Danielle L. Jones

Aims/hypothesis: Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency or both), and demonstrated associations with clinical outcomes. We aimed to assess whether using enhanced processing to determine indices of insulin secretion and sensitivity is analytically robust, reproducible in a different population, and useful diagnostically and prognostically in clinical practice. Methods: A total of 1308 pregnant women with one or more risk factors for GDM who underwent a 75 g OGTT at one of nine hospital sites were recruited to this observational study. Specimens were collected for determination of glucose levels using standard and enhanced procedures, HbA_1c and insulin analysis. GDM diagnosis and management followed National Institute for Health and Care Excellence guidance. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA2-S < 25th centile of the population with normal glucose tolerance [NGT]), insulin-insufficient GDM (HOMA2-B < 25th centile), both or neither. We assessed associations with pregnancy outcomes using logistic regression. Results: Using enhanced specimen handling, 1027/1308 (78.5%) women had NGT, with 281/1308 (21.5%) being classified as having GDM. Of this group, 135/281 (48.0%) had insulin-resistant GDM, 73/281 (26.0%) had insulin-insufficient GDM and 2/281 (0.7%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71 patients (25.3%) had GDM with both HOMA2-S and HOMA2-B ≥ 25th centile (GDM-neither). This novel subgroup appeared to be relatively insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinaemia, suggesting an isolated postprandial defect in insulin sensitivity that was not captured by HOMA2-B or HOMA2-S. Women within most GDM subgroups had comparable pregnancy outcomes to those of normoglycaemic women, and HOMA2-B and HOMA2-S were weak predictors of pregnancy outcomes. Maternal BMI predicted a similar number of outcomes to HOMA2-S, suggesting that there was no additional predictive value in adding HOMA2-S. Similar findings were obtained when using different indices and standard specimen handling techniques. Conclusions/interpretation: Precision categorisation of GDM using HOMA2-S and HOMA2-B does not provide useful diagnostic or prognostic information, but did distinguish a novel subgroup of patients with GDM, characterised by an isolated postprandial defect in insulin sensitivity. Graphical

Dietary fibre improves glycaemic control in type 2 diabetes, but its therapeutic role in women with diabetes in pregnancy is unclear. We assessed the effect of dietary fibre on markers of glycaemic control in women with diabetes in pregnancy.Methods: We searched four databases (Cochrane Library, MEDLINE, Embase and Web of Science) to identify RCTs exploring the effect of dietary fibre, high‐fibre diets or fibre supplementation on fasting blood glucose (FBG), 2‐h postprandial blood glucose (PBG) and requirement for insulin therapy, among other glycaemic makers in pregnant women with diabetes. Data were pooled for each outcome to calculate change from baseline mean (SD) and overall mean difference (MD) between control and intervention groups.Results: Of 1462 identified studies, data from 20 eligible trials containing 1061 participants were pooled. On meta‐analysis, a higher fibre intake was associated with reduced FBG (MD: −0.35 mmol/L, 95% CI: −0.53, −0.18, p < 0.01), PBG (MD: −0.90 mmol/L, 95% CI: −1.39, −0.40, p < 0.01) and requirement for insulin (OR: 0.24, 95% CI: 0.13, 0.46, p < 0.01). There was significant heterogeneity for FBG and PBG (>90%), attributable to differences in Intervention type for PBG (Dietary Approach to Stop Hypertension [DASH] diet, low glycaemic index, supplement; p < 0.01) and study duration (for FBG: p = 0.002; not for PBG). Studies were mostly scored as high risk of bias due to lack of blinding (Cochrane Risk of Bias Tool v.2.0).Conclusion: High‐quality dietary intervention studies in pregnancy are lacking. Our results suggest that high‐fibre diets improve fasting and postprandial glycaemia and reduce the likelihood of requiring insulin in women with diabetes in pregnancy.

Background: Gestational diabetes is associated with increased risk of obesity, type 2 diabetes and cardiovascular disease. Effective nutritional strategies are needed to reduce BMI and improve long-term maternal cardiometabolic health, but the relative contribution of maternal eating behaviour, a potential barrier to dietary change, has not been explored. We compared eating behaviour in women with gestational diabetes with that of men and non-pregnant women with comparable risk factors, and tested associations between eating behaviour traits and BMI in women with gestational diabetes. We hypothesized that eating behaviour would be unfavourable in gestational diabetes and would be associated with BMI. Methods: Participants (n = 417) including 53 men, 164 non-pregnant women and 200 women with gestational diabetes (singleton pregnancy; 29 weeks’ gestation) were recruited into three prospective studies assessing weight loss interventions, with similar entry criteria. The three-factor eating questionnaire (TFEQ-R18) assessed uncontrolled eating, emotional eating and cognitive restraint at study enrolment. Associations between BMI at study enrolment and TFEQ-R18 (% maximum score) were assessed using linear regression. Results: Women with gestational diabetes had significantly lower uncontrolled eating scores vs. men (53% vs. 65%; p < 0.001) and non-pregnant women (53% vs. 66%; p < 0.001), lower emotional eating scores vs. non-pregnant women (60% vs. 71%; p < 0.001) and higher cognitive restraint (p < 0.001 vs. men and non-pregnant women). In women with gestational diabetes, emotional eating scores were positively associated with BMI at study enrolment (beta coefficient 7.8 (95% CI 3.9 to 11.7), p < 0.001). Conclusions: Women with gestational diabetes have favourable eating behaviour compared with other population groups. Because BMI at study enrolment was associated with emotional eating, nutritional strategies which reduce emotional eating may provide new opportunities to improve long-term maternal health after gestational diabetes.

Aims: Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations. Methods: Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion. Results: Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised β’ 0.393 (0.289–0.498), p = 1.3 × 10^–12; n = 306), but not with glucose concentrations (p = 0.3). The association with insulin was still evident when adjusting for BMI (β’ 0.271 (0.180–0.362), p = 1.1 × 10^–8; n = 297). Likewise, at 120 min the OGTT GLP-1 concentrations were associated with plasma insulin concentrations (β’ 0.216 (0.100–0.331), p = 2.7 × 10^–4; n = 306) even after adjusting for BMI (β’ 0.178 (0.061–0.294), p = 2.9 × 10^–3; n = 296), but not with glucose (p = 0.9). GIP concentrations were not associated with insulin or glucose concentrations at either time point (all p > 0.2). In pregnancy plasma GLP-1, but not GIP, concentrations appear to be predictive of circulating insulin concentrations, independently of associations with BMIs. Conclusions: These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology.

Cardiovascular disease and its concurrent risk factors are prevalent after liver transplant (LT). Most of these risk factors are modifiable by diet. We aimed to synthesise the literature reporting the nutritional intake of liver transplant recipients (LTR) and the potential determinants of intake. We performed a systematic review and meta-analyses of studies published up until July 2021 reporting the nutritional intake of LTR. The pooled daily mean intakes were recorded as 1998 (95% CI 1889, 2108) kcal, 17 (17, 18)% energy from protein, 49 (48, 51)% energy from carbohydrates, 34 (33, 35)% energy from total fat, 10 (7, 13)% energy from saturated fat, and 20 (18, 21) g of fibre. The average fruit and vegetable intake ranged from 105 to 418 g/day. The length of time post-LT and the age and sex of the cohorts, as well as the continent and year of publication of each study, were sources of heterogeneity. Nine studies investigated the potential determinants of intake, time post-LT, gender and immunosuppression medication, with inconclusive results. Energy and protein requirements were not met in the first month post-transplant. After this point, energy intake was significantly higher and remained stable over time, with a high fat intake and low intake of fibre, fruits and vegetables. This suggests that LTR consume a high-energy, low-quality diet in the long term and do not adhere to the dietary guidelines for cardiovascular disease prevention.