Periodontitis-Aggravated Diabetic Kidney Disease with Altered Glycolysis
1Department of Stomatology, the Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Journal of Dental Research
|July 3, 2026
Summary
Experimental periodontitis worsens diabetic kidney disease (DKD) by altering renal glycolysis and promoting fibrosis and epithelial-mesenchymal transition (EMT). The mTOR/HIF-1α pathway links periodontal inflammation to these kidney changes.
Area of Science:
- Nephrology
- Endocrinology
- Periodontology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is a major cause of kidney failure, influenced by factors beyond blood sugar.
- Periodontitis, a gum disease, is linked to worse kidney outcomes in diabetics, but mechanisms are unknown.
Purpose of the Study:
- To investigate how experimental periodontitis (EP) affects DKD progression.
- To explore the association between EP and changes in kidney sugar metabolism (glycolysis).
Main Methods:
- Induced EP in diabetic mice (db/db) using silk ligation and Porphyromonas gingivalis.
- Assessed kidney function, structure, inflammation, and glycolysis in vivo.
- Analyzed transcriptomic data and conducted in vitro studies in human kidney cells (HK-2).
Main Results:
- EP worsened kidney dysfunction and fibrosis in diabetic mice without raising blood glucose.
- EP increased epithelial-mesenchymal transition (EMT), altered kidney glycolysis (more lactate, less ATP/NAD+), and activated mTORC1 pathways.
- mTOR inhibition partially reversed EP-induced kidney damage and metabolic changes.
Conclusions:
- Periodontitis exacerbates DKD via altered glycolysis, EMT, and fibrosis.
- The mTOR/HIF-1α pathway is a potential link between periodontal inflammation and kidney cell changes in DKD.
Related Concept Videos
01:28Diabetic Nephropathy
Definition Diabetic nephropathy is a chronic kidney complication that results from prolonged hyperglycemia.Prevalence It is the most common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, affecting up to half of individuals with diabetes.Pathophysiology • Sustained hyperglycemia triggers multiple hemodynamic and metabolic changes in the kidney. • Early in the disease, increased renal blood flow and glomerular hyperfiltration occur due to afferent arteriolar...
01:22Diabetic Neuropathy
DefinitionDiabetic neuropathy is nerve damage caused by long-standing diabetes mellitus. It results directly from prolonged high blood sugar levels.PathophysiologyThe pathophysiology of diabetic neuropathy involves both metabolic and vascular disturbances triggered by chronic hyperglycemia.Metabolic injury: Elevated glucose levels activate the polyol pathway within nerve cells, leading to the accumulation of sorbitol and fructose. This increases oxidative stress, disrupts normal nerve...
01:22Diabetic Ketoacidosis ll: Pathophysiology
Diabetic ketoacidosis (DKA) is a metabolic emergency characterized by hyperglycemia, ketonemia, and metabolic acidosis. It results from severe insulin deficiency and an excess of counterregulatory hormones, leading to uncontrolled lipolysis, ketogenesis, and widespread electrolyte and fluid disturbances.Pathophysiology The central event in DKA is a profound loss of insulin action. Without insulin, glucose uptake in insulin-dependent tissues is impaired, while hepatic glucose production...
01:27Diabetic Retinopathy
DefinitionDiabetic retinopathy is a microvascular complication of diabetes affecting the retinal blood vessels.Risk FactorsDiabetic retinopathy is present in almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes after two decades of disease.The risk increases with poor glycemic control, hypertension, dyslipidemia, smoking, pregnancy, and puberty.Although cataracts and glaucoma are also more frequent in people with diabetes, retinopathy remains the leading...
01:22Complications of Diabetes Mellitus
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to insulin deficiency, resistance, or both. Prolonged hyperglycemia disrupts metabolic homeostasis and leads to acute and chronic complications.Acute ComplicationsAcute complications result from sudden metabolic imbalance.Diabetic ketoacidosis (DKA) mainly appears in type 1 diabetes but may also develop in type 2 diabetes, particularly under extreme stress. It arises from severe insulin deficiency,...
01:29Hyperglycemia
Hyperglycemia is an abnormally high blood glucose level. It is diagnosed by fasting glucose ≥126 mg/dL, 2-hour oral glucose tolerance test (or OGTT) ≥200 mg/dL, random glucose ≥200 mg/dL with symptoms, or HbA1c ≥6.5%. However, HbA1c results may be unreliable in certain conditions, such as anemia or hemoglobinopathies, and the diagnosis should be confirmed unless classic symptoms are present. Postprandial hyperglycemia is typically considered significant when glucose levels exceed 180 mg/dL two...