Metabolic syndrome

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Metabolic Syndrome

The Metabolic Syndrome
Obesity, hypertension & type 2 diabetes mellitus [T2DM] are the common diseases prevalent in any modern society. Many a times, these diseases are seen in the same patient along with severe complications. These are atherosclerosis of blood vessels leading to angina pectoris, myocardial infarction & stroke. Diabetics also suffer from retinopathy leading to blindness, nephropathy leading to renal failure, neuropathy, and gangrene of the foot leading to amputation. Many diabetics are aware of their susceptibility to infections. Even worse, this cluster of diseases, which used to occur around the age of 50-60 years, is now appearing in younger population beginning from 10- 30 years. On an average, 1 in 3 individuals is likely to suffer from this cluster of diseases. It does not spare the rural folk either. As people in the prime of their careers suffer from these diseases, it affects productivity and is a cause of concern to both the developed & developing countries alike.
For decades many physicians have been wondering about the association of these diseases in the same individuals. With the rapid progress in molecular biology over the past 20 years, medical scientists are very close to know about the common cause behind this disease complex, coined " syndrome X" by Dr. Gerald Reaven in 1988. X stood for the unknown cause. As insulin resistance [IR] & a high level of insulin are seen in these patients, it is popularly known as IR syndrome.
Dr. Flier & his team observed that this cluster of diseases was seen in patients with "Cushing syndrome" due to excess of glucocorticoids from the adrenal cortex. This is also seen in patients receiving glucocorticoid therapy for prolonged periods. Therefore they hypothesised that excess of glucocorticoids in specific tissues might be the cause behind metabolic syndrome. After extensive research during the last ten years, they proved this hypothesis. They studied the visceral fat in the abdomen and found that an enzyme known as 11 beta hydroxy steroid dehydrogenase type-1 {11beta-HSD 1} was found in excess compared to the fat in non-obese people. This enzyme converts the inactive cortisone to active cortisol. Ultimately Flier & his team made transgenic mice expressing more 11 beta-HSD 1 in the fat cells. These mice developed abdominal obesity, insulin resistance, hypertension & dyslipidaemia, which form the core of metabolic syndrome. An 11 beta- HSD inhibitor is in phase-1 clinical trial.
What is worth noting is it is easier to prevent this syndrome than control or cure the disease once it sets in.
The following criteria help early detection of metabolic syndrome:

•     Abdominal obesity (men > 102 cm or 40 inches; women > 88 cm or 35 inches) , Body mass index > 25 kg/m2
•     Triglycerides > 150 mg/dL
•     High-density lipoprotein cholesterol < 40 mg/dL for men, < 50 mg/dL for women
•     Low-density lipoprotein particle size < 260 angstroms
•     Blood pressure: Systolic blood pressure >/= 140 mm Hg or Diastolic blood pressure >/= 90 mm Hg
•     Fasting glucose > 110 mg/dL
•     Strong family history
1 in 10 women will have polycystic ovarian syndrome [PCOS] characterised by amenorrhoea, infertility, hirsutism, abdominal obesity associated with IR. Some patients also have dark thickened patches on the skin known as acanthosis nigricans. Nonalcoholic fatty liver patients may also have IR.

In IR, there is reduced sensitivity of the tissues to insulin's action causing a subnormal effect on glucose metabolism. These changes result in hyperglycemia, which in turn stimulates the pancreatic beta cells to produce more insulin to maintain normal blood glucose level. The beta cells in the pancreas can expand functionally ten times after which they fail. Beta cell failure leads to hyperglycemia. The period from IR to beta cell failure & the diagnosis of T2DM may last 10-20 years. Early diagnosis of IR therefore plays a crucial role in the prevention of T2DM.

Prevention of metabolic syndrome:

1. Exercise: Walk 30 minutes/day in a calm environment.
2. Diet: Eat foods with low glycemic index.

The modern life is more hectic than it used to be. It is fast paced. We use motor vehicles to reach work place in time. The food we eat is junk. It means for example grain removed of the fiber & nutrient covering, starchy, quickly cooked, and easily digested causing quick peaks of blood sugar. This peak releases more insulin, which causes hypoglycemia. We feel hungry & crave for sweets. This again releases more insulin. The vicious cycle continues. This becomes a habit.
Eating whole grain products like wheat, Ragi & pulses can break this. Unpolished rice is better. Re-education of tongue is a must. Patience is required for cooking & serving food. These foods do not produce abnormal peaks of sugar as they are digested slowly over a long period. Green leafy vegetables give bulk & protective nutrients. We know some of them like vitamins, minerals & anti-oxidants. Reduced weight & reduced blood sugar levels improves sensitivity of tissues to insulin. Avoid hotel foods containing hydrogenated fat, which increase bad cholesterol.
When these measures fail, insulin sensitisers are used. Metformin, rosiglitazone & pioglitazone are the presently available insulin sensitisers. When early detection of the metabolic syndrome is made, these help to sensitise the tissues to endogenous insulin. This reduces burden on the beta cells & decrease Hyperinsulinemia. Thus it is assumed the dreaded syndrome can be prevented or postponed.
At present, clinical trials are going on to prevent the development of T2DM using drugs like rosiglitazone. Unfortunately these are not with out toxic effects. Therefore there are protests from the knowledgeable public & physicians against the use of glitazones in otherwise normal looking people.
Here is something important for every one to take note of. The herbals are safe & effective & especially suitable for prevention of diabetes. Eugenia Jambolana seed powder has insulin sensitiser property & is non toxic. This is known as Nerale in Kannada & jamun in Hindi. Previously they were studied in advanced diabetic patients & were compared with modern chemicals for their effect on reducing blood sugar levels. They were comparatively less effective in reducing blood sugar levels & ignored. Using insulin sensitisers for diabetes prevention is a new concept. Rosiglitazone is less effective than metformin & glibenclamide in reducing blood sugar. What is important is reduction of insulin level in prevention of diabetes. It is proven in animal experiments that jamun seed powder reduces blood glucose as well as blood insulin levels. It is well tolerated. For more than 1000 years Ayurvedic physicians have used Jamun seed powder in Madhumeha. It is freely prescribed in the west by nutritionists & herbal therapists. The study in our laboratory confirmed insulin sensitising property of jamun seeds.
Another herb popular in Ayurveda & recommended by western nutritionists is gymnema sylvestre. Gudmar is the Hindi name & madhunashini is the Sanskrit name. This is proved effective in diabetes in both animal experiments & human clinical trials. In addition to insulin sensitising property, this herb also numbs the taste for sweet thus reducing craving for sweets. it also reduces the absorption of glucose from the intestine & improves regeneration of pancreatic beta cells.
So one can start using these herbs. It will take at least ten years for the glitazone trials to be completed & licensed safe for use in diabetes prevention. What are we waiting for?

[Note: Rosiglitazone & pioglitazone are available for use in treatment of T2DM. These are also effective in PCOS]

Dr. Nagendra Nayak
MD
Associate Professor in Pharmacology
Kasturba Medical college
Mangalore.

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