We present the case of a 55-year-old male patient with diabetic ketoacidosis (DKA) whose final diagnosis was pancreatic adenocarcinoma causing Type 3c diabetes mellitus. This case highlights the importance of considering pancreatic carcinoma as an underlying cause of DKA, emphasizing the need for early detection and the careful monitoring of complications in such cases.

Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

This study protocol was reviewed and approved by Ethical Committee at the faculty of medicine, Ain Shams University, Cairo, Egypt.

The patient is a 55-year-old male who presented with an acute one-day history of confusion and disorientation. He had experienced lethargy for the previous two weeks and developed anorexia, nausea, abdominal pain, and intractable vomiting for the preceding two days. He reported no fever, altered bowel habits, jaundice, significant weight loss, alcohol consumption, drug abuse, or analgesic intake. His medical and surgical history was unremarkable.

Upon examination, the patient was confused (GCS: 11), dehydrated, and in hypovolemic shock. Vital signs showed a blood pressure of 70/40 mmHg, a regular pulse of 110 bpm, and a respiratory rate of 27 breaths/min (tachypnea). General examination revealed pallor. Local abdominal examination showed moderate epigastric tenderness. His random blood glucose was 435 mg/dL, and urine analysis was positive for acetone (2+). Arterial blood gas analysis confirmed metabolic acidosis. He was diagnosed with DKA and transferred to the ICU.

A comprehensive laboratory workup was performed, with significant findings summarized in Table 1.

The patient was aggressively rehydrated with intravenous fluids and insulin. The DKA was resolved after 48 hours, but he continued to complain of epigastric pain and vomiting. An abdominal ultrasound was performed, which showed only fatty hepatomegaly and colonic gaseous distension. With the patient's metabolic state fully recovered two weeks post-DKA, further diagnostic workup was pursued after full stabilization of the patient’s condition. An upper gastrointestinal endoscopy was performed as part of this process, which identified only mild gastritis and a small hiatus hernia.

An MRI of the abdomen and pelvis with MRCP was then obtained (An MRI was recommended by the nephrology consultant due to the patient's renal impairment, as the contrast agent used for MRI has a more favorable safety profile compared to the contrast used in a CT scan). It showed a diffusely swollen pancreas with high signal within its parenchyma, surrounded by minimal peri-pancreatic edema. After contrast injection, multiple scattered hyper-enhancing foci were visible throughout the pancreatic parenchyma, particularly in the distal pancreatic body and tail. The largest of these nodules, measuring 9.5 mm, was located at the posterior aspect of the head/uncinate process (Fig. 1). This nodule was posterior to the CBD and separated by 2.8 mm. The MRI showed a normal CBD caliber with no IHBRD.

A high degree of clinical suspicion for pancreatic malignancy prompted the performance of endoscopic ultrasound (EUS), since the MRI was not conclusive. EUS revealed a swollen pancreatic head, body, and tail, with lobulated and hyperechoic stria associated with a small, rounded isoechoic lesion measuring 0.59×0.5 cm in the pancreatic head. Elastography showed a greenish-to-bluish color in the small lesion (F2). The images were suggestive of either chronic focal pancreatitis or a pancreatic neoplasm. Therefore, an EUS-guided fine-needle biopsy (EUS-FNB) was performed for histopathological correlation to rule out any pancreatic malignancy (Figs. 2, 3).

Pathology results confirmed a final diagnosis of moderately differentiated pancreatic adenocarcinoma, Grade 2. The patient's condition was diagnosed as Type 3c diabetes mellitus, secondary to the exocrine pancreatic adenocarcinoma.

The patient was immediately referred for a pancreaticoduodenectomy. Unfortunately the surgery was delayed due to patient’s factors, but our hepatobiliary surgeons managed to successfully resect the pancreatic tumor. Post-operatively, his diagnosis was confirmed as Stage T3 N1 M0 with free resection margins. The pathology results confirmed the diagnosis of pancreatic adenocarcinoma. The procedure included a standard pancreaticoduodenectomy with lymphadenectomy and Roux-en-Y reconstruction. The pancreatic head contained a firm, ill-defined tumor measuring 3.2 cm in its greatest dimension. The mass was located in the uncinate process, infiltrating the posterior aspect of the gland. The mass extended beyond the pancreatic capsule into the adjacent posterior retro-peritoneal soft tissue. All surgical margins have been examined, the pancreatic neck, duodenal, common bile duct, and superior mesenteric artery groove margins, they were grossly negative for any tumor invasion. There was no gross invasion of the superior mesenteric vein or any other major vessel.

Following surgery, he exhibited marked initial hyperglycemia, which was managed in the ICU with an intravenous insulin drip to maintain glucose levels between 140–180 mg/dL. This tight glycemic control was critical for complication prevention. During his hospital stay, blood glucose was monitored frequently, and insulin was transitioned from intravenous to subcutaneous administration based on a sliding scale. Upon discharge, the patient was educated on home glucose monitoring and basal bolus insulin adjustments. A nutritionist was consulted to guide him on a post-operative diet low in fat and glucose.

Diabetic ketoacidosis is a rare but serious complication of Type 3c diabetes mellitus,¹ especially when the underlying cause is pancreatic cancer. Type 3c diabetes is a rare type of diabetes mellitus, it is known as pancreatogenic diabetes.² It is a type of diabetes that results from damage to the pancreas. The pathophysiology of Type 3c diabetes is the destruction of pancreatic tissue by the tumor invasion, which impairs both its endocrine and exocrine functions. The difference between it and Type 1 or Type 2 diabetes, is that Type 3c is caused by a disease or injury to the pancreas itself, which impairs the production of both insulin and other hormones and enzymes. The underlying etiology of Type 3c diabetes, leads to the progressive and irreversible damage of the pancreatic tissue, including the beta-cells (which produce insulin) and alpha-cells (which produce glucagon). The damage of beta-cells results in a significant decrease in insulin production, which leads to hyperglycemia. Although in Type 1 diabetes there is an absolute absence of insulin, on the other hand, in Type 3c, there can be a variable amount of insulin production which depends on the extent of pancreatic damage. A key difference between Type 3c and other types of diabetes is the simultaneous loss of glucagon-producing alpha-cells. Glucagon is an anti-insulin hormone that causes hyperglycemia, and its deficiency can lead to a blunted response to hypoglycemia. In pancreatic cancer (like our case), it can also be associated with increased insulin resistance. The exact mechanism for this is believed to be a paraneoplastic effect of the malignancy itself, but it is not fully understood till now.

The common etiologies and differential diagnosis of Type 3c diabetes are chronic pancreatitis (the most common etiology), acute pancreatitis, cystic fibrosis, hemochromatosis, pancreatic cancer (as in our case), or pancreatectomy.

There is a strong bidirectional link between pancreatic cancer and diabetes. Diabetes may be a risk factor for pancreatic cancer, as patients with diabetes, particularly new-onset diabetes after the age of 50, may have a higher risk of developing pancreatic cancer. Also pancreatic cancer may be a cause of diabetes. That is because pancreatic malignancy can cause direct damage to the beta cells, the insulin-producing cells in the pancreas, leading to the development of Type 3c diabetes. Consequently, any new-onset diabetes can serve as an early warning sign of pancreatic cancer.

Our patient's initial presentation with DKA is particularly serious. DKA typically occurs in the setting of severe insulin deficiency and is most commonly associated with Type 1 diabetes. However, it can occur in other forms of diabetes, including Type 3c, though it is considered a rare presentation in this subgroup.^3,4 The rarity is explained by the fact that the pancreatic damage causing Type 3c diabetes typically destroys both the insulin-producing beta cells and the glucagon- producing alpha cells. The deficiency of glucagon, a key ketogenetic hormone, makes DKA a less likely outcome.

However, DKA can occur in patients with Type 3c diabetes, especially if there is severe insulin deficiency. The pancreatic damage may be so extensive that insulin production is critically low. There are cases where DKA is the initial presenting symptom of pancreatic cancer, even in patients without a prior history of diabetes. So we must always be mindful of pancreatic malignancy, with a high level of suspicion, in new onset diabetes especially in old age population.

DKA can be a rare but important key for diagnosis of an underlying pancreatic cancer. Physicians are always advised to maintain a high level of suspicion for pancreatic cancer in any patient who presents with unexplained DKA, especially if they are over 50 years old. Early imaging as (MRI with pancreatic protocol) and if still suspicious we are advised to perform EUS (which is widely considered a gold standard for diagnosis of early pancreatic cancer).

EUS is a promising and important tool in the early diagnosis of pancreatic cancer, which is usually very difficult to detect in its early stages.^5,6 It is often used to diagnose small tumors that might be missed by other conventional imaging methods like CT or MRI scans. EUS can provide detailed and high-resolution images of the pancreas because the ultrasound transducer is very close to the pancreas. This close proximity allows for the detection of small lesions, as small as 2–5 mm, which is beyond the resolution of CT or MRI scans.⁷

Another key advantage of EUS is its interventional capability. The use of EUS-guided fine-needle aspiration (FNA) or FNB needles allows for the acquisition of an accurate tissue biopsy, which can be rapidly assessed via frozen section or on-site cytology to confirm malignancy.^8,9 EUS can also precisely determine the stage of the pancreatic cancer and its relationship to the surrounding vasculature. Advanced techniques, such as contrast-enhanced EUS and elastography, further improve diagnostic accuracy by assessing blood flow and tissue stiffness, respectively, helping to differentiate malignant from benign lesions.¹⁰

The diagnosis of chronic focal pancreatitis via EUS, in conjunction with an elevated lipase level and MRI-confirmed peri-pancreatic edema, presents a complex clinical scenario. The relationship between chronic pancreatitis and pancreatic cancer is bidirectional. While chronic pancreatitis is a well-established precursor to malignancy, a pancreatic tumor can also induce inflammatory changes in the pancreas that are clinically indistinguishable from pancreatitis. This diagnostic overlap highlights the critical need for comprehensive evaluation to rule out malignancy in any patient with new-onset pancreatitis, especially when traditional risk factors are absent. Furthermore, the release of inflammatory mediators by the tumor itself can contribute to the inflammatory state, thus blurring the line between the two conditions. In our case, the patient didn’t have any previous history of significant epigastric pain or any previous chronic pancreatitis.

This case report highlights the important link between diabetic ketoacidosis and Type 3c diabetes mellitus secondary to pancreatic cancer. While DKA is usually associated with Type 1 diabetes, this case emphasizes its potential to be the presenting symptom of an underlying pancreatic malignancy, despite the absence of a prior diabetes diagnosis in our patient.

The most important take-home message is that the development of new-onset diabetes, especially in older individuals (above 50-years-old) without a family history of diabetes or a clear precipitating factor, should always raise the suspicion for pancreatic malignancy.^11,12 This is opposite to the general idea that Type 3c diabetes, due to the destruction of glucagon- producing alpha cells, makes DKA a rare complication.

Another important reminder is that EUS provides detailed and high-resolution images of the pancreas. This close proximity allows for the detection of small lesions, as small as 2–5 mm, which is beyond the resolution of CT or MRI scans, making it the gold standard for early diagnosis of pancreatic cancer.