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Epidemiologia del piede diabetico

Ogni 30 secondi, uno degli arti inferiori o una parte di uno degli arti inferiori perso
in qualche parte del mondo come conseguenza del diabete.
Fino al 70% di tutte le amputazioni degli arti inferiori sono eseguite su persone con
diabete.
Fino al 70% delle persone che subiscono una minore amputazione allarto muoiono
entro 5 anni dallamputazione.
RAZIONALE DEL PROBLEMA:
IL PUNTO DI VISTA DEL DIABETOLOGO

Fino al 85% di tutte le amputazioni sono precedute da un ulcera.

Ogni anno, circa 4 milioni di persone sviluppano una nuova ulcera al piede.

GIULIO MARIANI
U.O. DIABETOLOGIA OSPEDALE SAN CARLO BORROMEO
RESPONSABILE PER LA LOMBARDIA DEL GRUPPO INTERASSOCIATIVO AMD SID PIEDE DIABETICO

History of the team approach to amputation

prevention: Pioneers and milestones
The partnership between the diabetologist, vascular surgeon, and podiatrist can be seen
as a natural marriage that complements the skills and knowledge of each partner and
results in more successful limb salvage and functional outcomes.
History has demonstrated that comprehensive multidisciplinary foot care programs
improve the quality of care and can reduce amputation rates by 36% to 86%.
Technology transfer from leprosy to diabetes has helped us to understand the role of
neuropathy in the pathogenesis of diabetic foot ulcers.
The pathophysiology of gangrene in the diabetic foot is complex, influenced by the
interaction of arterial insufficiency, neuropathy, ulceration, and infection.

Nei paesi sviluppati, fino al 4% delle persone con diabete hanno unulcera al piede,
con una spesa pari al 12-15% delle risorse sanitarie per il diabete. In paesi in via di
sviluppo, gli ultimi dati sono maggiori del 40%.

History of the team approach to amputation

prevention: Pioneers and milestones

The rise of multidisciplinary diabetic foot clinics in Europe.

Enthused by the St. Vincent declaration, the team approach to diabetic foot care
developed steadily in the 1990s. A number of major centers developed in Italy.
The unique nature of these centers was that they were directed by
endocrinologists who performed emergent and elective foot surgery. This new
specialty of surgically trained diabetologists evolved through the efforts of a
talented and dedicated group of physicians, among them Alberto Piaggesi, Luca
Dalla Paola, Carlo Caravaggi, Ezio Faglia, and Luigi Uccioli.

Development of distal revascularization techniques to restore pulsatile blood flow to the

foot has been a major advancement in limb salvage.
J Vasc Surg 2010;52:3S-16S

J Vasc Surg 2010;52:3S-16S

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I MITI DI ALLORA

Goldenberg: Nonatheromatous peripheral vascular

disease of the lower extremity in diabetes mellitus.
Diabetes 1959;8:261-273.

(the 1959 Micro-angiopathyc Theory)

Le lesioni del piede nei diabetici
sono dovute alla
microangiopatia
La rivascolarizzazione, soprattutto distale, nei diabetici
inutile perch manca il
run-off

For (too) many years, correction of

ischemia has been hampered by the
belief that there is an untreatable
microvascular occlusion

LoGerfo, NEJM 1984;311:16151619.

(the 1984

Macro-angiopathyc Evidence !)

When modern techniques of arterial reconstruction

are used, long-term salvage rates are nearly identical
to those in nondiabetics.
The term small-vessel disease
inasmuch as it suggests occlusive lesions,
is misleading and should not be used
to describe vascular disease
in the diabetic patients

LoGerfo, Cofman: N Engl J Med 1984

221 consecutive ischemic ulcerated DF

Antegrade femoral approach
85% Feasibility
Leg arteries recanalization included in 94%
5.2% major amputations

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There are Common Pathways in Diabetes

Complications
Peripheral & Autonomic Neuropathy
Gluco
se

Hexosamine
Pathway

AGE Formation
Cellular
Dysfunction

Oxidative
Stress

ROS

ROS

Vascular
Damage

Cell
Damage

Nephropathy
Retinopathy

Different complications (eye, kidney, nerve, blood vessels) arise from

limited number of triggers perturbing a limited number of metabolic
10
(Brownlee, 2001)
pathway(s)

Biochemistry and molecular cell biology of diabetic

complications
Michael Brownlee

NATURE | VOL 414 | 13 DECEMBER 2001

Understanding the Implications of Diabetes on the

Vascular System

VASC ENDOVASCULAR SURG 2011 45: 481

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Circ Res. 2007;100:967-978

Understanding the Implications of Diabetes on the

Vascular System

VASC ENDOVASCULAR SURG 2011 45: 481

Arterioscler Thromb Vasc Biol. 2005;25:932-943

Diabetic vascular disease effects and symptoms

Circulation Research August 31, 2007

International Journal of Vascular Medicine Volume 2012, Article ID 918267

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Metabolic memory: a vascular perspective

Thomas W Jax

Metabolic memory: a vascular perspective

Cardiovascular Diabetology 2010, 9:51

Thomas W Jax

Cardiovascular Diabetology 2010, 9:51

Intervenire presto e bene: UKPDS follow up 10 anni

Metformina

Proporzione con eventi

Proporzione con eventi
Proporzione con eventi

Proporzione con eventi

Proporzione con eventi

Proporzione con eventi

Insulinasulfonilurea

Proporzione con eventi

Proporzione con eventi

Sulfonilurea- Insulina
Terapia
convenzionale

IRL B. HIRSCH

Terapia
convenzionale

Ogni evento legato al diabete

Metformina

Infarto miocardico

Malattia microvascolare

Morte per ogni causa

Anni dalla randomizzazione

Holman R et al., N Engl J Med 2008;10.1056

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Diabetico senza complicanze o con lunga datazione di

malattia in compenso accettabile

HbA1c

Glicemia media (con

variabilit contenuta)

< 7%

< 155 mg%

Diabetico con complicanze o scompenso metabolico

inveterato

HbA1c

Glicemia media (con

variabilit contenuta)

Tra 7% e 8%

Tra 155 e 185 mg%

La Medicina centrata sulla persona

El Camino de la Muerte,
Ande, Bolivia

Grazie per lattenzione

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Diabetologia (2012) 55:15771596

Natural History of Type 2 Diabetes

Obesity

IFG

Diabetes Uncontrolled Hyperglycemia

350

Postmeal
glucose

Glucose
(mg/dL)

300
250

Fasting
glucose

200
150
100

Relative
Function (%)

50
250
200

Insulin resistance

150
100

Insulin level

50

-cell failure

0
-10

-5

10

15

20

25

30

Years of Diabetes
IFG=impaired fasting glucose.
Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.

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Insulin Resistance, Hyperglycemia, and Atherosclerosis

Cell Metabolism 14, November 2, 2011

Insulin Resistance, Hyperglycemia, and Atherosclerosis

Cell Metabolism 14, November 2, 2011

Insulin Resistance, Hyperglycemia, and Atherosclerosis

Cell Metabolism 14, November 2, 2011

26/09/2012

Hyperglycemic effects on the blood vessel

Inflammation and Atherosclerosis

Peter Libby; Paul M. Ridker; Attilio Maseri

International Journal of Vascular Medicine Volume 2012, Article ID 918267

Circulation. 2002;105:1135-1143

Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis

The Good, the Bad, and the Ugly

Circ Res. 2002;90:251-262

10

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With That In Mind, How Do We

Do?

Organized Chaos

Eff ects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin
for about 5 years in 20 536 high-risk individuals: a randomised controlled trial

J Clin Endocrinol Metab, February 2009, 94(2):410415

The Lancet November 23, 2011 DOI:10.1016/S0140-6736(11)61125-2

11

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The Mitochondrion
A Trojan Horse That Kicks Off Inflammation?

n engl j med june 3, 2010 362;22

Biochemistry and molecular cell biology of diabetic complications

Michael Brownlee

NATURE | VOL 414 | 13 DECEMBER 2001

12

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LA GLICEMIA MEDIA NON BASTA

Glycemic variability may be an

important mechanism increasing
oxidative stress and vascular
complications

So how do we best measure glycemic

variability in our patients with
diabetes?

Urinary 8-SO-PGF2 alpha Excretion Rates

(pg/mg creatinine)

Correlation Between Urinary 8-isoPGF2 alpha and MAGE in T2DM

1200
1000
800

R=0.86, p<0.0001

600
400
200

JAMA 295:1688-97,
2006

0
0
160

20

40

60

80

100

120

140

MAGE (mg glucose/dL)

13

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Hypoglycemia is a well-recognized side effect of glucoselowering therapies in patients

with diabetes mellitus.
The incidence of mild self-reported hypoglycemic episodes in patients with type 1
diabetes mellitus is approximately 30 episodes per patient per year, whereas the
incidence of severe hypoglycemic episodes (ie, those that require third-party
assistance) may be as high as 3.2 episodes per patient per year.
Hypoglycemic episodes occur much less frequently in patients with type 2 diabetes
mellitus, in whom the incidence of mild and severe hypoglycemic episodes is 2 to 10
per patient per year and 0.1 to 0.7 per patient per year,respectively.

Effetti cardiovascolari dellipoglicemia

Attivazione sistema nervoso simpatico
Aumento della noradrenalina circolante

Aumento della Pressione Sistolica

Diminuzione della Pressione Diastolica
Aumento della frequenza cardiaca
In critically ill patients, intensive glucose control leads to moderate and severe
hypoglycemia, both of which are associated with an increased risk of death. The
association exhibits a doseresponse relationship and is strongest for death
from distributive shock. However, these data cannot prove a causal relationship.

Aumento delloutput cardiaco

Aumento delle richieste di ossigeno miocardico

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