When and how should we start insulin?
Karoline Laarmann reports
Innumerable studies (e.g. Ceriello A., et. al. 2006) have shown that postprandial hyperglycaemia is an independent risk factor for cardiovascular disease (CVD) in all populations. In diabetics, according to IDF figures, CVD is even the major cause of death (some 50 % of all diabetes fatalities) and much disability. ‘Therefore, the primary goal in diabetes treatment should be not only lowering blood glucose levels judged by a target HbA1c value of ≤ 7,0 mmol/l, but also to significantly control postprandial blood glucose,’ says Professor Bruce H R Wolffenbuttel, Head of the Department of Endocrinology at the University Medical Centre Groningen, the Netherlands.
An intensified insulin therapy can help to achieve an adequate PPG – but there are some patient-oriented aspects that should be considered. Unfortunately, there is limited clinical trial evidence regarding the effects of intensive glucose control on the development of CVD. Why? ‘It’s difficult to evaluate a clinical trial that separates the effects of intensive insulin therapy on PPG from its effects on HbA1c, because if you lower PPG by insulin treatment, HbA1c goes down, too,’ he explains.
As a result, large studies, e.g. ACCORD or ADVANCED, do not concentrate on PPG but typically investigate overall glycaemia respectively HbA1c. Moreover, these kinds of studies were performed in an advanced diabetes group of patients among whom a large section already suffered CVD. ‘It may well be that, in this patient group, an intensive insulin therapy results in frequent hypoglycaemia and therefore instead increases the CVD risk,’ Prof. Wolffenbuttel surmises. The VADT study (Duckworth, W et al.; N Eng J Med 2009), for example, showed the benefit of intensive glucose control in patients with a short duration of diabetes, and side-effects in patients with long (> 15 years) duration of diabetes and in those with severe CVD.
A very recent Japanese study (Nishimura H., et al.; Diabetologia 2008) – till now not published as a full paper – is the first of its kind to concentrate on PPG alone and consider only diabetics free of CVD at the start of the survey. It provides a promising hint that addressing PPG reduced CV damage in the early course of diabetes.
Over 300 diabetics were divided into two study arms, one treated with regular insulin, the other with fast acting insulin analogue (insulin aspart). The trial resulted in same HbA1c values (7.5 mmol/l) between the two patient groups after five years, and lower PPG in the insulin aspart group. Result: a 43% reduction in CV endpoints.
‘What we can learn from these various clinical trials is that the potential benefits and risks of intensive treatment need to be assessed in every single patient, taking into account individual aspects such as risk of hypoglycaemia, age, lifestyle and life expectancy,’ the professor pointed out. ‘Even though it is known that Type 2 diabetes is a heterogeneous disease, all patients are still treated the same.’
In 2008, the treatment algorithm for Type 2 management was adjusted by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). It advocates beginning with the addition of one injection of basal insulin, when lifestyle changes and oral agents, e.g. metformin, begin to fail in maintaining an adequate glycaemic control level – the case in every diabetic career, sooner or later. ‘Although such therapy schemes are simple for patients and doctors, they can hardly be considered a ‘tailor-made’ personalised treatment, and it can be questioned whether they provide satisfactory control of PPG,’ he pointed out.
‘When you begin with insulin therapy, you have a lot of choices. The right insulin injection regime depends on the patient’s needs, as well as on the degree of glucose control. Generally, premixed insulin analogues or multiple daily injection regimens can be adjusted to daily activities and lifestyle of patient and are the best way to mimic normal physiology. By this, such insulin regimens are expected to add to the prevention of macrovascular complications.’
Age is one of the most important factors to decide on the right insulin treatment. In younger age, intensified treatment regimes with up to four insulin injections daily allow for an active and flexible lifestyle and prevent long-term future complications. However, in the elderly such a strict glucose control would mean a high burden for the patient with a risk of hypoglycaemia but, up to now, limited evidence for benefit. His conclusion: ‘Insulin therapy should always follow life, not life follows insulin therapy.’
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