Metabolic Syndrome, Insulin Resistance, and Risk of Type 2 Diabetes Mellitus

When the risk factors for different diseases co-occur in the same person, they work mutually to injure the body organs and systems even more than their individual additive effects. The injury can go multiplicatively rather than additively. That means their effects can be amplified. Having multiple risk factors is definitely a very serious matter that is often overlooked.

There is a condition called metabolic syndrome, where there is co-occurrence of different risk factors, including obesity, dyslipidemia, raised blood sugar, or blood pressure. There are five components, and if any three or more are present, then it is said to be metabolic syndrome.

What is the risk?
Obesity, particularly abdominal obesity, is associated with insulin resistance. That means there is resistance to the effects of insulin on peripheral glucose; as a result, there will be increased blood level of glucose, often leading to type 2 diabetes mellitus. There is a complex mechanism that may also lead to vascular endothelial dysfunction, an abnormal lipid profile, or hypertension, all of which promote the development of atherosclerotic cardiovascular disease (ASCVD), mainly including heart attack (myocardial infarction) and stroke. This is true for individuals with abdominal obesity, but normal total body weight, as well.

Researches have shown that if someone is having metabolic syndrome, then there is about five times the risk of developing type 2 diabetes mellitus, and three times risk of developing ASCVD in future than in the general population, even though every report looks normal at present. Moreover, there are also other diseases associated with metabolic syndrome, including fatty liver disease (NAFLD, cirrhosis), hepatocellular carcinoma, polycystic ovarian disease (PCOD), chronic kidney disease (CKD), obstructive sleep apnea (OSA), hyperuricemia, cognitive decline, dementia, etc.

How to diagnose?
Metabolic syndrome can be diagnosed with simple physical examination and blood tests. Physical examination includes:
1) Measurement of blood pressure
2) Measurement of waist circumference with a measuring tape

These two examinations can be done easily in the home or clinic.

Blood test after at least eight hours of overnight fasting, including blood glucose level and lipid profile (especially HDL and triglyceride). This can also be done in any reliable laboratory.

To diagnose metabolic syndrome, there are various definitions, among which NCEP ATP III 2005 is the most accepted one. According to it, if any three of the following five are present, it is called metabolic syndrome.
• Abdominal obesity, defined as a waist circumference ≥102 cm (40 inch) in males, and ≥88 cm (35 inches) in females. In case of south Asian countries like Nepal, waist circumference ≥ 90 cm in males and ≥80 cm in females is considered.
• Fasting serum triglycerides ≥150 mg/dL or drug treatment for elevated triglycerides
• Serum HDL cholesterol <40 mg/dL in males and <50 mg/dL in females or drug treatment for low HDL cholesterol
• Blood pressure ≥130/85 mm Hg or drug treatment for elevated blood pressure
• Fasting plasma glucose (FPG) ≥100 mg/dL or drug treatment for elevated blood glucose

Why prevention is necessary?
If blood glucose level is completely normal at present, there can be metabolic syndrome with other three components. So, there is still high risk of development of type 2 diabetes mellitus in such individuals with normal glucose level. Those with metabolic syndrome having only three components may eventually develop all five components if preventive interventions are not done in time. That means those with normal blood pressure may develop hypertension, those with normal blood glucose may develop type 2 diabetes mellitus, those with normal weight may develop obesity, and those with normal blood cholesterol level may develop dyslipidemia in the near future.

How to manage?
The key to the treatment of metabolic syndrome is lifestyle modification and weight reduction, rather than medicines.

Weight reduction:
Lifestyle modification should be focused on weight reduction and increased physical activity. Even 7% weight loss in obese people has shown to increase insulin sensitivity and prevent progression to type 2 diabetes mellitus. Weight reduction also normalizes blood pressure and cholesterol level, and so we can get out of metabolic syndrome and its complications. Furthermore, the human body system senses obesity as a metabolic abnormality, as a result of which it will be producing inflammatory cytokines that injure the body organs and systems. This shows how important it is to maintain normal weight. Weight reduction is optimally achieved with a multimodality approach, including diet, exercise, and possibly medicine (e.g. Orlistat), or sometimes, bariatric surgery. The primary aim should be to maintain body mass index (BMI) between 18.5 kg/m2 to 24.9 kg/m2, and in case of Asian population like Nepalis, between 18.5 kg/m2 to 22.9 kg/m2, along with waist circumference of less than 80 cm in females and 90 cm in males.

Several dietary approaches have been suggested for treatment of metabolic syndrome, including:
• A diet with low glycemic index/glycemic load, replacing refined grains (e.g. maida, rice, etc.) with whole grains (e.g. wheat, barley, millet, brown rice, etc.) and eliminating high-glycemic beverages like soft cold drinks and packaged juices.
• A high-fiber diet (≥30 g/day) including fruits and vegetables
• Dietary approaches to stop hypertension (DASH) diet with daily sodium intake limited to 2400 mg
• Fatty diet with zero intake of transfat (e.g. junk foods, chips, cake, bakery, cookies, doughnuts, processed foods, deep fried foods, etc.), less than 6% intake of saturated fats (e.g. red meat, dairy products like milk, curd, ghee, cheese, butter, paneer, etc.), and adequate intake of unsaturated fat like omega 3,6,9 (e.g. mustard oil, olive oil, sunflower oil, etc.)
• No smoking, and none to moderation of alcohol intake

Physical exercise:
Exercise may be beneficial beyond its effect on weight loss by more selectively removing abdominal fat. Physical activity guidelines recommend practical, regular, and moderate regimens for exercise. The standard exercise recommendation is a daily minimum of 30 minutes of moderate-intensity physical activity (such as at least brisk walking), or 15 minutes of high intensity physical exercise (such as running) at least 5 days in a week. Increasing the level of physical activity appears to further enhance the beneficial effect, as well.

Metabolic syndrome is a precondition before the appearance of actual diabetes mellitus or other related diseases. Most of the people are diagnosed to harbor metabolic syndrome after they have been diagnosed to have type 2 diabetes mellitus or other related diseases. If metabolic syndrome had been diagnosed prior, then with timely appropriate interventions, the development of type 2 diabetes mellitus or hypertension or dyslipidemia or ASCVD (heart attack, stroke) would have been prevented and prolonged the life span.


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