Ketosis-Prone Diabetes Syndromes and Metabolic Characteristics

Ketosis-prone diabetes encompasses a spectrum of clinical syndromes in which individuals develop diabetic ketoacidosis (DKA) yet exhibit features traditionally associated with type 2 diabetes. Patients often present with obesity or overweight, preserved β-cell function, negative islet autoantibodies and markers of insulin resistance. Following intensive insulin therapy to correct acute metabolic derangements, a substantial proportion of these individuals regain endogenous insulin secretion and may maintain glycaemic control with diet or oral agents. Distinct phenotypic subgroups have been characterised by the presence or absence of β-cell autoantibodies and residual C-peptide levels, reflecting divergent underlying pathophysiologies. Metabolically, ketosis-prone patients display elevated free fatty acids, increased oxidative stress and variable degrees of lipotoxicity, contributing to transient insulinopenia. Clinically, simple signs such as acanthosis nigricans can predict long-term insulin independence. Recognition of this entity has global importance, particularly in populations of African, Hispanic and Asian descent, and underscores the need for tailored diagnostic algorithms and management strategies.

Research from Nature Portfolio

Recent studies have shown that glycated haemoglobin (HbA1c) can serve as a practical screening tool to identify individuals with type 2 diabetes at high risk of ketosis. Specific HbA1c thresholds have been established—for newly diagnosed patients and those with established disease—to predict the likelihood of ketoacidosis. This approach offers a rapid, cost-effective method to prompt early intervention and reduce the morbidity associated with unrecognised ketosis.

Ketosis-Prone Diabetes Syndromes and Metabolic Characteristics publication trend

The graph below shows the total number of articles in ketosis-prone diabetes syndromes and metabolic characteristics across all publications each year (not limited to Nature Index journals).

Technical terms

Diabetic ketoacidosis (DKA): A life-threatening state of severe hyperglycaemia, ketonaemia and metabolic acidosis resulting from insulin deficiency and counter-regulatory hormone excess.

β-cell function: The capacity of pancreatic β-cells to synthesise and secrete insulin in response to circulating glucose.

Islet autoantibodies: Immune markers (e.g. against glutamic acid decarboxylase) whose presence indicates autoimmune destruction of β-cells.

C-peptide: A by-product of insulin synthesis used as a biomarker of endogenous insulin secretion.

Glycated haemoglobin (HbA1c): A measure of average blood glucose over the preceding two to three months, expressed as a percentage of total haemoglobin.

Free fatty acids (FFA): Non-esterified fatty acids released from adipose tissue, elevated levels of which contribute to insulin resistance and ketogenesis.

References

1. Ketosis-Prone Diabetes (Flatbush Diabetes): an Emerging Worldwide Clinically Important Entity. Current Diabetes Reports (2018).
2. Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study. Diabetologia (2024).
3. Development and validation of a novel nomogram for prediction of ketosis-prone type 2 diabetes. Frontiers in Endocrinology (2023).
4. High Prevalence of A−β+ Ketosis‐Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT). Pediatric Diabetes (2024).
5. HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus. Scientific Reports (2016).