Diabetes and decline of lung function

Question

Hello, does the diagnosis of a diabetes requiring treatment with oral anti-diabetic medication in adulthood invariably lead to a deterioration of health (especially regarding lung function and FEV1) even if the diabetes is correctly controlled?

Answer

Hello,
Thank you for your very good question.
Cystic fibrosis-related diabetes (CFRD) (I am going to use this abbreviation, it is easier/more correct) is due to the damaged pancreas in CF.
The pancreas is an organ composed of two parts: an exocrine part responsible for the secretion of the digestive enzymes and an endocrine part, the Langerhans islets, which contain the insulin secreting cells. The Langerhans islets are distributed here and there in the gland (like oases in the desert). The destruction of the gland as a consequence of CF is characterized by a fatty involution and fibrosis. Little by little these destructive processes may encompass the Langerhans islets which, then, tend to disappear. At a given moment there are too few Langerhans islets left to assure the required insulin production. At this time in point glucose intolerance and, then, diabetes become manifest.

The lack of an ADEQUATE insulin secretion is problematic for different reasons. First, there will be an imbalance in the sugar metabolism. At certain time-points there is going to be too much sugar in the body and this may have harmful effects, for example, on the function of a particular type of white blood cells - the neutrophils, which defend ourselves against infections - and may cause their dysfunction. There will also be a leak of sugar in the urine, which will cause a loss of calories and in turn weight loss. Secondly, the insulin has other functions in our organism. It works – amongst others – as a hormone necessary for the development and maintenance of the body's muscular mass. As a consequence, if the organism has not enough insulin, a breakdown of muscle mass may ensue.
Things are even more complicated because CFRD is NOT a STABLE state. In case of an infection, we may develop a state of insulin resistance, which means that the secreted insulin cannot have its usual impact on our metabolism, and we therefore have to produce even more insulin then usual to ensure all the functions which have to be ensured. We all know CF patients, who become diabetic and need insulin during a severe infection or in the immediate post-operative course after lung transplantation, and who – once recovered or stabilized – no longer require insulin.
So, there are two things to be kept in mind: 1) CFRD is a state where there is a relative lack of insulin and 2) CFRD may be worsened by a state of insulin resistance in case of inter-current events and, then, the relative ‘lack’ of insulin will be even greater.
To come back to your question ...
As you probably know, an unexplained decline of the respiratory function in a person with CF must lead to search for CFRD. So if there is CFRD and it goes undiagnosed, the patient's state can deteriorate. It is also known that patients with CFRD often have a worse longitudinal evolution. CFRD can lead to pulmonary exacerbations, which respond less or slower to treatment, and quicker relapses have also been described.
Now, in practice ‘CFRD’ can mean a lot of things. I explain myself. Based on the published data it is impossible to tell if the patients with ‘CFRD’, who have a pejorative evolution, have been diagnosed on time and/or have had an appropriate treatment. In my experience, the correct equilibration of CFRD often poses a lot of problems. The patients can have difficulties to equilibrate themselves properly either because they have other medical problems, which make the equilibration of the diabetes difficult (such as gastroparesis or delayed gastric emptying = the stomach doesn't empty itself properly and this leads to erratic absorption of meals, recurrent infections/hospitalizations, intermittent need of cortisone), or because CFRD is the last complication on a long list of complications and the patient can no longer cope with the addition of a cumbersome treatment to his already long treatment list and neglects the CFRD treatment.

The medical literature, will give very few information on the question “will an early diagnosed and correctly equilibrated CFRD still have a negative impact on the evolution of the respiratory function?”

Nowadays, the consensus is that insulin is the best CFRD treatment and that the metabolic control of CFRD is very important. Indeed, the medical literature reports cases, which indicate that the pulmonary function can recover after properly controlling a CFRD. There was even one report on a patient whose respiratory function deteriorated, he had to be put on the waiting list for lung transplantation and could be taken off the list once the control of diabetes had been achieved. Also, a recent study has shown the benefits of early insulin therapy. Twenty-eight patients (median age: 15 years), who had normal fasting blood sugar concentration, but a disturbed oral glucose tolerance test, received small doses of insulin. After three years of follow-up the respiratory function had stayed stable in this group whereas it had deteriorated in a control group which did not get insulin therapy. Furthermore, the nutritional parameters also improved in the treated group. I insist on the fact that this kind of study has to be confirmed on a larger scale and also on the fact that nowadays it is unknown whether or not the glycosylated hemoglobin is the best marker of CFRD control and which target value should be obtained for an optimal evolution (like in diabetes in the general population? or maybe even stricter as this is a younger population?).

As for the oral anti-diabetic medications, there are different types. So you should ask your doctor which one you are taking. The sulfonylureas and the glinides increase the secretion of insulin. Their mechanism of action is to stimulate the Langerhans cells to secrete more insulin. This treatment can work for CFRD, but has its limits because when there are not enough Langerhans cells left it makes no sense to stimulate them. The biguanides reduce the liver's glucose production and the intestine's glucose absorption, they also reduce insulin resistance, but insulin resistance is not the principal mechanism of CFRD so their relevance for CFRD is rather limited. There are also other types of oral anti-diabetic medications, but they have currently no place in the treatment of CFRD.

In your case, you have to check which medication you take and discuss it with your doctor to understand the mechanism of action. Afterwards, you have to be careful not to exceed the limit and try to detect early the moment when you start lacking insulin, but your doctor will take care of that. Also your situation could become unstable if you have an acute infection (always remember this) and you could transiently be in need of insulin.
To your question « is it necessarily an indicator of the aggravation of the disease ? » as you can see I can not answer your question with certainty and based on evidence in the medical literature, but from a personal point of view my answer would be NO. Nevertheless, be sure to get your diabetes under good control and to shift to insulin as soon as your doctor suggests this to you.

Yours sincerely,
Christiane Knoop

22.05.2012