HDL abnormalities in type 2 diabetes: Clinical implications

Martagon, Alexandro J.; Zubirán, Rafael; González-Arellanes, Rogelio; Praget-Bracamontes, Samantha; Rivera-Alcántara, J. Adrián; Aguilar-Salinas, Carlos A.

doi:10.1016/j.atherosclerosis.2023.117213

Cited by 9 publications

(7 citation statements)

References 93 publications

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“…High-density lipoprotein cholesterol (HDL-C), as a common marker of atherosclerosis ( 7 ), has been shown to have cardioprotective and anti-diabetic effects ( 8 – 10 ), and its levels and functions are related to glucose homeostasis ( 11 ), particularly in individuals with type 2 diabetes and hypertension ( 12 – 14 ). The liver, as a vital organ in the human body, plays a significant role in maintaining glucose homeostasis and insulin resistance (IR) ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study

He,

Yu,

Kuang

et al. 2023

Front. Endocrinol.

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ObjectiveBoth alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are closely related to glucose homeostasis in the body, and the main objective of this study was to investigate the association between ALT to HDL-C ratio (ALT/HDL-C ratio) and the risk of diabetes in a Chinese population.MethodsThe current study included 116,251 participants who underwent a healthy physical examination, and the study endpoint was defined as a diagnosis of new-onset diabetes. Multivariate Cox regression models and receiver operator characteristic curves were used to assess the association of the ALT/HDL-C ratio with diabetes onset.ResultsDuring the average observation period of 3.10 years, a total of 2,674 (2.3%) participants were diagnosed with new-onset diabetes, including 1,883 (1.62%) males and 791 (0.68%) females. After fully adjusting for confounding factors, we found a significant positive association between the ALT/HDL-C ratio and the risk of diabetes [Hazard ratios 1.06, 95% confidence intervals: 1.05, 1.06], and this association was significantly higher in males, obese individuals [body mass index ≥ 28 kg/m2] and individuals aged < 60 years (All P interaction < 0.05). In addition, the ALT/HDL-C ratio was significantly better than its components ALT and HDL-C in predicting diabetes in the Chinese population.ConclusionThere was a positive relationship between ALT/HDL-C ratio and diabetes risk in the Chinese population, and this relationship was significantly stronger in males, obese individuals, and individuals younger than 60 years old.

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Section: Introductionmentioning

confidence: 99%

Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study

He,

Yu,

Kuang

et al. 2023

Front. Endocrinol.

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“…This association does not necessarily mean causation; it could indicate underlying contributing conditions. In some cases, conditions like inflammatory diseases, thyroid disorders, liver disorders, and acute coronary syndrome can cause HDL particles to become dysfunctional or reduce the cholesterol efflux capacity [20][21][22][23][24]. A similar U-shaped relationship was also observed between HDL-C levels and the risk of hip fracture in older adults [25].…”

Section: Discussionmentioning

confidence: 69%

Sex-Specific Relationships between HDL-Cholesterol Levels and 10-Year Mortality in Individuals with Atherosclerotic Cardiovascular Disease: A Nationwide Cohort Study of South Koreans

Yang,

Jeong,

Kim

et al. 2023

Metabolites

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Large epidemiological studies show U-shaped relationships between high-density lipoprotein cholesterol (HDL-C) levels and all-cause mortality in individuals without atherosclerotic cardiovascular diseases (ASCVD). Association in those with ASCVD by sex is unclear. We examined the association between HDL-C levels and 10-year all-cause mortality in subjects (≥40 years of age) with ASCVD using the 2010 National Health Insurance Service and the National Death Registry of Korea. We categorized HDL-C levels into three groups (low: <40 mg/dL for males, <50 mg/dL for females; high: 40–90 mg/dL for males, 50–90 mg/dL for females; extremely high: >90 mg/dL) and 10 mg/dL intervals. We conducted a sex-stratified and adjusted Cox proportional hazards analysis. Out of 1,711,548 individuals (54% female, mean age 61.4 years), 10-year mortality was observed in 218,252 (12.8%). Males had a higher mortality rate than females (16.2% vs. 9.8%; p < 0.001). When adjusting for age, body mass index, LDL-cholesterol, triglycerides, hypertension, diabetes, smoking, and alcohol consumption, the low and extremely high HDL-C groups had significantly higher hazard ratios for 10-year mortality compared to the high HDL-C group in males [1.183 (1.166–1.199), 1.359 (1.288–1.434)] and in females [1.153 (1.138–1.169), 1.095 (1.029–1.167)]. The frequency distribution bars for the 10-year mortality rate showed sex-specific nadirs of 50–59 mg/dL in males and 70–79 mg/dL in females. In this ASCVD cohort, the extremely high HDL-C (>90 mg/dL) group had 35.9% and 9.5% higher 10-year mortality risks than the high HDL-C group for males and females, respectively. There was a slightly U-shaped relationship between baseline HDL-C levels and a 10-year mortality rate, with earlier inflection in males than in females.

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“…Analytical methods to subfractionate HDL particles include ultracentrifugation, differential ion mobility, two‐dimensional gel electrophoresis, and nuclear magnetic resonance (NMR) spectroscopy. Most HDL particles have a density between 1.063 and 1.21 g/mL 26 , and can be subdivided into two main subfractions HDL 2 and HDL 3 27 , 28 . HDL particles can be further subdivided by size into the smaller size particles HDL 3c , HDL 3b , HDL 3a , and the larger size HDL 2a and HDL 2b 22 , 28 , or by charge into pre‐α, pre‐β, and α‐HDL 28 .…”

Section: Hdl Composition Subfractions and Subspeciesmentioning

confidence: 99%

“…Most HDL particles have a density between 1.063 and 1.21 g/mL 26 , and can be subdivided into two main subfractions HDL 2 and HDL 3 27 , 28 . HDL particles can be further subdivided by size into the smaller size particles HDL 3c , HDL 3b , HDL 3a , and the larger size HDL 2a and HDL 2b 22 , 28 , or by charge into pre‐α, pre‐β, and α‐HDL 28 . Based on chemical shifts, NMR spectroscopy separated HDL into large, medium, and small particles 28 , 29 .…”

Section: Hdl Composition Subfractions and Subspeciesmentioning

confidence: 99%

“…HDL particles can be further subdivided by size into the smaller size particles HDL 3c , HDL 3b , HDL 3a , and the larger size HDL 2a and HDL 2b 22 , 28 , or by charge into pre‐α, pre‐β, and α‐HDL 28 . Based on chemical shifts, NMR spectroscopy separated HDL into large, medium, and small particles 28 , 29 . HDL subfractions isolated by different methods may not contain the same groups of HDL particles.…”

Section: Hdl Composition Subfractions and Subspeciesmentioning

confidence: 99%

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High‐density lipoprotein in diabetes: Structural and functional relevance

Lui,

Tan

2024

J of Diabetes Invest

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Low levels of high‐density lipoprotein‐cholesterol (HDL‐C) is considered a major cardiovascular risk factor. However, recent studies have suggested a more U‐shaped association between HDL‐C and cardiovascular disease. It has been shown that the cardioprotective effect of HDL is related to the functions of HDL particles rather than their cholesterol content. HDL particles are highly heterogeneous and have multiple functions relevant to cardiometabolic conditions including cholesterol efflux capacity, anti‐oxidative, anti‐inflammatory, and vasoactive properties. There are quantitative and qualitative changes in HDL as well as functional abnormalities in both type 1 and type 2 diabetes. Non‐enzymatic glycation, carbamylation, oxidative stress, and systemic inflammation can modify the HDL composition and therefore the functions, especially in situations of poor glycemic control. Studies of HDL proteomics and lipidomics have provided further insights into the structure–function relationship of HDL in diabetes. Interestingly, HDL also has a pleiotropic anti‐diabetic effect, improving glycemic control through improvement in insulin sensitivity and β‐cell function. Given the important role of HDL in cardiometabolic health, HDL‐based therapeutics are being developed to enhance HDL functions rather than to increase HDL‐C levels. Among these, recombinant HDL and small synthetic apolipoprotein A‐I mimetic peptides may hold promise for preventing and treating diabetes and cardiovascular disease.

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HDL abnormalities in type 2 diabetes: Clinical implications

Cited by 9 publications

References 93 publications

Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study

Alanine aminotransferase to high- density lipoprotein cholesterol ratio is positively correlated with the occurrence of diabetes in the Chinese population: a population-based cohort study

Sex-Specific Relationships between HDL-Cholesterol Levels and 10-Year Mortality in Individuals with Atherosclerotic Cardiovascular Disease: A Nationwide Cohort Study of South Koreans

High‐density lipoprotein in diabetes: Structural and functional relevance

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