Abstract
The variability in diabetes risk factors, such as uric acid and lipids, may influence the development of complications. This study aimed to investigate the influence of such variability on the occurrence of diabetic complications. A retrospective analysis of electronic medical records was conducted with type 2 diabetic patients who received treatment at a tertiary care hospital in Chengdu, Sichuan Province, between 2013 and 2022. The risk factor variability is presented as the standard deviation (SD). The associations between the variability and complications were examined using a binary logistic regression model. The study included 369 patients with type 2 diabetes. The findings revealed that outpatient special disease management served as a protective factor against the development of complications [OR = 0.53, 95% confidence interval (CI) (0.29–0.10)], particularly for the prevention of diabetic peripheral neuropathy [OR = 0.51, 95% CI (0.30–0.86)]. Variability in total cholesterol (TC-SD) was found to be a risk factor for the development of complications [OR = 2.42, 95% CI (1.18–4.97)] and acted as a risk factor for diabetic peripheral vasculopathy [OR = 2.50, 95% CI (1.25–5.02)]. TC-SD is a risk factor for the occurrence of diabetic peripheral neuropathy and diabetic peripheral vasculopathy, whereas outpatient special disease management functions as a protective factor against complications and diabetic peripheral neuropathy. Thus, in addition to glycaemic control, the regulation of lipid levels should be emphasized, particularly among patients without outpatient special disease management, to delay the onset of complications.
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Introduction
Due to factors such as the rapid growth of the domestic economy and increases in urbanization, the standard of living, and the ageing population, the prevalence of diabetes in China has been steadily increasing1. According to an epidemiological survey conducted by the Endocrinology Branch of the Chinese Medical Association on Diabetes between 2015 and 2017, the prevalence of diabetes among Chinese adults over the age of 18 was 11.2%, with approximately 90% of patients having type 2 diabetes mellitus (T2DM)2.
As a chronic condition, diabetes gradually progresses to complications that worsen with disease progression. These complications not only diminish patients' quality of life and increase medical expenses, treatment complexity, and mortality rates, but they also impose a significant socioeconomic burden3. In the United States, the cost of treating complications associated with T2DM constitutes 53% of the lifetime medical expenses for T2DM patients4. Several surveys that were conducted to assess the costs of diabetes treatment in several Asian countries have indicated that there is a positive correlation between the occurrence of complications in T2DM patients and the burden of treatment, and hospital expenditures for diabetic patients with complications are 2–3 times greater than those for patients without complications, suggesting that these patients consume substantial health care resources5,6.
Diabetic complications include both macrovascular and microvascular manifestations. Macrovascular complications primarily manifest as cardiovascular disease and peripheral vascular disease7, whereas microvascular complications mainly involve retinopathy, neuropathy, and nephropathy8. Diabetic peripheral neuropathy (DPN) represents the most prevalent microvascular complication in patients with diabetes mellitus9. DPN significantly contributes to lower-limb amputation and debilitating neuropathic pain10. Diabetic peripheral vasculopathy (DPV) is a prevailing chronic complication of diabetes mellitus. It represents a frequent cause of disability among individuals with diabetes and has detrimental effects on the digestive, neurological, and vascular systems as the disease progresses55. Dyslipidaemia contributes to elevated levels of oxidized LDL cholesterol and free fatty acids, culminating in increased production of inflammatory factors and heightened inflammatory response signalling, ultimately leading to vascular damage9,56. Prior research has also established a correlation between lipid variability and diabetic vascular complications57.
TC-SD serves as a risk factor for diabetic vasculopathy, and Waters et al.58 also found lipid variability to be a predictor of cardiovascular events in diabetic patients. It is widely recognized that lipid levels exhibit considerable variations among diabetic patients59. Another study demonstrated60 that individuals with diabetes exhibit a high incidence of vascular disease due to elevated levels of total plasma cholesterol, triglycerides, and dense lipoproteins, as well as a high sensitivity of platelets to aggregating agents and a hypercoagulable state. The impact of lipid variability on vascular complications is attributed to induced oxidative stress, where substantial fluctuations in lipids can destabilize plaques, leading to the release of atherogenic substances. The vascular endothelium sustains greater damage, thereby increasing the likelihood of develo** diabetic vascular disease61.
The influence of risk factors and their variability on diabetic complications should not be underestimated. Long-term variability in total cholesterol levels serves as a predictor of diabetic peripheral neuropathy and diabetic peripheral vasculopathy. The increased lipid fluctuations observed in diabetic patients under the age of 60 emphasize the importance of diligently managing lipid levels in the daily treatment of diabetes, particularly in this age group. Regular monitoring of lipid levels and timely pharmacological intervention should be provided for patients with abnormal or substantially variable lipid profiles. However, there is currently a lack of relevant studies establishing a direct causal relationship between long-term variability in total cholesterol levels and diabetic complications, although emerging evidence indicates that variability in diabetic risk factors is indeed associated with complications, necessitating further research.
The findings of this study demonstrated that outpatient special disease management serves as a protective factor against the progression of complications and diabetic peripheral neuropathy. Consistent with the findings of Lewing et al.62, the utilization of primary health care for diabetes was associated with complications. The consistent use of statins and glucose-lowering medications among patients receiving outpatient special disease management, coupled with regular monitoring and screening for complications, may represent an important aspect of outpatient special disease management in safeguarding against the development of complications in patients with diabetes. One study63 has shown that enhanced management and integration of individuals with chronic conditions within primary care settings yield improved health outcomes and cost savings. Notably, outpatient special disease management for patients with diabetes offers comprehensive testing, follow-up care, and disease management64. These practices contribute to better glycaemic control and reduced lipid fluctuations, subsequently mitigating the occurrence of unfavourable outcomes65.
However, this study did not establish a correlation between variability in risk factors and the onset of diabetic nephropathy or diabetic retinopathy, possibly due to the limited number of patients with those complications, which constitutes one of the limitations of this study. Furthermore, the study revealed that lipid levels and variability were lower in patients receiving special disease management for diabetes than in those not receiving such services. This observation underscores the impact of patient treatment adherence on lipid profiles. On the one hand, while managing patients via outpatient special disease management, health care providers can enhance public awareness to encourage diabetic individuals to enrol in such programs. Research has emphasized66 that outpatient special disease management can enhance patients' adherence to medical treatment and can regularly provide patients with disease knowledge guidance. Guidance related to chronic disease rehabilitation and relevant lifestyle recommendations are essential measures for maintaining disease stability and preventing complications67. On the other hand, for patients without outpatient special management, additional guidance on dietary choices, exercise regimens, and medication adherence should be provided during their visits. This approach aids in blood glucose control, lipid stabilization, and delay of complication occurrence and progression. Clinical staff involved in the care of diabetic patients should adhere to established standards of care for type 2 diabetes mellitus, promptly detecting and diligently monitoring diabetic complications.
This study has several limitations. First, it should be noted that this investigation is confined to a single-centre setting, resulting in a limited number of positive outcomes for certain complications. Consequently, this circumstance introduces a certain degree of bias to the results and may impede the generalizability of the findings. Furthermore, the absence of data concerning the duration and dosage of statin therapy within this study precludes the assessment of the impact of statin therapy on lipid variability. Subsequent research endeavours are warranted to elucidate the influence of lipid-lowering medications on lipid variability. The duration of the patients' illnesses was also not recorded, but the follow-up time was used instead, which may have biased the results of the study. Finally, this study did not explore the role of medications in complication incidence because the investigators considered that the effect of medications on complications is susceptible to differences in clinical treatment regimens, patient conditions, individual characteristics, medication adherence, and other factors; which biased the data collection and may have affected the results of this retrospective study to some extent. In future studies, it is recommended that multicentre explorations be conducted to include more diabetic patients with complications, and the effects of medications on the development of complications can be explored through a prospective design with further exploration of the causality and mechanism of risk factor variability and diabetic complications.
Conclusion
In this study, TC-SD was found to be a risk factor for the occurrence of diabetic peripheral neuropathy and diabetic peripheral vasculopathy, whereas outpatient special disease management functions as a protective factor against complications and diabetic peripheral neuropathy. In the comprehensive management of diabetic patients over the long term, regular assessment of lipid levels should be incorporated alongside routine blood glucose monitoring. By expanding the accessibility of the medical insurance system to include outpatient special disease management for patients with diabetes, patients can improve their adherence to treatment and follow-up to control their blood lipid levels in a normal and stable state, thereby slowing the progression of diabetic complications, improving patients' overall survival and quality of life, and alleviating the economic burdens faced by families and society.
Data availability
The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
The authors would like to thank all the study participants as well as all the investigators who participated in the study's development, revision, and supervision. The final manuscript was read and approved by all the authors.
Funding
This study was supported by the 2022 Clinical Medicine Research Center for Geriatric Diseases Open Topics (Grant number [2022 LHFSSYB-05]), Special Project for Strategic Cooperation between Sichuan University and Dazhou Municipal People’s Government (Grant number [2022CDDZ-17]), and Science and Technology Department of Sichuan Province (Grant number [2022YFS0349]).
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M.C. and L.P. contributed to formal analysis and investigation, writing—original draft; Y.G., X.W., L.K. contributed to conceptualization, methodology, data curation; M.G., H.Y. contributed to investigation, validation; Z.L. contributed to writing—review and editing; Z.X. contributed to writing—review and editing, supervision. All authors are in agreement with the content of the manuscript.
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Chen, M., Pu, L., Gan, Y. et al. The association between variability of risk factors and complications in type 2 diabetes mellitus: a retrospective study. Sci Rep 14, 6357 (2024). https://doi.org/10.1038/s41598-024-56777-w
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DOI: https://doi.org/10.1038/s41598-024-56777-w
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