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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)
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| 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.
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.
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.
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.
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Medications
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Antidepressants
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Serotonin reuptake inhibitors, tricyclic antidepressants,
monamine oxidase inhibitors, eg., amitryptiline, imipramine, doxepin,
desipramine, trazodone, lithium, etc.,
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Antiepileptics:
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valproate, carabamazepine, gabapentin, lithium
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Antipsychotics
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Atypical neuroleptic agents: clozapine, olanzapine,
risperidone etc.,
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Steroids and other hormones
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Estrogens, progesterone, hormonal contraceptives,
corticosteroids
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Diabetes medications
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Insulin, sulfonylureas, glitazones
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Antihypertensive Agents
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a- and ß-adrenergic receptor blockers
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Serotonin and histamine inhibitors
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NOTE: This is not a complete list.
The two drugs which are presently available and most commonly used weight
reducers are Orlistat and Sibutramine.
Characteristics of the Commonly used Antiobesity Medications
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Characteristic
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Sibutramine
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Orlistat
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Indicated for long-term treatment
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Yes
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Yes
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Special instructions
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Blood pressure monitoring is required before and
during therapy
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Patients must take a multivitamin supplement (2h
before a dose). No dose should be taken if a meal is missed or contains
no fat
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Adverse effects
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Hypertension, tachycardia, dry mouth, anorexia,
insomnia, constipation
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Abdominal pain, oily spotting, fecal urgency, flatulence
with discharge, fatty stools, fecal incontinence, increased defecation,
increased urinary oxalate
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Contraindications[a]
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Severe hypertension or poorly controlled hypertension,
heart failure, coronary artery disease, arrhythmias, or stroke
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Malabsorption syndrome and cholestasis. Use with
caution in patients with history of nephrolithiasis.
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Drug-drug interactions
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Monoamine oxidase inhibitors, selective serotonin-reuptake
inhibitors, drugs that increase blood pressure or heart rate, ketoconazole[b]
, erythromycin[b]
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Fat-soluble vitamins, beta-carotene, and possibly
cyclosporine
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Use with caution
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History of hypertension, seizures, narrow angle
glaucoma
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History of hyperoxaluria or calcium oxalate nephrolithiasis
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Patient instructions
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Take once daily in the mornings. Have blood pressure
and pulse checked regularly.
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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.
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- 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.
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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.
Many trials have shown that a 20 mg dose of rimobanant, which is used
in the management of obese diabetics, can lead to an average weight loss
of approximately 6 kg over a year when accompanied with lifestyle therapies.
Importantly, it leads to a decrease in abdominal obesity and improves
cardiovascular risk factors. The most common reported side effects include
depression, anxiety, and nausea and should not be used in patients on
anti-depressives. It is NOT accepted for use by the U.S. FDA.
GLP-1 analogues have been shown to be associated with weight loss, although
the DPP-IV inhibitors are weight neutral.
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.
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.
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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