Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Abstract Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data. Results As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.

Social adaptation of children with mild intellectual disability : effects of partial integration within primary school classes

Examined the social adaptation of 32 children in grades 3–6 with mild intellectual disability: 13 Ss were partially integrated into regular primary school classes and 19 Ss were full-time in separate classes. Sociometric status was assessed using best friend and play rating measures. Consistent with previous research, children with intellectual disability were less socially accepted than were a matched group of 32 children with no learning disabilities. Children in partially integrated classes received more play nominations than those in separate classes, but had no greater acceptance as a best friend. On teachers' reports, disabled children had higher levels of inappropriate social behaviours, but there was no significant difference in appropriate behaviours. Self-assessments by integrated children were more negative than those by children in separate classes, and their peer-relationship satisfaction was lower. Ratings by disabled children of their satisfaction with peer relationships were associated with ratings of appropriate social skills by themselves and their teachers, and with self-ratings of negative behaviour. The study confirmed that partial integration can have negative consequences for children with an intellectual disability.

Peripheral ocular aberrations in mild and moderate keratoconus

Purpose: To investigate the influence of keratoconus on peripheral ocular aberrations. Methods: Aberrations of 7 mild and 5 moderate keratoconics were determined over a 42°horizontal x 32° vertical visual field with a modified COAS-HD aberrometer. Control data were obtained from an emmetropic group. Results: Most aberrations in keratoconics showed field dependence predominately along the vertical meridian. Mean spherical equivalent M, oblique astigmatism J45 and regular astigmatism J180 refraction components and total root mean square aberrations (excluding defocus) had high magnitudes in the inferior visual field. The rates of change of aberrations were higher in moderate than in mild keratoconics. Coma was the dominant peripheral higher-order aberration in both emmetropes and keratoconics; for the latter it had high magnitudes in the centre and periphery of the visual field. Conclusion: Greater rates of change of aberrations across the visual field occurred for the keratoconic groups than for the emmetropic control group. Moderate keratoconics had more rapid changes in, and higher magnitudes of aberrations across the visual field than mild keratoconics. The dominant higher-order aberration for the keratoconics across the visual field was vertical coma.

Mild systemic hypoxia and photopic visual field sensitivity

Purpose: Flickering stimuli increase the metabolic demand of the retina,making it a sensitive perimetric stimulus to the early onset of retinal disease. We determine whether flickering stimuli are a sensitive indicator of vision deficits resulting from to acute, mild systemic hypoxia when compared to standard static perimetry. Methods: Static and flicker visual perimetry were performed in 14 healthy young participants while breathing 12% oxygen (hypoxia) under photopic illumination. The hypoxia visual field data were compared with the field data measured during normoxia. Absolute sensitivities (in dB) were analysed in seven concentric rings at 1°, 3°, 6°, 10°, 15°, 22° and 30° eccentricities as well as mean defect (MD) and pattern defect (PD) were calculated. Preliminary data are reported for mesopic light levels. Results: Under photopic illumination, flicker and static visual field sensitivities at all eccentricities were not significantly different between hypoxia and normoxia conditions. The mean defect and pattern defect were not significantly different for either test between the two oxygenation conditions. Conclusion: Although flicker stimulation increases cellular metabolism, flicker photopic visual field impairment is not detected during mild hypoxia. These findings contrast with electrophysiological flicker tests in young participants that show impairment at photopic illumination during the same levels of mild hypoxia. Potential mechanisms contributing to the difference between the visual fields and electrophysiological flicker tests including variability in perimetric data, neuronal adaptation and vascular autoregulation, are considered. The data have implications for the use of visual perimetry in the detection of ischaemic/hypoxic retinal disorders under photopic and mesopic light levels.

Formation of nanoporous materials via mild retro-Diels–Alder chemistry

Poly(styrene)-block-poly(ethylene oxide) copolymers synthesized via the combination of reversible addition fragmentation chain transfer (RAFT) polymerization and hetero Diels–Alder (HDA) cycloaddition can be cleaved in the solid state by a retro-HDA reaction occurring at 90 °C. Nanoporous films can be prepared from these polymers using a simple heating and washing procedure.

Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study

Background:  For those in the field of managing diabetic complications, the accurate diagnosis and monitoring of diabetic peripheral neuropathy (DPN) continues to be a challenge. Assessment of sub-basal corneal nerve morphology has recently shown promise as a novel ophthalmic marker for the detection of DPN. Methods:  Two hundred and thirty-one individuals with diabetes with predominantly mild or no neuropathy and 61 controls underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10 g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length, branch density and tortuosity were measured using corneal confocal microscopy. Differences in corneal nerve morphology between individuals with and without DPN and controls were investigated using analysis of variance and correlations were determined between corneal morphology and established tests of, and risk factors for, DPN. Results:  Corneal nerve fibre length was significantly reduced in diabetic individuals with mild DPN compared with both controls (p < 0.001) and diabetic individuals without DPN (p = 0.012). Corneal nerve branch density was significantly reduced in individuals with mild DPN compared with controls (p = 0.032). Corneal nerve fibre tortuosity did not show significant differences. Corneal nerve fibre length and corneal nerve branch density showed modest correlations to most measures of neuropathy, with the strongest correlations to nerve conduction study parameters (r = 0.15 to 0.25). Corneal nerve fibre tortuosity showed only a weak correlation to the vibration detection threshold. Corneal nerve fibre length was inversely correlated to glycated haemoglobin (r = -0.24) and duration of diabetes (r = -0.20). Conclusion:  Assessment of corneal nerve morphology is a non-invasive, rapid test capable of showing differences between individuals with and without DPN. Corneal nerve fibre length shows the strongest associations with other diagnostic tests of neuropathy and with established risk factors for neuropathy.

Postpartum diet quality in Australian women following a gestational diabetes pregnancy

BACKGROUND/OBJECTIVES: To describe the diet quality of a national sample of Australian women with a recent history of gestational diabetes mellitus (GDM) and determine factors associated with adherence to national dietary recommendations. SUBJECTS/METHODS: A postpartum lifestyle survey with 1499 Australian women diagnosed with GDM p3 years previously. Diet quality was measured using the Australian recommended food score (ARFS) and weighted by demographic and diabetes management characteristics. Multinominal logistic regression analysis was used to determine the association between diet quality and demographic characteristics, health seeking behaviours and diabetes-related risk factors. RESULTS: Mean (±s.d.) ARFS was 30.9±8.1 from a possible maximum score of 74. Subscale component scores demonstrated that the nuts/legumes, grains and fruits were the most poorly scored. Factors associated with being in the highest compared with the lowest ARFS quintile included age (odds ratio (OR) 5-year increase=1.40; 95% (confidence interval) CI:1.16–1.68), tertiary education (OR=2.19; 95% CI:1.52–3.17), speaking only English (OR=1.92; 95% CI:1.19–3.08), being sufficiently physically active (OR=2.11; 95% CI:1.46–3.05), returning for postpartum blood glucose testing (OR=1.75; 95% CI:1.23–2.50) and receiving riskreduction advice from a health professional (OR=1.80; 95% CI:1.24–2.60). CONCLUSIONS: Despite an increased risk of type 2 diabetes, women in this study had an overall poor diet quality as measured by the ARFS. Women with GDM should be targeted for interventions aimed at achieving a postpartum diet consistent with the guidelines for chronic disease prevention. Encouraging women to return for follow-up and providing risk reduction advice may be positive initial steps to improve diet quality, but additional strategies need to be identified.

Pilot study of an individualised early post partum intervention to increase physical activity in women with previous gestational diabetes

Background: Whilst the benefits of physical activity in preventing progression from impaired glucose tolerance to overt diabetes in older adults are well recognised, it is not clear which strategies may prevent progression to overt diabetes in women with recent gestational diabetes. We sought to devise and pilot test a convenient, home based exercise program with telephone support, suited to the early post partum period. Twenty eight women with recent gestational diabetes were enrolled six weeks post partum into a 12 week randomised controlled trial of Usual Care ("UC" Controls (n= 13)) vs. Supported Care ("SC" individualised exercise program with regular telephone support (n= 15)). Findings: Baseline characteristics for the whole cohort at six weeks post partum (Mean ± SD) were Age 33 ± 4 years, Weight 80 ± 20 kg and Body Mass Index (BMI) 30.0 ± 9.7 kg / m2. The primary outcome, planned physical activity, increased by Median (Range) 60 (0-540) mins/wk in the SC group vs. 0 (0-580) mins/wk in the UC group (p = 0.234, Mann Whitney U test). The change in planned physical activity predominantly comprised planned walking. Body weight, BMI, waist circumference, % body fat (measured by bioimpedance), fasting glucose and insulin did not change significantly over time in either group. Conclusions: The intervention designed to increase physical activity in post partum women with previous gestational diabetes was feasible. However, no evidence to suggest that this type of program provides any measurable improvement in metabolic or biometric parameters over a three month post partum follow up was observed.