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. 2023 Oct 17:16:3197-3211.
doi: 10.2147/DMSO.S430426. eCollection 2023.

The Metabolic Characteristics of Patients at the Risk for Diabetic Foot Ulcer: A Comparative Study of Diabetic Patients with and without Diabetic Foot

Xiucai Li #  1 , Song Wen #  1 , Meiyuan Dong  1   2 , Yue Yuan  1 , Min Gong  1 , Congcong Wang  1 , Xinlu Yuan  1 , Jianlan Jin  1 , Mingyue Zhou  3 , Ligang Zhou  1   2   4
Affiliations

The Metabolic Characteristics of Patients at the Risk for Diabetic Foot Ulcer: A Comparative Study of Diabetic Patients with and without Diabetic Foot

Xiucai Li et al. Diabetes Metab Syndr Obes. .

Abstract

Backgrounds and objective: Diabetic foot is a relatively severe complication in patients with type 2 diabetes (T2D), with peripheral neuropathy and angiopathy frequently serving as risk factors. However, it is unknown how the other major systemic metabolic factors impacted the profile of these patients, besides glucose management. Thus, we investigated the distinct characteristics of patients with diabetic foot ulcers and their relationships with angiopathy.

Materials and methods: We obtained the laboratory data of 334 diabetic patients at Shanghai Pudong Hospital from 2020 to 2023. The comparisons were performed between the groups with or without diabetic foot, including glucose metabolism, lipids profile, liver and kidney function, thyroid function, and serum iron. The association between metabolic factors and lower extremity computed tomography angiography (CTA) was analyzed.

Results: We found significant disparities between groups in relation to age, serum protein content, liver transferase, serum creatinine, estimated glomerular filtration rate (eGFR), serum uric acid (UA), small dense low-density lipoprotein (sdLDL), lipoprotein A (LP(a)), apolipoprotein A1 (APOA1), thyroid function, serum iron, and hemoglobin (Hb) (p<0.05). The Spearman correlational analyses showed that the severity of CTA, categorized by the unilateral or bilateral plaque or occlusion, was positively significantly correlated with UA (r=0.499), triglyceride (TG) (r=0.751), whereas inversely correlated with serum albumin (r=-0.510), alanine aminotransferase (r=-0.523), direct bilirubin (DBil) (r=-0.494), total bilirubin (TBil) (r=-0.550), Hb (r=-0.646).

Conclusion: This cross-section investigation showed that compared to T2D only, the patients with diabetic foot ulcer (DFU) might display similar glucose metabolic control context but adverse metabolic profiles, and this profile is associated with macrovascular angiopathy characteristics and their severity.

Keywords: CTA; diabetic foot; macrovascular angiopathy; serum bilirubin; serum iron; thyroid function.

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Conflict of interest statement

The authors declare that there is no potential conflict of interest in this work.

Figures

Figure 1
Figure 1
The age (A), duration of diabetes (B), smoking history (C), blood pressure (D), glucose metabolism (E), hemoglobin A1c (F), HOMA-IR (G), HOMA-β (H), and lipid profiles (I–N), sdLDL level (J), LP(a) level (K), APOA1 level (L), APOA2 (M), APOE (N) between the patients with and without DFU. The results showed that despite of matched parameters, there were significant disparities in age, smoking history, sdLDL level (J), LP(a) level (K), APOA1 level (L) between the DFU and non DFU.
Figure 2
Figure 2
The disparity in protein concentration (A), bilirubin (B), transferase (C), and BUN (D), SCr (E), UA (F), eGFR (G), UACR (H) between patients with and without DFU. The comparison results revealed that significant differences exist in hepatic and kidney function in terms of albumin content, ALT, SCr, UA, eGFR between the DFU and non DFU.
Figure 3
Figure 3
The distinction of thyroid hormones: FT3 (A), FT4 (B), TT3 (C), TT4 (D), TPOAb (E), procalcitonin (F), hemoglobin (G), serum iron (H) between the patients with DFU and non DFU. We found that compared with non DFU, the levels of FT3, FT4, TT3, Hb and serum iron were obviously different in DFU.
Figure 4
Figure 4
The heatmap shows the correlations between the severity and multiple metabolic parameters in patients with DFU. The gradient in red represents the degree of positive correlation, while the gradient in blue represents the degree of negative correlation, as shown by the color bar on the left side of the map. The correlational analyses indicated that CTA severity were positively correlated with UA, TG, while inversely with serum albumin, ALT, DBil, TBil, Hb. The level of serum iron were correlated with albumin, globin, ALT, SBil, TBil, TG, LDL, sdLDL, APOA1, FT3, FT4, TT3. We also found that FT3 is associated with age, FPG, albumin, globulin, SBil, TBil, iron, SCr, BUN, UA, eGFR, TC, HDL, LDL, sdLDL, APOA1, PCT.
Figure 5
Figure 5
(A) The presentation of bubble figure depicts the relationship between critical factors including eGFR, APOA1, HOMA-β and the change in FT3 levels. We found that as with the increase in eGFR, the FT3 level is improved as the APOA1 elevation, accompanied by the increase in HOMA-β. (B) The presentation of bubble figure depicts the relationship between critical factors including eGFR, APOA1, SBIL and the change in FT3 levels. We found that as with the increase in eGFR, the FT3 level is improved as the APOA1 elevation, accompanied by the increase in substituted SBil.
Figure 6
Figure 6
Multiple local and systemic factors affect the progression of DFU. The blank arrows represent permanent acknowledged causes, while the black arrows indicate systemic factors that could be rectified in whole or in part. It was uncertain whether abnormal thyroid function and bilirubin imbalance should be treated.
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Grants and funding

This work was supported by the Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118), Talents Training Program of Shanghai Pudong Hospital (YQ202101), the Project of Key Medical Discipline of Pudong Hospital of Fudan University (Zdxk2020-11), Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdzk2020-24), Special Department Fund of the Pudong New Area Health Planning Commission (PWZzk2017-03), Outstanding Leaders Training Program of Pudong Health Bureau of Shanghai (PWR12014-06), Pudong New Area Clinical Plateau Discipline Project (PWYgy-2021-03), the Natural Science Foundation of China (21675034), National Natural Science Foundation of China (81370932), and Shanghai Natural Science Foundation (19ZR1447500), the Project of Key Medical Specialty of Pudong Hospital of Fudan University (No Tszb2023-14), Pudong New Area Clinical Characteristic Discipline Project (PWYts2021-01), Wenzhou Medical University Education Grant (JG2021197).