacking.

  Metabolically unhealthy normal weight is associated with subclinical carotid atherosclerosis: cross-sectional and longitudinal evidence from a Chinese health examination cohort · 2026 · DOI

• Further studies with longer follow-up duration are needed, - Research on the associations between glucose tolerance status and all-cause mortality in rural Chinese populations is needed, - Studies on the lifestyle intervention in individuals with IGT to reduce long-term mortality risk are needed

  Glucose tolerance phenotypes and risks of incident first-ever stroke and all-cause mortality in low-income rural Chinese adults: a population-based prospective cohort study · 2026 · DOI

• The stroke risk gradient across the full glucose tolerance spectrum remains unresolved. The relative prognostic value of fasting versus postload glycaemia remains unresolved. Evidence is particularly scarce for low-income rural Chinese populations.

  Glucose tolerance phenotypes and risks of incident first-ever stroke and all-cause mortality in low-income rural Chinese adults: a population-based prospective cohort study · 2026 · DOI

• The study had to exclude studies with inconsistent TyG calculation methods or nonstandardized units. The study had to exclude studies with unclear BMI definitions or unavailable categorical thresholds. The study had to assess the risk of publication bias via funnel plot symmetry testing and Egger’s regression.

  Association between the triglyceride glucose-body mass index and the risk of incident type 2 diabetes: a systematic review and meta-analysis · 2026 · DOI

• The lack of systematic evaluation of the association between TyG-BMI and incident type 2 diabetes risk. The need for novel epidemiological evidence supporting the association between TyG-BMI and incident type 2 diabetes risk.

  Association between the triglyceride glucose-body mass index and the risk of incident type 2 diabetes: a systematic review and meta-analysis · 2026 · DOI

• Additional studies are warranted to thoroughly examine the relationship between TyG-BMI and prediabetes risk. Research is needed to clarify the underlying mechanisms of the relationship between TyG-BMI and prediabetes risk. Future studies should investigate the applicability of the TyG-BMI index in different populations.

  Nonlinear relationship between triglyceride glucose-body mass index and the risk of prediabetes: a multi-center retrospective cohort study · 2026 · DOI

• Prior studies on the association between the TyG index and depression are predominantly based on cross-sectional studies. There is a need to investigate the association between the TyG index and incident depression independent of genetic predisposition.

  Triglyceride–glucose index, genetic predisposition, and incident depression: a prospective cohort study from the UK Biobank · 2026 · DOI

• The study is a single-center retrospective cross-sectional study, - The study employed a convenience sample-based random sampling approach, - The sample size is limited to 1,473 participants

  Occupational disparities in chronic disease prevalence and metabolic covariation: a cross-sectional study of six occupational groups in Lanzhou · 2026 · DOI

• Further studies could investigate the underlying mechanisms of occupational disparities in chronic disease prevalence, - Longitudinal studies could be conducted to examine the temporal relationships between occupation and chronic disease development

  Occupational disparities in chronic disease prevalence and metabolic covariation: a cross-sectional study of six occupational groups in Lanzhou · 2026 · DOI

• The non-linear lipid remodeling processes underlying atherogenic dyslipidemia remain insufficiently defined. Prior studies have primarily focused on linear associations between HbA1c and traditional lipid markers. The dynamic trajectory and critical inflection points of atherogenic lipid remodeling that underlie the relationship between glycemic control and cardiovascular disease risk remain incompletely characterized.

  Nonlinear HbA1c thresholds reveal accelerated atherogenic remodeling and improved risk reclassification in type 2 diabetes · 2026 · DOI

• The study identifies the challenge of accurately measuring cardiometabolic risk factors in resource-limited settings. The study notes the challenge of explaining the complex relationship between adipose tissue distribution and metabolic dysfunction. The study does not explicitly state other technical or domain challenges.

  Cardiometabolic risk assessment by anthropometric and biochemical indices in mexican population · 2025 · DOI

• Investigate sex-specific insulin resistance mechanisms, - Explore alternative diagnostic approaches for females, - Examine the effectiveness of non-conventional indices in other populations

  Cardiometabolic risk assessment by anthropometric and biochemical indices in mexican population · 2025 · DOI

• The relationship between CKM syndrome and CVD is not well understood. The predictive performance of TyG index and related indices in CKM syndrome stages 0-3 is not thoroughly investigated.

  Comparison of triglyceride-glucose index and triglyceride-glucose related indexes in predicting cardiovascular disease incidence among populations with cardiovascular-kidney-metabolic syndrome stages 0-3: a nationwide prospective cohort study · 2025 · DOI

• The relationship between AIP and CVD in the context of CKM syndrome is not well understood. Prior studies have demonstrated a significant correlation between the AIP index and CVD in the general population, but not specifically in CKM syndrome.

  Atherogenic index of plasma and cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stage 1 to 3: a longitudinal study · 2025 · DOI

• Investigate the potential influencing variables and screening indicators of cardiorenal disease, - Research to investigate the associations between TYG, TyG-WHtR, TyG-WC, and TyG-BMI and the risk of CKD, CVD, and CRS

  Association between triglyceride-glucose index and its composite obesity indexes and cardio-renal disease: analysis of the NHANES 2013-2018 cycle · 2025 · DOI

• The association between triglyceride-glucose index and cardio-renal disease remains insufficiently researched. There is a need to investigate the potential influencing variables and screening indicators of cardiorenal disease.

  Association between triglyceride-glucose index and its composite obesity indexes and cardio-renal disease: analysis of the NHANES 2013-2018 cycle · 2025 · DOI

• Two studies were rated 'high risk' due to a lack of information, - The study only included RCTs, - The study did not investigate the long-term effects of exercise interventions, - The study did not control for all potential confounding variables

  Comparing the impacts of different exercise interventions on patients with type 2 diabetes mellitus: a literature review and meta-analysis · 2025 · DOI

• Investigate the long-term effects of exercise interventions on patients with type 2 diabetes mellitus, - Examine the effects of different exercise interventions on other health outcomes, - Conduct studies with larger sample sizes and more diverse populations

  Comparing the impacts of different exercise interventions on patients with type 2 diabetes mellitus: a literature review and meta-analysis · 2025 · DOI

• The high cost of the hyperinsulinemic-euglycemic clamp method limits its widespread clinical application. The study requires a large-scale population-based dataset to evaluate the relationship between the TyG index and diabetes. The study needs to address potential confounding variables to establish a reliable association between the TyG index and diabetes risk.

  Association of triglyceride glucose index with incident diabetes among individuals with normal fasting triglycerides and fasting plasma glucose values: a general population-based retrospective cohort study · 2025 · DOI

• Further research to explore the application of AIP in preventive strategies and therapeutic interventions - Research to explore the biological mechanisms linking higher AIP to increased MetS risk - Studies to validate the findings in different populations

  Evaluating atherogenic index of plasma as a predictor for metabolic syndrome: a cross-sectional analysis from Northern Taiwan · 2025 · DOI

Most-cited papers in Diabetes, Cardiovascular Risks, and Lipoproteins

• Diabetes and Cardiovascular Disease · JAMA · 1979 · 6,306 citations
• Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction · New England Journal of Medicine · 1998 · 5,283 citations
• Prevalence of the Metabolic Syndrome Among US Adults · JAMA · 2002 · 5,035 citations
• Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies · The Lancet · 2010 · 4,265 citations
• Prevalence of Obesity, Diabetes, and Obesity-Related Health Risk Factors, 2001 · JAMA · 2003 · 4,173 citations
• Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 · The Lancet · 2023 · 3,857 citations
• The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men · JAMA · 2002 · 3,593 citations
• The Disease Burden Associated With Overweight and Obesity · JAMA · 1999 · 3,352 citations
• Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants · The Lancet · 2016 · 2,868 citations
• National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants · The Lancet · 2011 · 2,773 citations

Most recent work

• Investigating the prediction potential of cholesterol, high-density lipoprotein, and glucose index surpasses TyG, AIP, and METS-IR for type 2 diabetes: a longitudinal cohort study · Frontiers in Endocrinology · 2026
• Cost-Effectiveness of ApoB, Non–HDL-C, and LDL-C Goals for Primary Prevention Lipid-Lowering Therapy · JAMA · 2026
• The Cardiovascular Burden of Diabetes: Risk Factors, Clinical Phenotypes, and Personalized Cardiometabolic Management · Journal of Clinical Medicine · 2026
• Metabolic traits in obesity and normal BMI in industrialised countries: a multi-country analysis of national population-based studies · The Lancet · 2026
• Nonlinear HbA1c thresholds reveal accelerated atherogenic remodeling and improved risk reclassification in type 2 diabetes · Frontiers in Cardiovascular Medicine · 2026
• Comment on Liu et al. Low-Carbohydrate Diets of Varying Macronutrient Quality and Risk of Type 2 Diabetes in Three U.S. Prospective Cohort Studies. Diabetes Care 2025;48:2095–2102 · Diabetes Care · 2026
• Screening gaps for prediabetes in US young adults under current American diabetes Association criteria · Diabetes Research and Clinical Practice · 2026
• Prevalence and Determinants of Type 2 Diabetes Mellitus in a North Indian Population: a Community-Based Cross-Sectional Study · MAEDICA – a Journal of Clinical Medicine · 2026
• Lipid ratios as early screening markers of dyslipidemia in normal-BMI university students: a cross-sectional epidemiologic study · Archives of Medical Science - Atherosclerotic Diseases · 2026
• Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis · The Journal of Clinical Endocrinology & Metabolism · 2026

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