Transcript Complications of Diabetes

Complications of Diabetes
영양병원 내과
이준엽
Classifications
Acute complications
1) Hypoglycemia
2) comas (DKA Vs HHS)
 Chronic complications
1) Diabetic microvascular Cxs.
(retinopathy, nephropathy,
neuropathy)
2) Diabetic macrovascular Cxs.
(coronary, cerbral a. , foot ulcers,
HTN)

Acute Complications
Complications
Cause
Early Signs
Prevention
Diabetic
Ketoacidosis
(DKA)
- Insulin deficit
causing
severe metabo
lic alterations
Weight loss
•
Increased urination
•
Increased thirst
•
Vomiting
•
Rapid breathing
- Insulin must
be given
Hyperosmolar
Hyperglycemi
c Nonketotic
- Excessive blood
glucose conce
ntration
Increased urination
•
Increased thirst
•
Fatigue
•
Lethargy
- Maintaining
blood glucose
within
lower range
- Blood glucose
drops
significantly b
elow healthy
range and can
not recover
naturally
because
of diabetes
medications.
Lightheaded
•
Dizzy
•
Shakey
•
Hungry
- Carbohydrate
food intake is
balanced wit
h medication
and activity
Coma (HHNK)
Hypoglycaemia
•
Weak, Tired
Chronic Complications
Systems Effected
Disease
Health Concern
Eyes
•
•
Retinopathy
Glaucoma
•
Blindness
•
Cataracts
•
•
•
Coronary artery disease
Cerebral vascular disease
Peripheral vascular disease
•
•
•
•
Hypertension
Heart attack
Stroke
Poor circulation in feet
and legs
Heart attack, stroke,
Blood Vessels
•
kidney damage
Kidneys
Nerves
•
Renal insufficiency
•
Insufficient blood filtering
•
Kidney failure
•
Loss of ability to filter blood
•
Neuropathies
•
Autonomic neuropathy
•
•
Chronic pain
Poor nerve signaling to
organ systems
Skin, Muscle, Bone
•
•
Advanced infections
Cellulitis
•
Gangrene
•
Amputation
Acute Complications
- Hypoglycemia
1.
2.
3.
IV or Oral glucoses
evaluations of cause
(drug overdose? – PO Vs Insulin
, other cause?)
managements?
Acute Complications
- Comas
1.
2.
3.
4.
** Hydrations
(ex. N/S 1 L full dropping)
** Insulin??
(ex. N/S 500 + HR 100 IU)
Evaluations and Causes?
(DKA Vs HHS)
Managements
(Key points: deficiency of insulin)
Chronic Complications
1)
Diabetic microvascular Cxs.
(retinopathy, nephropathy,
neuropathy)
2)
Diabetic macrovascular Cxs.
(coronary, cerebral a. , foot ulcers,
HTN)
Prevention and treatment of
microvascular complications
 Glycemic control and microvascular complications
 Blood pressure control and microvascular complications
 Other preventive and therapeutic measures
 Follow-up and specific treatment of nephropathy
 Follow-up and specific treatment of retinopathy
The Diabetes Control and
Complications Trial (DCCT)
Multicenter, randomized study of type
1 diabetes patients
 To assess effect of intensive glycemic
control vs conventional therapy on:
development and progression of
retinopathy and other long-term
complications
 Results of this trial led to similar
studies of type 2 diabetes patients

DCCT Research Group. N Engl J Med. 1993;329:977-986.
Overall Results of
the DCCT Trial

Intensive control of blood glucose reduced
risk of diabetic complications
1) retinopathy onset ↓76% in patients with no
retinopathy at baseline (P≤0.002)
2) retinopathy progression ↓54% in patients with
mild retinopathy at baseline (P≤0.002)
3) nephropathy ↓54% (P<0.04)
4) neuropathy ↓60% (P≤0.002)

There was, however, a 2- to 3-fold greater
incidence of severe hypoglycemia
DCCT Research Group. N Engl J Med. 1993;329:977-986.
Relative Risk of Progression of
Diabetic Complications
Possible molecular mechanisms
of diabetes-related complications.
Harrison's Principles of Internal Medicine, 16th Edn
Mechanisms of Glucose Related
Complications
ReuschJEB: J ClinInvest 2003;112:986-988
Consequences of hyperglycemiainduced activation of
protein kinase C (PKC)
Vascular Health and Risk Management 2007:3(6):823-832
Diabetic retinopathy

Annually ophthalmic exam
Retinal Anatomy and Mechanisms
of Diabetic Retinopathy.
N Engl J Med 350:48, January 1, 2004 Review Article
Diabetic retinopathy
실명
Follow-up of retinopathy
Optimal glycemic control
(HbA1c < 7%)
Target blood pressure
(< 130/80 mm Hg)
Monitor FO 12 monthly
FAG only if FO suspect
Identify and correct
reversible factors
Optimal glycemic control
(HbA1c < 7%)
Target blood pressure
(< 130/80 mm Hg)
Monitor FO 12 monthly
Monitor FAG every 2 yrs
Photocaogulation only in
case of macular edema
Optimal glycemic control
(HbA1c < 7%) with gradual
amelioration
Target blood pressure
(< 130/80 mm Hg)
Monitor FO 3-6 monthly
FAG pre- and postphotocaogulation
Photocaogulation
0
Optimal glycemic control
Surgery
Advanced (HbA1c < 7%) with gradual
amelioration
No
Target blood pressure
Prolif. (< 130/80 mm Hg)
Monitor FO 3-6 monthly
Bckg
FAG pre- and postPrephotocaogulation
Prolif.
Photocaogulation
Control common
CV risk factors
Optimal glycemic control
(HbA1c < 7%) with gradual
amelioration
Target blood pressure
(< 130/80 mm Hg)
Monitor FO 6 monthly
FAG in preparation for
photocaogulation
Photocaogulation
Pre-proliferative and
Proliferative Retinopathy
Clinically significant
Macular Edema
Photocoagulation
focal
grid
panphotocoagulation
panphotocoagulation + grid
Diabetic nephropathy

Annually 24hr urine protein
Stages of Renal Involvement According to the
Urinary Albumin Level in Patients
with Type 2 Diabetes Mellitus.
N Engl J Med 346:1145, April 11, 2002 Clinical Practice
Recommended Interventions to Slow the
Progression of Renal Disease
in Patients with Type 2 Diabetes.
N Engl J Med 346:1145, April 11, 2002 Clinical Practice
Suggested Medications for Hypertension in
Patients with Type 2 Diabetes.
N Engl J Med 346:1145, April 11, 2002 Clinical Practice
Refer to renal team
Follow-up of nephropathy
RRT education and modality
selection
Access creation (no temporary)
Start RRT early in diabetics
Optimal glycemic control
Avoid malnutrition
(HbA1c < 7%)
Optimise Hb and Ca/P control
Target blood pressure
Refer to renal team
(< 130/80 mm Hg)
Optimal glycemic control, but
0
Monitor UAE 12 monthly
avoid hypoglycemia
Monitor GFR 12 monthly
Macro & Target blood pressure
ESRD
Maintain RAS blockade, except
in patients with GFR>15 ml/min
Normo
Identify and correct
Macro Restrict
&
dietary protein (to
30
mg
reversible factors
 GFR 0.8 or even 0.6 g/kg bw/d),
Micro
but avoid malnutrition
Macro & Restrict P (add binders), K & Na
Optimal glycemic control
Control Hb with EPO & Fe
= GFR
Target blood pressure
Monitor UAE 3 monthly
300 mg
Control UAE irrespective
Optimal glycemic control
Monitor GFR 3 monthly
of BP with RAS blockade
Target blood pressure
Monitor UAE 6 monthly
(< 125/75 mm Hg)
Monitor GFR 12 monthly
Control UAE irrespective
Control common
of BP with RAS blockade
CV risk factors
Restrict dietary protein (to 0.8 g/
kg bw/d) in selected cases
Monitor UAE 3 monthly
Monitor GFR 6-12 monthly
Renal replacement therapy
Options
GFR
GFR
50
50
No
30
15
10
5
HD
Transplant ?
Kidney +
pancreas
Kidney
PD
cadaveric
living
Waiting
list
Waiting
list
Access
Start
HD
Yers
Start
PD
Trapianto
30
15
10
5
Diabetic neurophathy

Every visit, foot exam
Sensory Foot Exam Findings
Diabetic foot ulcers
Diabetic foot ulcers
Consensus guidelines: treatment planning options. Mayo Clin Proc. 2006;81[4 suppl]:S12-S25.
Monitoring Parameters for
Control of Complications
Every visit
Blood Pressure
Foot Exam (55% achieve goal)
_______________________________________________________
3-6 months
A1C
- Every 3 months if treatment changes or
not meeting goals
- Every 6 months if stable
_______________________________________________________
Annual
Dilated Eye Examination (63% achieve goal)
Lipid Levels*
Microalbumin
_______________________________________________________
*Every 2 years if levels fall in lower risk categories
Macrovascular complications
Coronary A. diseases
 Cerebral A. diseases
 Foot ulcers
 Hypertensions

Causes of Death
in People with Diabetes
50
40
% deaths
30
20
10
0
Ischaem Other
ic Heart Heart
Disease Disease
Diabetes
Cancer
Stroke
Infection
Other
Geiss LS, et al. In: Diabetes in America, 2nd ed. 1995. Bethesda, MD: NIH; 1995
TYPE 2 DIABETES
Hyperglycaemia
(Insulin resistance)
Hypertension
Dyslipidaemia
Endothelial
dysfunction
Central obesity
Hypertriglycaeridemia
Low
HDL-C
Small, dense
LDL-C
CVD
Impaired fibrinolysis
Proinflammatory
state
Relationship Between Glycemic Control
and Coronary Heart Disease Events in
Type 2 Diabetes Patients (Ages 65 to 74)
3.5-yr Incidence (%)
25
20
HbA1c <7.0%
15
HbA1c 7.0%
10
5
0
<6
6
Duration of Diabetes (yr)
Kuusisto J et al. Diabetes. 1994;43:960-967.
UKPDS Impact of Tight* vs Less Tight† Blood Pressure
Control on Diabetes-Related Endpoints
Any DM-related
endpoint
DM-related deaths
All-cause mortality
Myocardial
infarction
Stroke
Peripheral vascular
disease
Microvascular
complications
Relative risk
for tight control
(95% CI)
0.76 (0.62–0.92)
0.68 (0.49–0.94)
P Value
0.79 (0.59–1.07)
0.56 (0.35–0.89)
0.005
0.02
0.17
0.13
0.01
0.51 (0.19–1.37)
0.17
0.63 (0.44–0.89)
0.009
0.82 (0.63–1.08)
*n=758 (mean achieved blood pressure of 144/82 mmHg)
†n=390 (mean achieved blood pressure of 154/87 mmHg)
Adapted from UKPDS Group. BMJ. 1998;317:703–713.
Relative risk
reduction
(95% CI)
0.1
Favors tight
control
1
10
Favors less
tight control
Relative Risk Reduction With ACEIs
in ABCD, CAPPP and FACET
Acute
Myocardial
Infarction
0
Cardiovascular
Event
All-cause
Mortality
Stroke
-10
-24
-20
NS
-30
-43
-40
-51
-50
-60
-70
-63
P=0.01
P<0.001
P<0.001
Pahor M, et al. Diabetes Care. 2000;23:888-892.
DIABETIC HYPERTENSION
Combinations of two or more drugs are usually needed to
achieve the target goal of <130/80 mmHg.
Thiazide diuretics, BBs, ACEIs, ARBs, and CCBs are
beneficial in reducing CVD and stroke incidence in
patients with diabetes.
ACEI- or ARB-based treatments favorably affect the
progression of diabetic nephropathy and reduce
albuminuria, and ARBs have been shown to reduce
progression to macroalbuminuria.
The seventh Report of the Joint National Committee on Prevention, Detection, Evaluation
of High Blood Pressure, May 2003
Intensive blood pressure control in diabetic patients
hypotensive
effect
Function
Carbohydrate metabolism
kidney:  RPF ( Re>Ra) = GFR   P  proteinuria
 or = insulin secretion & sensitivity
retina:  capillary P;  endothelial dysfunction
protection
criteria
= response to influence
hypoglycemia on
vessels:  constr.
(resp. ET-1)  dilat (NO)
of function
target& coronary flowof
glycolipid
heart:  myocardial
organs
Lipid metabolism
choice
metabolism
Structure
 or = LDL-C & TG
 kidney, retina vessels & heart remodeling
 or = HDL-C
x  cell growth & matrix production
side
effects
Intensive blood pressure control in diabetic patients
Nephropathy Retinopathy
Thiazidic diuretics
Unknown
Coronaric
evelts
Stroke
Type A evidence
referred to UKPDS
(low
number of
Favorable
(A)events)
Favorable (A)
-blockers
Unknown
 CV events
(mainly heart failure)
Unknown
 ALLHAT
CV events
(mainly coronaric)
ABCD (nisoldipine)
Unknown
metanalysis
(nifedipine)
Favorable (A)
-blockers
Controversial
Unknown
Controversial
Unknown
Ca-channel blockers (DHP)
Controversial
Unknown
Controversial
Favorable (A)
Ca-channel blockers (non-DHP)
Favorable (C)
Unknown
Unknown
Unknown
ACE-inhibitors
Favorable (A)
Favorable (A)
Favorable (A)
Favorable (A)
AT1 receptor antagonists
Favorable (A)
Unknown
Favorable (A)
Favorable (A)
Loop diuretics
Central adrenergic agents
Unknown
Unknown
Favorable (A)
Unknown
Unknown
Reduce GFR and
doesn’t ameliorate
Unknown studiesUnknown
Short-term
proteinuria
with
few patients
(afferent
arteriole
Effective
on Favorable (A)
Favorable
(A)
vasodilation)
proteinuria (GFR ?)
2003 ADA Clinical Practice Recommendations
Intensive blood pressure control in diabetic patients
Step 1
Low sodium diet (100 mEq/day), body weight
control, physical exercise, stop smoking
Step 2
ACE-inhibitors or Ang-II antagonists
Step 3
Ca-antagonist (non-DHP)
Step 4
Diuretics, -blockers or -blockers
Step 5
Central adrenergic or vasodilators
Intensive blood pressure control in diabetic patients
Arterial hypertension
untreated BP level
other risk factors
target organ damage
one drug
at low-dose
other drug
at low-dose
BP target not reached
two drugs
at low-dose
same
combination
at full-dose
same drug
at full-dose
other drug
at low-dose
BP target not reached
monotheraphy
at full-dose
combination
combination
of three drugsi
at full-dose
Intensive blood pressure control in diabetic patients
diureticis
-blockers
AT1RB
-blockers
CCBs
ACEi
Antiplatelet therapy
Primary prevention
DM1 and DM2 patients >30 years
with high CV risk
CAD family history
Smoking
Hypertension
Obesity (>120% BMI); BMI >27.8
kg/m2 M or >27.3 kg/m2 F
 Dislipidemia: TC >190 mg/dl; LDL-C
>100 mg/dl; HDL-C <45 mg/dl M or
<55 mg/dl F; TG >150 mg/dl
 Albuminuria (micro or macro)




aspirin (tablets)
81–325 mg/day
Contraindications
 Allergy
 Bleeding tendency
 Anticoagulating treatment
 Recent gastro-intestinal bleeding
Secondary prevention
 Clinically active liver disease
DM1 and DM2 patients with clinical
history of cardiovascular disease
 Age <21 years ( Reye’s syndrome)




myocardial infarction or angina
Stroke or TIA
Peripheral vascular disease
By-pass surgery
clopidogrel
ticlopidine
Reduce macrovascular
complications
Good glycaemic control
 LDL-Cholesterol <100 mg/dL (Statins)
 BP <130/80 mm Hg (ACE inhibitors)
 Weight loss ~5% to 10% body
weight
 Aspirin
 No Smoking
 Realistic exercise

Key message
of Diabetic complications
Intensive glucose control
 Restrictive BP control by using ACEIs
(<130/80)
 Stop smoking
 Control dyslipidemia
 Exams
(foot, OPH, Lab …)
 Aspirins
