Diabetes mellitus I. (classification,

epidemiology, pathogenesis, diagnosis)

Prof. Péter Kempler

Budapest

2nd October, 2017

Clinical Impact of Diabetes Mellitus

DiabeticRetinopathy~ 50%Leading causeof blindnessin working ageadults1

DiabeticNephropathy~ 35%Leading cause of end-stage renal disease2

CardiovascularDisease~ 45%

Stroke

2 to 4 fold increase in cardiovascular mortality and stroke3

DiabeticNeuropathy~ 40%Leading cause of non-traumatic lower extremity amputations5

8/10 diabetic patients die from CV events4

1 Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 2 Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 3 Kannel WB, et al. Am Heart J 1990; 120:672–676. 4 Gray RP & Yudkin JS. In Textbook of Diabetes 1997.

5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79. Decision Resources., Inc.1999.

Causes of death among diabetic patients in the 20th century

Venhut Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for

diabetes mellitus in the United States. J Amer Med Ass 2003; 290: 1884-1890.

The estimated decrease of survival associated with

diabetes among individuals with diabetes diagnosed

at the age of 40.

in males: 11,6 yr

in females: 14,3 yr

NEJM 2011; 364:829-41.

Reduction in life expectancy in DM2

Early death

Diabetes ~ equivalent to MI

Diagnosis of diabetes

• Classical symptoms of diabetes (polyuria,

polydypsia, weight loss) +

• fasting glucose ≥ 7,0 mmol/l (after 10 hours

fasting)

• glucose at any time ≥ 11,1 mmol/l

• Without classical symptoms:

• fasting glucose two times ≥ 7,0 mmol/l

Normal glucose tolerance ≤ 6,0 mmol/l ≤ 7,8 mmol/l

Fasting

glucose

Postprandial

glucose

Impaired fasting glucose (IFG) ≥ 6,1 < 7,0 mmol/l < 7,8 mmol/l

Impaired glucose tolerance (IGT) ≤ 7,0 mmol/l ≥ 7,8 < 11,1 mmol/l

Diabetes mellitus ≥ 7,0 mmol/l ≥ 11,1 mmol/l

Classification of diabetes

• Type 1 diabetes mellitus

• autoimmun mechanism

• idiopathic

• sometimes other autoimmun diseases also

present (Basedow-Graves disease, Hashimoto

thyreoiditis, Addison’s disease)

• subtype: LADA (latent autoimmun diabetes in

adults)

Classification of diabetes

• Type 2 diabetes mellitus

• Other types of diabetes

• diabetes due to exocrin pancreas disease

• endocrin diseases

• diabetes related to drugs

• MODY (Maturity-Onset Diabetes of the Young)

• genetic background

• GDM (gestational diabetes mellitus)

GLOBAL PROJECTIONS FOR THE DIABETES

EPIDEMIC: 2003-2025 (millions)

25.0

39.7

59%

10.4

19.7

88%

38.2

44.2

16%

1.1

1.7

59%

13.6

26.9

98%

World

2003 = 189 million

2025 = 324 million

Increase 72%

81.8

156.1

91%

18.2

35.9

97%

IDF Diabetes Atlas. www.eatlas.idf.org

Diabetes: A global emergency

Prevalence of diagnosed and undiagnosed diabetes and IGT in the US population

Harris MI. Diabetes Care 1993; 16: 642-52.

0

5

10

15

20

25

30

35

40

45

20-44 45-54 55-64 65-74Age (years)

%

IGT

Undiagnosed diabetes

Diagnosed diabetes

<3% <4 % >4% > 6%

Diabetes Trends Among U.S. Adults1985

Trend of Diabetes in the USA in 1985

2000

<3% <4 % >4% > 6%

Trend of Diabetes in the USA in 2000

Polonsky KS. N Engl J Med 2012; 367: 1332-

1340.

Belgium

France

Germany

Ireland

Italy

Netherlands

Norway

Portugal

Spain

Sweden

UK

Romania

World

Belarus

Moldova

0% 2% 4% 6% 8% 10% 12% 14%

Estimated diabetes prevalence in selected

Western European countries

Afghanistan

Algeria

Armenia

Egypt

Iran

Iraq

Jordan

Kuwait

Lebanon

Libya

Morocco

Oman

Pakistan

Palestine

Qatar

Saudi Arabia

Sudan

Syria

Tunisia

United Arab Emirates

Yemen

World

Bahrain

0% 5% 10% 15% 20% 25%

2003

2025

www.eatlas.idf.org

Albania

Bulgaria

Croatia

Czech Republic

Estonia

Georgia, Republic of

Hungary

Latvia

Lithuania

Moldova, Republic of

Romania

Russian Federation

Slovenia

Turkey

Ukraine

World

Belarus

Moldova

0% 2% 4% 6% 8% 10% 12% 14%

www.eatlas.idf.org

Estimated diabetes prevalence in selected

Eastern European countries

Serbia & Montenegro

Bosnia & Herzegovina Afghanistan

Algeria

Armenia

Egypt

Iran

Iraq

Jordan

Kuwait

Lebanon

Libya

Morocco

Oman

Pakistan

Palestine

Qatar

Saudi Arabia

Sudan

Syria

Tunisia

United Arab Emirates

Yemen

World

Bahrain

0% 5% 10% 15% 20% 25%

2003

2025Slovakia

FEND-IDF. Diabetes. The policy puzzle: towards benchmarking in the EU 25. 2005: 85.

~30 years ago

IDDM

NIDDM

Nowadays

Type-1 diabetes mellitus

Type-2 diabetes mellitus

Type 1 diabetes mellitus

• A. Autoimmune:

T cell mediated autoimmune disease

- rapid progression

- slow progression (latent autoimmune diabetes in adults, LADA)

• B. Idiopathic

Type 1 Diabetes Mellitus

• Genetic susceptibility

• Triggering effect

• Period of immunologic abnormalities

• Manifestation of diabetes mellitus

Type 1 diabetes - genetic susceptibility

Prevalence of T1DM %

Average population before then age of 30 years 0,1-0,4

In case of diabetic sibling 6

In case of diabetic parent 3-6

If the father is diabetic by the age of 20 years 6-9

If the mother is diabetic by the age of 20 years 1-4

In identical twins is diabetic by the age of 30 years 34

In identical twins 12 years later after the diagnosis of the proband 43

In identical twins 40 years later after the diagnosis of the proband 50

In non-identical twins 10-12

HLA identical sibling 15

HLA haploidentical sibling 9

HLA non-identical sibling 1-2

Predisposing HLA haplotypes and

genotypes for T1DM

• HLA DR4-DQ8

• HLA DR3-DQ2

• HLA DR4-DQ8/HLA DR3-DQ2

• HLA DR4-DQ8/HLA DR4-DQ8

T1DM - Environmental factors

• Enteroviruses (Coxsackie-B4, polio,)

Antibody titer anti-CB4 is higher in DR3/DR4 > DR2,

it means a lower cellular reaction to the virus,

it could mean a persistent virus carrier status

CMV

• Bovine milk proteins (?)

• Nitrosourea compounds (?)

• Insufficient D3 vitamin supply(?)

Autoantibodies in T1DM

Markers

• ICA(islet-cell /cytoplasmatic/ autoantibodies)

• GADA (autoantibody to glutamic acid

decarboxylase )

• IA-2A (autoantibody to IA-2)

• IAA (insulin autoantibodies)

Development of Type 2 diabetes mellitus

Onset of diabetes

b-cell

function

Insulin

resistance

Development of Type 2 diabetes mellitus

Tabák et al. The Whitehall II study. Lancet, 2009; 373: 2215-21.

fasting blood glucose (mmol/l)

control

Time elapsed until the end of follow-up (years)

fasting blood glucose (mmol/l)

Time elapsed until the end of follow-up (years)

fasting blood glucose (mmol/l)

control

Time until the end of follow-up (years)

fasting blood glucose (mmol/l) - fasting blood glucose

control

Tabák et al. The Whitehall II study. Lancet, 2009; 373: 2215-21.

control

Time until the end of follow-up (years)

2h blood glucose (mmol/l) after glucose tolerance test

control

UKPDS. Diabetes 44:1249-1258, 1995.

The Whitehall II Study. Lancet 373:2215-21, 2009.

Decline of b-cell function before and after the

diagnosis of type 2 diabetes mellitus

Decline of b-cell function in type 2 diabetes:

the need of early intervention

UKPDS Group. Diabetes 1995;44:1249-58.

0

20

40

60

80

100

–5 –4 –3 –2 –1 0 1 2 3 4 5 6

Years Since Diagnosis

Sulfonylurea

Diet

Metformin

β-C

ell

Fu

nct

ion

(%

)*

Progressive loss of beta-cell function

occurs prior to diagnosis

*beta-cell function measured by HOMA

Risk of diabetes correlates linearly

with 2hPG levels

140

120

100

80

60

40

20

0

7.8–8.2 8.3–8.8 8.9–9.7 9.8–11.0

Pima Indian Study

San Luis Valley Diabetes Study

Nauru Study

Baltimore Longitudinal Study of Aging

Rancho Bernardo study

San Antonio Heart Study

2hPG level (mmol/L)

Dia

bete

s i

ncid

en

ce r

ate

(pe

r 1

,000 p

ers

on

-years

)

2hPG: 2-hour postchallenge plasma glucose Edelstein S, et al. Diabetes 1997;46:701–10.

Rubens – 1616 A.D.Venus from Willendorf

30 000 years B.C.

T.S. 2004 A.D.

03.10.2017 SYDNEY Study Group

NeuroDiab 2001, Aberdeen

41

THE DEADLY QUARTET

ObesityDiabetes Hypertension Dyslipidemia

Proposed mechanism of obesity-induced

insulin resistance and type 2 diabetes

Adapted fromBoden G. Diabetes 1997; 46: 3-10

Abdominalfat

Type 2 diabetes

Insulin resist.

FFA

Peripheral glucose

utilisation

Hepatic glucoseproduction

The National Health and Nutrition Examination Survey, JAMA 2003, 289, 187-193.

Years of life lost due to obesityPublic health officials and organizations have tried to warn the public about the dangers of obesity.

Years of life lost among white men and women

Abdominal obesity increases the

risk of developing diabetesR

elat

ive

risk

Waist circumference (cm)

Carey VJ et al. Am J Epidemiol 1997;145:614-9

<71 71–75.9 76–81 81.1–86 61.1–91 91.1–96.3 >96.3

24

20

16

12

8

4

0

Relationship Between Weight Gain in

Adulthood and Risk of Type 2 Diabetes

Mellitus

Willett et al. N Engl J Med 1999;341:427.

Rel

ativ

e R

isk

Weight Change (kg)

6

5

4

3

2

1

0

Men

Women

-10 -5 0 5 10 15 20

• Prevalence of obesity

increased 61%

between 1991 and

2000

• More than 60% of US

adults are overweight

• Only 43% of obese

persons advised to

lose weight during

checkups

• BMI and weight gain

major risk factors

for diabetes

Pre

val

ence

(%

)

kg

Year

Mokdad et al. Diabetes Care. 2000;23:1278.

Mokdad et al. JAMA. 1999;282:1519.

Mokdad et al. JAMA. 2001;286:1195.

Prevalence of Diabetes and Obesity

Diabetes

Mean body weight

4

4,5

5

5,5

6

6,5

7

7,5

1990 1992 1994 1996 1998 2000

72

73

74

75

76

77

78

Rapid increase in obesity

Rapid increase in diabetes

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

2005

The role of individual diet

Sattar N et al. Revisiting the links between

glycaemia, diabetes and cardiovascular

disease. Diabetologia 2013; 56: 686-695.

Risk of cardiovascular disease

n = 140,624

Sattar N et al. Revisiting the links between

glycaemia, diabetes and cardiovascular

disease. Diabetologia 2013; 56: 686-695.

n = 140,624

Risk of cardiovascular disease

Cardiometabolic Risk

Central adiposity

DeFronzo RA. Br J Diabetes Vasc Dis 2003; 3: S24-S40.

Insulin resistance – the link between

CVD and type 2 diabetes

• Up to 75% of mortality in type 2 diabetes is due to

CVD

• Insulin resistance is the major trigger for development

of type 2 diabetes

• Insulin resistance is an independent predictor of CVD

• Insulin resistance is closely linked to a number of CVD

risk factors associated with type 2 diabetes

• Cause of insulin resistance is multifactorial

• Adipocytokines especially IL-6, TNF, and

adiponectin play a significant role in insulin resistance

and cardiovascular disease

ACE/CDR/05/20746/1

Antiatherogenic properties

Expression of adhesion molecules

Monocyte adhesion to endothelial cells

Uptake of oxidized LDL

Foam cell formation

Proliferation and migration of SMCs

Antidiabetic properties

Insulin sensitivity

SM glucose uptake and FFA oxidation

Hepatic glucose production

Intracellular triglycerides

Adiponectin: a specific adipose

tissue-derived protein

Adipose tissue

Gerstein HC. Is glucose a

continuous risk factor for

cardiovascular mortality?

Diabetes Care 1999; 22: 659-660.

Bjornholt J et al.Fasting blood glucose level predicts

cardiovascular mortality in men. Results from 22 years follow-

up. European Heart Journal 1996;17(Suppl 1): 38.

n=2014 healthy men, 40-59 years men (p< 0,01 IV. vs. I-III quartile)

< 4,0 4,1-4,3 4,4-4,6 >4,70

5

10

15

20

card

iovasc

ula

r d

eath

%

12,7%11,0% 10,4%

17,1%

(n=575) (n=462) (n=488) (n=484)

fasting

glucose

mmol/l

Brunner EJ. et al. Relation between blood glucose and

coronary mortality over 33 years in the Whitehall Study.

Diabetes Care 2006; 29: 26-31.

Paris Prospective Study - 23 years follow up

Balkau et al. Is there a glycemic threshold for

mortality risk? Diabetes Care 1999; 22: 696-699.

all cause mortality all cause mortality

rela

tive

risk

of

dea

th

freq

uen

cy %

rela

tive

risk

of

dea

th

freq

uen

cy

%

fasting glucose (mmol/l) 2h postprandial glucose

(mmol/l)

Mortality in relation to fasting and postprandial

blood glucose values

DECODE Study Group, Lancet. 354: 617-21; 1999.

0

0,5

1

1,5

2

2,5

< 6,1 6,2-6,9 7,0-7,7 > 7,8

< 7,8

7,9-11,0

> 11,1

Fasting glucose (mmol/l)

1.000.920.84

0.66

0.540.500.47

0.82

0.590.56

0.52

0.58

0.0

0.2

0.4

0.6

0.8

1.0

1.2

<5.25 5.25-

6.24

6.25-

7.79

7.80-

10.25

10.26-

11.09

11.10 Known

DM

7.00 6.10-

6.99

5.75-

6.09

4.75-

5.74

<4.75

Ha

za

rds

ra

tio

(9

5%

CI)

2-hour glucose (mmol/L) Fasting glucose (mmol/L)

DECODE – all-cause mortality in asymptomatic people with elevated 2-hour plasma glucose is almost

as high as in patients treated for diabetes

DECODE. Diabetes Care 2003;26:688–96.

Incidence of myocardial infarction and mortality

according to fasting and postprandial blood glucose

Hanefeld M. et al. Diabetologia 1996; 39: 1577-83.

0

150

300

4,4-6,4 < 7,8 > 7,8

In

cid

en

ce/1

1 y

ea

rs Myocardial infarction MortalityFasting

blood

glucose

(mmol/l)

Postprandia

l blood

glucose

(mmol/l)

0

150

300

4,4-8,0 < 10,0 > 10,0

In

cid

en

ce/1

1 y

ea

rs

p=NS

p<0,05

DECODE

20012 Pacific and

Indian Ocean

19993

Funagata

Diabetes Study

19994

Whitehall, Paris

and

Helsinki Study

19985

Diabetes

Intervention

Study 19967

Rancho Bernardo

Study 19986

Postprandial

hyperglycaemia

Honolulu

Heart Program

19878

Cardiovascular

mortality

1. Nakagami T, et al. Diabetologia 2004;47:385–94. 2. DECODE. Arch Intern Med 2001;161:397–405.

3. Shaw J, et al. Diabetologia 1999;42:1050–54. 4. Tominaga M, et al. Diabetes Care 1999;22;920–24.

5. Balkau B, et al. Diabetes Care 1998;21:360–67. 6. Barrett-Connor E, et al. Diabetes Care 1998;21:1236–39.

7. Hanefeld M, et al. Diabetologia 1996;39:1577–83. 8. Donahue R. Diabetes 1987;36:689–92.

Postprandial hyperglycaemia is

linked to cardiovascular mortality

DECODA

20041

DECODA: Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia,

DECODE: Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe

HbA1C

(is a function of)

FBG PPBG+

Selvin E ea. NEJM 2010;362:800

Higher HbA1c more CV-disease

Selvin E ea. NEJM 2010;362:800

Higher HbA1c more stroke

Definition of the Metabolic Syndrome (ATP III, 2001)

1. Abdominal obesity (waist circumference

>102 cm - men; >88 cm - women)

2. Hypertriglyceridaemia 150 mg/dl (1.69 mmol/l)

3. Low HDL-cholesterol <40 mg/dl (1.04 mmol/l) - men

<50 mg/dl (1.29 mmol/l) - women

4. High blood pressure ( 130/85 mmHg)

5. High fasting glucose 110 mg/dl (6.l mmol/l)

Third Report of the National Cholesterol Education Program Expert Panel

on Detection, Evaluation, and Treatment of High Cholesterol in Adults

(Adult Treatment Panel III, 2001).

JAMA 285: 2486-2497, 2001.

Prevalence of the metabolic syndrome

according to ATP III definition

0 10 20 30 40 50 60

France

Mauritius*

Oman

Australia

Ireland

USA (NHW)

USA

Turkey

USA (MA)

India*

USA (Nat Am)

Age range

*Obesity criteria adjusted to waist circumference appropriate for an Indian population

45-49

20-75

30-79

32+

30-79

30-79

50-69

25+

21+

25+

30-64Men

Women

Prevalence of Comorbid Diabetes and

Hypertension

• Comorbidity appears to increase risk of cardiovascular disease twofold*

*Versus patients with hypertension but not diabetes

Adapted from American Diabetes Association Diabetes Care 2004;27(suppl 1):S65–S67; UKPDS BMJ 1998;317:703–713.

Patients with type 2 diabetes

Up to 60% have concomitant hypertension

Ferrannini et al. Insulin resistance in

essential hypertension.

N.Engl.J.Med. 1987; 317: 350-357.

Combined Impact of Hypertension

and Diabetes on CVD Death Rate

0

50

100

150

200

250

300

≥200180–199160–179140–159120–139<120

Systolic blood pressure(mmHg)

CV

D d

eat

h r

ate

(p

er

10

,00

0 p

ers

on

-ye

ars)

Without diabetes

With diabetes

Adapted from Stamler J et al Diabetes Care 1993;16(2):435–444.

The frequency of different forms of glucose

intolerance among

805 patients with hypertension

%

8,3 %14,5%

24,6%

39,1%

47,4%

Maros Z, Csötönyi G, Füzi M, Hancsicsák J, Simek Á, Nyirati G, Kempler P.

Diabetologia 2002; 45 (Suppl 2): A102-103.

0

5

10

15

20

25

30

35

40

45

50

IFG

IGT

Type 2 diabetes

IGT and Type 2diabetes

alltogether

Lebovitz H. Insulin resistent Type 2 diabetes:

a lipid and vascular disorder that causes

hyperglycemia.

ADA, 2004.

Laakso et al. Diabetes Reviews 1997; 5: 294-315

The spectrum of risk in macrovascualr disease of type 2 diabetes

Risk factor Coronary heart

disease

Stroke Amputation

Hyperglycemia + ++ +++

Hemoglobin A1c + ++ +++

Total cholesterol ++ + +

HDL cholesterol +++ ++ (+)

Total triglycerides +++ ++ (+)

Hypertension (+) ++ (+)

Duration of diabetes + + +++

Medial arterial

calcification

+++ + +++

Atherogenic risk markersassociated with insulin resistance

Abdominal obesity WHR, FFA, TNF, Resistin

Dyslipidaemia FFA, Triglycerides, Small dense LDL

HDL, Large less-dense LDL

Hypertension Blood pressure

Inflammation C-reactive protein, matrix

metalloproteinase-9

Oxidative stress Oxidised LDLs and F2-isoprostanes

Endothelial dysfunction PAI-1, Cellular adhesion molecules

Coagulation Fibrinogen, PAI-1, tPa

Hyperglycaemia AGEs, Circulating AGE derivatives

Hyperinsulinaemia Plasma insulin (pre- and early diabetes)

Microalbuminuria Urinary albumin excretion

tPa: tissue plasminogen activatorAdapted from Ross R. N Engl J Med 1999; 340: 115-126 and Festa A et al. Circulation 2000; 102: 42-47

Jarrett RJ. et al. Microalbuminuria predicts

mortality in non-insulin-dependent diabetes.

Diabetic Med 1; 17-19, 1984.

Mogensen CE.: Microalbuminuria predicts clinical

proteinuria and early mortality in maturity-onset

diabetes.

N Engl J Med 310; 356-360, 1984.

Relative prognostic value of

microalbuminuria in Type 2 diabetes

Eastman RC, Keen H. Lancet 1997;350(Suppl 1):29–

32.

Microalbuminuria

Smoking Diastolic BP

Mortality

from

CHD

(odds

ratio)

Cholesterol

10.02

6.52

2.32

3.20

10

8

6

4

2

0

EURODIAB IDDM Complications Study

Standardised Estimates of Relative Risk (SERR)

for Incidence of Complications

NEPHROPATHY

AGE/DURATION* -

HbA1c 1.57 (1.26 - 1.97)

AER 1.45 (1.13 - 1.87)

TRIGLYCERIDE 1.31 (1.05 - 1.65)

WHR 1.27 (1.02 - 1.58)

BMI -

RETINOPATHY

1.32 (1.07 - 1.61)*

1.93 (1.52 - 2.44)

-

1.42 (1.01 - 1.54)

1.32 (1.07 - 1.63)

-

NEUROPATHY

1.39 (1.13 - 1.61)

1.20 (1.00 - 1.44)

-

1.33 (1.11 - 1.60)

-

1.39 (1.16 - 1.65)

Insulin Resistance?

* adjusted for age, duration and HbA1C

** testing difference from non-smoking

Crude Adjusted*

relative risk of abnormal R-R ratio(p-value, testing for trend)

Smoking - ex

- current

p < 0,01**

p < 0,0001**

p < 0,05**

p < 0,0001**

Blood pressure - systolic

- diastolic

p < 0,05

p < 0,05

N.S.

N.S.

Total cholesterol p < 0,001 N.S.

HDL-cholesterol p < 0,01 p < 0,01

LDL-cholesterol p < 0,001 N.S.

Total cholesterol/HDL cholesterol ratio p < 0,001 p < 0,001

Fasting triglyceride p < 0,0001 p < 0,0001

Kempler P, Tesfaye S, Chaturvedi N. et al. Autonomicneuropathy is associated with increased cardiovascular riskfactors: the EURODIAB IDDM Complications Study. DiabeticMed 2002; 19: 900-09.

Risk Factors for Neuropathy after Adjustment for

HBA1c and Duration of Diabetes

Tesfaye et al NEJM 352: 341-350,2005

Eurodiab: 276/1172 patients developed neuropathy in 7.3y

Variable Odds Ratio P valueCVD 2.74 <0.0001

Albuminuria 1.48 0.02

Hypertension 1.92 <0.001

Smoking 1.55 <0.001

BMI 1.40 <0.001

Triglycerides 1.35 <0.001

Total Cholesterol 1.26 0.001

LDL-C 1.22 0.001

Pathophysiology of type 2 diabetes

Impaired insulin secretion

Unsuppressed glucose production

Impaired insulin action

Decreased glucose uptake

Impaired insulin action

Hyperglycaemia

HOMA model, diet-treated (n = 376)

Adapted from Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl): S21–S25.

100

80

60

40

p < 0.0001

Time (years)

100

β-c

ell f

un

ctio

n (

%) 80

60

40

20

0

Start of treatment

50% β-cell function at diagnosis

0 1 2 3 4 5 6-1-2-3-4-5-6-7-8-9-10

At the time of diagnosis b-cell function is

already significantly reduced

b-cell function starts to decline even in

advance of IGT

Adapted from Ferrannini E et al. J Clin Endocrinol Metab 2005; 90: 493–500.

100

90

80

70

60

50

40

30

20

10

04 10 16 22 24

Per

centa

ge

dec

reas

e

(bes

t obes

e N

GT

stu

dy

gro

up)

2-h plasma glucose (mmol/L)

6 8 12 14 18 20

NGT IGT

b-cell

response

Insulin

sensitivity

T2D

Limitations of physical activity

Adapted from Brown JB et al. Diabetes Care 2004; 27: 1535–1540.

Early intervention offers the potential to avoid

glycaemic burden and microvascular

complications

Time in months since treatment initiation

Hb

A1

c %

Unavoidable glycaemic burden

Avoidable glycaemic burden

Treatment goal

Early intervention

•Empathy is an essential part of the

physician-patient relationship – could

be linked to a positive patient outcome

•Hypothesis: patients with diabetes from

empathic physicians have better

outcomes

•Research in 7,269 patients (2006-2009)

of 29 physicians

•Department of Family and Community

Medicine at Thomas Jefferson

University

•Empathie measured by Jefferson Scale

of Empathy (JSE): validated

questionaire

Methods

Physicians’

empathy is an

important factor

associated with

clinical

competence and

patient outcomes

Obesity around the world (Newsweek 2003. aug. 11.)

Thank you for your kind attention!