Biochemical assays of the 75 patients admitted in the Diabetic Foot Unit
Characteristics
Mean value ± standard deviation
HbA1c (mmol/mol)
67.9 ± 22.3
Blood Glucose (mg/dL)
196.9 ± 105.9
White blood cells (109/L)
10.8 ± 4.9
Neutrophils white-blood cells (109/L)
9.3 ± 8.9
Hb (g/dL)
11.5 ± 1.8
Sideremia (μg/dL)
38.1 ± 22.1
Transferrin (mg/dL)
189.7 ± 52.1
Transferrin saturation (%)
15.2 ± 10.0
Ferritin (ng/mL)
301.6 ± 479.9
CRP (mg/dL)
9.4 ± 8.6
Procalcitonin (ng/mL)
2.7 ± 8.4
Blood Urea (mg/dL)
60.3 ± 40.6
Creatinin (mg/dL)
1.4 ± 0.9
Total cholesterol (mg/dL)
144.4 ± 55.7
HDL (mg/dL)
32.4 ± 10.7
LDL (mg/dL)
89.5 ± 45.1
TG (mg/dL)
146.6 ± 56.2
Uric acid (mg/dL)
5.6 ± 2.2
Total Bilirubinemia (mg/dL)
0.7 ± 0.4
Direct Bilirubinemia (mg/dL)
0.2 ± 0.1
AST (U/L)
21.0 ± 15.3
ALT (U/L)
20.3 ± 24.2
GGT (U/L)
63.9 ± 74.9
ALK-P (U/L)
113.6 ± 56.7
B12 vitamin (ng/L)
345.9 ± 228.7
D-vitamin (ng/mL)
16.4 ± 17.5
Folic acid (ng/mL)
9.1 ± 9.7
BNP (ng/L)
728.9 ± 1083.7
Albumin (g/dL)
3.1 ± 0.5
Declarations
Author contributions
MM and CC conceived and designed this study. MM, AC, PA and FG designed the statistical analysis and analyzed the data. MM, FG, CC, AC and LR interpreted the results. MM wrote the first draft of manuscript. MM, FG, CC and LR contributed to the writing of the manuscript. All authors have read and confirmed the data in the manuscript and they can take the responsibility for the integrity of the data and the accuracy of the data analysis, read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflict of interest.
Ethical approval
The study was approved by the local Ethics Committee (reference number 855/2019).
Consent to participate
Informed consent to participate in the study was obtained from all participants.
Consent of publication
Not applicable.
Availability of data and materials
The raw data supporting the conclusions of this manuscript will be made available by the authors to any qualified researcher. The datasets generated and/or analyzed during the current study are not publicly available as they are held by AOU Modena Health Organization as an integral part of their statutory activity. Any request for access should be directly submitted to Principal Investigator/Author.
Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y.Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis. Ann Med.2017;49:106–16. [DOI] [PubMed]
Navarro-Flores E, Cauli O.Quality of life in individuals with diabetic foot syndrome. Endocr Metab Immune Disord Drug Targets.2020;20:1365–72. [DOI] [PubMed]
Schaper NC, van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA, et al. Practical guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update). Diabetes Metab Res Rev.2020; 36Suppl 1:e3266. [DOI] [PubMed]
Hingorani A, LaMuraglia GM, Henke P, Meissner MH, Loretz L, Zinszer KM, et al. The management of diabetic foot: a clinical practice guidelines by the Society for Vascular Surgery in 88 collaboration with the American Podiatric Medical Association and the Society for Vascular Medicine. J Vasc Surg.2016;63:3S–21S. [DOI] [PubMed]
Prompers L, Schaper N, Apelqvist J, Edmonds M, Jude E, Mauricio D, et al.; Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia.2008;51:747–55. [DOI] [PubMed] [PMC]
Prompers L, Huijberts M, Apelqvist J, Jude E, Piaggesi A, Bakker K, et al. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study. Diabetologia.2007;50:18–25. [DOI] [PubMed]
Mauvais-Jarvis F, Merz NB, Barnes PJ, Brinton RD, Carrero J, DeMeo DL, et al. Sex and gender: modifiers of health, disease and medicine. Lancet.2020;396:565–82. [DOI] [PubMed] [PMC]
Targher G, Lonardo A, Byrne CD.Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Nat Rev Endocrinol.2017;14:99–114. [DOI] [PubMed]
Shatnawi NJ, Al-Zoubi NA, Hawamdeh HM, Khader YS, Garaibeh K, Heis HA.Predictors of major lower limb amputation in type 2 diabetic patients referred for hospital care with diabetic foot syndrome. Diabetes Metab Syndr Obes.2018;11:313–9. [DOI] [PubMed] [PMC]
Bohn B, Grunerbel A, Altmeier M, Giesche C, Pfeifer M, Wagner C, et al. Diabetic foot syndrome in patients with diabetes. A multicenter German/Austrian DPV analysis on 33,870 patients. Diabetes Metab Res Rev.2018;34:e3020. [DOI] [PubMed]
Seghieri G, Policardo L, Gualdani E, Anichini R, Francesconi P.Gender difference in the risk of cardiovascular events or mortality of patients with diabetic foot syndrome. Acta Diabetol.2019;56:561–7. [DOI] [PubMed]
Kerr M, Barron E, Chadwick P, Evans T, Kong WM, Rayman G, et al. The cost of diabetic foot ulcer and amputations to the National Health Service in England. Diabet Med.2019;36:995–1002. [DOI] [PubMed]
Bus SA, van Netten JJ, Monteiro-Soares M, Lipsky BA, Schaper NC.Diabetic foot disease: “the times they are a changing”. Diabetes Metab Res Rev.2020;36:e3249. [DOI] [PubMed] [PMC]
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). Clinical practice guidelines for the management of non-alcoholic fatty liver disease. Obes Facts.2016;9:65–90. [DOI] [PubMed] [PMC]
Bielby A.Understanding foot ulceration in patients with diabetes. Nurs Stand.2006;20:57–67.
Pisanti P.Piano Strategico Nazionale sulla malattia diabetica. (Italian) G It Diabetol Metab.2014;34:1–4.
Becchi MA.Il caregiver del paziente complesso ed il suo addestramento. Manuale di educazione terapeutica ad uso degli operatori sanitari e socio-assistenziali. Italian ed. Roma: Panorama della Sanità; 2011.
van Acker K, Leger P, Hartemann A, Chawla A, Siddiqui MK.Burden of diabetic foot disorders, guidelines for management and disparities in implementation in Europe: a systematic literature review. Diabetes Metab Res Rev.2014;30:635–45. [DOI] [PubMed]
Ballestri S, Romagnoli D, Nascimbeni F, Francica G, Lonardo A.Role of ultrasound in the diagnosis and treatment of nonalcoholic fatty liver disease and its complications. Expert Rev Gastroenterol Hepatol.2015;9:603–27. [DOI] [PubMed]
Petta S, Valenti L, Bugianesi E, Targher G, Bellentani S, Bonino F; Special Interest Group on Personalised Hepatology of the Italian Association for the Study of the Liver (AISF), Special Interest Group on Personalised Hepatology of Italian Association for Study of Liver AISF. A “system medicine” approach to the study of nonalcoholic fatty liver disease. Dig Liv Dis.2016;48:333–42. [DOI]
Sayiner ZA, Can FI, Akarsu E.Patients’ clinical charecteristics and predictors for diabetic foot amputation. Prim Care Diabetes.2019;13:247–51. [DOI] [PubMed]
Regensteiner JG, Golden S, Huebschmann AG, Barrett-Connor E, Chang AY, Chyun D, et al. Sex differences in the cardiovascular consequences of diabetes mellitus: a scientific statement from the american heart association. Circulation.2015;132:2424–47. [DOI] [PubMed]
Rossaneis MA, Haddad MCLF, Mathias TAF, Marcon SS.Differences in foot self-care and lifestyle between men and women with diabetes mellitus. Rev Lat Am Enfermagem.2016;24:e2761. [DOI] [PubMed] [PMC]
Pollak AW.PAD in women: the ischemic continuum. Curr Atheroscler Rep.2015;17:513. [DOI] [PubMed]
Sigvant B, Wiberg-Hedman K, Bergqvist D, Rolandsson O, Andersson B, Persson E, et al. A population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex difference. J Vasc Surg.2007;45:1185–91. [DOI] [PubMed]
Katsiki N, Giannoukas AD, Athyros VG, Mikhailidis DP.Lipid-lowering treatment in peripheral artery disease. Curr Opinion Pharmacol.2018;39:19–26. [DOI]
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J.2020;41:111–88. [DOI] [PubMed]
Meloni M, Izzo V, Giurato L, Lázaro-Martínez JL, Uccioli L.Prevalence, clinical aspects and outcomes in a large cohort of persons with diabetic foot disease: comparison between neuropathic and ischemic ulcers. J Clin Med.2020;9:1780. [DOI]
Aiello A, Anichini R, Brocco E, Caravaggi C, Chiavetta A, Cioni R, et al. Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE). Nutr Metab Cardiovasc Dis.2014;24:355–69. [DOI] [PubMed]
American Diabetes Association. Cardiovascular disease and risk management: standards of medical care in diabetes. Diabetes Care.2019;42:S103–23. [DOI] [PubMed]
Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patelet A, et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA.2015;313:603–15. [DOI] [PubMed]
Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet.2016;387:435–43. [DOI] [PubMed]
Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J.2020;41:255–323. [DOI] [PubMed]
Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 Update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2020:43:487–93. [DOI] [PubMed] [PMC]
Callaghan BC, Little AA, Feldman EL, Hughes RAC.Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev.2012;6:CD007543. [DOI]
Gregersen S.Good glycaemic control can prevent diabetic peripheral neuropathy. Ugeskr Laeger.2013;175:2022–5. [PubMed]
ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med.2012;367:319–28. [DOI] [PubMed]
Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med.2017;377:723–32. [DOI] [PubMed] [PMC]
Vatankhah N, Jahangiri Y, Landry GJ, Moneta GL, Azarbal AF.Effect of systemic insulin treatment on diabetic wound healing. Wound Repair Regen.2017;25:288–91. [DOI] [PubMed] [PMC]
Grebe A, Hoss F, Latz E.NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ Res.2018;122:1722–40. [DOI] [PubMed]
Garofolo L, Ferreira SRG, Miranda Júnior F.Association between peripheral arterial disease and C-reactive protein in the japanese-brazilian population. Rev Colégio Bras Cir.2014;41:168–75. [DOI]
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med.2008;359:2195–207. [DOI] [PubMed]
Lavery LA, Ahn J, Ryan EC, Bhavan K, Oz OK, La Fontaine J, et al. What are the optimal cutoff values for ESR and CRP to diagnose osteomyelitis in patients with diabetes-related foot infections?Clin Orthop Relat Res. 2019;477:1594–602. [DOI] [PubMed] [PMC]
Hagstrom H, Nasr P, Ekstedt M, Hammar U, Stål P, Askling J, et al. Cardiovascular risk factors in non-alcoholic fatty liver disease. Liver Int.2019;39:197–204. [DOI] [PubMed]
Mantovani A, Petracca G, Beatrice G, Tilg H, Byrne CD, Targher G, et al. Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501.022 adult individuals. Gut.2020;[Epub ahead of print].
Lonardo A, Lugari S, Ballestri S, Nascimbeni F, Baldelli E, Maurantonio M, et al. A round trip from nonalcoholic fatty liver disease to diabetes: molecular targets to the rescue? Acta Diabetol. 2018;56:385–96. [DOI]
Zou Y, Li X, Wang C, Wang J, Wang F, Ma L, et al. Association between non-alcoholic fatty liver disease and peripheral artery disease in patients with type 2 diabetes. Intern Med J.2017;47:1147–53. [DOI] [PubMed]
Italian Association for the Study of the Liver (AISF). AISF position paper on nonalcoholic fatty liver disease (NAFLD): updates and future directions. Dig Liver Dis.2017;49:471–83. [DOI] [PubMed]
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB.Atherosclerotic cardiovascular disease and heart failure in type 2 diabetes — mechanism, management and clinical considerations. Circulation.2016;133:2459–02. [DOI] [PubMed] [PMC]
Ridker PM, Hennekens CH, Buring JE, Rifai N.C-reactive protein and other markers of inflammation in the prediction of cardiovascular events in women. N Engl J Med.2000;342:836–43. [DOI] [PubMed]
Maurantonio M, Ballestri S, Odoardi MS, Lonardo A, Loria P.Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty liver disease: a novel approach to reduce cardiovascular risk?Archives Med Res. 2011;42:337–53. [DOI]