DR. dr.

Eva Decroli, SpPDKEMD, FINASIM

Curriculum Vitae :
T.TGL-L : Padang Panjang,19 Desember 1959
Jabatan Sekarang :
- KPS PPDS I FK Unand
- Ketua Subbagian Metabolik
Endokrinologi Bag. IPD FK Unand
Jabatan Yang Pernah Disandang :
2004-2008 : Sekretaris Bagian IPD FK Unand
2008-2011 : Sekretaris PPDS IPD FK Unand

Komplikasi Diabetes Melitus

Dr. dr. Eva Decroli, Sp.PD-KEMD, FINASIM

Simposium Umum PIB XIV

Padang, 9 Februari 2014
Pangerans Beach Hotel

Recap: The goal of diabetes management is to secure optimal

glycemic control to avoid complications
Microvascular
Diabetic
retinopathy

Leading cause
of blindness
in working-age
adults1
Diabetic
nephropathy

Leading cause of
end-stage renal
disease2 Erectile Dysfunction
The most secretive
Complication of DM

Macrovascular

Stroke

1.2- to 1.8-fold
increase in
stroke3
Cardiovascular
disease
75% diabetic

patients
die from CV
events4
Diabetic
neuropathy

Leading cause of
non-traumatic
lower extremity
amputations5
Diabetic Foot

Fong DS, et al. Diabetes Care 2003;e 26 (Suppl.1):S99S102. 2Molitch ME, et al. Diabetes Care 2003; 26 (Suppl.1):S94S98. 3Kannel WB, et al. Am Heart J 1990; 120:672
676. 4Gray RP & Yudkin JS. Textbook of Diabetes 1997. 5Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl.1):S78S79.
1

Incidence per 1.000

patient-years

Recap: Risk of Complications increases as Hb1Ac increases

5/3/16
5/3/16

Updated Mean HbA1c (%)

Adjusted for age, sex, and ethnic group

Stratton IM et al. BMJ 2000;321:40512

Recap: Its the diabetes-related complications not the diabetes

medicine - that carries the biggest cost to the society
Cost increases with a factor of 22.5 if patients develop complications
(ASKES Data)
US$

22.5X

5/3/16
5/3/16

ASKES 2010 Unpublished data

5/3/16

Positive legacy effect of earlier glucose control

Provides long-term reductions in both microvascular and

macrovascular complications
RRR* at end of UKPDS
RRR* at end F/U (median 8.5 years)

16%
p=0.052

15%
p=0.01

Myocardi
al
infarctio
n

25%
p=0.0099

24%
p=0.001

Microvascul
ar disease

6%
p=0.44

13%

12%

9%

p=0.007

p=0.03

p=0.04

Death
(any
cause)

Any
diabetes
endpoint

RRR: relative risk reduction of intensive therapy

over conventional therapy
UKPDS 80. Holman et al. NEJM 2008; 359:1577-89.

Diabetes Nephropathy
Characteristics

Persistent albuminuria
Diabetic retinopathy
Hypertension
Decline in kidney function (about 12 ml/min/year)

Diabetes Nephropathy
Prevention and Treatment

Maintain tight glycaemic and blood

pressure control

Probability of
microalbuminuria

Multifactorial disease
management:
0.8

0.6
0.4
0.2
0.0
5

10

11

Glycated haemoglobin (%)

DCCT. Diabetes 1996;45:128998

12

antihypertensive agents
good blood glucose control
control of dyslipidaemia
monitoring renal function
lifestyle changes, including
smoking cessation and
low-protein diet

Micro / Macro-albuminuria

In 2 of 3 measurements

Micro
24h:

30 - 299 mg/24h

Macro
>300 mg/24h

Random spot:

30 - 299 mcg/mg

>300 mcg/mg

Morning spot:

30 299 mcg/mg

>300 mcg/mg

Dipstick/overnight albumin: low sensitivity and specificity

Natural history of diabetic nephropathy

Urinary protein excretion

Pre
1

Incipient diabetic
nephropathy
3

Overt diabetic
nephropathy
4

End-stage
renal disease
5

150

5000

1000

100

200

50

20
0

10

15

20

25

Years
Functional

GFR

Microalbuminuria,
hypertension

(90-95%)

Proteinuria, nephrotic
syndrome, GFR

Vora JP, et al. In: Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. New York: Mosby; 2000

Urinary protein excretion (mg/d)

Glomerular filtration rate (GFR) (mL/min)

GFR

Diabetes Retinopathy
NonDiabetic
Retina

Diabetic
Maculopathy

Proliferative
Diabetic
Retinopathy

Diabetes Retinopathy
Retinopathy incidence (odds ratio)

Risk Factors and Classification

Poor glycaemic and blood

pressure control increase
the risk of retinopathy
Five categories:

35
30
25
20

Mild Nonproliferative
Moderate
Nonproliferative
Severe Nonproliferative

15
10
5
0
4

5.7

6.7

8
9
7
London HbA1c (%)
7.7

9.8
8.8
DCCT HbA1c (%)

Chaturvedi et al. Diabetes Care 2001;24:2849

10.8

10

11.9

proliferative
advanced diabetic eye
disease
maculopathy

Diabetes Retinopathy
Prevention and Treatment

Maintain tight glycaemic and blood pressure control

Regular eye examinations
Treat with laser photocoagulation and vitreoretinal surgery

Klein et al. Ann Intern Med 1996;124:906

Diabetes Neuropathy
Risk Factors and Common Types

Symmetrical diffuse
sensorimotor
neuropathy

Femoral neuropathy
(amyotrophy)

Other acute
mononeuropathies
III

Pressure palsies

VI

Truncal
Ulnar

Median
Lateral
popliteal

Sensory loss 0 +++

Sensory loss 0 +

Sensory loss 0 +

Sensory loss + +++

Pain + +++

Pain + +++

Pain + +++

Pain + ++

Tendon reflexes N

Tendon reflexes 0

Tendon reflexes N

Tendon reflexes N

Motor deficit 0 +

Motor deficit + +++

Motor deficit + +++

Motor deficit + +++

Hyperglycaemia is
the leading cause of
diabetic neuropathy
Alcohol makes
neuropathy worse
A number of clinical
syndromes are
recognisable

Pickup & Williams. In: Slide Atlas of Diabetes 2004

Watkins et al. In: Diabetes and Its Management 2003. Pickup & Williams. In: Slide Atlas of Diabetes 2004

Diabetes Neuropathy

Percentage of cases affected

Prevention and Treatment

Maintain tight glycaemic

control to reduce the risk or
progression of neuropathy
Exclude or treat
contributory factors:
alcohol excess
vitamin B12 deficiency
uraemia
Offer pain relief based on
the dominant symptoms

16
Conventional therapy

12
p<0.001

4
Intensified therapy

0
0

Time (years)

DCCT. NEJM 1993;329:97786

Erectile Dysfunction
Definition
ED is the inability to achieve and maintain an erection
adequate for intercourse to the mutual satisfaction of
the man and his partner.
Remember, both partners in a relationship are affected

Erectile Dysfunction
Background
35%-75% of men with diabetes will experience at least some
degree of ED
Men with diabetes tend to develop erectile dysfunction 10 to
15 years earlier than men without diabetes.
Men with diabetes will have ED
50%-60% in > 50 years old
95% in >70 years old

Erectile Dysfunction
Risk Factors

Risk Factors
Neuropathy
Peripheral vascular disease
Poor glycemic control
Diabetes duration and complications
Age and high BMI
Smoking doubles the risk

Cardiovascular Diseases
Patients with Type 2 Diabetes at a increased risk of CVD

Patients (%)

Incidence of myocardial
infarction over 7 years

Risk of cardiovascular disease

is greater in patients with
diabetes than in those without
Having diabetes results in a
similar risk of heart attack as a
prior heart attack

With diabetes n=1059

Without diabetes n=1373

Haffner et al. N Engl J Med 1998;339:22934

Cardiovascular Diseases
Risk for Myocardial infaction and stroke increases with progression to Type 2 Diabetes

Relative risk

Relative risk for MI and stroke in

women

No diabetes
during study

Prior to
diagnosis

*Nurses Health Study (NHS) cohort comprised women only

Adapted from Hu et al. Diabetes Care 2002; 25:1129-34

After
diagnosis

Diabetic at
baseline

Prevention of Cardiovascular Diseases

Number of deaths per 10,000 patient-years

Reduce risk factors for

cardiovascular disease:

Non-diabetic
subjects

140

Subjects with
type 2 diabetes

120

100
80
60
40
20
0
0

Number of risk factors

Adapted from Stamler et al. Diabetes Care 1993;16:43444

stop smoking
treat hypertension
treat hyperlipidaemia
improve glycaemic control
reduce weight in the obese
take regular exercise

Poor Control of CV Risk Factors in Diabetes (NHANES)

CV risk factors target

Frequency

S-Cholesterol < 200 mg/dl (5.2 mmol/l)

BP < 130/80 mmHg
HbA1c < 7.0%
All three risk factors controlled

52 %
36 %

37 %
7%

Unchanged CV risk factors from 1991 to 2000

Saydak SH et al. JAMA 2004

Treatment of Cardiovascular Diseases Risk factors

1.
2.
3.
4.
5.

Hypertension
Dyslipidemia
Antiplatelet agents
Smoking cessation
CHD screening and treatment

Diabetes Care 2012

Treatment of Cardiovascular Diseases Risk factors

Hypertension

SBP 130-139 or DPB 80-89 mmHg: lifestyle

modification (DASH) for 3 months, if fails
pharmacological agents
SBP 140 or DBP 90 mmHg:
Lifestyle modification +pharmacological
therapy

Dyslipidemia

Lifestyle modification + statins

Antiplatelet agents*

Aspirin and/or clopidogrel

Smoking cessation

Stop smoking, counseling

CHD screening and

treatment

ACE-I and aspirin and statin (if not

contraindicated)

*Depends on risk factors (???)

Diabetes Care 2012

Hypertension
SBP 140 or DBP 90 mmHg lifestyle mod + pharmacological
therapy
SBP 130-139 or DPB 80-89 mmHg: lifestyle modification (DASH)
for 3 months, if fails pharmacological agents
Administer one or more anti-HT meds at bedtime
Monitor kidney function and serum potassium in pt receiving ACEIs, ARBs, or diuretics
Remember: ACE-Is and ARBs are contraindicated in pregnancy
BP target SBP <130mmHg & DBP <80mmHg
Diabetes Care 2012

Meta-analysis of Statin Treatment in Diabetes

Risk reduction of clinical outcomes

per 40 mg/dL (1.0 mmol/L) reduction in LDL cholesterol

21% reduction major vascular events
25% reduction in coronary revascularisation
21% reduction in stroke
9% reduction in all-cause mortality
13% reduction in CVD mortality
No difference in non-vascular mortality
Independent of baseline LDL or prior CVD

Lancet 371, 117-25. 2008

Statin Conclusion

Statin therapy should be considered for all individuals

with type 2 diabetes
independent of baseline lipid levels

However lack of data for age < 40y

and should be considered for individuals with type 1
diabetes at high risk of CVD or with signs of diabetic
complications

What is hypoglycemia?
A statesymptoms
of neuroglycopenic
and/or
neurogenic
neurogenic
due to low
plasma
glucose levels
symptoms due to low plasma glucose levels

Low plasma glucose levels defined as:

70 mg/dL (ADA)1
<60 mg/dl (PERKENI)2
<72 mg/dL (CDA)3

Symptoms respond to the administration of carbohydrate3

ADA, American Diabetes Association; CDA, Canadian Diabetes Association;

1. ADA. Diabetes Care 2005;28:12459; 2. PERKENI Konsensus 2011. 3. Yale et al. Canadian J Diabetes 26:2235

Why address hypoglycemia in diabetes training

Reducing HbA1c levels associated with prevention or delay in
complications and death
Hypoglycaemia is a limiting factor in achieving glycaemic
targets
Hypoglycaemia is associated with morbidity and rarely even be
fatal

Optimising glycaemic control is of obvious importance:

$465 billion USD spent to treat diabetes and its complications in
2011; hypoglycaemia is cost-intensive
6.8% of global all-cause mortality attributed to diabetes in 2010
(4 million deaths)

Cryer et al 2003. Diabetes Care; 26,6: 1902-1912. IDF Diabetes Atlas tth ed., 2009. Roglic and Unwin 2010. Diabetes
Research and Clinical Practice; 87: 15-19

Most common symptoms of Hypoglycemia

Sweating
Blurred vision
Weakness
Tremor
Slurred speech
Palpitations
Hunger
Circumoral paraesthesia
Vertigo
Headache
Cold feeling
Anxiety
Euphoria
Nausea
Difficulties in concentration
0

20

40

60

Patients (%)
Pramming 1991

80

100

Risk Factors of Hypoglycemia

General risk factors for hypoglycaemia:1,2

delayed or missed meal

consuming a smaller meal than planned
exercise
use of diabetes medications
drug/alcohol consumption
increased insulin sensitivity or decreased insulin clearance

Risk factors for major hypoglycaemia:3,4

age/duration of diabetes treatment
intensive glycaemic control
hypoglycaemia unawareness
sleep
antecedent hypoglycaemia
history of major hypoglycaemia

1.Briscoe & Davis. Clin Diabetes 2006;24:11521; 2. ADA Workgroup on Hypoglycemia. Diabetes Care
2005;28:12459. 3. Frier. Diabetes Metab Res Rev 2008;24:8792; 4. Cryer. Diabetes 2008;57:316976

Prevention of Hypoglycemic Events

Education
Symptoms
Self management
Proper food intake in therapy
For elderly patients, caregiver should also be educated
Repetitive education in patients with decreased cognitive function
Self monitoring blood glucose (SMBG)
Exercise planning
Measuring blood glucose before exercise
Consuming carbohydrate
Adjust insulin dose based on the blood glucose level
Right type and dose for therapy

Treatment of mild Hypoglycemia

Treating early signs

First: 1020 g fast-acting carbohydrate, e.g.:
36 glucose tablets*
90180 ml fizzy drink or squash (not diet)**
Two teaspoons of sugar added to a cup of cold drink
50100 ml energy drink (e.g. Lucozade)*

Then:
If next meal is due, add extra carbohydrate
If next meal is not due, eat longer-acting carbohydrate,
such as biscuits or a sandwich
*not widely available in Indonesia
** Indonesia processed drinks (tea, etc)

RCN 2004

Treatment of moderate-to-major Hypoglycemia

Treating late signs

Patient requires assistance with treatment
If conscious:
Carer should help the patient to consume
1020 g fast-acting carbohydrate
Dextrose gel* may be useful

If unconscious:
Dont put anything in patients mouth
IM or SC glucagon* or IV glucose should be
administered
Emergency services should be called

IM: intramuscular, SC: subcutaneous, IV: intravenous

RCN 2004; Cryer 2010

Thank You