Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?

I have the full-text PDF of this article. VERY interesting!

Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed?


Exocrine pancreatic insufficiency is frequently associated with diabetes, with high prevalence in both insulin-dependent or insulin-independent patients. Exocrine pancreatic failure has often been perceived as a complication of diabetes. In contrast, recent clinical observations lead to the notion that nonendocrine pancreatic disease is a critical factor for development rather than a sequel to diabetes. The incidence of diabetes caused by exocrine pancreatic disease appears to be underestimated and may comprise 8% or more of the general diabetic patient population. Nonendocrine pancreas disease can cause diabetes by multiple mechanisms. Genetic defects have been characterized, resulting in a syndrome of both exocrine and endocrine failure. Regulation of beta-cell mass and physiological incretin secretion are directly dependent on normal exocrine function. Algorithms for diagnosis and therapy of diabetes should therefore address both endocrine and exocrine pancreatic function.

Liver disease as risk factor for cystic fibrosis-related diabetes development.

Liver disease as risk factor for cystic fibrosis-related diabetes development.

AIM: To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. METHODS: Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. RESULTS: Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43-93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1 = 58.4 +/- 27% predicted versus 67.4 +/- 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. CONCLUSION: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.

Characteristics of adults with and without cystic fibrosis-related diabetes.

I have this in full-text PDF--

Characteristics of adults with and without cystic fibrosis-related diabetes.

AIMS: The prevalence of diabetes in adults with cystic fibrosis (CF) approximates 25%, yet few studies have defined risk factors. We examined the association between biochemical and clinical factors and CF-related diabetes. METHODS: We performed a study in adults with CF in 2004 in Cambridgeshire, UK. Of 160 individuals, 51 had diabetes (cases) on the basis of medical history or screening using a 75-g oral glucose tolerance test, and 107 did not have diabetes (control subjects); two were excluded. We used logistic regression to model the cross-sectional association between potential risk factors and diabetes. RESULTS: The mean age was 26 (16-58) years, mean body mass index (BMI) was 21 (16-28) kg/m(2), and mean forced expiratory volume in 1 s was 60 +/- 24% (mean +/- sd). All of the cases and 88% of control subjects had pancreatic insufficiency. Cases did not differ from control subjects with respect to age, sex, body mass index, or dose of oral pancreatic enzymes. Cases were more likely to have low serum magnesium, haemoglobin, and pulmonary function, and higher serum gamma-glutamyl transferase (GGT) activity, plasma fibrinogen levels, erythrocyte sedimentation rate, use of oral corticosteroids, and number of CF-related complications. In multivariate analyses, GGT, previous organ transplantation, plasma fibrinogen and the presence of CF-related complications were independently associated with diabetes, after controlling for corticosteroid use. CONCLUSIONS: These data confirm the high prevalence of diabetes in adults with CF, and identify plasma fibrinogen and GGT, and organ transplantation as factors independently associated with CF-related diabetes. A prospective study would clarify the nature of these associations.

I have this one in full-text PDF.

New criteria for impaired fasting glucose and screening for diabetes in cystic fibrosis.

Cystic fibrosis-related diabetes mellitus (CFRD) is the most frequent comorbidity in cystic fibrosis. Its clinical relevance is stressed by the association with increased mortality, and decreased pulmonary and nutritional status. An annual oral glucose tolerance test (OGTT) is recommended as a screening test for CFRD, but this is often not realised because of its time- and resource-consuming nature. Therefore, alternative approaches are welcome. In 2003, the American Diabetes Association (ADA) lowered the cut-off point separating normal from elevated fasting plasma glucose from <6.1 mmol x L(-1) to <5.6 mmol x L(-1), suggesting the performance of an OGTT only in those with impaired fasting glucose (IFG; range 5.6-6.0 mmol x L(-1)). The current authors tested whether this approach was reliable for the early identification of patients with CFRD. OGTTs from 1,128 patients (53% males; 47% females; median age 17.1 yrs) were available for analysis. A total of 101 (8.9%) OGTTs were classified as diabetic. The new ADA criteria for IFG increased the sensitivity to 82% (versus 65%) and decreased the specificity to 70% (versus 94%) compared with the old criteria used to identify patients with diabetic OGTTs. In conclusion, the American Diabetes Association approach of using impaired fasting glucose as an indication for performing selective oral glucose tolerance tests is definitely unsuitable when aiming at the early identification of patients with cystic fibrosis-related diabetes mellitus, and it cannot replace annual oral glucose tolerance tests.

Epidemiology of cystic fibrosis-related diabetes.

I have the full-text PDF of this one.

Epidemiology of cystic fibrosis-related diabetes.

OBJECTIVES: Cystic fibrosis-related diabetes (CFRD) has emerged as an important complication of CF. To better understand who is at risk of developing CFRD, to gain insight into the impact of CFRD on pulmonary and nutritional status, and to assess the association of CFRD with various practice patterns and comorbid conditions, we characterized the Epidemiologic Study of Cystic Fibrosis (ESCF) patient population. STUDY DESIGN: Analyses were performed on the 8247 adolescents and adults who were evaluated at one of 204 participating sites during 1998. CFRD was defined as the use of insulin or an oral hypoglycemic agent at any time during the year. RESULTS: Previously reported risk factors for CFRD including age, gender (female), and pancreatic insufficiency were confirmed in this study. Patients with CFRD had more severe pulmonary disease, more frequent pulmonary exacerbations, and poorer nutritional status as compared with those without diabetes. CFRD also was associated with liver disease. CONCLUSIONS: CFRD is a common complication in adolescents and adults that is associated with more severe disease.

Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study.

I have the full-text PDF of this one.

Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study.

BACKGROUND: Insulin is the recommend therapeutic agent of choice for the management of Cystic Fibrosis Related Diabetes (CFRD), despite only sub-optimal reductions in glycemic control and increased morbidity and mortality reported by centers using this agent. The newer insulin sensitizing agents demonstrated to have anti-inflammatory mechanisms may provide an alternative management option for CFRD. METHODS: A prospective case based therapeutic comparison between insulin, sulfonylurea, metformin and thiazolidinedione was observed over one decade with 20 CFRD patients diagnosed using American Diabetes Association guideline standards. Patients entering the study elected treatment based on risk and benefit information provided for treatment options. Patients receiving organ transplant or requiring combination diabetic medications were excluded from the study. RESULTS: No statistical advantage was achieved regarding overall glycemic control for oral agents over insulin. Additional outcome measures including changes in weight, liver function testing and FEV1 were not statistically significant. CONCLUSION: Insulin alone may not be the only therapeutic option in managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin.

A review of the management of two common clinical problems found in patients with cystic fibrosis: cystic fibrosis-related diabetes and poor growth.

I have the full-text in PDF:

A review of the management of two common clinical problems found in patients with cystic fibrosis: cystic fibrosis-related diabetes and poor growth.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) and glucose intolerance often occur in teens and adults with CF. The initial deficiency is an impaired first-phase insulin response; as patients age, peak insulin response is delayed and less robust than normal. Decreased insulin sensitivity (insulin resistance) is also present in patients with CF. Insulin is the only currently recommended therapy for all types of CFRD, and many clinicians find that basal/bolus regimens are optimal. Another common finding in children with CF is poor linear growth and inadequate weight gain. Recombinant human growth hormone (rhGH) is being explored in this patient population; studies overall show improvements in height and weight, without development of glucose intolerance. CONCLUSIONS: rhGH may be a useful growth-promoting therapy in children with CF. Copyright (c) 2007 S. Karger AG, Basel.

I have this in full-text PDF.

Use of sensor-augmented insulin pump in patient with diabetes and cystic fibrosis: evidence for improvement in metabolic control.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis. We report the significant improvement of diabetes control and quality of life in a CFRD patient using the sensor-augmented insulin pump. The system gives the patient the highest degree of flexibility, which is required in CFRD since food intake and activity levels vary widely from day to day, depending on the rapid changes of health status.

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UF Study ShedsLight on cystic fibrosis-related diabetes

http://news.ufl.edu/2006/07/05/cystic/

The article below comes from the above link.

UF study sheds light on cystic fibrosis-related diabetes

Wednesday, July 5, 2006.
GAINESVILLE, Fla. — A growing number of cystic fibrosis patients are battling a second, often deadly complication: a unique form of diabetes that shares characteristics of the type 1 and type 2 versions that strike many Americans.
Many of these patients are teens who take enzymes to help digest their food and undergo daily physical therapy to loosen the thick, sticky mucus that clogs their lungs. But despite treatments that are helping thousands to live decades longer than ever before, when diabetes strikes, their life expectancy plummets — on average by two years for men and an astounding 16 for women.
Now a University of Florida study in animals suggests diabetes in cystic fibrosis patients is not caused by the destruction of insulin-producing cells in the pancreas — as is often the case in patients with the traditional form of type 1 diabetes — but by differences in how these cells function. The findings were published this month in the American Diabetes Association’s journal Diabetes.
Cystic fibrosis patients with diabetes produce some insulin on their own, but they require daily injections to boost their levels when eating so they can properly use sugar and other food nutrients for energy. At times they also become very resistant to the insulin they do make, similar to people with type 2 diabetes.
“For the longest time, the development of diabetes in cystic fibrosis has been thought to be chronic destruction of pancreas, so eventually you get loss of the insulin-producing beta cells,” said Dr. Michael Stalvey, an assistant professor of pediatrics at UF. “Our study provides some early evidence to suggest there is an inherent difference in beta cell function.”
Cystic fibrosis patients suffer recurrent episodes of infection and inflammation that slowly destroy the lungs. The pancreas is also affected, interfering with proper digestion. The disease stems from a faulty gene that blocks the normal passage of salt and water through the body’s cells. It is this gene deficiency that is proposed to cause insulin-producing cells to malfunction, Stalvey said.
About 30,000 Americans have cystic fibrosis, making it the nation’s most common lethal hereditary disorder. On average, they will not live past 35, though some are living through their 40s and even into their 60s. As each year passes, the likelihood they will develop diabetes increases. As many as 16 percent of all patients with cystic fibrosis also have diabetes, a number that is expected to rise as overall life expectancy for cystic fibrosis patients increases. Half will show signs of diabetes by age 30 and will suffer a rapid decline in overall health and lung function, muscle mass and body mass index.
“It’s becoming more and more frequent because of the increasing age of patients,” Stalvey said. “That’s part of the reason why new recommendations call for screening patients 14 years and older yearly with an oral glucose tolerance test. Each year we know their likelihood of developing diabetes gets higher and higher.
“These young people, teenagers or young adults in their early 20s, have been fighting all their lives to stay healthy and keep their nutrition up,” he added. “Now they’ve just been given something that potentially will overwhelm them. It’s a huge thing for them, given the consequences that diabetes means to their underlying condition.”
In the UF study, researchers developed the first animal model for the study of cystic fibrosis-related diabetes. They used mice that scientists from the University of North Carolina engineered to be missing the gene that makes the protein responsible for transporting salt and water across the cell membrane. People with cystic fibrosis have a mutated form of this protein.
UF scientists administered a low dose of a chemotherapy drug that weakened insulin-producing cells but did not destroy them. They then tested the animals’ ability to regulate their blood sugar while fasting and after receiving glucose, simulating the rise in blood sugar that occurs after eating food.
Animals with the protein deficiency were more sensitive to the effects of the chemotherapy drug and had more difficulty regulating blood sugar levels, both while fasting and after receiving glucose. Mice that were still able to produce the crucial protein that prevents cystic fibrosis were able to maintain normal blood sugar levels, even after the drug had damaged some of their insulin-producing cells.
“This goes beyond improving our understanding of patients with cystic fibrosis-related diabetes; it also will help us improve our understanding of other forms of diabetes and help us work on strategies for a future cure,” Stalvey said.
Stalvey’s collaborators included Dr. Desmond Schatz, Dr. Terence Flotte and Mark Atkinson. The study was supported in part by the Lawson Wilkins Pediatric Endocrinology Society, the Cystic Fibrosis Foundation and the National Institutes of Health.
“Twenty-five percent of adolescents and 40 percent of adults with cystic fibrosis have diabetes, and diabetes is associated with poorer survival in this population,” said Dr. Antoinette Moran, division head of pediatric endocrinology and director of the Pediatric Diabetes Program at the University of Minnesota Medical School. “The cause of cystic fibrosis-related diabetes is not completely understood, but it is clearly different from other forms of diabetes. The study by Stalvey and colleagues is important because it is the first to show that there are intrinsic abnormalities in the insulin-producing cells of the pancreas related to the genetic defect that causes cystic fibrosis.”

SDS Diabetes article

We often talk about diabetes on the SDS Support list There are several of us with children who either have diabetes or insulin resistance (like my two boys). There is a known link between CF and Diabetes, here is a link for CF Diabetes info. There is also an article on SDS and Diabetes titled: A case of Shwachman-Diamond syndrome presenting with diabetes from early infancy.

If you would like more information on the article above, please feel free to contact me.

Don't forget that Shwachman-Diamond America has links to over 50 full-text medical articles on Shwachman-Diamond Syndrome. Visit the SDA website and click on th "Mdical Articles" link.

CF Related Diabetes

Here is another link where you can find information on CF related diabetes, which may be helpful for those of us dealing with SDS related diabetes and insulin resistance.

CF Diabetes Info

Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.

Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin.


The diagnosis of cystic fibrosis (CF) can be confusing when only a part of the typical symptoms is present. In children, CF is usually suspected when dealing with chronic pulmonary symptoms (chronic productive cough, recurrent pneumonia or bronchiolitis). The pediatric gastroenterologist will exclude CF in all children with a meconium ileus, rectal prolaps or a poor weight gain. Atypical CF symptoms are hypochloremic alkalosis, recurrent pancreatitis and increased appetite to compensate for the pancreatic insufficiency. This case report shows how a diagnosis can be delayed when you are mislead by atypical symptoms. It shows the importance of looking in napkins and argues for the inclusion of CF in the differential diagnosis of polyuria in infants.