Diabetogenesis in Rheumatoid Arthritis: Do Inflammation and Glucocorticoid-induced Incretin Overproduction Cause β-Cell Overcompensation and Consequent Premature Decompensation?
Bibliographic record
Abstract
Metabolic abnormalities occur frequently in rheumatoid arthritis (RA)1. In this regard, metaanalyses documented an enhanced diabetes prevalence (OR 1.74, 95% CI 1.22–2.50) in RA2. Diabetes increases the risk of combined cardiovascular (CV) morbidity including myocardial infarction, angina, heart failure, stroke, and peripheral artery disease (RR 1.94, 95% CI 1.58–2.30) in RA3. Poor RA activity control strongly predicts incident-impaired fasting glucose and type 2 diabetes4. Diabetes is likely to account for a substantial proportion of the enhanced CV disease burden in RA. In healthy persons, glucose homeostasis is maintained by optimal (1) insulin sensitivity; (2) hepatic insulin extraction; (3) pancreatic β-cell insulin secretion; and (4) interactions of all three5. Type 2 diabetes development typically comprises the sequential stages of long-lasting adverse lifestyle factor (excess adiposity and physical inactivity)–induced insulin resistance and reduced hepatic insulin extraction that exacerbates reduced insulin sensitivity, compensatory increased β-cell insulin secretion, and β-cell decompensation with reduced insulin secretion that results in prediabetes [impaired fasting glucose (5.6–6.9 mmol/l), impaired glucose tolerance (7.8–11.0 mmol/l), and/or raised hemoglobin A1c concentrations (6.0–6.4%/42–46 mmol/l)] and ultimately diabetes (Figure 1). Figure 1. Proposed sequential diabetogenesis stages in patients with RA compared to those without. The main differences are shown in bold italics. RA: rheumatoid arthritis. Insulin resistance is a pathological state in which the ability of insulin to transport glucose into the cells is impaired. It associates with other metabolic abnormalities and increases CV risk, but in itself does not cause diabetes6,7,8. By contrast, impaired β-cell function is essential in diabetes development and is genetically mediated7,8. Whereas genetic factors are also implicated in impaired hepatic insulin extraction, its main determinant is pulsatile pancreatic insulin secretion extent (insulin release pulse mass) into the portal vein … Address correspondence to Dr. P.H. Dessein, Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, University of the Witwatersrand Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa. E-mail: patrick.dessein22{at}gmail.com
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.010 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".