Type 3c Diabetes Misdiagnosed; Patients at Risk of Complications

Liam Davenport

October 31, 2017

Patients with a form of diabetes due to pancreatic dysfunction are commonly misdiagnosed as having type 2 diabetes, resulting in poor glycemic control and suboptimal care, the first large-scale analysis of this underrecognized form of the disease indicates.

Diabetes of the exocrine pancreas, also known as type 3c diabetes, arises when pancreatic inflammation, neoplasia, or resection results in beta-cell dysfunction, affecting the production of insulin.

As it occurs in individuals of a similar age group, type 3c diabetes may be misdiagnosed as type 2 diabetes. Those with type 3c diabetes require insulin therapy more urgently than those with type 2, so the consequence of this misdiagnosis are delays in delivering appropriate treatment, which can lead to nerve, eye, and kidney damage, say the authors of the new study, led by Dr Chris Woodmansey of the University of Surrey, Guildford, United Kingdom, and colleagues, which was published online in Diabetes Care on October 23.

In their analysis of more than 30,000 cases of incident diabetes in the United Kingdom, type 3c diabetes was almost twice as common as type 1 diabetes but was misdiagnosed as type 2 diabetes in over 87% of patients.

Type 3c diabetes patients were approximately 1.5 times as likely to have poor glycemic control than those with type 2 diabetes and were almost 10 times more likely to use insulin.

"Greater awareness of type 3c diabetes within the medical profession is required immediately to improve management of this disease, which now has a higher incidence than type 1 diabetes in adults," said senior author Simon de Lusignan, MD, PhD, department of clinical and experimental medicine, University of Surrey, in a press release.

He added that the misdiagnosis of type 3c diabetes, particularly as type 2 diabetes, puts the short- and long-term health of patients at risk and "builds on our previous work that suggests that failure to flag the right diagnosis is associated with lower-quality care."

Almost 90% of Type 3c Diabetes Misdiagnosed as Type 2

Type 3c diabetes has been estimated to account for 9% of diabetes cases among hospitalized patients. However, there has been no previous systematic assessment of the rates of prior pancreatic disease among diabetes patients in primary care.

The researchers therefore conducted a retrospective study of data from the Royal College of General Practitioners Research and Surveillance Centre, which covers over 2 million primary-care patients from which data are extracted once weekly, including information on acute hospital admissions.

They assessed all adult patients diagnosed with diabetes between 2005 and 2016 and then further determined who had a prior diagnosis of pancreatic disease. Specifically, they looked at acute pancreatitis, alongside chronic pancreatitis, pancreatic cancer, hemochromatosis, cystic fibrosis, and surgical pancreatic resection.

During the study period, there were 31,789 new diagnoses of adult-onset diabetes, with a median follow-up time of 4.5 years from the date of diagnosis.

Of these diagnoses, 559 followed pancreatic disease, including 361 after acute pancreatitis and 198 following chronic pancreatic disease.

The 559 cases of diabetes following pancreatic disease were mostly classified incorrectly by physicians as type 2 diabetes (87.8%). It was very uncommon that the correct diagnosis of diabetes of the exocrine pancreas, or type 3c, was made (2.7%); 7.7% were misclassified as having type 1 diabetes.

The median age at diagnosis for type 3c diabetes was 59 years, and 58.9% were male. The median body mass index among these patients was 29.2 kg/m2.

Type 3c diabetes patients had higher mean HbA1c levels than those with type 2 diabetes at presentation (= .002) and at 1 year (< .001) and at 5 years (< .001) following diagnosis. There were no HbA1c differences between those diagnosed after acute pancreatitis vs chronic pancreatic disease.

Poor glycemic control was also more common among type 3c diabetes patients than type 2 diabetes patients at 1 year following diagnosis, at 40.3% vs 32.5% (< .001) and an adjusted odds ratio for poor control of 1.3 (= .001).

And at 5 years after diagnosis, type 3c diabetes patients were still more likely to have poor glycemic control than type 2 diabetes patients, at 61.9% vs 46.3% (< .001) and an adjusted odds ratio of 1.7 (< .001).

Among type 2 diabetes patients, insulin use was 1.4% at 1 year and 4.1% at 5 years following diagnosis.

This compared with 16.3% and 29.6%, respectively (< .001 for both), in those patients diagnosed with type 3c disease.

This yielded adjusted odds ratios for insulin use in type 3c diabetes patients of 9.6 at 1 year and 9.9 at 5 years (< .001 for both).

Calling for greater awareness of type 3c diabetes, the researchers write: "Clinicians should elicit whether a patient has any history of pancreatic disease when they first present with diabetes and consider the diagnosis of diabetes of the exocrine pancreas."

Helping GPs to Make the Correct Diagnosis in Diabetes

The researchers say they were surprised to find that the incidence of type 3c diabetes was higher than that for adult-onset type 1 diabetes, at 2.59 per 100,000 person-years vs 1.64 per 100,000 person-years (< .001), although still substantially lower than that for type 2 diabetes, at 142.89 per 100,000 person-years.

This shows that this underrecognized form of diabetes is more common than previously thought, they say.

"This is the largerst study to include all forms of diabetes of the exocrine pancreas to date, and to our knowledge the only study to systematically identify pancreatic disease in a cohort of people with newly diagnosed diabetes," they note.

"Diabetes following pancreatic disease is frequently labeled type 2 diabetes but follows a markedly different clinical course, with worse glycemic control and a markedly greater requirement for insulin."

"[It] must be appropriately recognized to tailor management, including choice of antihyperglycemic therapy and consideration of malabsorption requiring pancreatic enzyme and vitamin D prescription," they conclude.

Speaking to Medscape Medical News, Dr de Lusignan said that he hopes these latest findings will help general practitioners to make the correct diagnosis when they are treating a patient with a history of pancreatic disease.

He also sees them as adding another piece to the jigsaw in terms of furthering understanding of diabetes. Dr de Lusignan said: "I think, over time, we will see more and more subdivisions of diabetes and this, to me, is a really interesting step on that journey."

No funding declared. Dr Woodmansey reports no relevant financial relationships. Dr Lusignan heads a diabetes Real World Evidence Centre funded by Eli Lilly and reports a research grant from AstraZeneca; neither are directly related to this study. Disclosures for the coauthors are listed in the paper.

Diabetes Care. 2017;40:1486–1493. Abstract

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