The Impact of Insulin Resistance on Proinsulin Secretion in Pregnancy
Bibliographic record
Abstract
OBJECTIVE: Excessive secretion of the insulin precursor proinsulin, as manifested by an increased serum proinsulin-to-insulin ratio, has been associated with beta-cell dysfunction. In women with gestational diabetes mellitus (GDM), previous studies of the proinsulin-to-insulin ratio have yielded conflicting results, despite the presence of beta-cell dysfunction. The interpretation of the proinsulin-to-insulin ratio, however, may be confounded by the variable effects of hepatic insulin extraction. Thus, we sought to determine whether GDM is characterized by relative hyperproinsulinemia as measured by the proinsulin-to-C-peptide ratio, an alternate measure of proinsulin secretion that is not affected by hepatic insulin extraction. RESEARCH DESIGN AND METHODS: Serum proinsulin, C-peptide, and insulin were measured in a cross-sectional study of 180 women undergoing oral glucose tolerance tests (OGTTs) in the late second or early third trimester. Based on the OGTT, participants were stratified into three groups: 1) normal glucose tolerance (NGT; n = 93), 2) impaired glucose tolerance (IGT; n = 39), and 3) GDM (n = 48). Insulin sensitivity (IS) was measured using the IS(OGTT) index of Matsuda and DeFronzo, which has been previously validated in pregnant women. RESULTS: There were no significant differences in mean fasting proinsulin-to-C-peptide ratio between the three glucose tolerance groups (NGT, 0.024; IGT, 0.022; GDM, 0.019; P = 0.4). Furthermore, adjustment for age, weeks' gestation, prepregnancy BMI, ethnicity, previous GDM, and family history of diabetes did not reveal any association between the proinsulin-to-C-peptide ratio and glucose tolerance status. Using Spearman univariate correlation analysis, fasting proinsulin-to-C-peptide ratio was significantly correlated with IS(OGTT) (r = 0.29, P < 0.0001) and inversely related to the homeostasis model assessment of insulin resistance (r = -0.36, P < 0.0001) and prepregnancy BMI (r = -0.23, P < 0.005). On multiple linear regression analysis, IS(OGTT) emerged as the strongest independent correlate of the dependent variable proinsulin-to-C-peptide ratio. Furthermore, after adjustment for potential covariates, a stepwise decrease in proinsulin-to-C-peptide ratio was observed per decreasing tertile of IS(OGTT) (trend P = 0.0019), consistent with enhanced efficiency of proinsulin processing (i.e., reduced proinsulin-to-C-peptide ratio) as insulin resistance increases. CONCLUSIONS: GDM is not independently associated with hyperproinsulinemia as measured by the proinsulin-to-C-peptide ratio. Instead, in pregnant women, increased insulin resistance is associated with decreased proinsulin-to-C-peptide ratio, independently of glucose tolerance status. These data suggest that relative proinsulin secretion in late pregnancy is primarily related to insulin resistance and does not necessarily reflect beta-cell function.
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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 | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".