Aspirin therapy is reasonable for those with 10-year CVD risk >10% who are not at increased risk of bleeding  Aspirin therapy is recommended for those with a history of CVD to reduce the risk of recurrent events Diabetes Care. 2012 Jan;35 Suppl 1:S11-63 Circulation. 2007;116:e418-e499. BMJ 2012 Feb 22;344:e874 22 Management Plan Glycemic control  Goal: HbA1c < 7% for most adults  Lifestyle modification:  Diet and exercise  Or

1. Diabetes Mellitus and
Hyperlipidemia
Case report
December 20th, 2012
臨藥科技所 碩一 陳秋縈
指導老師 張智仁醫師

2. Case 1
2

3. Case 1
Age 65 Gender female
HT/BW 152cm/52.6kg BMI 22.8
Present illness
• 罹患糖尿病已有十幾年之久，並無規則性治療
• 近日內發現下肢水腫及眼睛視力模糊，於94年9月5日來院求診
Past medical history
• 數年前開過白內障手術
• 糖尿病病史已有十幾年
Family history
• 雙親皆罹患肺癌死亡
• 高血壓及糖尿病病史不清楚
Physical examination
• 左眼紅腫潮紅，上下肢沒有特殊發現
• 血壓 130/70 mmHg
3

4. Lab Data
Normal 09/07 11/02 12/18
AC Sugar (mg/dl) 70-110 176 110 99
HbA1c (%) <6 9.4 - -
Cholesterol (mg/dl) <200 289 263 -
TG (mg/dl) <150 1180 287 -
Blood
Creatinine (mg/dl) 0.4-1.5 2.8 2.8 -
GPT (U/L) <60 28 24 -
Uric acid (mg/dl) 2.6-6.0 9.3 8.9 -
Hb (g/dl) 12-16 - 7.2 -
尿蛋白 ++ ++
尿糖 + -
Urine WBC - -
RBC - -
Ketone - -
4

5. Case 1
如何解讀該病患之數據?
如何使用藥物來治療?
5

6. Initial Diabetes Evaluation
 Classify the diabetes
 Review previous treatment and glycemic control
 Detect the presence of diabetes complications
 Formulating a management plan
 Provide a basis for continuing care
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
6

7. Initial Diabetes Evaluation
65yr, BMI:22.8, 糖尿病病史已有十幾年, 並無規則性治療
AC Sugar: 176 mg/dl HbA1C: 9.4%
 Classify the diabetes
 Long-standing type 2 DM
 Review previous treatment and glycemic control
 Poor glycemic control
 Without regular treatment Correlation of A1C with Average Glucose
→ Poor compliance?
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
7

8. Detect the Presence of Diabetes Complications
Nephropathy- Assess albuminuria status
Our patient 9/7, 12/18: 蛋白尿 ++,下肢水腫, 左眼紅腫潮紅
Definitions of abnormalities in albumin excretion
24-Hour Collection Spot Collection Timed Collection
Category
(mg/24 h) (mg/g creatinine) (µg/min)
Normal <30 <30 <20
Microalbuminuria 30–299 30–299 20–200
Macroalbuminuria ≥300 ≥300 ≥200
 Spot urine: albumin/Cr ratio≈ g/d of albuminuria
 Urine dipstick testing: semiquantitative measurements
 Insensitive for microalbuminuria
+ 30 mg/dL (≈ estimate protein loss ≥300 mg/d )
++ 100 mg/dL Macroalbuminuria
+++ 300 mg/dL
++++ 1000 mg/dL
Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154 8

9. Detect the Presence of Diabetes Complications
Nephropathy- Assess renal function
Our patient 65y, female, 52.6kg, Cr 2.8 mg/dL
 MDRD equation eGFR= 18.02 ml/min/1.73 m2
 Cockcroft-Gault equation CCr= 16.63 ml/min
Stage Description GFR (ml/min/1.73 m2)
1 Kidney damage with normal or increased GFR ≥90
2 Kidney damage with mildly decreased GFR 60–89
3 Moderately decreased GFR 30–59
4 Severely decreased GFR 15–29
5 Kidney failure <15 or dialysis
Likelihood of DKD According to Staging by GFR and Level of Albuminuria
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63 Diabetic Kidney Disease
Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154 9

10. Detect the Presence of Diabetes Complications
Retinopathy
Our patient 數年前白內障手術, 近日眼睛視力模糊
 Glaucoma, cataracts, and other disorders of the eye occur earlier
and more frequently in people with diabetes
 26% of adults with type 2 DM developed retinopathy over 4 years
 Risk factors
 Duration of diabetes -main risk factor
 Poor glycemic control Relation of glycemic control and DM duration to retinopathy
 Nephropathy
 Hypertension
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
BMJ 2012 Feb 22;344:e874
Harrison's Principles of Internal Medicine, 18e 10

11. Detect the Presence of Diabetes Complications
Hypertension
Our patient BP 130/70 mmHg
 Diagnosis
 Repeat SBP ≥130 mmHg or DBP ≥80 mmHg
 The diagnostic cutoff is lower in diabetes than those
without diabetes (BP ≥140/90 mmHg)
 BP should be confirmed on a separate day
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
11

12. Detect the Presence Of Diabetes Complications
Dyslipidemia
09/07 11/02 Total Cholesterol (mg/dL)
Cholesterol (mg/dl) 289 high 263 high <200 Desirable
TG (mg/dl) 1180 very high 287 high 200-239 Borderline high
≥ 240 High
 Factors contribute to elevated TG
 Obesity Triglyceride (mg/dL)
 Physical inactivity <150 Normal
 Cigarette smoking 150-199 Borderline high
 Excess alcohol intake 200-499 High
 High carbohydrate
≥ 500 Very high
 Genetic disorders
 Drugs
 Several diseases: type 2 DM, CKD, nephrotic syndrome
 Hyperlipidemia in type 2 DM
 Hypertriglyceridemia and low HDL cholesterol
 Associated with high levels of insulin and insulin resistance
NCEP ATP III. Circulation. 2002;106:3143-3421.
Harrison's Principles of Internal Medicine, 18e 12

13. Other Conditions
Anemia
Our patient Hb : 7.2 g/dl
 Possible cause: complications of CKD
 Need further test for evaluation
 CBC, reticulocyte count, Fe, TIBC, TSAT, ferritin, stool OB
Asymptomatic hyperuricemia
Our patient Uric acid : 9.3 mg/dl
 Possible cause: secondary hyperuricemia due to decreased renal
clearance
 Drug therapy is not justifiable by risk/benefit analysis
Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154
13

14. Formulating a Management Plan of Diabetes
Problem list
• Long-standing Type 2 DM
• Diabetic nephropathy with CKD stage 4
• Diabetic retinopathy
• Dyslipidemia
Treatment strategies
• Glycemic control
• Slow progression of of diabetic nephropathy
• BP control
• Lipid management
• Antiplatelet agent
• Patient education
14

15. Management Plan
Treatment of diabetic nephropathy
 Goal: slow the progression of nephropathy
 Reduction of protein intake
 Earlier stages of CKD: 0.8-1g/kg/d
 Later stages of CKD: 0.8 g/kg/d
 Treat with ACE or ARB
 If micro- or macroalbuminuria
 Monitor Creatinine and K level
− Discontinue when K > 5.6 mmol/L or Creatinine ↑> 30% above baseline
 Continued monitoring of urine albumin excretion to assess both
response to therapy and progression of disease
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
Arch Intern Med 2000 Mar 13;160(5):685 15

16. ACEI/ARB
Drug approved for DM nephropathy Our patient Clcr=16.63 ml/min
Strength Dosage for DM Dose adjustment in CYP450
per tab nephropathy renal dysfunction metabolism
ACEI
25mg tid Clcr 10-50 mg/min
Captopril 25 mg CYP2D6 (major)
AC1h PC2h 75% q12-18h
Clcr 10-30 mg/min
Lisinopril 10mg 10-20mg qd -
2.5-5mg/d
ARB
Irbesartan 150 mg 300 mg qd No CYP2C9 (minor)
CYP2C9 (major)
Losartan* 50 mg 50-100 mg qd No
CYP3A4 (major)
*成大醫院無此品項
16

17. Lipid Management
Risk assessment and treatment goal
 LDL-C level vs. CHD risk: Log-linear relationship
 30mg/dL change in LDL-C, 30% changed in relative risk for CHD
 LDL-C: primary target of lipid-lowering therapy
 Risk assessment: high risk
 Goal: LDL-C < 100 mg/dl
NCEP Goals for LDL-C
LDL-C Goal Optional
Risk Level Risk Category
mg/dL Goal
CHD or
High risk < 100 < 70
CHD risk equivalent DM
Moderately ≥ 2 risk factors
< 130 < 100
high risk 10-year risk 10%-20%
≥ 2 risk factors
Moderate risk < 130
10-year risk < 10%
Lower risk ≤ 1 risk factor < 160
NCEP ATP III guidelines
17
Circulation 2004; 110:227.

18. Lipid Management
LDL-C lowering therapy
 LDL-C goal
 < 100 mg/dl
 Reduction of 30-40% from baseline is alternative if not achieved
on maximum tolerated drug therapy
 Add statin therapy to lifestyle therapy regardless of
baseline lipid levels in adults with diabetes if either
− Overt CVD
− Age > 40 y with one or more other CVD risk factors
(ADA Grade A)
NCEP ATP III. Circulation. 2002;106:3143-3421.
Circulation 2004; 110:227. 18

19. Lipid Management Cholesterol (mg/dl)
09/07
289
11/02
263 high
high
Hypertriglyceridemia TG (mg/dl) 1180 very high 287 high
Very high TG (≥ 500mg/dl)
Drug of choice
 Goal of therapy
 TG lowering to prevent acute pancreatitis (first priority)
 Prevention of CHD (second priority) Fibrate
 Consider LDL-C reduction only after TG < 500 mg/dL or
Nicotinic acid
Drug of choice TG-lowering Use in very high TG
Fibrate or niacin Most effective First choice
Statin Not powerful Not first-line
Bile acid sequestrants tend to ↑TG contraindicated
High TG (200-499mg/dl)
 Goal
Statin
 Primary: achieve LDL-C target
 Secondary: achieve non-HDL-C target
− 30mg/dL higher than LDL-C goal: 130mg/dl
NCEP ATP III. Circulation. 2002;106:3143-3421.
19

20. Our patient
Lipid Management • DM
• Clcr=16.63 ml/min
Drug of consideration • Hyperuricemia
Metabolism
Drug Class agent Renal dose adjustment
enzyme
Niacin Relative contraindication: Hyperglycemia, hyperuricemia
Gemfibrozil CCr 10-50 mg/min 50% dose
Fibrate
Fenofibrate Avoid use in CCr <30 mL/min
Atorvastatin No CYP3A4
Pravastatin Initial 10 mg qd in significant impairment None
Fluvastatin Use with caution in severe impairment CYP2C9
Statin
CYP2C9/
Rosuvastatin Initial 5 mg qd in Ccr <30 ml/min
2C19
Simvastatin Initial 5 mg qd in Ccr< 30 ml/min CYP3A4
Drug information handbook 21th edition
20

21. Summary of Lipid Management
09/07 11/02
Cholesterol (mg/dl) 289 high 263 high
TG (mg/dl) 1180 very high 287 high
11/02
9/07
Goal:
Goal:
LDL-C < 100 mg/dl (primary)
TG < 500 mg/dl
non-HDL-C < 130mg/dl (secondery)
Therapy:
Therapy:
TG lowering to prevent acute pancreatitis
LDL lowering to prevent CHD
Drug of choice:
Drug of choice:
Gemfibrozil
Pravastatin
Monitor parameters:
Monitor parameters:
Cholelithiasis
AST/ALT and CPK
NCEP ATP III. Circulation. 2002;106:3143-3421.
21

22. Management Plan
Antiplatelet agents
 Consider aspirin therapy (75-162 mg/day) as a primary
prevention strategy in those with type 1 and type 2
diabetes at increased CV risk (10-yr risk > 10%)
 Includes men > 50 years or women > 60 years with at least one
additional major risk factor
− Family history of CVD, HTN, smoking, dyslipidemia,
albuminuria
Diabetes Care. 2012 Jan;35 Suppl 1:S11-63
22

23. Intensive glycemic control
UKPDS: A 1% fall in HbA1c results in a reduction of
relative risk of complications
0
Reduction in risk (%)*
-10 -12
-16
Any diabetes-related endpoint
p=0.029
p=0.052 -21 Microvascular endpoint
-20 -25 p=0.015
p=0.0099 MI
-34
-30
p=0.000054 Retinopathy
-40 Albuminuria at 12 years
-50
UKPDS: United Kingdom Prospective Diabetes Study
*Percent risk reduction per 0.9% decrease in HbA1C
UKPDS. Lancet. 1998;352:837-853. 23

24. Three Clinical Trials Assessing
Intensive vs. Conventional Glycemic Control in Type 2 DM
Patients baseline characteristics
ACCORD ADVANCE VADT
Number of Pts. 10,251 11,400 1,791
Age (yrs) 62.2 66.0 60.4
BMI (kg/m²) 33.2 28.5 31.3
Duration of diabetes (yrs) Long-standing 10.0 8.0 11.5
Previous CV disease (%) 35.2 32.2 31.3
Mean A1C (%) 8.3 7.5 9.4
Median achieved A1C
ACCORD ADVANCE VADT
Intensive control 6.4 % 6.5 % 6.9 %
Conventional control 7.5 % 7.3 % 8.6 %
Difference - 1.1 % - 0.8% - 1.7%
N Engl J Med. Jun 12 2008;358(24):2560-2572. ACCORD: Action to Control Cardiovascular Risk in Diabetes
N Engl J Med. Jan 8 2009;360(2):129-139. ADVANCE: Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
N Engl J Med. Jun 12 2008;358(24):2545-2559. VADT: Veterans Affairs Diabetes Trial 24

25. Effect of Intensive Glucose Lowering in
Macrovascular Complications of Type 2 DM
ACCORD ADVANCE VADT
Primary Non-fatal MI Non-fatal MI Non-fatal MI
outcome Non-fatal stroke Non-fatal stroke Non-fatal stroke
CVD death CVD death CVD death
Revascularization
Hospitalization for CHF
Hazard ratio 0.87 (0.730 – 1.04) 0.90 (0.78 – 1.04) 0.94 (0.84 – 1.06)
for primary
outcome (95% CI)
Hazard ratio 1.065 (0.801 – 1.416) 1.22 (1.01 – 1.46) 0.93 (0.83 – 1.06)
for mortality (95% CI) (P= 0.04)
 No significant reduction in CVD outcomes with intensive glycemic
control in long-standing diabetes (mean duration 8-11 years)
N Engl J Med. Jun 12 2008;358(24):2560-2572.
N Engl J Med. Jan 8 2009;360(2):129-139.
N Engl J Med. Jun 12 2008;358(24):2545-2559.
25

26. Glycemic Control
“Individualized” treatment target
A1C
More Stringent Less Stringent
ADA < 7%
as close to normal
(6%) as possible
AACE ≤ 6.5% < 8%
Life expectancy 65yr
Duration of diabetes Long-standing
Presence of complications Neuropathy retinopathy
Risk of hypoglycemia, adverse events CKD stage 4, elderly
Patient attitude and expected treatment efforts 之前無規則性治療?
Support system Unknown
Endocr Pract. 2009; 15:540-59.
Endocr Pract. 2011; 17(suppl 2):287-302.
Diabetes Care. 2012; 35(1 suppl):S11-63. 26

27. Diabetes Care 2012;35:1364–1379
Diabetologia 2012;55:1577–1596

28. 28

29. Endocr Pract. 2009; 15:540-59.

30. Factors to Consider When Selecting Therapy
A patient-centered approach
 Long-standing Type 2 DM, HbA1C: 9.4%
 Remaining ß-cell function
 Combination therapy or insulin
 Age: 65yr
 At risk for adverse events and drug interactions from polypharmacy
 Weight: BMI 22
 Weight loss is not a major goal
 CKD stage 4
 Potential for hypoglycemia
 Dose adjustment
 Retinopathy
 Injection require good visual
(and also motor skills, cognitive ability, caregivers support)
 Patient preference and supporting system
 Poor compliance?
Diabetes Care. 2012; 35(1 suppl):S11-63.
Diabetes Care 2012;35:1364–1379 30

31. Drug Of Choice Class and agents Use in renal impairment
Considerations in CKD Metformin Contraindicated in Scr ≥1.4 mg/dl
1st generation SU Avoid use
2nd generation SU
Glipizide No dose adjustment
Gliclazide No dose adjustment
Glimepiride Initial at low dose
Glyburide Avoid use
Meglitinides
Repaglinide Initial at low dose
Nateglinide Initial at low dose, avoid in stage5
Thiazolidinedione
Pioglitazone No dose adjustment
Alpha-glucosidase inhibitors
Acarbose Avoid in Scr >2mg/dl
DPP-4 inhibitor
Sitagliptin Reduce dose
Saxagliptin Reduce dose
Vildagliptin Reduce dose
Linagliptin No dose adjustment
GLP-1 agonists
Exenatide Avoid in GFR < 30 mL/min/1.73 m2
Am J Kidney Dis. 2012 Nov;60(5):850-86.
Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154 31

32. Glycemic Control- Drug of consideration
Class and agents Major concerns
Meglitinides
• Drug interaction (Contraindicated)
Repaglinide
Gemfibrozil increases repaglinide concentrations and half-life
Thiazolidinedione
Pioglitazone • Fluid retention (4-15%), Bone fractures (5.1%)
2nd generation SU
Glipizide • Preferred SU in CKD
Gliclazide • Preferred SU in CKD
Glimepiride • Active metabolite
DPP-4 inhibitor
Sitagliptin • Common SE: Hypoglycemia, Headache, URI, Nasopharngitis
Cost: 7.58/day • Common SE: Peripheral edema (1.2-8.1% ), Hypoglycemia, Headache, UTI, URI,
Saxagliptin Nasopharyngitis
• Drug interaction: CYP3A4 inhibitors
• Common SE: Peripheral edema (3.8-5.9% ), Hypertension, Hypoglycemia,
Vildagliptin
Headache, URI, Nasopharngitis
Linagliptin • Hypoglycemia, Nasopharngitis
Cost: 30.3/day 32

33. Summary of Glycemic control
 Glycemic goal
 A1C<7% or less-stringent (<8%)
 Consideration for therapy
 Remaining ß-cell function
 Injection require good visual and caregivers support
 Patient preference of administration route
 Compliance
Non-insulin regimens Insulin regimen
SU + DPP-4 inhibitor Basal insulin + DPP-4 inhibitor
Glipizide 2.5mg QD PO Insulin glargine 10IU QD SC
Sitagliptin 25mg QD PO Sitagliptin 25mg QD PO
33

34. Patient education
 認識糖尿病
 糖尿病有什麼症狀？
 糖尿病會有什麼併發症？
 心理社會因素?
 降血糖藥與胰島素
 藥物的使用方法與副作用
 使用藥物的重要性
 血糖自我監測
 高血糖與低血糖
 運動與健康飲食原則
 日常護理保健
Taiwan Association of Diabetes Educators
34

35. Summary of Case 1
Management plan
Strategy Management
• Protein-restricted diet
Diabetic nephropathy
• Irbesartan
• BP should be confirmed on a separate day
BP control
• Goal: <130/80 mmHg
• Treat very high TG with gemfibrozil
Goal: TG < 500 mg/dl
Lipid management • Then shift to pravastatin
Goal: LDL-C < 100 mg/dl (primary)
non-HDL-C < 130mg/dl (secondary)
Antiplatelet agent • Aspirin
• SU + DPP-4 inhibitor
Glycemic control • Basal insulin + DPP-4 inhibitor
• Goal: HbA1C < 7%
Patient education
35

36. Case 2
36

37. Lab Data of a 45yr male
Normal 2/11 8/11 11/16
AC Sugar (mg/dl) 60-100 109 106 110
Creatinine (mg/dl) 0.7-1.5 1.09 1.13 1.03
eGFR 73 70 78
ALT (U/L) 0-54 24 22 25
Cholesterol (mg/dl) <200 205 273 276
TG (mg/dl) <150 921 1960 1400
HDL-C (mg/dl) > 40 30 35 34
LDL-C (mg/dl) <100 59 35 46
Sample lipemia + ++++ ++
Q 如何解讀該病患之數據?
如何使用降血脂的用藥?
37

38. Lab Data of a 45yr male
Normal 2/11 8/11 11/16
AC Sugar (mg/dl) 60-100 109 106 110
Creatinine (mg/dl) 0.7-1.5 1.09 1.13 1.03
eGFR 73 70 78
ALT (U/L) 0-54 24 22 25
Cholesterol (mg/dl) <200 205 273 276
TG (mg/dl) <150 921 1960 1400
HDL-C (mg/dl) > 40 30 35 34
LDL-C (mg/dl) <100 59 35 46
Sample lipemia + ++++ ++
High TC
Very high TG
Low HDL
Low LDL
38

39. Overview of Lipoprotein
Lipoprotein = Lipids + Phospholipid + Proteins
Chylomicron Cholesterol (Apolipoprotein)
VLDL, IDL, LDL Triglyceride ApoA, B, C…
HDL
*insoluble in *serve as enzyme cofactors
plasma receptor ligands,
lipid transfer carriers
Lipid compositions of lipoprotein
Chylomicron VLDL LDL HDL
TG % TG rich 85 55 10 6
Cholesterol esters % 3 18 50 40
Cholesterol % 2 7 11 7
Phospholipids % 8 20 29 46
Protein % 2 10 25 55
39

40. Metabolism of TG-rich Lipoproteins
Chylomicrons and VLDL
Exogenous
from dietary fat
chylomicrons
Endogenous
from the liver
VLDL
Lypolysis
by lipoprotein lipase (LPL)
apoCII as a cofactor
in fat and muscle tissue
fat and muscle tissue Nat Med. 2002 Feb;8(2):112-4. 40

41. Development of Hypertriglyceridemia
Increased production and decreased clearance
Exogenous
from dietary fat
chylomicrons
Production of chylomicrons and
Endogenous
VLDL from intestine and liver
from the liver
VLDL
Clearance
Lipolysis
by lipoprotein lipase (LPL)
Reduced lipoprotein lipase activity
apoCII as a cofactor
in fat and muscle tissue
Abnormality in lipoprotein receptor
41

42. Causes of Elevated Triglycerides
Genetic, dietary and metabolic
Low prevelance
TG 200-500 mg/dL
TG> 1000 mg/dL
Usually combined causes LDL-C usually low
Our patient:
very high TG
TC = HDL + LDL + VLDL
high low low
CMAJ 2007;176(8):1113-20
42

43. If TG >1000 mg/dL
Initial goal
 TG lowering to prevent
acute pancreatitis
Treatment
 Non pharmacotherapy
 TG-lowering drugs
 Fibrate
 Niacin
 Fish oil
NCEP ATP III. Circulation. 2002;106:3143-3421.
Am Fam Physician. 2007 May 1;75(9):1365-1371. 43

44. Choice for Treatment of Severe Hypertriglyceridemia
Drug class Effect on LDL↓ Effect on HDL↑ Effect on TG↓ Major use
Statins 20-60% 5-10% 10-30% LDL-C
Resins 15-30% 0 to slight No change or LDL-C
increase may ↑
fibrate 5-15% 5-20% 35-50% TG
Niacin 10-25% 15-35% 40% LDL-C, HDL-C, TG
Omega 3 fatty acid ↑4-49% 5-9% 30-40% TG
 Statins: not powerful TG-lowering
 Resin: contraindicated, tend to raise TG
 Fibrate: most effective
 Niacin: less potent then fibrate but more effective at raising HDL-C
NCEP ATP III. Circulation. 2002;106:3143-3421.
44

45. Choice for Treatment of Severe Hypertriglyceridemia
Fibrate, niacin, omega-3 fatty acid
Drug Mechanism Major side effect
Fibrate PPAR-α agonist Dyspepsia, elevated transaminases,
Fenofibrate ↑VLDL clearance cholesterol gallstones, myopathy
Gemfibrozil ↓VLDL hepatic synthesis
Niacin ↓VLDL hepatic synthesis Flushing, GI upset
Acipimox Worsen glucose intolerance
hyperuricemia, hepatotoxicity
Omega-3 fatty acid ↓VLDL hepatic synthesis Fishy aftertaste
(EPA/DHA) GI upset
Metabolic side effect
Increase LDL
 Fibrate be used as a first-line agent for reduction of TG in
patients at risk for TG-induced pancreatitis
DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid.
PPAR-α = Peroxisome proliferator-activated receptor- α
J Clin Endocrinol Metab, September 2012, 97(9):2969–2989 45

46. Omega-3 Fatty Acids
As adjunctive therapy
 Dosage range: 3-12 g/day
 2-4 g of total EPA/DHA daily can lower TG levels by 30-50%
 Dose-dependent for TG-lowering
 Require months or years of intake
JAMA 2006; 296:1885.
46

47. Summary of case 2
For severe hypertriglyceridemia
 Goal of therapy
 First priority: TG-lowering to prevent pancreatitis
 Second priority: prevention of CHD
 Combine therapeutic lifestyle change and drug therapy
 Therapeutic lifestyle changes are recommended for all patients
with elevated triglyceride levels
 Fibrates recommended as first-line therapy
 Niacin or omega-3 fatty acids may also be considered
J Clin Endocrinol Metab, September 2012, 97(9):2969–2989
47

48. Thanks for Your Attention
48