cours en anglais nov 2012

Type 2 Diabetes

Florence.travert@bch.aphp.fr

Basic knowledge about type 2 diabetes

Lessons from large scale trials

Diabetes complications

Training

1.The disease2.The treatment3.The prognosis

Basic knowledge Type 2 diabetes

THE DISEASE

Is type 2 diabetes another world ?

What for a diabetologist

KetoacidosisChronic complicationsMicrovascular

MI, sudden deathChronic complications

Macrovascular

« Death prevention! »

Increasing prevalence of type 2 diabetes

• Increasing ‘westernisation’

is leading to the rapid spread of type 2 diabetes, especially in developing countries

Prevalence of diabetesworldwide

125

130

135

140

145

150

155

1995 2000year

pop

ulat

ion

(mill

ion)

0

Type 2 diabetes is our today's’ challenge And it is complex to treat …

8

Diabetes: 2003 prevalence and projected increase by 2025

25.0M 59%

81.8M 91%

13.6M 98%

18.2M 97%

38.2M 16%

10.4M 88% World prevalence

2003: 189 million2025: 324 million 72% increase

1.1M 59%

Zimmet et al. Diab Med 2003;20:693–702

THE PROGNOSIS

PROGNOSIS

GeneticsHypertensionSmokingDiabetes

What for a diabetologist ?

Complications of type 2 diabetes

The story of a vascular disease ….

Complications of type 2 diabetes

What they suffer from?Incidence /prevalenceCheck up and detectionImpact on morbi-mortality

Complications of type 2 diabetes

What they suffer from?Incidence /prevalenceCheck up and detectionImpact on morbi-mortality

Suffering or not?• Patients do not suffer directly from

their hyperglycemia (high blood glucose level)

• But they suffer from some of the chronic or acute complications

Suffering or not?Acute hyperglycemia

• Ketoacidosis is due to a lack of insulin, it’s the apanage of type 1 dabetes,

• In type 2 polyuropolydipsy (cardinal syndrom) can be seen

• Glycosuria, weight loss, asthenia…)

Suffering or not?Acute hypoglycemia

never occurs in a normal subject

occurs only if the patient receives certain drug targeting the stimulation of insulin secretion

Suffering or not?Acute hypoglycemia

the first signs are an adrenergic reaction including: sweating, paleness tremor dizziness, fatigue. Neurological signs occur then as visual, hearing, reading or

writing troubles, elocution disorders, concentration and progressive loss of consciousness and finally coma

Complications• Patients do not suffer directly from

their hyperglycemia (high blood glucose level)

• But they suffer from some of the chronic or acute complications

Where are located these complicationseyes Rétinopathy, glaucoma,

cataractBlindness

Heart & Vessels CHDVascular cerebral attack

Periph arteriopathy Hypertension

CardiomyopathyCardiac failure

DeathMI

HemiplegiaAmputation

Kidney Renal failure Dialysistransplantation

Nerves peripheral neuropathy autonomic neuropathie

painVarious

consequences

others Infection, tees, footErectile dysfonction

Various consequences

Macro-angiopathy

Coronaryarteries

Carotidarteries

Cerebralarteries

Periperalarteries

Lowlimbs

Micro-angiopathy

eyes kidney nerves skin

DIABETES ……. today Mainly a vascular diseaseMainly a vascular disease

Macro angiopathyartery diameter > 200 µm.

•Lesions similar to non diabetics•earlier, more serious, more scattered

Atherosclerosis :Remodelling of the intima of big and medium size arteries (accumulation of lipids, complex CHD, blood components, fibrosis & calcium

Mediacalcosis :calcification of the média and of the external limit of the vessels

Atherosclérosis :

Mucle cells

Endothélium

platelets

Lipoprotéins

Monocyte

Intima Media Adventice

Erythrocytes

1) accumulation of LDL in intima 2) inc ome of monocytes and fibroblasts3) prolifération of mucular cells 4) Intensified by tissular and circulating (oxidative stress)

Consequences

•Coronary Heart disease•Hypertension •Cardiac failure•Diabetic myocardiopathy•Peripheral arteriopathy•Cerebrovascular attack

CoronaryHeart Disease

• 30% of ischemia are painless (silent)

• Non typical symptoms• When present (jaw,

stomach)

• Possible onset :• Sudden death, MI

“classical” acute proximal lesion

Diffuse distal disease of diabetes

Coronary angiogramsDr Archer Broughton, Cardiology, The Alfred

Coronary artery atherosclerosis

To detect silent myocardial infarction Perform systematic annual ECG

TransluminalAngioplasty

coronarography before / after stenting

CoronaryBypass

Venous bridges

ObstructedCoronaryarteries

Blood Hypertension

• Associated pathology or consequence

• Vascular stiffness is characteristic from diabetes

• more often and more serious

Blood pressure ObjectiveAverage 10 mmHg of SBP

risk decrease

UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes : UKPDS 38. BMJ 1998, 317: 703-13.

Myocardial infarction – 21 %

Stroke – 44 %Microangiopathy – 37 %UKPDS

Systolic Blood Pressure and CV deathSystolic Blood Pressure and CV death

250

225

200

175

150

125

100

75

50

0

25

< 120 120–139 140–159 160–179 180–199 200Systolic Blood pressure (mmHg)

Cardiovascular deaths

rate/10 000 sub/year

Non diabetics

Diabetics

Stamler J et al. Diabetes Care. 1993;16:434-444.

Goal : 130/80 mmHg

Heart failure

• Incidence x 2 to 6 in diabetic population•Shorten the life•May cause sudden death•Results from 2 others :

• CHD• HTA

Peripheral arteriopathy 8% at diagnosis, 15% (10 years) 45% ( 20 years).

• Atheroma plaques more scattered, more distal• Associated risk factors Smoking, HTA, obesity, renal transplantation• Risk of amputation = 10,3 (male) 13,8 (female)• 1 /3 proximal (+ HTA/ dyslipidemia/ smoking)• 1/3 distal below the knee (hyperglycemia / duration of diabetes)• - 1/3 both

-

•Symptoms :• Intermittent limp

• Calf pain when walking • Missing pulses• If < 200m requires surgery

• Pain at rest / nocturnal pain• Due to nerves ischemia• More during the night force to let the legs hang• If permanent requires surgery

Peripheral arteriopathy

Cerebrovascular attack

Stroke risk x 2

Brain scan : left infarction (sylvien territory)

Microangiopathy

•Diabetic retinopathy•Diabetic nephropathy•Diabetic neuropathy•Diabetic foot

Diabetic retinopathy•Background:

• Increased capillar permeability• œdema microexsudates

•Retinal ischemia:• micro aneurysms• punctiformes haemorrhages

•Proliferative retinopathy:• Neovessels

• Ruptures causing haemorrhages• Development of glial tissu• Retina retraction and detachment

•Macular oedema

•cataract

Diabetic nephropathy

40% of type 2 diabetics

have at least background

lesions in their course

Hollenberg NK. J Hypertens 1997,15(S7): 7-13.

STAGES Time of occurence

Hypertrophy & early

hyperfiltrationKidney

histologic lesionsMicroalbuminuria

backround

nephropathyProteinuria

Néphropathy (clinical)

Renal failure

1

2

3

4

5

diagnosis

2 - 3 years

7 - 15 years

10 - 30 years

20 - 40 years

NDiabetic nephropathy

Diabetic neuropathy

• An estimated 50 percent of those with diabetes have

some form of neuropathy, but not all with neuropathy have symptoms.

• The highest rates of neuropathy are among people who have had the disease for at least 25 years.

• Neuropathy can affect nerves throughout the body, causing numbness and sometimes pain in the hands, arms, feet, or legs, and problems with the digestive tract, heart, and sex organs.

• Mechanism is very complex

Peripheral Neuropathy

Peripheral neuropathy affects the nerves in arms, hands, legs, and feet.

• numbness or insensitivity to pain or temperature

• a tingling, burning, or prickling sensation• sharp pains or cramps • extreme sensitivity to touch, even a light

touch

Peripheral Neuropathy

• loss of balance and coordination • These symptoms are often worse at night.• Peripheral neuropathy may also cause

muscle weakness and loss of reflexes, especially at the ankle, leading to troubles in walking

Autonomic Neuropathy

Unawareness of HypoglycemiaHeart and Circulatory SystemDigestive SystemUrinary Tract and Sex OrgansSweat GlandsEyes

Diabetic foot

infection

neuropathy

Skin disease

mIcrovascular

macrovascular

Complications of type 2 diabetes

What they suffer from?Incidence /prevalenceCheck up and detectionImpact on morbi-mortalityADVANCE what for ?

Complications of type 2 diabetes

What they suffer from?Incidence /prevalenceCheck up and detectionImpact on morbi-mortality

« Detection attitude »In diabetes population = any vascular complication look for all other types

- eye examination- Urinary tests, kidney function-ECG, exercise test, myocardial scintigraphy-Vascular echo-doppler-Nerves lesions detection-Focus on foot

Complications of type 2 diabetes

What they suffer from?Check up and detectionImpact on morbi-mortalityImpact on morbi-mortality

Risk for Coronary heart disease x 2-4Risk for Coronary heart disease x 2-4

Risk for Stroke x 1.4-2.2 Risk for Stroke x 1.4-2.2

Risk for Arteriopathy x 10Risk for Arteriopathy x 10

Type 2 diabetes means

Not decreased Not decreased during the last during the last 30 years30 years

1st cause of blindness < 50 years (500 – 1000 /year)

50 % of amputations (8500 /year)

20 - 30 % of hémodialysis (2500 /year)

15 % of MI (30 000 / year)

THE TREATMENT

“I don’t feel sick”

“I suffer from being overweight”

“I prefer to live normally now, even if I have to pay it in the future”

Visits at the clinicsCardiovascular riskGlucometersDietExerciseMore than 10 tablets/dayInsulin injections

“never forget that you have a serious disease !!!!”

Treatment (1)SuphonylureaGlinideMetforminGLP1AcarboseInsulinPump…..Molecules in development…

Whatever you prescribe …

The only points you have to consider is:

1) Compliance2) HbA1c

Barriers to insulin therapy

Patient

Needle anxiety

Hypoglycemia

Weight gain

Health Professional

? CV Risks

Hypoglycemia

Weight gain

Date Presentation title 57

Hypoglycaemia

What are the signs and symptoms of hypoglycaemia?

What are the causes of hypoglycaemia? How is a ‘hypo’ managed? How is a ‘hypo’ prevented?

What are the complications associated with prolonged hypoglycaemia?

Oral Diabetes Medication

What are the target ranges for home blood glucose monitoring?

FastingPre-meals

2 hours after meals

What factors would you need to take into consideration

before starting oral diabetes medication?

Insulin

What insulins' are you aware of?How is insulin given?

What is meant by ‘basal’ insulin?What is meant by ‘bolus’ insulin?Where may insulin be injected?

How often should the pen needle be changed on the insulin injection pens?

May insulin be injected through clothes?How should insulin be stored?

What are the side effects of insulin?How often may insulin doses be titrated?