Choice of insulin in type 2 diabetes: a south east asian perspective

CHOICE OF INSULIN IN TYPE 2 DIABETES:

A SOUTH EAST ASIAN PERSPECTIVE

Dr. Sanjay Kalra, Department of Endocrinology, Bharti Hospital, Karnal, India

Prof. Hong Quang Thai, President ,Vietnamese Asociation of Diabetes
and Endocrinology, Vietnam

Prof. Chaicharn Deerochanawong, Rajavithi Hospital, College of Medicine,

Rangsit University, Ministry of Public Health, Bangkok, Thailand

Dr. Goh Su-Yen, Department of Endocrinology, Singapore General Hospital, Singapore.

Prof. Dato’ Dr Mafauzy Mohamed, Director of Campus, Universiti Sains Malaysia,
Health Campus in Kelantan, Malaysia.

Prof. Tint Swe Latt, President, Myanmar Diabetes Association, Yangon, Myanmar

Prof. Than Than Aye, Department of Medicine, University of Medicine 2, Yangon, Myanmar

Prof. Zafar Ahmed Latif, Director, BIRDEM Academy, Dhaka, Bangladesh.

Dr. Prasad Katulanda, Diabetes Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.

Dr. Touch Khun, Diabetology Unit, Preah Kossamak Hospital, Phnom Penh, Cambodia

Dr. Sum Satha, Department of Medicine, Calmettee Hospital, Phnom Penh, Cambodia

Dr. Vadsana Vongvandy, Center of Diabetes, Mahosod Hospital, Vientiane, Laos

 ABSTRACT

South East Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and health care seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, non-intrusive, and suitable for use in multiple clinical situations, including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidance.

Key words:Asia, basal insulin, biphasic aspart, biphasic lispro, dual action insulin, and diabetes, patient centered care, postprandial glycaemia, premixed insulin

Main correspondence: Dr. Sanjay Kalra

Submission date:7 Feb 2017

Revised date:19 Feb 2017

Acceptance date:15Mar 2017

DIABETES IN SOUTH EAST ASIA

South East Asia is one of the hotspots of the diabetes pandemic, and bears more than its fair burden of the disease. Belonging to the Western Pacific region of the International Diabetes Federation, the zone reports a diabetes prevalence of 9.3%, and a large number of deaths, most of which occur in individuals below the age of 60 (1).

An earlier onset of diabetes, rapid development of complications, and longer life expectancy have led to an increase in the burden of diabetes, and diabetes complications. This strains the existing health care system, which finds it challenging to handle the twin burden of communicable and non-communicable disease which South East Asia nations face.

IMPORTANCE OF CLINICAL PATHWAYS

The role of clinical pathways and clinical recommendations is very important in such a scenario. Well-crafted pathways and algorithms, based on evidence, help in providing much needed guidance to physicians and other health care providers who deal with diabetes. Such documents are expected to offer a comprehensive management strategy, which includes screening and diagnostic tools, as well as non-pharmacologic and pharmacological interventions. They empower general physicians to tackle diabetes in peripheral clinical setups, and encourage timely management of the disease, thus reducing preventable complications.

Detailed suggestions are available from professional bodies such as the American Diabetes Association, European Association for Study of Diabetes, American Association of Clinical Endocrinologists, and International Diabetes Federation (2, 3, 4). There is criticism however, regarding the actual patient centeredness of these publications, and their pan—ethnic appropriateness (5, 6).  The techniques of diagnosis, thresholds for intervention, targets of management, and tools used to achieve them (the Four T’s) must be pragmatic, realistic, and concordant with dietary and lifestyle patterns. In view of this, many Asian countries have developed their own national guidelines, relevant to their local needs (7). This is in tune with the national list of essential medicines that each country develops: the subtle differences in these lists reflect the peculiar needs and requirements of each country (8).

NEED FOR SOUTH EAST ASIA SPECIFIC CLINICAL PATHWAYS

In diabetes care, we often tend to follow a Western-oriented management strategy. Data and recommendations from the Western world is usually extrapolated directly to South East Asia, without realizing that unique anthropometry, lifestyle and glucopheno-type of South East Asia modulates responses to pharmacotherapy. It should also be recognized that many South East Asian countries, especially the more urbanized and multiracial ones, are experiencing rising rates of obesity and diabetes

The Asian type 2 diabetes phenotype is well known (9). South East Asians have a relatively lower body mass index, and insulin secretory defect plays a more important role in the pathogenesis of diabetes. Caucasians, on the other hand, present with predominant insulin resistance. Thus, insulin replacement, both prandial and basal, is needed at an earlier stage in Asians with diabetes. There is a unique Asian lifestyle, “diet-type”, and health care seeking behavior, which is prevalent across most of the continent.  In many countries of South East Asia, persons present to the health care system at a relatively later stage, with significant glucotoxicity and lipotoxicity. Reversal of this toxicity may entail administration of adequate amounts of both prandial and basal insulin.

Animal studies have proven that malnutrition during pregnancy can lead to decreased β-cell function and mass in newborns. Mothers who had suffered the Dutch Famine gave birth to children who developed impaired glucose tolerance and type 2 diabetes in later life (10). The Great Chinese Famine sufferers experienced an increase in the risk of hyperglycemia during adulthood. This association appears to be exacerbated by a nutritionally rich environment in later life (11).  While most countries in Asian have experienced chronic food shortages in the past, and this pathophysiologic pathway may have contributed to diabetes in elder generations, food sufficiency has been achieved now.

Rice forms the staple diet of all of South East Asia, and the high carbohydrate load requires prandial insulin coverage in persons with diabetes. The South East Asian diet pattern is also peculiar. Many persons take two heavy meals in a day, and find it difficult to adjust to a 3+3 meal pattern which is an essential correlate of a basal bolus regime.

The high post prandial glucose levels, observed in Asian populations, are due to intake of high carbohydrate meals in large quantity, a relatively higher glycemic index of food staffs in this ethnic group (12), delayed presentation of the patient, and acceptance of insulin therapy. The prescription and use of insulin therapy must correctly and appropriately address the Asian pathophysiology and lifestyle habits.

INSULIN FOR TYPE 2 DIABETES IN SOUTH EAST ASIA

Such control can be achieved by various regimes, including basal, pre-mixed, basal bolus, basal plus, and different delivery devices, viz. vials /syringes, disposable / reusable pens, can be utilized  this purpose. The choice of regimes, preparation, and delivery devices, should be made in a patient-centered manner (13), following the spirit of informed and shared decision –making.

In a national clinical pathway or algorithm, however, preference should be given to therapeutic options which have the potential to provide maximum benefit to the maximum number of intended beneficiaries. Choosing an inappropriate insulin may delay control, worsen complications and negatively impact the patient’s (and community’s) trust in the health care system. On the other hand, initiating an insulin which provides effective, safe, well –tolerated, convenient and non –intrusive glucose control helps improve both biomedical and psychosocial outcomes.

Clinical pathways and algorithms designed for South East Asia should be based upon pathophysiological abnormalities, dietary content, dietary pattern, lifestyle and health care seeking behavior. Thus is especially important with respect to guidance related to choice of insulin for initiation. Asian evidence which proves the need for greater prandial insulin coverage (14), and the advantages of specific insulin preparations should be taken into consideration (15).

Most persons request for insulin therapy which does not interfere with, or intrude into, their lifestyle. In an overstretched health care system, it also make sense to use common stock and to dispense minimum number of pharmaceutical preparations. Thus, an insulin which can be used both for initiation and intensification, should take precedence over preparations which are limited to use in only specific clinical settings.

PREMIXED INSULIN FOR SOUTH EAST ASIA

In the South East Asian content, this option seems to be premixed insulin. This class of insulins provides comprehensive glucose control, including both fasting and postprandial euglycemia, with a lesser number of injections. Premixed analogues, such as biphasic aspart (BIAsp) and biphasic lispro (LisproMix) have the advantage of lower hypoglycemia, lower levels of postprandial glucose excursions, better adherence, improved quality of life, and higher patient satisfaction with treatment. The dual action co-formulation, insulin degludec aspart (IDegAsp), which is an improvement over existing insulin preparations, has added advantages of even lower hypoglycemia, nocturnal hypoglycemia, and greater flexibility (16).

Premixed, or dual action insulin, is the insulin of choice across most of Asia and Africa (17). This is borne out by statistics which reveal that premixed insulin is the most popular type of insulin used in the South East Asian Region (18). The A1chieve observational study also showed that premixed insulin analogues were the preferred mode of insulin use in Indonesia (19).

Premixed insulin can be used once daily, twice daily or thrice daily, depending upon the clinical situation. It can be used for initiation as well as intensification, and lends itself to easy self-titration by the user, and to physician-led dose titration. Various regimes, such as high mix, hetero-mix, and reverse hetero-mix regimes (20), allow for control of difficult-to-control or refractory diabetes.

Premixed insulin is included as an insulin of choice for initiation as well as intensification in guidelines from the International Diabetes Federation (3), Australasia (21), Cambodia (22), India (7), Japan (23), Myanmar (24), South Africa (25), and Vietnam (26). This reinforces the utility of this preparation in diabetes care. Premixed insulin is also mentioned in the national lists of essential medicines of various South East Asian countries (8), including Cambodia (27), Myanmar (28) and Vietnam (29). The comprehensive Laotian formulary of essential medicines (30) also mentions “insulin zinc (mixed)” as an essential drug. This preparation therefore seems optimal for inclusion in various national clinical pathways and guidelines across South East Asia.

Data from DiabCare Asia suggest that conventional strategies and practices are ineffective in achieving good glycemic control. In Malaysia, for example, only 41% of participants achieved a target HbA1c < 7.0%, with a mean HbA1c of 7.8 ± 2.2% (31). Indonesia reported a mean HbA1c of 8.2 ± 2.0%, with 32.1% participants achieving target (32).  Results from Bangladesh showed a mean HbA1c of 8.6±2.0% with only 23.1% of the patients achieving the target of <7% (33). Surveys in Thailand show similar trends, with 29.7% to 41.3% participants reaching HbA1c goal in various studies (34). These figures suggest that we need to enhance efforts for timely initiation of insulin, with preparations that are effective in controlling both fasting and postprandial glucose.

SOUTH EAST ASIAN LEADERSHIP

South East Asia is recognized as a global leader in provision of essential medicines for chronic disease, with best practices from Vietnam being highlighted by the World Health Organization website (35).

It seems natural, therefore, for South East Asian nations to continue their proactive and patient centered approach towards management of diabetes. This can be done ensuring publication and adoption of updated national clinical pathways and guidelines, which reflect and respond to the lifestyle, dietary patterns and biomedical as well as psychosocial needs of their citizens

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