Evaluation of CONUT Score and Serum Zinc Levels in Patients with Diabetic Foot Ulcers

Abstract

Background

Diabetic foot ulcer (DFU) is a severe complication of diabetes. Nutritional deficiencies, including poor nutritional status reflected by a high CONUT score and low serum zinc have been implicated in the severity and wound healing failure of DFU. However, the association between these factors and DFU remains unclear.

Methods

A retrospective cohort study was performed in 319 patients categorized into three groups: healthy controls (HC, n = 213), patients with diabetes without foot ulcer (DM, n = 67), and patients with diabetes with foot ulcer (DFU, n = 39). Demographic, clinical, nutritional, and biochemical data were collected, including age, sex, body mass index, the presence of chronic limb-threatening ischemia (CLTI), the presence of maintenance dialysis, CONUT score, hemoglobin A1c, hemoglobin (Hb), total protein (TP), and zinc levels. The severity of DFU was assessed using the PEDIS score, while wound healing failure was defined based on specific clinical criteria. Statistical analyses were conducted to identify factors associated with DFU severity and wound healing failure.

Results

DFU cases had significantly lower Hb, TP, and zinc levels and higher CONUT score compared to the HC and DM cases. Within the DFU group, high PEDIS score (>8) was associated with significantly higher CONUT score, lower TP levels, and the presence of CLTI. Patients with wound healing failure had significantly lower zinc and Hb levels and a higher prevalence of CLTI. Multivariable logistic regression identified CONUT score and the prevalence of CLTI as independent factors associated with DFU severity, while serum zinc levels and the prevalence of CLTI were independently associated with wound healing failure.

Conclusions

This study highlighted the critical role of poor nutritional status, as indicated by high CONUT score, and zinc deficiency in the severity and poor healing outcomes of DFU. These findings underscore the critical role of nutritional management in comprehensive treatment of DFU.

Keywords

diabetic foot ulcers CONUT score zinc PEDIS score wound healing

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References

Peng

Lavigne

. Editorial: Pathogenesis of diabetic foot ulcers. Front Pharmacol. 2023;14:1218201. doi: https://doi.org/10.3389/fphar.2023.1218201

Perez-Favila

Martinez-Fierro

Rodriguez-Lazalde

, et al. Current therapeutic strategies in diabetic foot ulcers. Medicina (Kaunas). 2019;55(11):714. doi: https://doi.org/10.3390/medicina55110714

Armstrong

Tan

Boulton

AJM

Bus

. Diabetic foot ulcers: A review. JAMA. 2023;330(1):62-75. doi: https://doi.org/10.1001/jama.2023.10578

Kavalukas

Barbul

. Nutrition and wound healing: An update. Plast Reconstr Surg. 2011;127(Suppl 1):38S-43S. doi: https://doi.org/10.1097/PRS.0b013e318201256c

Palmieri

Vadalà

Laurino

. Nutrition in wound healing: Investigation of the molecular mechanisms, a narrative review. J Wound Care. 2019;28(10):683-693. doi: https://doi.org/10.12968/jowc.2019.28.10.683

Ignacio de Ulíbarri

González-Madroño

de Villar

, et al. CONUT: A tool for controlling nutritional status. First validation in a hospital population. Nutr Hosp. 2005;20(1):38-45.

Mine

Sugihara

Fujita

, et al. Impact of controlling a nutritional Status score on wound healing in patients with chronic limb-threatening ischemia after endovascular treatment. Nutrients. 2021;13(11):3710. doi: https://doi.org/10.3390/nu13113710

Furuyama

Yamashita

Yoshiya

, et al. The controlling nutritional Status score is significantly associated with complete ulcer healing in patients with critical limb ischemia. Ann Vasc Surg. 2020;66:510-517. doi: https://doi.org/10.1016/j.avsg.2019.12.031

Yagi

Oshita

Okano

, et al. Controlling nutritional status score predicts postoperative complications after hip fracture surgery. BMC Geriatr. 2020;20(1):243. doi: https://doi.org/10.1186/s12877-020-01643-3

10.

Lin

Sermersheim

Lee

PHU

Steinberg

. Zinc in wound healing modulation. Nutrients. 2018;10(1):16. doi: https://doi.org/10.3390/nu10010016

11.

Zorrilla

Salido

López-Alonso

Silva

. Serum zinc as a prognostic tool for wound healing in hip hemiarthroplasty. Clin Orthop Relat Res. 2004;420:304-308. doi: https://doi.org/10.1097/00003086-200403000-00043

12.

Lim

Levy

Bray

. Dietary zinc alters early inflammatory responses during cutaneous wound healing in weanling CD-1 mice. J Nutr. 2004;134(4):811-816. doi: https://doi.org/10.1093/jn/134.4.811

13.

Lansdown

Mirastschijski

Stubbs

Scanlon

Agren

. Zinc in wound healing: Theoretical, experimental, and clinical aspects. Wound Repair Regen. 2007;15(1):2-16. doi: https://doi.org/10.1111/j.1524-475X.2006.00179.x

14.

Mineoka

Ishii

Hashimoto

, et al. Nutritional Status assessed with objective data assessment correlates with a high-risk foot in patients with type 2 diabetes. J Clin Med. 2022;11(5):1314. doi: https://doi.org/10.3390/jcm11051314

15.

Zhu

Wang

, et al. Risk factor analysis for diabetic foot ulcer-related amputation including controlling nutritional Status score and neutrophil-to-lymphocyte ratio. Int Wound J. 2023;20(10):4050-4060. doi: https://doi.org/10.1111/iwj.14296

16.

Monteiro-Soares

Hamilton

Russell

, et al. Guidelines on the classification of foot ulcers in people with diabetes (IWGDF 2023 update). Diabetes Metab Res Rev. 2024;40(3):e3648.

17.

Leese

Soto-Pedre

Schofield

. Independent observational analysis of ulcer outcomes for SINBAD and University of Texas ulcer scoring systems. Diabetes Care. 2021;44(2):326-331.

18.

Hicks

Canner

Mathioudakis

, et al. The society for vascular surgery wound, ischemia, and foot infection (WIfI) classification independently predicts wound healing in diabetic foot ulcers. J Vasc Surg. 2018;68(4):1096-1103.

19.

Kanda

. Investigation of the freely-available easy-to-use software “EZR” (easy R) for medical statistics. Bone Marrow Transplant. 2013;48(3):452-458.

20.

Stechmiller

. Understanding the role of nutrition and wound healing. Nutr Clin Pract. 2010;25(1):61-68.

21.

Sanz París

García

Gómez-Candela

Burgos

Martín

Matía

, Study VIDA group. Malnutrition prevalence in hospitalized elderly diabetic patients. Nutr Hosp. 2013;28(3):592-599.

22.

Zhang

Tang

Fang

Qian

Ning

. Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis. Exp Ther Med. 2013;5(1):215-222.

23.

Frassinetti

Bronzetti

Caltavuturo

Cini

Croce

. The role of zinc in life: A review. J Environ Pathol Toxicol Oncol. 2006;25(3):597-610.

24.

Myers

. Zinc transporters and zinc signaling: New insights into their role in type 2 diabetes. Int J Endocrinol. 2015;2015:167503.

25.

Rutter

Chabosseau

Bellomo

, et al.

Intracellular zinc in insulin secretion and action: A determinant of diabetes risk?

Proc Nutr Soc. 2016;75(1):61-72.

26.

Sun

van Dam

Willett

. Prospective study of zinc intake and risk of type 2 diabetes in women. Diabetes Care. 2009;32(4):629-634.

27.

Kubota

Matsuda

Yamamoto

Yoshii

. Association of Serum zinc level with severity of chronic kidney disease in diabetic patients: A cross-sectional study. BMC Nephrol. 2022;23(1):407.

28.

Weller

Foitzik

Paus

Syska

Maurer

. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 2006;20(13):2366-2368.

29.

Nishida

Hasegawa

Yamasaki

, et al. Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis. Sci Rep. 2019;9(1):10842.

30.

Nakamura

Sekiguchi

Ogawa

, et al. Zinc deficiency exacerbates pressure ulcers by increasing oxidative stress and ATP in the skin. J Dermatol Sci. 2019;95(2):62-69.

31.

. Cachexia - an intrinsic factor in wound healing. Int Wound J. 2010;7(2):107-113.

32.

Hanna

. Sarcopenia and critical illness: A deadly combination in the elderly. JPEN J Parenter Enteral Nutr. 2015;39(3):273-281.

33.

Makiguchi

Yamaguchi

Nakamura

, et al. Impact of skeletal muscle mass volume on surgical site infection in free flap reconstruction for oral cancer. Microsurgery. 2019;39(7):598-604.

34.

Nakamura

Makiguchi

Yamaguchi

Suzuki

Yokoo

. Impact of sarcopenia on postoperative surgical site infections in patients undergoing flap reconstruction for oral cancer. Int J Oral Maxillofac Surg. 2020;49(5):576-581.

35.

Nakamura

Makiguchi

Yamaguchi

Fujii

Shirabe

Yokoo

. Impact of skeletal muscle mass on complications following expander breast reconstruction. J Plast Reconstr Aesthet Surg. 2020;73(7):1285-1291.

36.

Apelqvist

Elgzyri

Larsson

Löndahl

Nyberg

Thörne

. Factors related to outcome of neuroischemic/ischemic foot ulcer in diabetic patients. J Vasc Surg. 2011;53(6):1582-1588.e2.

37.

Azuma

Koya

Uchida

Saito

Uchida

. Ulcer healing after peripheral intervention-can we predict it before revascularization? Circ J. 2014;78(8):1791-1800.

38.

Shiraki

Iida

Takahara

, et al. Predictors of delayed wound healing after endovascular therapy of isolated infrapopliteal lesions underlying critical limb ischemia in patients with high prevalence of diabetes mellitus and hemodialysis. Eur J Vasc Endovasc Surg. 2015;49(5):565-573.

39.

Inoue

Onohara

Mikasa

Furuyama

. Early-phase wound healing and long-term outcomes of a selective endovascular-first approach for treating rutherford 5 critical limb ischemia with infrainguinal lesions. Surg Today. 2016;46(11):1301-1309.