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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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