**8. Protocol for early sporadic pancreatic cancer detection**

The program of early SPC detection has three steps [2]:

in pancreatic juice when new-onset diabetes is suspected as a paraneoplastic symptom of SPC [72]. Exosomes trafficking within pancreatic juice may facilitate the development of a pre-metastatic niche well before any symptomology that might support an early diagnosis of

It appears that an early diagnosis is increasingly dependent on a combination of biomarkers

Diagnosis based on visualization of the tumor and classification of its stage is necessary for clinical decisions regarding treatment and the use of high-resolution imaging methods (HRIMs) is therefore immediately recommended in patients suspected of having SPC. The results of different methods were compared using a large database [73]. Effective screening procedures for early detection of pancreatic cancer were described by Hanada et al. [74, 75]. A review of the advances in various imaging methods, as well as their proper selection is

Early diagnosis and subsequent successful treatment of SPC associated with diabetes depends

**a.** With decreasing body weight (>2 kg) and anorexia as the only clinical symptom

**b.** With failure of introductory antidiabetic drug therapy during the first 3 months and

**c.** With persistent impairment of glucose homeostasis despite the additional of a second antidiabetic drug during the next 3 months or a decrease in body weight (>2 kg) **2.** Patients with long-term diabetes and obesity when there is a failure of antidiabetic drug therapy that developed during the preceding 6 months combined with a decreasing body

In patients from the first group, the new-onset diabetes and the loss of body weight may be **early symptoms** of SPC. In the second group, long-term diabetes and obesity are **risk factors** for SPC [76]. A decline in diabetes control, as measured by glycated hemoglobin HbA1c, may precede clinical detection of pancreatic cancer by several months up to 5 years [77]. The failure of the antidiabetic drug treatment characterized by either poor or worsening diabetes control is a common feature of both T3c and T2 diabetic patients with pancreatic cancer [21].

with sufficient sensitivity to disclose localized tumors or, better still, their precursors.

**7. Risk groups of diabetic patients suggested for screening of** 

on proper evaluation of the **risk groups** of patients >50 years of age:

**1.** Patients with new-onset prediabetes or diabetes:

stagnation or a decrease in body weight (>2 kg)

pancreatic cancer [72].

62 Advances in Pancreatic Cancer

**6.2. Imaging methods**

beyond the scope of this review.

**sporadic pancreatic cancer**

weight (>2 kg).


A multidisciplinary team approach should improve the prognosis of this malignant disease. The early symptoms (new-onset T3cDM and weight loss), the effect of the initial antidiabetic drug therapy, as well as the failure of antidiabetic therapy in long-term diabetes control, with newly developing weight loss, should be properly evaluated by a GP or a diabetologist.

We suggested an algorithm for the examination of patients with new-onset diabetes (**Figure 1**) [2]. Regular screening of blood glucose in the general population above 50 years of age may disclose abnormalities in glucose homeostasis. Additionally, the evaluation of body weight and any changes during the months prior to the visit is critical. A decrease in body weight > 2 kg in a patient with newly confirmed prediabetes or diabetes should arouse suspicion of its paraneoplastic origin. In this case, a gastroenterologist should be consulted.

A patient with new-onset diabetes should be treated with the first line antidiabetic drug according to the guidelines for Type 2 diabetes. If the diabetes control is not satisfactory during the first 3 months and body weight remains stable or increases, then a second antidiabetic drug should be added. An inadequate response to intensified treatment or unintentional weight loss should lead to a suspicion of T3cDM. In this situation, the collaboration with a gastroenterologist, preferably in a tertiary center, is necessary. The patient should be tested for PP and GIP secretion after nutritional stimulation. A response by PP and GIP that is diminished or absent confirms the pancreatogenic origin of the diabetes (T3cDM). A gastroenterologist should arrange the next steps involving an endoscopic examination and HRIMs.

A patient with long-term diabetes with failing antidiabetic drug treatment combined with decreasing body weight should be included in the same multistep screening program as described for T3cDM patients.

of the earlier stages of pancreatic cancer. A multistep and multidisciplinary preventive program based on collaboration between GPs, diabetologists and gastroenterologists offers an opportunity for timely SPC diagnosis. This approach may improve the prognosis for

Sporadic Pancreatic Cancer: Glucose Homeostasis and Pancreatogenic Type 3 Diabetes

http://dx.doi.org/10.5772/intechopen.75740

65

This manuscript was supported by the Research Project of Charles University, PROGRES Q25

, Pavel Škrha4

1 Third Department of Internal Medicine, 1st Faculty of Medicine, Charles University,

2 Department of Medicine/Gastroenterology, Military University Hospital, 1st Faculty of

3 Institute of Biochemistry and Experimental Oncology, 1st Faculty of Medicine, Charles

4 Second Department of Medicine, University Hospital, 3rd Faculty of Medicine, Charles

[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA: a Cancer Journal for Clinicians.

[2] Frič P, Šedo A, Škrha J, Bušek P, Laclav M, Škrha P, Zavoral M. Early detection of sporadic pancreatic cancer: Time for change. European Journal of Gastroenterology &

[3] Pittman ME, Rao R, Hruban RH. Classification, morphology, molecular pathogenesis, and outcome of premalignant lesions of the pancreas. Archives of Pathology &

Laboratory Medicine. 2017;**141**:1606-1614. DOI: 10.5858/arpa.2016-0426-RA

Hepatology. 2017;**29**:885-891. DOI: 10.1097/MEG.0000000000000904

and Aleksi Šedo<sup>3</sup>

these patients.

and Q28.

**Acknowledgements**

**Conflict of interest**

**Author details**

Prague, Czech Republic

Jan Škrha1

**References**

The authors have no conflict of interest.

\*, Přemysl Frič<sup>2</sup>

University, Prague, Czech Republic

University, Prague, Czech Republic

2016;**66**:7-30. DOI: 10.3322/caac.21387

, Petr Bušek3

\*Address all correspondence to: jan.skrha@lf1.cuni.cz

Medicine, Charles University, Prague, Czech Republic

**Figure 1.** Differential approach to a patient with new onset diabetes/prediabetes. Unintentional weight loss, anorexia or no improvement in glucose control with appropriate treatment should prompt an evaluation by a gastroenterologist. OAD, oral antidiabetics; EUS, endoscopic ultrasonography; GP, general practitioner.

#### **9. Conclusion**

The association of SPC with diabetes mellitus offers an opportunity for early detection of this malignant disease. While long-term Type 2 diabetes is an important risk factor of SPC, new-onset T3cDM represents an early symptom as well as a pathogenetic feature of SPC. Thus, proper assessment of new-onset diabetes with a focus on the analysis of early symptoms, that is, failure of antidiabetic drug treatment including unstable diabetes requiring insulin administration, represents a promising step in shifting the diagnosis of SPC to an earlier stage. New biomarkers and high-resolution imaging methods may help discriminate between different pathologies with better accuracy, including identification of the earlier stages of pancreatic cancer. A multistep and multidisciplinary preventive program based on collaboration between GPs, diabetologists and gastroenterologists offers an opportunity for timely SPC diagnosis. This approach may improve the prognosis for these patients.
