Diabetes, as a major challenge in the global public health field, has a significantly increased susceptibility to infectious diseases among its patient population due to metabolic homeostasis imbalance. Influenza, as a highly prevalent respiratory infectious disease, not only causes lung inflammation but also dealt a devastating blow to the glucose metabolism, lipid metabolism and energy homeostasis of diabetic patients through a complex “metabolic toxicity” mechanism. Clinical data shows that after being infected with influenza, the risk of hospitalization for diabetic patients is 3.6 times that of non-diabetic people, and the rate of severe illness and mortality increases by 2.4 times and 1.8 times respectively. This article will systematically expounding on how the “metabolic toxicity” of influenza disrupts the homeostasis of diabetes from three dimensions: metabolic disorder mechanism, clinical impact, and prevention and treatment strategies, providing a theoretical basis for clinical management.
1. The core mechanism of the “metabolic toxicity” of influenza: from inflammatory storm to metabolic network imbalance
After influenza viruses (such as H1N1 and H3N2) invade through respiratory epithelial cells, they trigger the body’s innate immune response, releasing a large amount of pro-inflammatory cytokines (such as IL-6, TNF-α, and IFN-γ), forming an “inflammatory storm”. This systemic inflammatory response disrupts the metabolic homeostasis of diabetic patients through the following pathways:
1.1 Cascade amplification of insulin resistance
Inflammatory factors can directly interfere with the insulin signaling pathway: IL-6 inhibits IRS-1 phosphorylation by activating the JAK/STAT3 pathway, while TNF-α down-regulates the expression of insulin receptors (INSR) on the surface of adipocytes and muscle cells, resulting in a decrease in the ability of peripheral tissues to take up glucose. Meanwhile, under stress, the sympathetic nerve becomes excited, which prompts the adrenal medulla to secrete catecholamines, further inhibiting insulin secretion and promoting the breakdown of liver glycogen, thus forming a vicious cycle of “hyperglycemic – insulin resistance”.
1.2 “Pathological Remodeling” of Energy Metabolism
Influenza infection causes the body to enter a “hypermetabolic state” : on the one hand, fever increases the basal metabolic rate (for every 1℃ increase in body temperature, the metabolic rate increases by 13%), and the breakdown of muscle tissue accelerates to provide energy, leading to the depletion of muscle glycogen reserves; On the other hand, viral replication consumes a large amount of ATP, forcing the liver to maintain blood sugar through gluconeogenesis (utilizing non-sugar substances such as lactic acid and amino acids), further exacerbating insulin resistance. For patients with type 2 diabetes, this metabolic remodeling can reduce insulin sensitivity by 30% to 50% and increase the fluctuation range of blood sugar by 2 to 3 times.
1.3 Lipid metabolism disorder and uncontrolled ketone body production
Inflammatory factors (such as IL-1β) can activate hormone-sensitive lipase (HSL) in adipose tissue and promote the release of free fatty acids (FFA). A large amount of FFA is oxidized in the liver to form ketone bodies (β -hydroxybutyric acid, acetoacetic acid), and insulin deficiency or resistance can inhibit the utilization of ketone bodies, leading to the accumulation of ketosis. Patients with type 1 diabetes have an absolute insulin deficiency, and the incidence of post-infection ketoacidosis (DKA) is as high as 12% to 18%. Patients with type 2 diabetes are prone to hyperosmolar hyperglycemia (HHS), with a mortality rate of over 20%.
2. The clinically devastating impact of influenza on diabetic homeostasis
The “metabolic toxicity” of influenza not only aggravates chronic metabolic disorders but also can induce acute metabolic crises, causing multi-system damage to the organ functions of diabetic patients.
2.1 The “Cliff-like Collapse” of Blood Glucose Homeostasis
After infection, the fasting blood glucose of diabetic patients can suddenly rise above 13.9 mmol/L, the postprandial blood glucose fluctuation range exceeds 8 mmol/L, and the sensitivity to insulin treatment significantly decreases. A cohort study involving 1,200 patients with type 2 diabetes showed that during influenza infection, the daily insulin dose needs to be increased by 20% to 40% to maintain blood sugar control, and about 30% of the patients experienced treatment failure due to aggravated insulin resistance.
2.2 The risk of acute metabolic complications surges
Diabetic ketoacidosis (DKA) : Influenza infection is one of the primary triggers of DKA. Vomiting and reduced food intake caused by the virus result in insufficient energy supply to the body, accelerated fat breakdown, and ketone body production exceeding metabolic capacity. Clinical data show that among hospitalized patients with DKA during the flu season, 42% are directly related to the flu.
Hyperosmolar hyperglycemic state (HHS) : It is more common in elderly patients with type 2 diabetes. Due to infection, it causes dehydration (fever, accelerated breathing) and hyperglycemia (osmotic diuresis), with plasma osmotic pressure >320 mOsm/L, and the mortality rate is as high as 35%[8].
2.3 Exacerbating the Situation with chronic complications
The metabolic toxicity of influenza can accelerate the progression of chronic complications of diabetes: hyperglycemia leads to a temporary increase in glomerular filtration rate, increasing the burden on the kidneys and inducing acute exacerbation of diabetic nephropathy. Retinal microvessels leak due to hypertonic conditions, increasing the risk of diabetic retinopathy. Peripheral nerves undergo demyelinating lesions under the dual effects of hyperglycemia and inflammatory factors, leading to abnormal sensations or pain.
3. Prevention and Control Strategies: Multi-dimensional intervention to block “metabolic toxicity”
In response to the disruption of diabetes homeostasis caused by influenza, it is necessary to establish a three-in-one management system of “prevention – monitoring – treatment” to reduce the risk of metabolic toxicity.
3.1 Primary Prevention: The “Metabolic Protective Effect” of Influenza Vaccine
Getting the flu vaccine is a core measure to reduce the risk of infection for diabetic patients. Studies have shown that after diabetic patients receive the influenza vaccine, the influenza-related hospitalization rate drops by 50%, and the incidence of DKA decreases by 38%[10]. It is recommended that all diabetic patients receive the inactivated influenza vaccine as a priority in autumn (October to November) every year, especially those at high risk of chronic kidney disease and cardiovascular diseases.
3.2 Secondary monitoring: Early warning of dynamic metabolic indicators
During the infection period, the frequency of blood glucose monitoring should be increased (4 to 7 times a day), with a focus on fasting blood glucose, 2-hour postprandial blood glucose and urine ketone bodies. When blood glucose remains above 13.9 mmol/L or symptoms such as nausea, vomiting, and shortness of breath occur, blood ketone bodies and osmotic pressure should be immediately tested to be alert to DKA or HHS. Meanwhile, the levels of C-reactive protein (CRP) and IL-6 should be monitored regularly to assess the degree of inflammatory activity.
3.3 Tertiary treatment: Precise correction of metabolic disorders
Insulin treatment adjustment: During the infection period, it is recommended to discontinue oral hypoglycemic drugs (especially SGLT-2 inhibitors to avoid the risk of ketosis), and switch to intensive insulin therapy (such as the basal + mealtime insulin regimen), adjusting the dosage every 4 to 6 hours based on blood sugar levels.
Fluid replacement and electrolyte balance: For dehydrated patients, normal saline should be given priority (infusion of 500-1000 mL within the initial 1-2 hours). When blood glucose drops below 13.9 mmol/L, 5% glucose solution should be used instead to prevent hypoglycemia.
Anti-inflammatory and supportive treatment: Short-term use of low-dose glucocorticoids (such as dexamethasone 4-8 mg/d) can suppress the inflammatory storm, but blood glucose should be closely monitored. For severe patients, IL-6 receptor antagonists (such as tocilizumab) can be considered to block the metabolic toxicity cascade reaction.
The “metabolic toxicity” of influenza is the core mechanism for the deterioration of the condition in diabetic patients after infection. It causes a devastating blow to glucose homeostasis through insulin resistance mediated by inflammatory factors, energy metabolism reconstruction and lipid metabolism disorders. Clinical management should be based on vaccination, strengthen the monitoring of metabolic indicators, and block the toxic cascade reaction through insulin adjustment, fluid replacement and anti-inflammatory treatment. Future research should focus on the interaction between influenza viruses and metabolic networks, develop novel intervention strategies targeting inflammation-metabolic pathways, and provide more precise theoretical support for infection prevention in diabetic patients.
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Post time: Jan-24-2026