Normolipidemic Dysglycemia in Type 2 Diabetes: Clinical and Biochemical Characteristics of a Cohort Free of Lipid-Lowering and Chronic Anti-Inflammatory Therapy

Abstract In type 2 diabetes, hyperglycaemia usually clusters with atherogenic dyslipidaemia and low-grade inflammation; yet, these axes may dissociate in some patients. We aimed to estimate the prevalence of a normolipidemic dysglycemia phenotype in adults with type 2 diabetes and characterise its clinical–biochemical profile within an analytical window free of lipid-lowering and chronic anti-inflammatory/immunomodulatory therapy. In this retrospective, cross-sectional study, we analysed records of 1,046 adults aged 25–60 years with type 2 diabetes from a tertiary care hospital between 2020 and 2024. Individuals with other diabetes types, acute inflammatory conditions, malignancy, advanced organ failure and non-euthyroid status were excluded. Normolipidemic dysglycemia was defined as glycated hemoglobin≥64 mmol/mol with low-density lipoprotein cholesterol<100 mg/dL, triglycerides<150 mg/dL, high-density lipoprotein cholesterol≥40 mg/dL in men or≥50 mg/dL in women, and high-sensitivity C-reactive protein<5 mg/l in the absence of lipid-lowering or chronic anti-inflammatory/immunomodulatory therapy. Comparative analyses were restricted to a hyperglycaemic subpopulation free of lipid-lowering and chronic anti-inflammatory/immunomodulatory therapy (glycated hemoglobin≥64 mmol/mol; n=183), while glucose-lowering treatment status was recorded separately and evaluated as a potential confounder. Normolipidemic dysglycemia was identified in 47/1,046 individuals (prevalence: 4.49%; 95% confidence interval: 3.40–5.92) and 47/183 individuals (prevalence: 25.7%; 95% confidence interval: 19.9–32.5) within the analytical subpopulation. Compared with atherogenic dysglycemia, normolipidemic dysglycemia showed lower triglycerides, lower high-sensitivity C-reactive protein, higher high-density lipoprotein cholesterol, higher fasting plasma glucose and higher creatinine-based estimated glomerular filtration rates. In multivariable models, higher fasting plasma glucose, longer diabetes duration and higher creatinine-based estimated glomerular filtration rates remained associated with normolipidemic dysglycemia, whereas age, sex and body mass index were not independently associated with normolipidemic dysglycemia. These findings identify a clinically detectable subgroup in which marked hyperglycaemia coexists with relatively preserved lipid and inflammatory markers. The normolipidemic dysglycemia construct reflects metabolic heterogeneity rather than established prognostic distinction and requires prospective validation with cardiovascular and renal outcomes.