Glycosuria

IntroductionResults from studies examining associations of maternal diabetes in pregnancy with offspring cognitive outcomes have been inconclusive.MethodsWe used data from the Avon Longitudinal Study of Parents and Children, a UK prospective pregnancy cohort. Outcomes were School Entry Assessment (SEA) scores (age 4, N = 6, 032) and WISC-III IQ (age 8, N = 5, 282-5,307) and General Certificate of Secondary Education (GCSE) results (age 16, N = 7, 615).ResultsExisting diabetes, gestational diabetes, and, to a lesser extent, glycosuria were associated with lower offspring SEA scores (age 4), IQ (age 8), and GCSE results (age 16) even when adjusting for offspring sex, maternal age, prepregnancy BMI, smoking in pregnancy, parity, caesarean section, maternal education, and occupational social class. Offspring of mothers with existing diabetes had a threefold risk of achieving no GCSEs graded A*-C, whilst offspring of women with gestational diabetes had, on average, a five point lower IQ compared to offspring of women with no diabetes or glycosuria.ConclusionsMaternal diabetes in pregnancy is consistently associated with lower offspring cognition and educational attainment though confidence intervals were wide. The weaker associations with glycosuria suggest a dose-dependent adverse association with IQ.

Heart failure (HF) continues to be a serious public health challenge despite significant advancements in therapeutics and is often complicated by multiple other comorbidities. Of particular concern is type 2 diabetes mellitus (T2DM) which not only amplifies the risk, but also limits the treatment options available to patients. The sodium-glucose linked cotransporter subtype 2 (SGLT2)-inhibitor class, which was initially developed as a treatment for T2DM, has shown great promise in reducing cardiovascular risk, particularly around HF outcomes - regardless of diabetes status.There are ongoing efforts to elucidate the true mechanism of action of this novel drug class. Its primary mechanism of inducing glycosuria and diuresis from receptor blockade in the renal nephron seems unlikely to be responsible for the rapid and striking benefits seen in clinical trials. Early mechanistic work around conventional therapeutic targets seem to be inconclusive. There are some emerging theories around its effect on myocardial energetics and calcium balance as well as on renal physiology. In this review, we discuss some of the cutting-edge hypotheses and concepts currently being explored around this drug class in an attempt better understand the molecular mechanics of this novel agent.

BackgroundLittle is known about early life determinants of non-alcoholic fatty liver disease (NAFLD). We examined associations of maternal pregnancy diabetes/glycosuria and pre-pregnancy body mass index (BMI) with offspring markers of NAFLD and liver pathology and examined mediation by birthweight and concurrent offspring adiposity.MethodsWe used data from a UK prospective pregnancy cohort. Offspring underwent abdominal ultrasonography (USS) at mean age 17.8 years. Outcomes included USS-assessed fatty liver, estimated liver volume and shear velocity, a variant of elastography (a marker of liver fibrosis) (N = 1 215) and blood-based markers of liver pathology [alanine amino transferase, aspartate amino transferase, gamma- glutamyltransferase and haptoglobin] (N = 2 359).Results2.1 % (N = 25) of participants had USS-assessed fatty liver [maternal diabetes/glycosuria (N = 7) and no diabetes/glycosuria (N = 18)]. Maternal diabetes/glycosuria was associated with greater odds of offspring USS fatty liver in confounder adjusted models [adjusted odds ratio (aOR) 6.74 (95 % confidence interval (CI) 2.47, 18.40)] and higher shear velocity [adjusted ratio of geometric mean (aRGM):1.10 (95 % CI 1.05, 1.15)]. These associations were not mediated by offspring birthweight or concurrent adiposity. Maternal diabetes/glycosuria was not associated with liver volume or blood-based outcomes. Greater maternal pre-pregnancy BMI was associated with greater odds of offspring USS fatty liver [aOR 2.72 (95 % CI: 1.20, 6.15)], higher liver volume [aRGM 1.03 (95 % CI 1.00, 1.07)] and shear velocity [aRGM1.03 (95 % CI: 1.01, 1.06)] in confounder adjusted models. These associations were largely mediated by offspring adiposity. Maternal pre-pregnancy BMI was not consistently associated with blood-based outcomes.ConclusionsResults suggest that maternal pregnancy diabetes/glycosuria is associated with offspring NAFLD through mechanisms other than offspring's own adiposity.

BackgroundGestational diabetes mellitus (GDM) poses significant risks, particularly for nulliparous women of advanced maternal age (AMA ≥35 years), a growing demographic due to delayed childbirth. However, effective early-pregnancy prediction tools tailored for this high-risk subgroup are lacking. This study aimed to identify readily available early biomarkers for GDM risk stratification in AMA nulliparous women.MethodsThis retrospective cohort study analyzed 354 AMA nulliparous women (140 GDM, 214 non-GDM). GDM was diagnosed by a 75g oral glucose tolerance test at 24-28 weeks using IADPSG criteria (fasting ≥5.1 mmol/L, 1-h ≥10.0 mmol/L, 2-h ≥8.5 mmol/L). Clinical and laboratory data at 10-13 gestational weeks were compared. Multivariate logistic regression identified independent risk factors.ResultsThe GDM group had significantly higher body mass index (BMI), fasting blood glucose (FBG), white blood cell (WBC) count, neutrophil count (NEU), and urinary glucose (U-GLU) positivity (P9/L; 95% CI: 1.05-1.40), elevated WBC (aOR = 1.15 per 109/L; 95% CI: 1.01-1.30), and ART use (aOR = 1.63; 95% CI: 1.02-2.59) as independent risk factors for GDM. The multivariable model achieved an AUC of 0.70 (95% CI 0.65 - 0.76), with sensitivity of 57.1% and specificity of 76.2% at the optimal cutoff.ConclusionsIn this single-center retrospective cohort of AMA nulliparous women, early-pregnancy urinary glucose positivity, elevated fasting blood glucose, neutrophilia, leukocytosis, and the use of assisted reproductive technology were independently associated with an increased risk of GDM, with urinary glucose showing the strongest association. These findings suggest that a tiered screening strategy incorporating these readily available biomarkers might be explored for early risk stratification between 10-13 weeks' gestation. Their clinical utility requires prospective validation in larger, multicenter cohorts.