Beneficial Role of Increased Glucose Infusion in Decompensated Type 2 Diabetes Patient

Abstract

Introduction: Managing glycemic fluctuations in critically ill elderly patients with type 2 diabetes mellitus (T2DM) poses significant challenges. This case report presents a unique scenario in which increased intravenous glucose (Glc) infusion, together with insulin therapy, improved glycemic control and reduced insulin requirements during a septic episode. This finding adds to the scientific literature by suggesting that adequate Glc administration may enhance insulin sensitivity in critically ill T2DM patients. Case report: An 84-year-old female patient with T2DM, hypertension, and chronic renal failure was admitted to the intensive care unit with fever, nausea, loss of appetite, and profound weakness. Laboratory findings revealed severe hyperglycemia, electrolyte imbalances, and markedly elevated inflammatory markers, leading to the diagnosis of decompensated T2DM that was complicated by sepsis. The initial treatment consisted of continuous intravenous (IV) insulin, crystalloid infusions, and broad-spectrum antibiotics. Despite insulin therapy and the absence of nutritional intake, the patient experienced extreme fluctuations in their blood glucose levels, ranging from hyperglycemia to hypoglycemia. Due to persistent glycemic instability, IV Glc infusion was initiated alongside continuous insulin therapy. Paradoxically, increasing Glc infusion administration rate led to a reduction in the required insulin doses and stabilization of blood glucose levels below 10 mmol·L⁻¹. The patient’s C-peptide levels were initially elevated but subsequently decreased following Glc administration as well, suggesting a reduction in endogenous insulin secretion and therefore higher insulin sensitivity. The patient’s clinical condition improved, allowing for the transition to a subcutaneous insulin regime and the initiation of oral feeding. She was later transferred to a general medical ward and discharged without further complications. Conclusions: This case highlights the complex interplay between Glc and insulin in critically ill elderly patients with T2DM during sepsis. The main takeaway is that carefully managed Glc infusion, in conjunction with flexible insulin therapy, can enhance insulin sensitivity and stabilize blood glucose levels without causing further hyperglycemia. Frequent glycemia monitoring and adaptable glycemic management strategies are essential in the ICU to address rapid glycemic fluctuations in this patient population.

1. Introduction

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder that is often associated with the lifestyle characteristics of modern civilization. A central aspect of this disease’s pathophysiology is insulin resistance (IR), which implies that a higher dose of insulin is required to clear ingested glucose. The increased prevalence of IR is frequently linked to abdominal obesity and is a consequence of both acute and chronic inflammation, higher secretion of counter-regulatory hormones such as glucocorticoids and catecholamines, and physiological states like growth, regeneration, pregnancy, lactation, and fasting [1]. However, the full physiological significance and underlying mechanisms of IR remain poorly understood [1,2].

Older individuals often suffer from multiple chronic diseases, many of which are associated with IR, and they are also particularly vulnerable to malnutrition [1,2,3]. Paradoxically, the current dietary recommendations for T2DM patients emphasize reducing carbohydrate (CHO) intake, even though the body’s CHO stores, specifically glucose (Glc), are limited compared to its protein and lipid stores [1,2]. Glc is a fundamental substrate for the synthesis of numerous biomolecules, including proteoglycans, lipids, amino acids, nucleic acids, and mucopolysaccharides. It is also essential for producing reducing equivalents that are needed for anabolic, antioxidative, regulatory, and immune processes [3,4,5,6]. When Glc intake is limited, non-oxidative pathways are prioritized to conserve Glc [1,5,7,8]. During this non-oxidative metabolism, lactate is produced and, along with other three-carbon molecules, serves as a substrate for Glc resynthesis [9]. The conservation of Glc with increased gluconeogenesis is often perceived as IR [3].

In this report, we present the case of an 84-year-old patient with decompensated T2DM during sepsis who experienced extreme fluctuations in glycemia. These fluctuations were managed with increased intravenous Glc infusions, resulting in a stable glycemia below 10 mmol·L⁻¹, even without external insulin treatment, and a decrease in endogenous insulin secretion, as measured by C-peptide levels. This case report confirms our previous hypothesis that glucose decreases, rather than increases, insulin resistance [3].

2. Case Report

An 84-year-old female patient with a history of hypertension, chronic renal failure, dyslipidemia, hypothyroidism, and type 2 diabetes mellitus (T2DM) managed with a combination of oral antidiabetic medications (metformin 1.7 g daily, glimepiride 3 mg daily, linagliptin 5 mg daily) was admitted to the intensive care unit (ICU) due to sepsis and decompensated T2DM.

On initial physical examination, the patient exhibited profound overall fatigue, abdominal palpation revealed epigastric tenderness, and left-sided costovertebral angle tenderness was present. Additionally, bilateral lower extremity edema was noted. A chest X-ray showed a small bilateral pleural effusion. An abdominal ultrasound revealed mild dilatation of the left renal pelvis, while abdominal computed tomography (CT) confirmed nephropathic changes in both kidneys without evidence of obstruction and other significant abnormalities.

Laboratory findings were notable for severe hyperglycemia (>40 mmol·L⁻¹), profound hyponatremia (116 mmol·L⁻¹), hyperkalemia (5.9 mmol·L⁻¹), and markedly elevated inflammatory markers, including C-reactive protein (CRP), procalcitonin, and leukocytosis. Given the patient’s clinical presentation and underlying renal dysfunction, metformin-associated lactic acidosis was considered; however, her serum metformin levels were within the normal range, ruling out metformin toxicity. She was admitted to the ICU with a preliminary diagnosis of sepsis from urinary tract infection and decompensated T2DM.

Upon admission, continuous intravenous (IV) insulin therapy, crystalloid infusions, and broad-spectrum antibiotics were initiated to gradually correct the electrolyte imbalance and treat the suspected urinary tract infection. Within 9 h, her glycemia levels dropped below 10 mmol·L⁻¹, leading to the discontinuation of continuous IV insulin and the initiation of subcutaneous insulin administration (Figure 1A). However, later that day, her glycemia levels rapidly increased above 20 mmol·L⁻¹ despite the absence of oral food intake, Glc infusion, or parenteral nutrition (Figure 1B). Consequently, continuous IV insulin therapy was resumed, resulting in a rapid decrease in glycemia to below 5 mmol·L⁻¹. Following this, IV insulin was discontinued once again, but her glycemia levels rose without any enteral or parenteral feeding or any other source of Glc (Figure 1C).

To manage these fluctuations, despite elevated glycemia, IV Glc infusion was initiated together with continuous IV insulin (Figure 1C). Initially, this combined treatment caused the glycemia to rise further above the physiological range, necessitating an increase in the IV insulin dose. However, over the following 12 h, as the Glc infusion dose was gradually increased, the required dose of IV insulin for glycemic control surprisingly decreased. After 12 h, IV insulin therapy was stopped, and despite the ongoing IV Glc infusion, the patient’s glycemia remained stable below 10 mmol·L⁻¹. This unexpected outcome prompted measurement of C-peptide levels to assess endogenous insulin secretion. During the initial hours of IV Glc infusion, the C-peptide levels increased (Figure 2A), but they subsequently decreased in parallel with the administered IV insulin and Glc infusions.

Glucose infusion was well tolerated, and the patient’s clinical condition improved, allowing for the initiation of oral feeding and transition to a subcutaneous intensified insulin regime. The hospitalization continued in the standard ward, where the final insulin therapy was established without any unanticipated events, and the patient was educated by the diabetology nurse and discharged home.

3. Discussion

This case report describes a paradoxical response in which an increased dose of exogenous Glc caused decreasing doses of IV insulin to maintain glycemic control. Several physiological mechanisms may explain this phenomenon. Critically ill patients frequently experience stress-induced hyperglycemia due to elevated levels of counter-regulatory hormones such as cortisol and catecholamines [10,11,12]. Lower levels of pro-inflammatory cytokines, such as TNF-α and IL-6, are known to inhibit insulin signaling pathways [13]. Increased IR is also likely a consequence of the high demand for non-oxidative Glc metabolism, combined with insufficient Glc stores to support these processes in the body [3,5]. Effective sepsis management through antibiotic therapy and supportive care can reduce systemic inflammation (Figure 2B), potentially improving overall insulin sensitivity due to reduced gluconeogenesis and decreased counter-regulatory hormone secretion as sepsis resolves. However, meeting the increased need for Glc is also essential [2,3,14]. It was described previously that a carbohydrate drink is given before surgery to reduce postoperative insulin resistance under the so-called ERAS protocol [15].

Continuous insulin therapy is crucial for maintaining insulin receptor activation, which enhances Glc uptake [4]. In the ICU, effective insulin therapy ensures activation of the PI3K-Akt pathway, a key regulator of Glc uptake [4,16]. Additionally, the administration of Glc may reduce the stress-induced release of counter-regulatory hormones, leading to increased insulin sensitivity [17,18]. This process aligns with non-oxidative metabolic mechanisms, such as the Cori cycle, in which Glc is resynthesized from lactate [3,9]. In the presented case report, this observation led us to an evaluation of C-peptide levels, which initially increased but subsequently decreased in parallel with the administration of IV insulin (Figure 2A). As Glc levels rise, cells become more responsive to insulin, thus requiring lower doses of exogenous insulin to achieve the same level of glycemic control [4,19]. Another potential modulator in this case is the presence of renal impairment and hypothyroidism. Thyroid hormones, even within the low–normal range, have been associated with various metabolic abnormalities [20]. However, in this case, the patient was receiving appropriate thyroid hormone replacement, and their plasma thyroid hormone levels remained within the normal limits throughout hospitalization. Moreover, given that insulin sensitivity improved within days, we do not assume a major contribution from thyroid dysfunction. In contrast, impaired kidney function significantly affects the metabolism and clearance of insulin and C-peptide, leading to fluctuations in Glc control and alterations in C-peptide measurements. Patients with reduced kidney function, particularly those with an estimated glomerular filtration rate (eGFR) below 50 mL·min⁻¹, typically exhibit lower glucose-to-C-peptide ratios, independently of glycemic control, a phenomenon that is more pronounced in older patients or those using insulin secretagogues. These alterations are associated with a higher risk of hypoglycemic episodes due to reduced renal clearance of insulin and C-peptide [21,22]. However, in this case, the patient’s renal function improved progressively over the course of hospitalization (Figure 2C,D). Although the improved kidney function may have contributed to the decline in serum C-peptide concentrations, it would also enhance insulin clearance, potentially increasing the required dose of exogenous insulin for effective glycemic control. Therefore, while renal insufficiency may have contributed to the sudden drop in glycemia prior to glucose administration, it does not account for the observed improvement in insulin sensitivity. This suggests that additional mechanisms, independent of renal function, are involved in enhancing peripheral glucose uptake and utilization.

The current guidelines for the management of decompensated T2DM recommend the use of intensive insulin therapy in the intensive care unit (ICU) setting [23,24,25]. This case report does not seek to challenge standard ICU insulin protocols or established recommendations. Emerging evidence suggests that tight glycemic control in critically ill patients may confer fewer benefits than previously assumed and may increase the risk of hypoglycemia, with a limited impact on the overall outcomes [26]. Clinical guidelines from ADA, ESPEN, and SCCM recommend moderate glycemic control targets (<180 mg·dL⁻¹ or <10 mmol·L⁻¹) to avoid adverse outcomes associated with hyperglycemia and hypoglycemia [27,28,29]. Our findings, while preliminary, do not contradict these recommendations but rather emphasize the potential benefit of individualized glucose management protocols. The NICE-SUGAR trial demonstrated that a more liberal blood glucose target of <180 mg·dL⁻¹ (10 mmol·L⁻¹) is associated with lower mortality compared to strict control (81–108 mg·dL⁻¹, or 4.5–6 mmol·L⁻¹) [30]. Conversely, other studies have indicated that tight glucose control in ICU patients who are not receiving early parenteral nutrition does not significantly affect the ICU length of stay or mortality [31,32]. These findings support a more individualized approach to glycemic management in the ICU, with glucose targets being tailored to specific patient populations [33].

Several studies have assessed the effects of glucose–insulin–potassium (GIK) infusions on hemodynamics and clinical outcomes in critically ill patients. In septic shock, GIK administration improved cardiac output and overall hemodynamic stability, particularly when conventional therapies proved insufficient [34,35,36]. Similar beneficial effects were observed in patients with hypovolemic shock due to peritonitis, as well as in burn victims [37].

In patients experiencing acute cardiac disorders, GIK infusions have been associated with reduced hospital mortality, a lower incidence of acute kidney injury and atrial fibrillation, shorter durations of mechanical ventilation, and earlier hospital discharge [38]. Meta-analyses and randomized controlled trials further suggest that GIK infusions can decrease mortality and reduce major adverse cardiac events following acute myocardial infarction and cardiac surgery [39,40,41].

However, the evidence remains inconsistent, with some studies—including a meta-analysis by Puskarich et al. [42]—failing to demonstrate clear mortality benefits in critically ill patients, particularly those with septic or circulatory shock. Nevertheless, all aforementioned studies describe GIK infusions as generally safe, with minimal adverse effects or serious complications. Interestingly, current clinical guidelines from ADA, ESPEN, and SCCM do not explicitly recommend or discuss the use of combined GIK infusions [27,28,29]. Instead, these guidelines typically suggest separate administration of insulin infusions, intravenous fluids (with optional glucose supplementation as needed), and electrolyte supplementation including potassium, guided by serum electrolyte levels and the patient’s clinical status.

The role of glucose administration in the management of decompensated diabetes warrants reconsideration. The authors of this report suggest that new therapeutic strategies—particularly those involving the initiation and titration of glucose infusions in conjunction with insulin therapy—should be evaluated. Incorporating such approaches into ICU treatment protocols may support the prevention of both hyperglycemia and hypoglycemia and could potentially improve patient outcomes during effective sepsis management.

CHO intake is essential for inducing anabolic processes necessary for cell division, tissue repair, the modulation of oxidative and reductive reactions, inflammation control, and muscle strength improvement [1,2,3,5,19]. Under these conditions, non-oxidative Glc metabolism is prioritized, with Glc being resynthesized from lactate via the Cori cycle, followed by gluconeogenesis in the liver and, to a lesser extent, in the kidneys [1,2,9,19]. The observed improvement in glycemic control with combined Glc and insulin administration suggests that adequate CHO intake may enhance insulin sensitivity [1,2,14]. The stabilization of glycemia through simultaneous Glc and insulin infusions that was observed in this case suggests that carefully managed Glc infusion can meet metabolic needs without exacerbating hyperglycemia [1,2,14]. Adequate CHO intake is essential for providing the necessary building blocks for recovery and tissue repair [1,5,6,19]. This case demonstrates that appropriate Glc administration together with the effective sepsis management and reduced systemic inflammation can enhance insulin sensitivity, support anabolic processes, and prevent glycemic fluctuations, particularly in older patients [1,2,3,5]. Our initial findings support the hypothesis that increased CHO intake can positively affect IR [1,2,14]. This is corroborated by studies demonstrating the beneficial effects of Glc on insulin resistance in surgical patients and critically ill individuals in intensive care units [14,43,44,45,46].

Despite providing valuable insights, this case study has several important limitations. First, no direct assessments of insulin sensitivity were performed; C-peptide levels and insulin dose adjustments served only as indirect markers. Second, the report describes the clinical course of a single 84-year-old female patient, and we acknowledge that findings from an individual case cannot be generalized to the broader population of patients with T2DM, given the variability in patient characteristics and treatment responses. Third, although the observed improvement in glycemic control correlates with glucose infusion, causality cannot be firmly established from a single case without comparative data. Lastly, the observation period was limited to the patient’s ICU stay, leaving long-term outcomes and the sustainability of improvements in insulin sensitivity and glycemic control unassessed. To validate these findings and optimize glucose and insulin management strategies for critically ill patients with diabetes, further research, including retrospective analyses and controlled comparative studies, is needed.