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26/09/2012
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GIULIO MARIANI U.O. DIABETOLOGIA OSPEDALE SAN CARLO BORROMEO
RESPONSABILE PER LA LOMBARDIA DEL GRUPPO INTERASSOCIATIVO AMD SID PIEDE DIABETICO
RAZIONALE DEL PROBLEMA:
IL PUNTO DI VISTA DEL DIABETOLOGO
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. 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. 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%.
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. Development of distal revascularization techniques to restore pulsatile blood flow to the foot has been a major advancement in limb salvage.
History of the team approach to amputation prevention: Pioneers and milestones
J Vasc Surg 2010;52:3S-16S
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.
J Vasc Surg 2010;52:3S-16S
History of the team approach to amputation prevention: Pioneers and milestones
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I MITI DI ALLORA
Le lesioni del piede nei diabetici
sono dovute alla
microangiopatia
La rivascolarizzazione, soprattutto distale, nei diabetici
inutile perch manca il
run-off
Goldenberg: Nonatheromatous peripheral vascular disease of the lower extremity in diabetes mellitus.
Diabetes 1959;8:261-273.
(the 1959 Micro-angiopathyc Theory)
For (too) many years, correction of ischemia has been hampered by the belief that there is an untreatable microvascular occlusion
LoGerfo, NEJM 1984;311:1615-1619.
(the 1984 Macro-angiopathyc Evidence !)
LoGerfo, Cofman: N Engl J Med 1984
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 221 consecutive ischemic ulcerated DF Antegrade femoral approach 85% Feasibility Leg arteries recanalization included in 94% 5.2% major amputations
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10
There are Common Pathways in Diabetes Complications
Oxidative
Stress
Cellular
Dysfunction
AGE Formation
Cell
Damage
Hexosamine
Pathway
ROS
ROS
Gluco
se
Peripheral & Autonomic Neuropathy
Nephropathy
Retinopathy
Vascular
Damage
Different complications (eye, kidney, nerve, blood vessels) arise from limited number of triggers perturbing a limited number of metabolic pathway(s) (Brownlee, 2001)
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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Understanding the Implications of Diabetes on the
Vascular System
VASC ENDOVASCULAR SURG 2011 45: 481
Circ Res. 2007;100:967-978
Arterioscler Thromb Vasc Biol. 2005;25:932-943
Circulation Research August 31, 2007
Diabetic vascular disease effects and symptoms
International Journal of Vascular Medicine Volume 2012, Article ID 918267
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Cardiovascular Diabetology 2010, 9:51
Metabolic memory: a vascular perspective Thomas W Jax
Metabolic memory: a vascular perspective Thomas W Jax
Cardiovascular Diabetology 2010, 9:51
Ogni evento legato al diabete
Infarto miocardico
Malattia microvascolare
Morte per ogni causa
Sulfonilurea- Insulina Metformina
Anni dalla randomizzazione
Insulina-sulfonilurea
Metformina
Terapia convenzionale
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Pro
porz
ione c
on e
venti
Terapia convenzionale
Holman R et al., N Engl J Med 2008;10.1056
Intervenire presto e bene: UKPDS follow up 10 anni IRL B. HIRSCH
http://it.wikipedia.org/wiki/File:Newton_Cannon.svg
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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
0
50
100
150
200
250
-10 -5 0 5 10 15 20 25 30
Years of Diabetes
Glu
co
se
(mg
/dL
) R
ela
tiv
e
Fu
nc
tio
n (
%)
Insulin resistance
Insulin level -cell failure
IFG=impaired fasting glucose.
50
100
150
200
250
300
350
Fasting
glucose
Postmeal
glucose
Adapted from International Diabetes Center (IDC), Minneapolis, Minnesota.
Obesity IFG Diabetes Uncontrolled Hyperglycemia
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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
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Hyperglycemic effects on the blood vessel
International Journal of Vascular Medicine Volume 2012, Article ID 918267
Inflammation and Atherosclerosis Peter Libby; Paul M. Ridker; Attilio Maseri
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
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With That In Mind, How Do We
Do?
Organized Chaos
J Clin Endocrinol Metab, February 2009, 94(2):410415
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
The Lancet November 23, 2011 DOI:10.1016/S0140-6736(11)61125-2
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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
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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?
Correlation Between Urinary 8-iso-
PGF2 alpha and MAGE in T2DM
1200
1000
800
600
400
200
0
0 20 40 60 80 100 120 140
160
Uri
nary
8-S
O-P
GF
2 a
lph
a E
xcre
tio
n R
ate
s
(pg
/mg
cre
ati
nin
e)
MAGE (mg glucose/dL)
R=0.86, p
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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.
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.
Effetti cardiovascolari dellipoglicemia
Attivazione sistema nervoso simpatico
Aumento della noradrenalina circolante
Aumento della Pressione Sistolica
Diminuzione della Pressione Diastolica
Aumento della frequenza cardiaca
Aumento delloutput cardiaco
Aumento delle richieste di ossigeno miocardico
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