Monday, October 21, 2013

Plenary 3--CFRD

The third Plenary Session of NACFC 2013 explored the topic of Cystic Fibrosis Related Diabetes (CFRD) and was entitled: CFRD: From Bench to Bedside & Back again.  Andrea Kelly, M.D., MSCE was the first speaker in this session.

Patients with CF are living longer than ever before (YES!), but age can bring new health issues--including CFRD.  CFRD is very common--50% of CF patients will develop it by age 30.  Current guidelines recommend annual oral glucose tolerance tests beginning at age 10.

Insulin secretion defects are present early in CF patients, and are progressive. We know that CFRD doesn't behave exactly like Type 1 or Type 2 what is the mechanism driving the impaired glucose tolerance here? Understanding precisely why so many CF patients develop CFRD could lead to better, earlier therapeutic interventions.  After all, CFRD is associated with a lower survival rate and higher rates of lung transplant in CF patients.  Not good.  Not to mention that CFRD can have a real negative impact on your life. Successfully managing CFRD can be burdensome and time consuming. Symptoms can include decline in BMI and FEV1.


Some readers might be thinking, "My child is young and her sugars are normal--this doesn't apply to me."  Dr. Kelly would argue that it DOES.  She goes on to explain the typical oral glucose tolerance test (OGTT)--a sugary drink (75 g glucose) is administered, and after 2 hours, the patient's blood is drawn to test blood glucose levels.  Levels below 140 mg/dL are considered normal.  140-199 classifies as "glucose sensitive." Levels above 200 mg/dL are diagnostic for CFRD.  Dr. Kelly believes that that the standard OGTT may actually miss many CF patients exhibiting early signs of glucose intolerance and goes on to show some evidence.  She suggests that CF patients have an initial delayed and blunted insulin secretion, similar to type II diabetics, and believes early indications of this could be picked up more accurately with the non-fasting, 50g glucose test, where blood glucose is tested after 1 hour instead of 2.  Her argument is that early insulin abnormalities can be seen in the time immediately after ingesting glucose, and this test could be better at identifying and treating those individuals exhibiting the earliest signs of CFRD.  If dealing with CF has taught me anything, it is that it is almost always better to nip problems in the bud before they get big and ugly. Controlling blood sugars is no exception.

She went on to describe how pancreatic enzyme replacement has an effect on insulin secretion.  Individuals who take their enzymes properly have improved insulin secretion and blood sugar control!  Some of those individuals who screen positive for early glucose intolerance might be able to see some improvement by simply tweaking their enzymes a bit (may need support to be diligent in taking them, others may need a dosage adjustment.)  That is nice to know.  Others may need alternate interventions.

The mechanism driving CFRD isn't completely understood, but Dr. Kelly describes important cells in the pancreas called beta cells--whose primary function is to store and release insulin.  Patients with CF have impaired beta cell function.  Preserving the function of these cells is crucial to controlling blood sugar levels.

There is also a question whether CFTR function could impact insulin secretion, and Dr. Kelly described a pilot study sponsored by the CFF to answer that question.  This study will examine if Kalydeco (Ivacaftor) has a direct impact on insulin secretion.

Before concluding her discussion, Dr. Kelly mentioned that standard nutritional recommendations for CFers may HASTEN the progression of impaired glucose control and development of CFRD.  Patients should still strive to meet the fat/calorie recommendations for CFers, but modifications to carb intake and regular exercise could lead to better glucose control. 

The next speaker in the Plenary session was Dr. John Engelhardt, who works with CF ferrets and CF pigs to gain understanding to the mechanism behind CFRD.  CF pigs and ferrets develop lung and pancreatic disease similar to humans, and provide an effective model of study.  Newborn pigs have severe pancreatic disease.  Ferrets have milder disease, but rapidly develop disease and pancreatic fibrosis.  Many have blood sugars greater than 200 mg/dL arising at about 1 mo. of age.  It is unclear whether infants with CF exhibit the same early abnormalities, but there is certainly evidence that we should study further.  

Engelhardt shows that 42% of patients aged 1-5 exhibit abnormalities in glucose tolerance.  He goes on to describes the current hypotheses to describe the pathogenesis of CFRD.  Some believe that the exocrine disease in the pancreas (inability to secrete digestive enzymes), spills over to affect the endocrine function (ability to secrete the hormone insulin) of the pancreas.  Others predict that insulin secretion is tied to CFTR function.  I am really curious to see the results of the upcoming studies to examine this link.

Engelhardt described regions of the pancreas called islets, which contain insulin producing cells. Islets contain detectable levels of CFTR, which suggest that CFTR function may play a role in maximizing islet function.  The Plenary session concluded with the recommendation that tight nutritional control may have a large impact on the progression of CFRD, and that further studies in pig and ferret models may lead to therapies that slow the beta cell dysfunction in CF.  

The message that I took away from this Plenary session is that impaired insulin secretion begins early in life for CF patients, and can progress undetected by our current OGTT methods.  While there are many ways that CFRD differs from type II diabetes, similar management strategies may be useful for both groups (reduced carb intake and regular exercise).  It can be really tough to meet CF fat and calorie needs when you place ANY kind of restrictions on the diet, but it looks like we are going to need to get real about the amount of carbs being used to reach those dietary goals.  The earlier we are able to detect, intervene, and manage glucose intolerance--the longer beta cell function can be preserved, improving blood sugar control.     

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