European Journal of Cardiovascular Medicine

Hypertriglyceridemia (HTG) is among the most common lipid disorders encountered in clinical practice and is increasingly recognized in South Asian populations, where genetic susceptibility and lifestyle factors heighten the risk [1]. While mild to moderate elevations (150–500 mg/dl) predispose primarily to atherosclerotic cardiovascular disease, severe elevations, particularly when triglyceride (TG) levels exceed 1,000 mg/dl, are strongly associated with acute pancreatitis and contribute significantly to morbidity and mortality [2]. Indian data highlight the rising prevalence of dyslipidemia among patients with diabetes and metabolic syndrome, with HTG being a major contributor [3].

Extremely severe HTG, defined as TG >2,000 mg/dl, is uncommon and typically presents with abdominal pain, acute pancreatitis, eruptive xanthomas, or lipemia retinalis [4]. However, rare cases may remain asymptomatic despite very high TG levels, posing diagnostic and therapeutic challenges. Such situations are especially concerning in patients with uncontrolled diabetes, where secondary metabolic derangements can further elevate TG levels [5]. Delay in recognition and treatment of these silent but high-risk cases can result in life-threatening complications.

Conventional therapeutic options include insulin infusion, heparin, fibrates, and lifestyle modification, but plasmapheresis remains the most effective and rapid intervention for achieving significant TG reduction in extremely severe cases [5].

We present a rare case of extremely severe asymptomatic hypertriglyceridemia in a diabetic female, successfully managed with plasmapheresis.

A 42-year-old female with a six-year history of type 2 diabetes mellitus on insulin therapy (Mixtard regimen) presented with excessive thirst, increased frequency of urination, and burning sensation in both feet. She denied alcohol intake, smoking, or use of other medications, and there was no family history of dyslipidemia or premature cardiovascular disease. The baseline clinical profile is summarized in Table 1.

Table 1. Baseline Clinical Profile of the Patient

On admission, the patient was hemodynamically stable with a body mass index (BMI) of 22.7 kg/m². Systemic examination revealed no organomegaly or xanthomas, and cardiovascular, respiratory, and abdominal examinations were unremarkable.

Laboratory investigations demonstrated markedly elevated serum triglycerides of 2229 mg/dl and total cholesterol of 326 mg/dl. High-density lipoprotein (HDL) was reduced (20 mg/dl), while low-density lipoprotein (LDL) was 33 mg/dl. Glycemic control was poor with glycated hemoglobin (HbA1c) of 11.9%. Centrifuged blood appeared lipemic, and fundus examination revealed lipemic retinalis. Serum lipase and thyroid-stimulating hormone were within normal limits. Abdominal ultrasonography and cardiovascular evaluation were unremarkable. The laboratory and diagnostic findings are detailed in Table 2.

Table 2. Laboratory and Diagnostic Findings

Initial management with intravenous insulin infusion combined with dextrose-containing fluids and subcutaneous heparin did not result in sufficient triglyceride reduction. Hence, therapeutic plasmapheresis was performed, which led to a significant decrease in triglyceride levels to 350 mg/dl. The therapeutic interventions are outlined in Table 3.

Table 3. Therapeutic Interventions

Following plasmapheresis, the patient remained clinically stable, with no evidence of complications such as acute pancreatitis. Her hospital course was uneventful, and she was discharged in good condition. The treatment outcome is presented in Table 4.

This case highlights the importance of early recognition and timely intervention with plasmapheresis in the management of extremely severe hypertriglyceridemia.

Table 4. Treatment Outcome

Figure 1. Lipemic appearance of centrifuged blood, suggestive of severe hypertriglyceridemia.

Figure 2. Fundus photograph showing lipemic retinalis, a rare ocular manifestation of extremely severe hypertriglyceridemia.

Severe hypertriglyceridemia (HTG) is a well-recognized precipitant of acute pancreatitis, particularly when triglyceride (TG) levels exceed 1,000 mg/dl. The risk rises steeply beyond 2,000 mg/dl, with multiple studies documenting acute and occasionally fulminant pancreatitis in this range [6]. In South Asian settings, the coexistence of diabetes, metabolic syndrome, and dietary factors further increases the risk of dyslipidemia and very severe HTG [7]. Despite this, our patient with TG of 2,229 mg/dl remained completely asymptomatic for abdominal or gastrointestinal symptoms, making this case unusual.

The rarity of such silent presentations has been highlighted in published reports. Case summaries describe asymptomatic individuals with TG levels >10,000 mg/dl, who subsequently developed acute pancreatitis if left untreated [10]. Similarly, lipemia retinalis or lipemic plasma have occasionally been the only manifestations in otherwise symptom-free patients [11]. In our case, lipemic retinalis on fundus examination provided an important clinical clue, reinforcing that TG >2,000 mg/dl may sometimes remain “silent” yet carries a significant risk if not promptly recognized.

The therapeutic objective in very severe HTG is to reduce TG rapidly to <1,000 mg/dl to minimize pancreatitis risk, with long-term goals aiming at <500 mg/dl [6,7]. Conventional strategies include insulin infusion to enhance lipoprotein lipase activity, heparin to mobilize endothelial lipase, strict glycemic control, fibrates, and fat-restricted diets [7,11]. However, these approaches may not be sufficient in the acute phase. Therapeutic plasmapheresis offers a more rapid alternative, achieving 50–80% TG reduction within 24 hours, and has been shown to shorten the duration of organ failure in patients with HTG-induced pancreatitis [8,12]. In our patient, plasmapheresis successfully reduced TG from 2,229 mg/dl to 350 mg/dl, illustrating its effectiveness.

Nevertheless, the evidence base for plasmapheresis remains limited. Systematic reviews suggest biochemical improvement occurs faster than with conservative therapy, but the effect on overall mortality or pancreatitis outcomes remains less certain [6,12]. Even so, guidelines and consensus statements continue to support its use in selected high-risk patients [8]. Early intervention in our case likely prevented progression to pancreatitis.

Another critical factor in our patient was uncontrolled diabetes, reflected by HbA1c of 11.9%. Hyperglycemia contributes to increased hepatic very-low-density lipoprotein (VLDL) production and reduced lipoprotein lipase activity, thereby exacerbating TG elevation [7]. Addressing glycemic control is therefore fundamental, not only to stabilize acute episodes but also to prevent recurrence of severe HTG.

From this case, three learning points emerge. First, TG levels >2,000 mg/dl can occasionally be asymptomatic, and subtle signs such as lipemic serum or retinal changes warrant immediate investigation [10,11]. Second, plasmapheresis is a highly effective method for rapid TG lowering, particularly when conservative therapy is inadequate [8,12]. Third, poor glycemic control significantly amplifies TG derangements, emphasizing the importance of diabetes management as part of comprehensive care [7].

Our patient’s uneventful recovery and rapid biochemical improvement illustrate that early recognition and timely intervention, including plasmapheresis, can prevent catastrophic outcomes. This case therefore contributes to the limited literature on extremely severe yet asymptomatic HTG and reinforces the importance of vigilance in high-risk diabetic patients [6–12].

Extremely severe hypertriglyceridemia, even at levels exceeding 2,000 mg/dl, can occasionally remain asymptomatic, creating a diagnostic challenge. Despite the absence of abdominal pain or pancreatitis, such patients remain at high risk for sudden and serious complications. Early recognition of subtle clinical clues, such as lipemic serum or retinal changes, is vital. Prompt and aggressive intervention with plasmapheresis, along with optimization of glycemic control, can rapidly reduce triglyceride levels and prevent adverse outcomes. This case emphasizes vigilance in managing silent but severe metabolic derangements.

Patient Consent

Written informed consent was obtained from the patient for publication of this case report.

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