Metabolic Syndrome

Question 1

Metabolic Syndrome

Answer 1

A cluster of common conditions that increases T2DM and CVD risk:

Insulin resistance drives MS and triggered by:
→ POST PRANDIAL HYPERINSULINEMIA → FASTING HYPERINSULINEMIA → HYPERGLYCEMIA → insulin resistance → MS

–Plus any three of the following:

Abdominal obesity
Impaired glucose tolerance
↓HDL
↑triglycerides
HTN

Question 2

NCEP/ATP III Criteria for the Metabolic Syndrome

Answer 2

Need to have 3 or more
1. Central obesity: waist circumference
Male > 40 inches, Female > 35 inches

2. Fasting Plasma Glucose ≥100 mg/dL or on specific medication or diagnosed with T2DM
3. HTN: BP ≥ 130 mmHg systolic or ≥ 85 mm diastolic or on specific medication
4. Hypertriglyceridemia:
   Triglycerides ≥ 150mg mg/dL or on specific medication
5. Low HDL cholesterol: Male < 40 mg/dL, Female <50 mg/dL

Question 3

Weight Dependence of Metabolic Syndrome

Answer 3

Weight dependent
Normal weight = 5% risk
Overweight 22% risk
Obese 60% risk

Weight gain increases MS risk
2.25 kg weight gain in 16 years = 21-45% ↑risk factor

Current obesity epidemic = predicts future MS epidemic

↑ Waist circumference = identifies ~ 46% of pts at MS risk

Question 4

Prevalence of Metabolic Syndrome

Answer 4

Continues to ↑ in women, but men are catching up

Common in Mexican-America women—other Latinos

Native Americans have highest ethnic prevalence

Question 5

Risk Factors for Metabolic Syndrome

Answer 5

High Carbohydrate diet
T2DM
CHD (coronary heart disease)
Post-menopausal
Sedentary life style
LSES
No Alcohol
Smoking
Non-diet soft drinks
Parental history

Question 6

Complications of Metabolic Syndrome

Answer 6

↑ Triglycerides, ↓ HDL, ↑ BP
Best predictors for MS complications and progression

T2DM, CVD

Obesity
Cancer
Fatty liver disease
Osteoarthritis
Alters Adiponectin function and availability (due to Insulin Resistance)
Not able to Modulate food intake and energy expenditure
Not able to Suppress  gluconeogenesis
Not able to increase insulin sensitivity

Question 7

There’s a strong correlation between atherosclerosis and

Answer 7

Vascular Dementia
Alzheimer’s Dementia
Mild cognitive impairment

Question 8

Pathophys for Metabolic Syndrome

Answer 8

Begins with Obesity and Insulin Resistance:
The more presenting MS conditions = ↑ T2DM/CVD incidence
Obesity, hyperlipidemia, hyperglycemia, hypertension

↑ circulating fatty acids → increases Insulin Resistance and decreases insulin Sensitivity → ↑ MS risks

Insulin Resistance → endothelial damage and ↑ in Plasminogen Activator inhibitor increasing CVD/PVD/stroke risks

Insulin Resistance → postprandial hyperinsulinemia → fasting hyperinsulinemia → eventual T2DM /CVD

Question 9

Treatment for Metabolic Syndrome

Answer 9

Prevention/reduction of risk factors are primary goals
Treat underlying causes such as:
Obesity
Exercise and diet
Exercise will ↓ Abdominal obesity = ↓ insulin resistance, LDL →↑insulin S and HDL

Pharmacotherapy
orlistat, phentermine (3 month use only)

Behavioral Modification

Bariatric surgery for BMI >40 kg/m2 or >35mg/m2 with co-morbidities

Question 10

Exercise Treatment for Metabolic Syndrome

Answer 10

Exercise
150 min/wk plan—this is an optimal goal for obese patients
Decreases abdominal fat (men and women)
Increases glucose uptake in muscle
Liposuction does not ↑ insulin Sensitivity or ↓ CVD risks
Need to lose calories, to gain metabolic effect
Smoking Cessation
Diet
Low saturated fat, low GI, low density foods, diet plan

Question 11

Dietary Issues and Treatment

Answer 11

↑Carbohydrate diet = ↓ HDL, ↑ glucose and insulin, ↑ triglycerides and BP →CHD/T2DM

Lean poultry and fish vs. beef and other fatty red meat

Concentrate on Low Energy Density (volumetrics) foods
Fresh vegetables and fruit: high fiber, water, low in fats
Whole grains, whole wheat, oat meal, low fat meats

Concentrate on Low Glycemic Foods

Question 12

Type 2 DM Treatment for Metabolic Syndrome

Answer 12

T2DM: Drug Treatment alone will not solve the problem of MS more effectively than exercise and diet will

IFG: Metformin and life changes, but life style change is more effective.

Insulin resistance: Metformin, thiazolidinediones (TZDs) increase insulin sensitivity
Use precaution with TZDs (Pioglitazone [Rosiglitazone is off the market])

Question 13

Criteria for dyslipidemia intervention

Answer 13

Smokers
HTN (≥ 140/90 mmHg)
FHx of premature CVD
1st degree ♂ relative < 65 years old
Age of patient
♂ ≥  55 years old
♀ ≥ 65 years old

Question 14

Treatment Options for LDL-C lowering

Answer 14

Life style modifications

Pharmacotherapeutics:

1st choice: Statins (HMG-CoA reductase inhibitors)

Rx therapy for LDL cholesterol lowering
Can ↓ CVD risk 20-30%
↓ 14-63% LDL-C
LFTs and myopathy

2nd choice Rx therapy
Ezetimibe
15-20% ↓ in LDL-C
Statin intolerance

Question 15

Pharmacotherapeutics: LDL-C lowering

Answer 15

Bile acids sequestrants

Cholestyramine
10-15% ↓ in LDL-c
Can use with Statins/Nicotinic Acid
Increases Triglyceride levels

Nicotinic Acid
< 20% ↓ in LDL-c
Can use with Bile acid sequestrants/Statins

Fibrates (fenofibrate, gemfibrozil)
lowers LDL-C and Triglycerides
Can use with Ezetimibe (Fenofibrate)
Avoid with Statins (gemfibrozil)

Question 16

Pharmacotherapeutics: Triglyceride lowering

Answer 16

Fibrates (fenofibrate, gemfibrozil)
Most effective
35-50% ↓ Triglycerides
Fenofibrate >> gemfibrozil
Avoid with Statins 

Nicotinic Acid (Niacin, Vitamin B3)
<20-40% ↓ in Triglycerides
↑FBG

Omega-3 fatty acids
40% ↓ in Triglycerides

Question 17

Pharmacotherapeutics: HDL-C Enhancing

Answer 17

Statins, Fibrates, Bile acids:
 ↑ HDL-C 5-10%
Nicotinic Acid
 ↑ HDL-C 30%
Ezetimibe and Omega-3
 ↑ HDL-C 0%
Not clear that rising HDL-C alone has CVS benefit