Diabetic foot syndrome: Immune-inflammatory features as possible cardiovascular markers in diabetes

Table 1 Prevalence of previous cardiovascular events in patients with and without diabetic foot

	Pts with diabetic foot (n = 102) <	Pts without diabetic foot (n = 123)	P
CAD (%)	33 (32.3)	24 (19.5)	0.0043
TIA (%)	15 (14.7)	9 (7.3)	< 0.0001
Stroke (%)	18 (17.6)	11 (8.9)	< 0.05
Stroke toast subtypes
LAAS	6 (33.3)	5 (45.4)
Lacunar	12 (66.6)	6 (54.5)
CEI	0	0
Diabetic retinopathy (%)	55 (53.9)	47 (38.2)	< 0.0001
Renal failure (%)	6 (5.8)	7 (5.6)	NS

Modified from Pinto et al[19]. CAD: Coronary artery disease; TIA: Transient ischemic attack; LAAS: Large artery atherosclerotic stroke; CEI: Cardioembolic.

Table 2 Cox regression analysis of demographic and clinical variables associated with cardiovascular morbidity n (%)

	Pts with diabeticfoot(n = 102)	Pts without diabetic foot(n = 123)	P
CAD	12 (11.7)	7 (5.6)	< 0.005
Angina	4 (3.9)	3 (2.4)	< 0.005
Myocardialinfarction	8 (7.8)	4 (3.5)	< 0.001
TIA	6 (5.8)	4 (3.2)	< 0.0001
Stroke	7 (6.8)	5 (4.0)	< 0.005
Renal failure	4 (3.9)	5 (4)	NS
Deaths	14 (13.7)	10 (8.1)	< 0.005
Cardiovascular cause	13 (12.7)	9 (7.3)
AMI	(3.9)	1 (0.81)	NS
Stroke	3 (2.9)	2 (1.6)
CHF	3 (2.9)	3 (2.4)
Other vascular cause	3 (2.9)	3 (2.4)
Other cause	1 (0.9)	1 (0.81)

From Pinto et al[19]. CAD: Coronary artery disease; TIA: Transient ischemic attack; AMI: Acute myocardial infarction; CHF: Congestive heart failure.

Table 3 Previous cerebro-vascular events in patients with and without diabetic foot

	Diabetic foot(n = 102)	No diabetic foot (n = 123)	P
TIA	15 (14.7)	9 (7.3)	< 0.0001
Ischemic stroke	18 (17.6)	11.8 (8.9)	< 0.0001
Stroke toast subtype
LAAS	6 (33.3)	5 (45.4)	< 0005
LAC	12 (66.6)	6 (54.5)	< 0.005
CEI	0	0

From Pinto et al[20]. TIA: Transient ischemic attack; LAAS: Large artery atherosclerotic stroke; LAC: Lacunar stroke; CEI: Cardioembolic.

Table 4 Incidence of stroke at follow-up in subjects with and without diabetic foot

	Diabetic foot(n = 102)	No diabetic foot(n = 123)	P
TIA	6 (5.8)	4 (3.2)	< 0.0001
Ischemicstroke	7 (6.8)	5 (4.0)	< 0.005
LAAS	4	3	< 0.005
LAC	3	2	< 0.005
CEI	0	0	NS

From Pinto et al[20]. TIA: Transient ischemic attack; LAAS: Large artery atherosclerotic stroke; LAC: Lacunar stroke; CEI: Cardioembolic.

Table 5 General and demographic variables in cases and controls n (%)

	Pts with diabeticfoot	Pts without diabetic foot	P
n	34	37	0.75
Age	66.7 ± 8.5	66.9 ± 7.9	0.027
Sex male	16 (47.1)	15 (41.7)	0.41
Diabetes duration
< 10 yr	7 (20.6)	21 (58.3)	0.027
= 10 yr	8 (23.5)	11 (30.6)	0.045
= 20 yr	19 (55.9)	4 (11.1)	< 0.001
Treatment
Diet	4 (11.8 )	3 ( 8.3)	0.65
Oral antidiabetics	3 (8.8 )	10 (27.8)	< 0.001
Mixed	6 (17.5)	13 (36.1)	< 0.001
Insulin	21 (61.8 )	10 (27.8)	< 0.001
Smoking	7 (20.6)	9 (25)	0.71
Hypertension	20 (58.8)	25 (69.4)	0.041
Dyslipidaemia	14 (41.2)	16 (44.4)	0.35
Obesity	19 (55.9)	13 (36.1)	0.021
Chronic renal failure	15 (44.1)	13 (36.1)	0.064
Mycroalbuminuria	22 (64.7)	6 (14.7)	< 0.001
Retinopathty	19 (55.9)	36 (100)	< 0.001
PAD	10 (29.41)	9 (25)	0.54
CAD	17 ( 50)	7 (19.4)	< 0.001
TIA/Stroke	14 (41.17)	6 (16.66)	0.021
Other district atherosclerosis	28 (82.35	21 (58.33)	< 0.001
Artropathy	11 (32.4%)	2 (5.6)	< 0.001
Neuropathy	25 (73.52)	14 (38.88)	< 0.001
Diabeticfootgrade
Grade 0	1 (2.9)
Grade 1	6 (17.6)
Grade 2	8 (23.5)
Grade 3	10 (29.4)
Grade4	4 (11.8)
Grade 5	1 (2.9)
Grade 6	4 (11.8)

Data are expressed as median and interquartile (lower and upper quartile). Modified from Tuttolomondo et al[21]. PAD: Peripheral artery disease; CAD: Coronary artery disease.

Table 6 Laboratory variables in cases and controls

	Diabetic foot patients	Diabetics without foot complications	P
HbA1c	8 (7.28-9.40)	6.85 (6.10-8.00)	0.018
CRP	4 (2.25-5.15 )	2.25 (1.90-3.08)	0.041
Total cholesterol (mg/dL)	215.50 (166.50-243.00)	204.00 (185.50-210.00)	0.054
LDL cholesterol (mg/dL)	121.70 (98.75-148.75)	104.50 (78.00-123.00)	0.032
Tryglicerids (mg/dL)	160.50 (119.50-209.25)	180.50 (144.50-199.00)	0.012
Globuli bianchi	12.675 (10775.00-14140.00 )	10.700 (8850.00-12027.50)	0.032
Adiponectin (μg/mL)	7.1450 (4.47-12.17)	8.480 (5.15-12.87)	0.022
Resistin (ng/mL)	5.160 (2.96-6.29)	3.290 (2.37-6.5)	0.021
IL-6 (pg/mL)	3.21 (1.23-5.34)	2.13 (1.24-3.97 )	0.033

Demographic and anamnestic data are expressed as n° (percentage). Modified from Tuttolomondo et al[21]. HbA1c: Hemoglobin A1c; CRP: C-reactive protein; IL-6: Interleukin-6.

Table 7 Correlations of interleukin-1β, adiponectinresistin with clinical and laboratory variables in subjects with diabetic foot

Variable	Adipenectin		Resistin		IL-6
	R	P values	R	P values
Diabetes duration	0.36 (s)	< 0.001 (s)	0.09	0.37
Smoking	0.35 (s)	< 0.001 (s)	0.10	0.22
Hypertension	0.27 (s)	< 0.05 (s)	0.12	0.35
Dyslipidaemia	0.42 (s)	< 0.001 (s)	0.14	0.15
Obesity	0.13	0.42	0.12	0.22
Chronicrenalfailure	0.11	0.56	0.12	0.35
Mycroalbuminuria	0.08	0.37	0.08	0.37
Retinopathty	0.10	0. 7	0.10	0. 7
AOPC	0.11	0.81	0.10	0.77
CHD	0.46	< 0.001 (s)	0.38 (s)	< 0.0001 (s)
TIA/stroke	0.12	0.42	0.13	0.32
Other district atherosclerosis	0.15 (s)	0.42 (s)	0.14 (s)	0.36 (s)

Coefficients (R) and P values are calculated by the Pearson correlation mode. Modified from Tuttolomondo et al[21]. s: Significative; CRP: C-reactive protein; TNF-α: Tumor necrosis factor-α; IL-1β: Interleukin-1β; IL-6: Interleukin-6; IL-10: Interleukin-10; ICAM-1: Intercellular adhesion molecule-1; V-CAM-1: Vascular cell adhesion molecule-1; vWF: Von willebrand factor; TPA: Tissue plasminogen activator; PAI-1: Plasminogen activator inhibitor-1.

Table 8 Diabetic foot infection classification schemes: Infectious Diseases Society of America Infectious Diseases

Clinical description	Infectious Diseases Society of America
Wound without purulence or any manifestations of inflammation	Uninfected
≥ 2 Manifestations of inflammation (purulence or erythema, pain, tenderness, warmth, or induration); anyc ellulitis or erythemaextends 52 cm around ulcer, and infection is limited to skin or superficial subcutaneous stissues; no localcomplications or systemic illness	Mild
Infection in a patientwho is systemicallywell and metabolicall ystable buthas 2 cm; lymphangitis; spread beneath fascia; deeptissue abscess; gangrene; muscle, tendon, joint, or bone involvement	Moderate
Infection in a patient with systemic toxicity or metabolic instability (e.g., fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, hyperglycemia, or azotemia)	Severe

Adapted from Lavery et al[67].