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Download Metabolic Syndrome

OBESITY


Obesity, especially "central", "visceral", "truncal", "android" (i.e. abdominal) is a major (AHA/NHLBI) or sine qua non (IDF) criteria for the diagnosis of the Metabolic Syndrome. Whilst its presence is an absolute requirement for the diagnosis of the metabolic syndrome as per the IDF guidelines, it is only one out of five criteria, the presence of any three of which leads to a diagnosis of the metabolic syndrome as per the modified ATP-III guidelines.

Atherosclerosis is now considered in part to be a consequence of chronic low-grade inflammation and inflammation is an important feature of plaque initiation, progression, and thrombosis. Along with the traditional risk factors, it is these inflammatory adipokines which play a key role in initiating the process and progression of endothelial dysfunction and atheroma formation in the arteries leading to an increased risk and severity of cardiovascular disease. Inflammation is also considered to play an important role in leading to T2DM.

Abdominal obesity, due to intra-abdominal adiposity, drives the progression of multiple cardiometabolic risk factors independently of body mass index. This occurs both through altered secretion of adipocyte-derived biologically active substances (adipokines), including free fatty acids, adiponectin, interleukin-6, tumour necrosis factor alpha, and plasminogen activator inhibitor-1, and through exacerbation of insulin resistance and associated cardiometabolic risk factors.

Metabolic and Cardiovascular Risk Factors Associated With Visceral Obesity

Raised blood pressure ( systolic and /or diatolic)
Increased levels of insulin resistance / hyperinsulinemia
Atherogenic dyslipidemia
Raised levels of LDL-C and apo-B
Endothelial dysfunction
Increased prothomboitic and procoagulant state
Raised pro-inflammatory status
Decrease in levels of antiatherogenic levels of adiponectin
Premature atherosclerosis ( leading to early onset CHD and stroke)
Raised levels of serum uric acid
Sleep apnoea syndrome and related
Polycystic ovary syndrome
Microalbuminuria is an integral component of the cardiometabolic syndrome, and patients with this syndrome have a propensity to develop type 2 diabetes.

At the same time, generalized obesity is also associated with many other disorders and increases to the morbidity as well as even mortality associated with these disorders. Thus, the management strategy has to be a decrease in all obesity, but special attention must be paid to reducing the abdominal obesity.

OPTIMAL WEIGHT

Generalised obesity is best measured by estimation of the Body Mass Index (BMI)

Body Mass Index (BMI)

            Weight in Kg
BMI = -------------------------
            Height in meters2

Normal: 20-23; > 23-25 = Overweight; > 25 = Obese

Care must be taken that the weight is not decreased below the lower limits, as a BMI of 18.5 signifies low body weight.

Waist Measurements

Central or visceral obesity is best measured by the waist circumference

MEASUREMENT OF THE WAIST CIRCUMFERENCE

To measure waist circumference, locate the top of the right iliac crest. Place a measuring tape in a horizontal plane around the abdomen at the level of the iliac crest. Before reading the tape measure, ensure that tape is snug but does not compress the skin and is parallel to the floor. Measurement is made at the end of a normal expiration.

A waist measurement of <90cms for men and <then 80cms of women is optimal for our patients. A waist measure more than this, signifies central obesity.

Management

Goals

The management strategy has to be a decrease in all obesity, but special attention must be paid to reducing the abdominal or visceral obesity.


Lifestyle Management

Effective weight loss requires a combination of caloric restriction, physical activity, and motivation; effective lifelong maintenance of weight loss essentially requires a balance between caloric intake and physical activity.

DIET

Aim initially at slow reduction of 7% to 10% from baseline weight. Even small amounts of weight loss are associated with significant health benefits. Continue weight loss thereafter to extent possible with goal to ultimately achieve desirable weight.

Many of these aspects have been discussed in detail in the section dealing with lifestyle changes.

PHYSICAL ACTIVITY AND EXERCISE

Increased physical activity along with regular exercise is recommended as an important component of all lifestyle management regimens to prevent and manage the metabolic syndrome as well as all diabetes management regimen.

Increasing physical activity assists in weight reduction, reduces insulin resistance, has beneficial effects on metabolic risk factors; and importantly, it reduces overall ASCVD risk beyond that provided by weight reduction alone.

Many of these aspects have been discussed in detail in the section dealing with lifestyle changes.


Behavior therapy

Behavior therapy is a useful adjunct to diet and physical activity.


Pharmacotherapy

Lifestyle therapy should be considered before drug therapy and should be continued during the pharmacotherapy.

Weight loss drugs may be used as part of a comprehensive weight loss program for patients with a BMI >=23 kg per m2 or significantly increased waist circumference.

Avoid use of drugs without accompanying lifestyle modification.

Avoid medications which are known to be associated with weight gain.


Medications with weight gain as a side effect.

These medications should preferably not be used if weight loss is the aim. Moroever, some of these medications lead to lethargy and drowsiness and may make increased physical activity difficult. Some of these medications are given in Table.

Medications
Antidepressants
Serotonin reuptake inhibitors, tricyclic antidepressants, monamine oxidase inhibitors, eg., amitryptiline, imipramine, doxepin, desipramine, trazodone, lithium, etc.,
Antiepileptics:
valproate, carabamazepine, gabapentin, lithium
Antipsychotics
Atypical neuroleptic agents: clozapine, olanzapine, risperidone etc.,
Steroids and other hormones
Estrogens, progesterone, hormonal contraceptives, corticosteroids
Diabetes medications
Insulin, sulfonylureas, glitazones
Antihypertensive Agents
a- and ß-adrenergic receptor blockers
Serotonin and histamine inhibitors
   

NOTE: This is not a complete list.

Anti-Obesity Drugs

The two drugs which are presently available and most commonly used weight reducers are Orlistat and Sibutramine.

Characteristics of the Commonly used Antiobesity Medications

Characteristic
Sibutramine
Orlistat
Indicated for long-term treatment
Yes
Yes
Special instructions
Blood pressure monitoring is required before and during therapy
Patients must take a multivitamin supplement (2h before a dose). No dose should be taken if a meal is missed or contains no fat
Adverse effects
Hypertension, tachycardia, dry mouth, anorexia, insomnia, constipation
Abdominal pain, oily spotting, fecal urgency, flatulence with discharge, fatty stools, fecal incontinence, increased defecation, increased urinary oxalate
Contraindications[a]
Severe hypertension or poorly controlled hypertension, heart failure, coronary artery disease, arrhythmias, or stroke
Malabsorption syndrome and cholestasis. Use with caution in patients with history of nephrolithiasis.
Drug-drug interactions
Monoamine oxidase inhibitors, selective serotonin-reuptake inhibitors, drugs that increase blood pressure or heart rate, ketoconazole[b] , erythromycin[b]
Fat-soluble vitamins, beta-carotene, and possibly cyclosporine
Use with caution
History of hypertension, seizures, narrow angle glaucoma
History of hyperoxaluria or calcium oxalate nephrolithiasis
Patient instructions
Take once daily in the mornings. Have blood pressure and pulse checked regularly.
Take one capsule t.id. with each meal. If meal is missed or contains no fat, then dose can be skipped. Take a multivitamin daily 2 hr before or after dose. Comply with a low-fat diet.
  • None of these medications should be used in patients with a history of anorexia nervosa or bulimia.
  • Interactions do not appear to be clinically significant.


Metformin

Metformin was used in the past as a weight reducing agent even in people with normal glucose levels. But its use has decreased with the availability of sibutramine and orlistat.
With the increasing awareness of the critical role played by insulin resistance, which leads to many disorders such as Polycystic Ovary Syndrome (PCOS), etc., as well as being a serious risk factor for diabetes and premature cardiovascular disease, its use especially in patients with impaired glucose tolerance, and this is especially so in patients with a family history of diabetes and premature cardiovascular disease.

Incretins

GLP-1 analogues have been shown to be associated with weight loss, although the DPP-IV inhibitors are weight neutral.

Glitazones

The glitazones tend to increase the weight. But it is now being increasingly realized that whilst the glitazones may slightly increase the fat levels in the body, they very significantly decrease the levels of central or visceral obesity. At the same time questions have been raised about the cardiovascular safety of rosiglitazone and it remains to be seen whether this is a class effect and applies to pioglitazone as well.

Other drugs including sympathomimetics are now rarely used.

Other Drugs

Although some other drugs such as bupropion and topiramate are being "pushed" as agents to use in obesity, but are not widely accepted as antiobesity drugs.

Phentermine by itself continues to be occasionally used.

Drugs such as fenfluramine, ephedra and phenylpropanolamine should NEVER be used. One has to be very careful as many OTC drugs and herbal products contain them or similar agents and can be dangerous in the long term.

Surgery

Weight loss surgery is an option in carefully selected patients with clinically severe obesity with comorbid conditions when less invasive methods have failed and the patient is at high risk for obesity-related morbidity and mortality.


BMI Charts





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