staged diabetes management complications of diabetes and metabolic syndrome

International Diabetes Center
International Diabetes Center
Staged Diabetes
Management: Complications
of Diabetes and Metabolic
Syndrome
2004 Priorities of Care for Adults with Diabetes
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Glucose
Insulin Resistance
Glucose
Insulin Resistance
Microvascular
Complications
Microvascular
Complications
Other Essential
Areas of Care
Other Essential
Areas of Care
Glycemic Targets
HbA1c < 7.0%

SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L- 7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L- 7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Lipid Targets
LDL < 100 mg/dL

(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Annual Screening

Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Diabetes Self-Management Skills
Lifestyle Behavioral Health
Patient Education Emotional assessment
BG Monitoring distress, depression, complications
Medical Nutrition Support needs
Physical Activity family, peers, medical
Macrovascular Complications
ASA, Tobacco cessation ACEI / ARB, Statin

Lipids
Lipids
Hypertension
Hypertension
International Diabetes Center
International Diabetes Center
Rates of Coronary Heart Disease
Nondiabetic vs.Type 2 Diabetes Subjects
3.5
20.2
18.8
45
0
10
20
30
40
50
No Diabetes Diabetes
No History of CVD
Prior MI
Haffner SM.
Haffner SM.
N Engl J Med
N Engl J Med
1998;339:229-34
1998;339:229-34
CHD Events
CHD Events
(% over 7 years)

(% over 7 years)
N = 1373
N = 1059
2004 Priorities of Care for Adults with Diabetes
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Glucose
Insulin Resistance
Glucose
Insulin Resistance
Microvascular
Complications
Microvascular
Complications
Other Essential
Areas of Care
Other Essential
Areas of Care
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL

(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL

(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Annual Screening
Nephropathy
Microalbuminuria

Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Diabetes Self-Management Skills
Lifestyle Behavioral Health
Patient Education Emotional assessment
BG Monitoring distress, depression, complications
Medical Nutrition Support needs
Physical Activity family, peers, medical
Macrovascular Complications
ASA, Tobacco cessation ACEI / ARB, Statin
Lipids
Lipids

Hypertension
Hypertension
International Diabetes Center
International Diabetes Center
Medical Nutrition Therapy for
Dyslipidemia
•
Physical activity and weight loss
–
modest decrease in TRI and increase in HDL
•
Fat < 30% total calories
–
Saturated fat <10%
–
Lean meats and low-fat dairy products
•
Avoid alcohol
–
Increased fatty acid synthesis and TRI level
•
Maximum lowering of LDL by 15-25 mg/dL (0.39-0.64
mmol/L)
International Diabetes Center
International Diabetes Center
Medical Nutrition - Non Drug Therapy
Medical Nutrition - Non Drug Therapy
Dietary changes Physical activity Weight management
Dietary changes Physical activity Weight management
Fibrate

Fibrate
Glucose Control
Glucose Control
Fibrate
Fibrate
Glucose Control
Glucose Control
Statin
Statin
Glucose control
Glucose control
Statin
Statin
Glucose control
Glucose control
Statin
Statin
Glucose control
Glucose control
Statin
Statin
Glucose control
Glucose control
↑
↑


LDL
LDL↑
↑

LDL
LDL
Mixed Disorders
Mixed Disorders
↑
↑


LDL and
LDL and
↑
↑
Trigs
Trigs
Mixed Disorders
Mixed Disorders
↑
↑


LDL and
LDL and
↑
↑
Trigs
Trigs
↑
↑

Trigs
Trigs
Low HDL
Low HDL
↑
↑


Trigs
Trigs
Low HDL
Low HDL
Add Atorvastatin or
Add Atorvastatin or
Simvastatin if LDL >100
Simvastatin if LDL >100


Consider-Nicotinic Acid
Consider-Nicotinic Acid
Thiazolidinediones???
Thiazolidinediones???
Add Atorvastatin or
Add Atorvastatin or
Simvastatin if LDL >100
Simvastatin if LDL >100

Consider-Nicotinic Acid
Consider-Nicotinic Acid
Thiazolidinediones???
Thiazolidinediones???
Add Fibrate*
Add Fibrate*
Consider-Nicotinic Acid
Consider-Nicotinic Acid
Add Fibrate*
Add Fibrate*
Consider-Nicotinic Acid
Consider-Nicotinic Acid
Add Resin
Add Resin
Add Resin
Add Resin
* when using a statin and fibrate in combination therapy, monitor for
myositis (muscle pain and weakness)
Therapy Selection
International Diabetes Center
International Diabetes Center
Treatment with Simvastatin
in Patient With
Diabetes and Heart Disease
0
5
10
15
20
25

30
35
40
45
50
Diabetes No Diabetes
Placebo
Simvastatin
55%
55%
reduction
reduction
32%
32%
reduction
reduction
4S Trial Investigators. Pyorala K
4S Trial Investigators. Pyorala K
, Diabetes Care
, Diabetes Care
20:614, 1997
20:614, 1997
5 Year CVD Event Rate (%)
5 Year CVD Event Rate (%)
N = 202 N = 2,242
International Diabetes Center
International Diabetes Center
Potential Benefits of Different Therapies:
Increasing HDL and Decreasing
Triglycerides

(% change)


↓
↓
Triglyceride (%)
Triglyceride (%)
-60
-60
-50
-50
-40
-40
-30
-30
-20
-20
-10
-10
0
0
Glucose
Glucose
control
control
Statin
Statin
Fibrates
Fibrates

TZD
TZD
Metformin
Metformin
Niacin
Niacin
-25
-25
-35
-35
-60
-60
-25
-25
-15
-15
-35
-35
↑
↑


HDL %
HDL %
<10%
<10%
5-10%
5-10%
5-10%

5-10%
10-30%
10-30%
10-20%
10-20%
Minimal
Minimal
0
0
5
5
10
10
15
15
20
20
25
25
30
30
*DM Kendall. Data adapted from multiple reference (meta-analysis).
*DM Kendall. Data adapted from multiple reference (meta-analysis).
International Diabetes Center
International Diabetes Center
Aspirin Therapy
•
Effective in primary and secondary prevention
•
Blocks thromboxane (vasoconstrictor and platelet

aggregant) synthesis
–
Reduces inflammation
•
Enteric coated aspirin 81-325 mg/day for those >30
years of age
•
Consider alternative antiplatelet therapy (i.e.
clopidogrel) if aspirin not tolerated or allergy
Hansson, Lancet 351:1755-1762, 1998
Peterson, et al Am J Med 109371-377, 2000
2004 Priorities of Care for Adults with Diabetes
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Glucose
Insulin Resistance
Glucose
Insulin Resistance
Microvascular
Complications
Microvascular
Complications

Other Essential
Areas of Care
Other Essential
Areas of Care
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL

(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy

Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Diabetes Self-Management Skills
Lifestyle Behavioral Health

Patient Education Emotional assessment
BG Monitoring distress, depression, complications
Medical Nutrition Support needs
Physical Activity family, peers, medical
Macrovascular Complications
ASA, Tobacco cessation ACEI / ARB, Statin
Lipids
Lipids
Hypertension
Hypertension
International Diabetes Center
International Diabetes Center
BP Control: Results from the UKPDS
N= 5102
•
Tight BP control (Avg. BP 144/82 mmHg) compared to
“less” tight BP control (Avg. BP 154/87 mmHg)
resulted in reduction in risk of:
–
37% for microvascular complications (nephropathy
& retinopathy)
–
32% for diabetes related deaths (44% for strokes)
•
ACE inhibitor (captopril) or beta-blocker (atenolol)
equally effective in reducing risk
•
Continuous relationship between systolic BP and
diabetes related complications above 130 mmHg
International Diabetes Center

International Diabetes Center
Type 2 Diabetes: Risk, Blood
Glucose and Blood Pressure
0
2 5
5 0
7 5
1 00
risk
1
2
3
4
HbA1c
BP
1. Any increase in HbA
1c
or BP raises
the risk of vascular complications.
2. Any increase in both raises the risk
of vascular disease still more.
United Kingdom
Prospective
Study (UKPDS)
International Diabetes Center
International Diabetes Center
Blood Pressure Target in Diabetes
<130/80 mmHg
<120/75 mmHg
With Renal Disease

International Diabetes Center
International Diabetes Center
Number of Major Cardiovascular Events in
Subjects with Diabetes
The Hypertension Optimal Treatment (HOT) Trial
24.4
18.6
11.9
0
5
10
15
20
25
30
<90 < 85 <80
Major CV Events/
1000 pt. years
Hanson et al Lancet 351: 1757, 1998
Target Diastolic BP (mmHg)
N = 1501
P = 0.005 for trend
International Diabetes Center
International Diabetes Center
Is hypertension being
controlled? How do you know?
International Diabetes Center
International Diabetes Center
110
120

130
140
150
160
12:00 AM
2:00 AM
4:00 AM
6:00 AM
8:00 AM
10:00 AM
12:00 PM
2:00 PM
4:00 PM
6:00 PM
8:00 PM
10:00 PM
12:00 AM
Mean Systolic BP 136 +/- 7 mmHg
Blood Pressure Profile
90
th
percentile
75
th
percentile
Median
25
th
percentile
10

th
percentile
90
th
percentile
75
th
percentile
Median
25
th
percentile
10
th
percentile
BP Threshold
BP Threshold
International Diabetes Center
International Diabetes Center

:
100
125
150
175
200
12:00 AM
2:00 AM
4:00 AM
6:00 AM

8:00 AM
10:00 AM
12:00 PM
2:00 PM
4:00 PM
6:00 PM
8:00 PM
10:00 PM
12:00 AM
50
75
100
125
12:00 AM
2:00 AM
4:00 AM
6:00 AM
8:00 AM
10:00 AM
12:00 PM
2:00 PM
4:00 PM
6:00 PM
8:00 PM
10:00 PM
12:00 AM
Blood Pressure Profile
using self-monitored
BP at home for 2 weeks
of a person with Type 2

Diabetes and normal BP
( 129/79 mmHg) based
on office measurement
DX: Normotensive
Systolic BP
(mmHg)
Diastolic BP
(mmHg
Although the patient
had the same mean BP
based on SMBP, 63% of
systolic and 80% of the
diastolic values were
above the threshold for
hypertension
DX: Hypertensive
International Diabetes Center
International Diabetes Center
Staged Management
Treatment of Hypertension in Diabetes
ACE Inhibitor
ACE Inhibitor
Drugs of choice
Drugs of choice
Limits progression of nephropathy - Lowers CVD risk
Limits progression of nephropathy - Lowers CVD risk
Alternative = A II Receptor Blocker
Alternative = A II Receptor Blocker
Thiazide
Thiazide

Combo. with ACEI
Combo. with ACEI
Useful in Elderly
Useful in Elderly
Central
Central
α
α
-Blockers
-Blockers
Vasodilators
Vasodilators
Combination Rx
Combination Rx
Beta - Blockers
Beta - Blockers
Effective Post MI
Effective Post MI
Avoid if severe
Avoid if severe
hypoglycemia
hypoglycemia
Ca++ channel
Ca++ channel


Blockers
Blockers
Useful in combination
Useful in combination

Non-DHP preferred
Non-DHP preferred
Diagnosis of Hypertension
Diagnosis of Hypertension
> 130/80 mmHg
> 130/80 mmHg
Non Pharmacologic Therapies
Non Pharmacologic Therapies
2004 Priorities of Care for Adults with Diabetes
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Prevention - Diagnosis
Preventions Prediabetes (IFG -IGT) & Metabolic Syndrome
Diagnosis Fasting glucose > 126 mg/dL (7 mmol/L) or
Casual glucose > 200 mg/mL (11.1 mmol/L) + Symptoms
History and Physical Exam
Glucose
Insulin Resistance
Glucose
Insulin Resistance
Microvascular
Complications
Microvascular
Complications
Other Essential
Areas of Care
Other Essential

Areas of Care
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Glycemic Targets
HbA1c < 7.0%
SMBG (~ 50% of readings)
Pre Meal 70-140 mg/dL
(3.8 mmol/L-7.8 mmol/L)
Post Meal <160 mg/dL
(8.9 mmol/L)
Combination therapy
Insulin therapy
Insulin sensitizers
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy

Combination therapy
Lipid Targets
LDL < 100 mg/dL
(2.6 mmol/L)
Triglyceride < 150 mg/dL
(1.7 mmol/L)
HDL > 40 mg/dL
(1.0 mmol/L)
Statin therapy
Fibrate therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Blood Pressure
Targets
Mean BP <130/80 mmHg
ACEI or Thiazide
therapy
Combination therapy
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot

examination
Sexual Heath assessment
Annual Screening
Nephropathy
Microalbuminuria
Retinopathy
Dilated retinal examination
Neuropathy
Neurological and Foot
examination
Sexual Heath assessment
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Care of the Hospitalized
Patient with Diabetes
Care of Gestational DM
Foot Care
Oral & Dental Care
Immunizations
Flu Shot + Pneumovax
Diabetes Self-Management Skills
Lifestyle Behavioral Health
Patient Education Emotional assessment
BG Monitoring distress, depression, complications
Medical Nutrition Support needs

Physical Activity family, peers, medical
Macrovascular Complications
ASA, Tobacco cessation ACEI / ARB, Statin
Lipids
Lipids
Hypertension
Hypertension
International Diabetes Center
International Diabetes Center
Effect of Elevated Glucose
on the Kidney
Normal Glomerulus
Afferent Arteriole
Efferent Arteriole
Waste Products
Salts
Afferent ArterioleEfferent Arteriole
Waste Products
Salts
Protein (Albumin)
Glucose?
Abnormal Glomerulus
International Diabetes Center
International Diabetes Center
Screening for Microalbuminuria
Normal < 30 mg/g creatinine
Microalbuminuria 30-300 mg/g
Macroalbuminuria >300 mg/g
Random Urine
Albumin/creat ratio

24 Hour Urine Overnight Urine
Normal < 30 mg/24 hr
Microalbuminuria 30-300 mg/24 hr
Macroalbuminuria >300 mg/24 hr
Normal < 20 ug/min
Microalbuminuria 20-200 ug/min
Macroalbuminuria >200 ug/min
Start ACE inhibitor if
Start ACE inhibitor if
microalbuminuria
microalbuminuria
Start ACE inhibitor if
Start ACE inhibitor if
microalbuminuria
microalbuminuria
International Diabetes Center
International Diabetes Center
Albumin/Creatinine Ratio
•
Random, spot urine collection
•
First-void or other AM collection preferred
•
Albumin level corrected with creatinine
•
Normal: <30 mg/g
Microalbuminuria: 30-300 mg/g
Macroalbuminuria: >300 mg/g
International Diabetes Center
International Diabetes Center

Treatment Strategies for Nephropathy
•
Improved glycemic control HbA1c <7.0%
•
Control blood pressure <120/75 mmHg
–
ACE Inhibitor and/or Angiotensen II Receptor Blocker
preferred
•
Smoking cessation
•
Low protein diet (<0.8 g/kg/day) improves renal
function (slows increase in albumin level or the
decline in GFR or creatinine clearance)
–
For macroalbuminuria only
International Diabetes Center
International Diabetes Center
Benefit of ACE Inhibitor Therapy in
Diabetic Nephropathy
Lewis EJ. N Engl J Med 1993;329:1456-62
International Diabetes Center
International Diabetes Center
Meta-Analysis of Antihypertensive Therapy
in Persons with Diabetes and Kidney
Disease
Mean change*
in proteinuria
from baseline
-0.6

-0.5
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
Calcium
channel
blockers
Control
(Placebo)
ACE
inhibitors
Beta
Blockers
Others
* Natural logarithm
† P < .05, ACE
inhibitor vs calcium
channel blocker and
control
†