Author: Yoshitsugu Obi

Dr. Anuj Maheshwari, MD, FICP, FACE, FACP, FRCP (London, Edinburgh)
Professor & Head in General Medicine, BBD University, Lucknow, India
Organising Secretary, Annual Congress of ACP-India Chapter “Medicine 2018” at Lucknow

It has been my first visit to Japan. I had heard lot of good things about this country but found it much better than of my imagination. It has really been a wonderful experience for me and my family. It has been an excellent hospitality with flawless arrangements from beginning to the end. First of all, I shall like to pay my gratitude to our India Chapter Governor Dr Muruganathan who recommended and given me opportunity to represent India Chapter during annual conference of Japan Chapter. At the same time I can never forget to pay sincere thanks from core of my heart to Dr. Takahiko Tsutsumi and Dr. Tetsuya Makiishi who were our guest speakers in annual conference of ACP-India Chapter 2018 at Lucknow. Not only their deliberations were outstanding here in India but they must had praised us well there in Japan. After receiving a lovely invitation by Dr. Sugihiro Hamaguchi, chair Scientific program committee, ACP Japan Chapter, Dr. Yuka Kitano helped me in understanding the learning objectives of physicians in Japan regarding Diabetes. For me It was really seeming tough to keep audience attentive for one hour of my lecture. Yuka not only encouraged me but also helped me in deciding content to be included in my presentation which can create interest in Japanese audience. Evening before, I got an opportunity to see and pay my gratitude to Governor Japan chapter outgoing and incoming both together with Robert M. McLean, the President of the American College of Physicians (ACP) elected in 2019 with his wife.

As I have been given the topic to speak on treatment options, I tried to focus my talk on common factor between two populations, India & Japan. Although diabetes prevalence is increasing in both the countries, but faster is the progression in India for conspicuous reasons like carbohydrate rich diet, sudden affluence and luxury lifestyle with lack of physical activity. All this has happened in last 20-30 years which has changed typical Asian phenotype in India to overweight and obesity making Indians more prone to diabetes in lack of physical activity. In addition to these reasons our large population is also responsible for ten times more number of diabetic patients. In Japan 7.2 millions are suffering with diabetes while this number is 72 million in India second highest in the world next to China. Diabetes prevalence in Japan is 7.7 % while it is 8.8% in India.

If we really talk about common factors, typical Asian phenotype is actually a common characteristic between people of India and Japan. This typical Asian phenotype is characterised with accumulation of visceral fat with lean phenotype in extremities. Healthy Food habits and good amount of physical activities in Japan keeps away abdominal obesity and insulin resistance at large while in India same phenotype has progressed to abdominal obesity and Insulin resistance causing type 2 diabetes. What I noticed in ten days visit to Japan, plants & vegetables are used in good amount with food but with much less oil and fat contrary to India. Lot of lessons are there for Indians in Japanese life style.

Glucose control in diabetes deteriorates over time with the progressive nature of disease resulting in risk of developing various micro and macro vascular complications. Many classes of anti-diabetic drugs are available for treatment including metformin, sulfonylureas, glitazones, glinides, α glucosidase inhibitors and nearly a century old insulin. Newer drugs like gliptins (DPP-4 inhibitors), GLP1 agonist, flozins (SGLT-2 inhibitors) and insulin analogues have been added to the list during the last few years. These drugs effectively address various pathophysiological defects. However, given the need for multiple drug therapy, there is still a significant unmet need in the management of T2DM. Non-insulin antidiabetic agents have a potential to reduce HbA1c by an average of 1% and the simultaneous use of combination therapy can result in greater HbA1c reduction. Position statement on Standard of Care by ADA, recommends metformin as preferred initial pharmacological agent. Though we Asians do not match exactly with Americans, we need different recommendations to treat diabetes as we are not only different genetically but environmental factors, body habitus are also different.

A lot of questions had arisen out of these recommendations from audience citing Japanese are not usually obese or overweight then why is it necessary to begin treatment with metformin? It is true that Japanese may have many genes susceptible to diabetes including thrifty genes. Various environmental factors, added to these genetic factors, are considered responsible for the onset of disease, and the number of patients is increasing rapidly reflecting recent lifestyle changes. Impaired insulin secretion is characterized by lowered glucose responsiveness. In particular, the decrease in postprandial-phase secretion is an essential pathophysiological condition. Glucolipotoxicity, if left untreated, results in the decrease in the functional pancreatic cell mass. So it is not only an issue to improve insulin sensitivity. Metformin facilitates peripheral utilisation of glucose and equally beneficial in Insulin deficient type 2 diabetes mellitus. Although it may have some concerns for Indians as many of them are vegetarian having Vitamin B12 deficiency causing anaemia but not in Japanese. So it is appropriate selection of pharmaceutical agent which has immense importance. Now further recommendations should continue as follows:

• If metformin monotherapy at highest tolerated dose does not achieve the optimum level, a second oral or injectable agent should be added.
• Choice of the second pharmaceutical agent should be a based on environmental factors influencing therapeutic response.

Apart from this AACE suggests to start with dual drug therapy if HbA1c is 7.5 or more. If HbA1c is 9 or more at beginning, triple therapy is recommended to start with. If patient is symptomatic at 9 or more HbA1c, insulin should be a part of triple therapy.

Queries came from audiences regarding relevance of using pharmaceutical agents with weight loss potential in Japanese population like GLP1RA & SGLT-2 Inhibitors. A convincing explanation lies in visceral fat causing abdominal obesity giving rise a peculiar Asian phenotype. SGLT2 inhibitors act on the non-classical pathway and reduce hyperglycaemia by inhibiting renal reabsorption of glucose and thereby increasing urinary glucose excretion.  They also lead mild reduction in blood pressure due to chronic osmotic diuresis and associated with lower risk of hypoglycemia.

SGLT-2 Inhibitors can only be justified if a person is having significant amount of visceral fat reducing insulin sensitivity. It also promotes usage of alternative fuels like fat for production of energy. As far as GLP-1RA is concerned, they increase insulin secretion in response to oral glucose ingestion, induce satiety by slowing gastric emptying, suppresses appetite, inhibit glucagon secretion and also have been proposed to cause ß cell regeneration. Endogenous GLP1 released from intestinal L cells has a short half-life of 4 – 11 min. To overcome this, GLP1 analogues resistant to degradation by DPP4 have been devised. Low dose usage can be safely done for Japanese population with central adiposity.

Later I got an opportunity to judge selected research papers for oral presentations by students, residents, Fellows & early career physicians. One of the most stimulating session with high class research had made it more challenging to decide the best. All research papers and presentations were so good that it was difficult to select one for “Kurokawa Prize”.

Then I got a chance to attend few plenary sessions which were in Japanese language but I am thankful of my interpreter Mr. Hideta Teshirogi who is pursuing his medical studies there. He has been so wonderfully translated all sessions on the spot sitting aside me. I appreciate his knowledge and translation power so fast. My medico daughter Shivangi who is also pursuing medical studies in India enjoyed all English sessions and Kurokawa Prize session.

Overall it has been a wonderful academic feast for me and my family at one of the most beautiful city of world Kyoto. We attended welcome dinner in evening with all attendees and faculties. Next day enjoyed sightseeing at Arashiyama before leaving back home India. It has been an unforgettable experience while being at Japan. I wish to thanks all members of organizing team and Governor Japan Chapter Dr. Kenji Maeda for great conference with wonderful hospitality. We shall surely try our best to reciprocate when Dr. Kenji Maeda comes India for our annual conference at Kolkata. We can plan many joint ventures together including Asia specific guidelines in future.