Diabetes mellitus, Classification and Treatment of Diabetes mellitus
Diabetes mellitus I. (classification, epidemiology ...
Transcript of Diabetes mellitus I. (classification, epidemiology ...
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Diabetes mellitus I. (classification,
epidemiology, pathogenesis, diagnosis)
Prof. Péter Kempler
Budapest
2nd October, 2017
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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.
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Causes of death among diabetic patients in the 20th century
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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
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NEJM 2011; 364:829-41.
Reduction in life expectancy in DM2
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Early death
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Diabetes ~ equivalent to MI
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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
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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
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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)
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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)
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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
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Diabetes: A global emergency
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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
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<3% <4 % >4% > 6%
Diabetes Trends Among U.S. Adults1985
Trend of Diabetes in the USA in 1985
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2000
<3% <4 % >4% > 6%
Trend of Diabetes in the USA in 2000
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Polonsky KS. N Engl J Med 2012; 367: 1332-
1340.
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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
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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
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FEND-IDF. Diabetes. The policy puzzle: towards benchmarking in the EU 25. 2005: 85.
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~30 years ago
IDDM
NIDDM
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Nowadays
Type-1 diabetes mellitus
Type-2 diabetes mellitus
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Type 1 diabetes mellitus
• A. Autoimmune:
T cell mediated autoimmune disease
- rapid progression
- slow progression (latent autoimmune diabetes in adults, LADA)
• B. Idiopathic
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Type 1 Diabetes Mellitus
• Genetic susceptibility
• Triggering effect
• Period of immunologic abnormalities
• Manifestation of diabetes mellitus
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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
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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
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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(?)
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Autoantibodies in T1DM
Markers
• ICA(islet-cell /cytoplasmatic/ autoantibodies)
• GADA (autoantibody to glutamic acid
decarboxylase )
• IA-2A (autoantibody to IA-2)
• IAA (insulin autoantibodies)
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Development of Type 2 diabetes mellitus
Onset of diabetes
b-cell
function
Insulin
resistance
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Development of Type 2 diabetes mellitus
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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
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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
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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
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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
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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.
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Rubens – 1616 A.D.Venus from Willendorf
30 000 years B.C.
T.S. 2004 A.D.
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03.10.2017 SYDNEY Study Group
NeuroDiab 2001, Aberdeen
41
THE DEADLY QUARTET
ObesityDiabetes Hypertension Dyslipidemia
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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
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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
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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
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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
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• 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
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Rapid increase in obesity
Rapid increase in diabetes
1990
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
2005
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The role of individual diet
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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
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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
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Cardiometabolic Risk
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Central adiposity
DeFronzo RA. Br J Diabetes Vasc Dis 2003; 3: S24-S40.
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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
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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
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Gerstein HC. Is glucose a
continuous risk factor for
cardiovascular mortality?
Diabetes Care 1999; 22: 659-660.
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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
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Brunner EJ. et al. Relation between blood glucose and
coronary mortality over 33 years in the Whitehall Study.
Diabetes Care 2006; 29: 26-31.
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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)
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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)
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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.
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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
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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
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HbA1C
(is a function of)
FBG PPBG+
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Selvin E ea. NEJM 2010;362:800
Higher HbA1c more CV-disease
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Selvin E ea. NEJM 2010;362:800
Higher HbA1c more stroke
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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.
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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
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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
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Ferrannini et al. Insulin resistance in
essential hypertension.
N.Engl.J.Med. 1987; 317: 350-357.
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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.
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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
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Lebovitz H. Insulin resistent Type 2 diabetes:
a lipid and vascular disorder that causes
hyperglycemia.
ADA, 2004.
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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
+++ + +++
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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
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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.
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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
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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?
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* 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.
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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
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Pathophysiology of type 2 diabetes
Impaired insulin secretion
Unsuppressed glucose production
Impaired insulin action
Decreased glucose uptake
Impaired insulin action
Hyperglycaemia
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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
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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
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Limitations of physical activity
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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
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•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
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•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
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Physicians’
empathy is an
important factor
associated with
clinical
competence and
patient outcomes
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Obesity around the world (Newsweek 2003. aug. 11.)
Thank you for your kind attention!