Metabolic Syndrome/ Insulin resistance syndrome

Metabolic syndrome is also called “syndrome X” and “insulin resistance syndrome”.

It consists of metabolic abnormalities that increase the risks of cardiovascular diseases (CVD) and diabetes mellitus.

The main features of the metabolic syndrome are:

Central obesity
Hypertriglyceridemia
Low levels of high-density lipoprotein (HDL) cholesterol
Hyperglycemia
Hypertension

Prevalence of Metabolic syndrome:

The highest recorded prevalence worldwide is among the Native Americans, with nearly 60% of women ages 45-49 and 45% of men ages 45-49.

The National Health and Nutrition Examination Survey (NHANES) 2003-2006 suggests the age-adjusted prevalence of the metabolic syndrome in U.S. adults without diabetes is 28% for men and 30% for women.

Risk factors for metabolic syndrome:

Obesity:

Central adiposity is a key feature of the syndrome, and there is a strong relationship between waist circumference and increasing adiposity.

However, patients who are of normal weight may also be insulin resistant and may have metabolic syndrome.

Sedentary lifestyle:

A sedentary lifestyle is associated with increased adipose tissue (predominantly central), reduced HDL cholesterol, and increased triglycerides, blood pressure, and glucose in genetically susceptible persons.

Compared with individuals who watch television or videos or use the computer for less than one hour daily, those who do so for more than four hours daily have a twofold increased risk of metabolic syndrome.

Advancing Age:

The metabolic syndrome affects nearly 50% of the U.S. population older than age 50 years.

At the ages of more than 60 years, women are more often affected than men.

Diabetes Mellitus:

It is estimated that the great majority ( about 75%) of patients with type 2 diabetes or impaired glucose tolerance have metabolic syndrome.

The presence of the metabolic syndrome in diabetics relates to a higher prevalence of CVD than in patients who have type 2 diabetes or impaired glucose tolerance.

Cardiovascular diseases:

Individuals with metabolic syndrome are twice as likely to die of cardiovascular disease as those who do not.

The approximate prevalence of the metabolic syndrome among patients with coronary heart disease (CHD) is 50%, with a prevalence of about 35% among patients with premature coronary artery disease (before or at age 45).

Lipodystrophy:

Lipodystrophy may predispose a person to metabolic syndrome. It can be either genetic or acquired.

Genetic lipodystrophy:-

- - Berardinelli- Seip congenital lipodystrophy
  - Dunnigan familial partial lipodystrophy

Acquired:-

- - HIV related dystrophy in patients receiving antiretroviral medicines.

Etiology of metabolic syndrome:

Insulin resistance/ glucose intolerance
Increased waist circumference
Dyslipidemia
Hypertension
Proinflammatory cytokines excess
Adiponectin deficiency

Clinical Features of metabolic syndrome:

Increased waist (more than 35 inches in women and more than 40 inches in men)
Elevated BP (prehypertension or hypertension)
Lipoatrophy
Acanthosis nigricans
Xanthomas, xanthelasma

Associated conditions:

Diagnosis of metabolic syndrome:

Waist circumference
Fasting lipid profile
Fasting glucose
BP monitoring
Uric acid
Hormonal profile
Inflammatory markers
ECG and echo

Treatment of metabolic syndrome:

Diet:

Fruits, vegetables, whole grain, lean poultry, and fish
Carbohydrate restriction with physical activity

Lifestyle modifications:

Weight loss drugs

- Appetite suppressants
  - Phentermine for 3 months period
  - Phentermine (norepinephrine)
  - liraglutide (a GLP-1 analog) and
  - lorcaserin (activates 5-HT2c receptors) without the restriction of time
- Absorption inhibitors
  - Orlistat (reduces 30 percent fat absorption and also reduces the risk of T2DM in patients with glucose intolerance)

Bariatric surgery (Gastric bypass surgeries and sleeve gastrectomy)

Bariatric surgery is recommended in the following situation:
- With a BMI more than 35 for Asians
- With BMI more than 32 with comorbid
- BMI more than 30 and central obesity with at least 2 criteria for metabolic syndrome

LDL cholesterol:

Dietary restriction in saturated fatty acids
Statins (atorvastatin, rosuvastatin)
Cholesterol absorption inhibitor (ezetimibe)
Bile acid sequestrants
- Cholestyramine, colestipol, and colesevelam increase the serum triglyceride levels, they should not be given when the triglyceride levels are more than 250mg/dl
Fibrates
- Fenofibrate and gemfibrozil:
  - They increase the synthesis of lipoprotein lipase, used when both LDL and TG are raised.
PCSK 9 inhibitors (ALIROCUMAB and evolocumab)

Hypertriglyceridemia:

Fibrates
Nicotinic acid is 20-30 % effective, although less effective than fibrates. They may increase the fasting blood glucose levels
Omega 3 fatty acids in high doses 1.5 – 4.5 grams per day may lower triglycerides by 30 – 40%
Potent Statins like atorvastatin, rosuvastatin in intermediate or high doses

HDL cholesterol:

Statins, fibrates, and bile acid sequestrants have modest effects (5-10%)
Nicotinic acid has better effectiveness of about 30%

Blood Pressure:

ln patients who have the metabolic syndrome without diabetes, the best choice for the initial antihypertensive medication is either an ACE inhibitor or the Angiotensin II receptor blocker

General instructions:-

a sodium-restriction dietary pattern enriched in fruits and vegetables, whole grains, and low-fat dairy products
Home monitoring of blood pressure

Impaired fasting glucose:

Type 2 diabetes:-

Aggressive glycemic control may favorably modify fasting levels of triglycerides and HDL cholesterol.

Non-diabetics:-

a lifestyle intervention that includes weight reduction, dietary fat restriction, and increased physical activity has been shown to reduce the incidence of type 2 diabetes.
Metformin

Insulin resistance:

Several drug classes (biguanides, thiazolidinediones [TZDs]) increase insulin sensitivity.
TZDs, also improve insulin-mediated glucose uptake in muscle and adipose tissue.
The benefits of both drugs have been seen in patients with nonalcoholic fatty liver disease and polycystic ovary syndrome as well, and the drugs have been shown to reduce markers of inflammation.