Sunday, December 7, 2014

The diabetic dilemma - A complex disorder with diverse dimensions

Is it not shocking when we are told that in this planet one human being dies every 6 seconds because of diabetes and complications arising from this scourge? The staggering figure of 384 million people being affected in his world by diabetes is indeed disturbing and look at the death rate-1.5 million (mn) dying because of this disease every year. How come this so called metabolic syndrome was allowed to creep in slowly without being taken seriously a few years ago? Probably adequate knowledge might not have been available then to understand unambiguously the basic reasons for human beings to develop diabetes. Progress in medical science and human physiology has created a fund of knowledge regarding various causes that can be responsible for spreading of metabolic syndrome in practically every country in this globe.

Saudi Arabia, UAE, Kuwait and Qatar are prominent countries where those affected by diabetes is as high as 20-24% of their population. That means 1 in 5 citizens suffers from this disease. According to the WHO the diabetic is expected to be prevalent among 600 million people by the year 2035. What about India? While as a percentage of the population it is small, about 5%, in absolute numbers, this country can be called the diabetic capital of the world. From 31.7 mn in the year 2000, the number of diabetics has jumped to 62 mn in 2014 which is predicted to reach almost 80 mn by 2030. India, China and the US have most diabetics compared to other countries though in terms of percentage figures, these countries have relatively less affected by diabetes measured per thousand population. Though statistics can be quite revealing, what is not understood is why some are more vulnerable while others are immune to this disorder, considered a life style disease caused by sedentary living conditions giving no scope for the body to expend the calories consumed through physical activities. 

If one asks the crucial question as to what is really responsible for this surge in diabetic population, the most common answer would be "obesity". According to present understanding about diabetes, over weight and obesity contribute to insulin insensitivity leading to a condition when body finds it difficult to push glucose into the cells where it is supposed to be converted to energy. However a closer look at the situation will reveal that obesity cannot be the sole factor causing diabetes. In the US there are almost 100 million obese people while the diabetic population is only 23 mn and it will reach a figure of 30 mn only by 2030. Similarly China the second largest obesity prone country has 46 mn cases of obesity whereas its diabetic population is only 30 mn. The third ranked India on obesity scale with 30 mn people suffering from obesity, has a whopping number of diabetics, viz 62 million. Thus it is difficult to establish a direct linkage between obesity and diabetes. There must be other reasons for developing diabetes which need to be looked into.

Three new studies carried out fairly recently have brought to surface the role of genetic make up, disturbed Amylin hormone cycle and disturbances in the body's natural circadian clock  Qualitatively some conclusions can be drawn regarding the role of genes and mutations undergone by them. The fact that certain ethnic groups are more prone to diabetes than others has been pointed out in support of genetic factors influencing the onset of diabetes. The inherent contradiction, that some lean people get diabetes while many over weight people are protected from diabetes, cannot be explained easily unless we fall back on genetic factors. A probable interpretation could be that the diabetes can occur with a 50:50 chance determined by family history and life styles followed by different people.

Those who contend that gene factor is important cite the 9 variations possible in the gene PPARG which has some influence on obesity development and which is not strictly related to BMI. Building up of fat around abdomen in some people who do not appear to be "fat" to look at, can be explained only though the above basis. Decreased function of PPARG can simulate such a condition. According to this school of thought diabetes that is seen in India and Pakistan is of this type. This is reflected by the fact that in India obesity is much less as a proportion to diabetic population than that found in the US and China. Diabetics to obese population in the US, China and India are 23:100:,30:40 and 62: 30 respectively reflecting the difference found in the above countries. 

The Amylin hormone produced by pancreas works in conjunction with insulin and plays a role in preventing over production or under utilization of insulin affecting glucose levels in the blood plasma. According to those who support the theory of Amylin hormone's role in developing diabetes, too much production of this hormone can get deposited around pancreas as toxic clumps causing death of insulin producing cells. This theory lacks precise scientific evidence regarding the cause of Amylin over production though it is thought to be related to inactivation of concerned enzymes involved in the metabolism of Amylin. But the qualitative finding as reported recently cannot be brushed away easily. Further studies can only throw more light on this aspect related to development of diabetes, at least among some people, not vulnerable to obesity.

The Circadian clock theory also appears rational though the evidence generated so far is with mice as subjects. The finding that during the night when mice are active, they showed high insulin efficiency to burn the foods they consumed into energy while in the same mice during day time when they sleep, their insulin resistance increases leading to accumulation of fat and weight gain. Insulin after all is  the driving tool for pushing glucose in the blood into liver, muscle and other cells. Mice population in which the gene responsible for circadian rhythm is knocked out were found to develop insulin resistance and consequently gained weight abnormally. Same thing was found when they were exposed to uninterrupted light for 24 hours upsetting their circadian rhythm. If such a phenomenon is confirmed by clinical trials with humans, it provides logical explanation for the vulnerability people working in night shifts and others ignoring the normal sleep cycle to diabetes more often. 

The above three findings throw lot of insight into diabetes epidemic the world is facing and must serve as a guide to future development for appropriate therapy to deal with this disease in the coming years. While diabetes related to genetic factors will have to be dealt with at the genetic level involving gene manipulating intervention drugs,  Amylin therapy to reduce insulin resistance will have to work at the enzyme level and circadian clock disruption will need to be avoided to pre empt this causing diabetes. The world is headed for an exciting era ahead when more precise and reliable drug therapy may emerge based on the latest findings. 

Beware, a person looking lean need not be free from diabetes while another person looking obese may be really non-diabetic!  


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