Incidence, prevalence, and mortality of type 1 diabetes in children and youth in Burkina Faso 2013-2022.

AIM: There are no data on type 1 diabetes (T1D) incidence and prevalence in Burkina Faso. We aimed to determine these in persons aged <25 years (y) since the implementation of Life for a Child (LFAC) program in 2013. PATIENTS AND METHODS: Data were collected from the prospective program register. Diagnosis of T1D was clinical, based on presentation, abrupt onset of symptomatic hyperglycemia, need for insulin replacement therapy from diagnosis, and no suggestion of other diabetes types. RESULTS: We diagnosed 312 cases of T1D <25y in 2013-2022. Male-to-female ratio was 1:1. T1D incidence <25y per 100,000 population/year increased from 0.08 (CI 95% 0.07-0.60) in 2013 to 0.34 (CI 95% 0.26-0.45) in 2022 (p=0.002). Incidence <15y/y rose from 0.04 (CI 95% 0.01-0.10) to 0.27 (CI 95% 0.18-0.38) per 100,000/year in 2013 and 2022, respectively (p < 0.002). Prevalence per 100,000 population <25y was 0.27 (CI 95% 0.19-0.37) in 2013 and rose to 1.76 (CI 95% 1.546-1.99) in 2022 (p<0.0001). Mortality rate was 20 (CI 95% 13-29.6) per 1,000-person y. CONCLUSIONS: There is a low but sharply rising T1D incidence and prevalence rates in children and youth in Burkina Faso since LFAC program implementation. It is very likely this is partly due to improved case detection. Mortality remains substantial.

The T1D Index: Implications of Initial Results, Data Limitations, and Future Development.

PURPOSE OF THE REVIEW: Current global information on incidence, prevalence, and mortality of type 1 diabetes (T1D) is limited, particularly in low- and middle-income countries. To address this gap in evidence, JDRF, Life for a Child, International Society for Pediatric and Adolescent Diabetes, and International Diabetes Federation have developed the T1D Index, which uses a Markov mathematical model, and machine learning and all available data to provide global estimates of the burden on T1D. This review assesses the methodology, limitations, current findings, and future directions of the Index. RECENT FINDINGS: Global prevalence was estimated at 8.4 million in 2021, with 1.5 million <20 years (y). T1D prevalence varied from 1.5 to 534 per 100,000, with T1D accounting for <0.1-17.8% of all diabetes in different countries. A total of 35,000 young people <25 y are estimated to have died at clinical onset of T1D from non-diagnosis. An estimated 435,000 people <25 y were receiving "minimal care." Health-adjusted life years (HALYs) lost for individuals diagnosed with T1D at age 10 y in 2021 ranged from 14 to 55 y. These results show that interventions to reduce deaths from non-diagnosis, and improve access to at least an intermediate care level, are needed to reduce projected life years lost. The results have significant uncertainties due to incomplete data across the required inputs. Obtaining recent incidence, prevalence, and mortality data, as well as addressing data quality issues, misdiagnoses, and the lack of adult data, is essential for maintaining and improving accuracy. The index will be updated regularly as new data become available.

Type 1 diabetes patient experiences and management practices during the COVID-19 pandemic in rural Uganda.

Background: The COVID-19 pandemic has impacted various aspects of the lives of persons with chronic diseases, including type 1 diabetes (T1D). However, the diabetes care experiences and practices adopted by persons living with T1D after the declaration of the COVID-19 pandemic in Uganda have not been well documented. Objectives: We investigated diabetes management practices and experiences of persons with T1D during the COVID-19 pandemic lockdown in a rural district of southwestern Uganda. Methods: Using interactive sequential explanatory mixed methods, we conducted a cross-sectional study of persons with T1D aged 18-25 years, their caregivers and health workers. Quantitative data was exclusively collected from patients with T1D using Kobo Toolbox™ and analysed with SPSS™ version 26; qualitative interviews were used to elicit responses from purposively selected patients with T1D, plus caregivers and health workers that were analysed using a thematic framework approach. Results: The study enrolled 51 (24 males) patients with T1D; diabetes duration (mean ± SD) 6.6 ± 5 years. Access to insulin syringes significantly worsened in 19.6% of participants (p = 0.03). Insulin injection frequency (p = 0.01), blood glucose monitoring (p = 0.001) and meal frequency (p = 0.0001) significantly decreased. Qualitative interviews highlighted COVID-19 restriction measures had reduced household income, frequency of clinic visits, and access to food, diabetes support and social services. Conclusions: Experiences and practices were consistent with decisions to prioritise survival, even with known risks around metabolic control. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01222-4.

Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study.

BACKGROUND: Accurate data on type 1 diabetes prevalence, incidence, associated mortality and life expectancy are crucial to inform public health policy, but these data are scarce. We therefore developed a model based on available data to estimate these values for 201 countries for the year 2021 and estimate the projected prevalent cases in 2040. METHODS: We fitted a discrete-time illness-death model (Markov model) to data on type 1 diabetes incidence and type 1 diabetes-associated mortality to produce type 1 diabetes prevalence, incidence, associated mortality and life expectancy in all countries. Type 1 diabetes incidence and mortality data were available from 97 and 37 countries respectively. Diagnosis rates were estimated using data from an expert survey. Mortality was modelled using random-forest regression of published type 1 diabetes mortality data, and life expectancy was calculated accordingly using life tables. Estimates were validated against observed prevalence data for 15 countries. We also estimated missing prevalence (the number of additional people who would be alive with type 1 diabetes if their mortality matched general population rates). FINDINGS: In 2021, there were about 8·4 (95% uncertainty interval 8·1-8·8) million individuals worldwide with type 1 diabetes: of these 1·5 million (18%) were younger than 20 years, 5·4 million (64%) were aged 20-59 years, and 1·6 million (19%) were aged 60 years or older. In that year there were 0·5 million new cases diagnosed (median age of onset 39 years), about 35 000 non-diagnosed individuals died within 12 months of symptomatic onset. One fifth (1·8 million) of individuals with type 1 diabetes were in low-income and lower-middle-income countries. Remaining life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. Missing prevalent cases in 2021 were estimated at 3·7 million. In 2040, we predict an increase in prevalent cases to 13·5-17·4 million (60-107% higher than in 2021) with the largest relative increase versus 2021 in low-income and lower-middle-income countries. INTERPRETATION: The burden of type 1 diabetes in 2021 is vast and is expected to increase rapidly, especially in resource-limited countries. Most incident and prevalent cases are adults. The substantial missing prevalence highlights the premature mortality of type 1 diabetes and an opportunity to save and extend lives of people with type 1 diabetes. Our new model, which will be made publicly available as the Type 1 Diabetes Index model, will be an important tool to support health delivery, advocacy, and funding decisions for type 1 diabetes. FUNDING: JDRF International.

Incidence of type 1 diabetes in children in Dominican Republic, 2010-2019: A national collaborative study.

The Dominican Republic has no recent data on type 1 diabetes (T1D) incidence in children. Therefore, a study was undertaken to determine this in persons aged <15 years (y). Data were collected on all new T1D diagnoses between 2010-2019 from the four institutions caring for children with T1D. Diagnosis was made according to standard criteria. No secondary ascertainment source was available. The trend and the effect of age and sex of T1D incidence was analyzed using Poisson regression. A total of 1224 new cases of T1D were diagnosed <15 y; mean ± standard deviation (range) 122 ± 12 (96-135) cases per year. Age at T1D diagnosis was 8.8 ± 3.7 y, with a significant female preponderance (n = 708, 57.8%, p < 0.001). When examined per 5-y age group, cases were consistently highest in 10-14 y, and lowest in 0-4 y in all study years. Mean crude T1D annual incidence was 4.3 (95% CI 3.5-5.1) per 100,000 population. There was no significant difference between incidence across the country's three departments (regions): Southeast (4.4 [3.4-5.7]/100,000 population), North (4.1 [2.9-5.6]), and Southwest (3.9 [2.4-5.9]). Mean standardized annual incidence was 4.1 (4.1-4.2) per 100,000 population, with no significant trend of increase over the study period. The incidence of T1D in children aged <15 y is relatively low in Dominican Republic, but consistent with the limited data from other countries in the region. However, the incidence is eight times higher than the previous estimate during 1995-1999. Ongoing surveillance is warranted.

Epidemiology and phenotypes of diabetes in children and adolescents in non-European-origin populations in or from Western Pacific region.

BACKGROUND: Type 1 diabetes (T1D) incidence varies substantially between countries/ territories, with most studies indicating increasing incidence. In Western Pacific region (WPR), reported rates are much lower than European-origin populations. In contrast, there are reports of substantial numbers of young people with type 2 diabetes (T2D). A deeper understanding of T1D and T2D in the WPR may illuminate factors important in pathogenesis of these conditions. Furthermore, with varying resources and funding for diabetes treatment in this region, there is a need to more clearly determine the current burden of disease and also any gaps in knowledge. AIM: To compile and summarise published epidemiologic and phenotypic data on childhood diabetes in non-European populations in and from WPR. METHODS: Research articles were systematically searched from PubMed (MEDLINE), Embase, Cochrane library, and gray literature. Primary outcome measures were incidence and prevalence, with secondary measures including phenotypic descriptions of diabetes, including diabetes type categorization, presence of diabetic ketoacidosis (DKA) at onset, autoantibody positivity, C-peptide levels, and human leucocyte antigen phenotype. Extracted data were collected using a customized template. Three hundred and thirty relevant records were identified from 16 countries/territories, with analysis conducted on 265 (80.3%) records published from the year 2000. RESULTS: T1D incidence ranged from < 1-7.3/100000 individuals/year, rates were highest in emigrant/ mixed populations and lowest in South-East Asia, with most countries/territories (71.4%) having no data since 1999. Incidence was increasing in all six countries/territories with data (annual increases 0.5%-14.2%, highest in China). Peak age-of-onset was 10-14 years, with a female case excess. Rate of DKA at onset varied from 19.3%-70%. Pancreatic autoantibodies at diagnosis were similar to European-origin populations, with glutamic acid decarboxylase-65 autoantibody frequency of 44.1%-64.5%, insulinoma-associated 2 autoantibody 43.5%-70.7%, and zinc transporter-8 autoantibody frequency 54.3% (one study). Fulminant T1D also occurs. T2D was not uncommon, with incidence in Japan and one Chinese study exceeding T1D rates. Monogenic forms also occurred in a number of countries. CONCLUSION: T1D is less common, but generally has a classic phenotype. Some countries/ territories have rapidly increasing incidence. T2D is relatively common. Registries and studies are needed to fill many information gaps.

Global estimates of incidence of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Atlas, 10th edition.

BACKGROUND: Type 1 diabetes (T1D) incidence in children and adolescents varies widely, and is increasing in many nations. The 10th edition of the International Diabetes Federation Atlas estimated incident cases in 2021 for 215 countries/territories ("countries"). METHODS: Studies on T1D incidence for young people aged 0-19 years were sourced and graded using previously described methods. For countries without studies, data were extrapolated from similar nearby countries. RESULTS: An estimated 108,300 children under 15 years will be diagnosed in 2021, a number rising to 149,500 when the age range extends to under 20 years. The ratio of incidence in 15-19 years compared to those aged 0-14 years was particularly high in some countries in sub-Saharan Africa, North Africa/Middle East, and in Mexico. Only 97 countries have their own incidence data, with extrapolation required for some very populous nations. Most data published were not recent, with 27 countries (28%) having data in which the last study year was 2015 or afterwards, and 26 (27%) having no data after 1999. CONCLUSIONS: Many countries have recent data but there are large gaps globally. Such data are critical for allocation of resources, teaching, training, and advocacy. All countries are encouraged to collect and publish current data.

Transcriptomic signature of early life stress in male rat prefrontal cortex.

Early life stress (ELS) is associated with adverse mental health outcomes including anxiety, depression and addiction-like behaviours. While ELS is known to affect the developing brain, leading to increased stress responsiveness and increased glucocorticoid levels, the molecular mechanisms underlying the detrimental effects of ELS remain incompletely characterised. Rodent models have been instrumental in beginning to uncover the molecular and cellular underpinnings of ELS. Limited nesting (LN), an ELS behavioural paradigm with significant improvements over maternal separation, mimics human maternal neglect. We have previously shown that LN leads to an increase in one of the behavioural measures of anxiety like-behaviours in rats (percent of entries in the EPM open arm). Here we assessed gene expression changes induced by ELS in rat prefrontal cortex by RNA-sequencing. We show that LN leads primarily to transcriptional repression and identify a molecular signature of LN in rat PFC that is observed across ELS protocols and replicable across rodent species (mouse and rat).

Incidence of diabetes in children and adolescents in Dhaka, Bangladesh.

OBJECTIVES: Bangladesh has limited information regarding incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in young people. The objective of this study was to measure minimum incidence of T1D and T2D, and record other types of new-onset diabetes in children and adolescents <20 years (y), in Dhaka District, Bangladesh, from 2011-2018. METHODS: Retrospective study using clinical records from Diabetic Association of Bangladesh clinics. Cases were classified by clinical evaluation. RESULTS: 725 cases were diagnosed. 482 (66.5%) had T1D, 205 (28.3%) T2D, 14 (1.9%) fibrocalculous pancreatic diabetes, and 24 (3.3%) other types. Male:female ratios for T1D/T2D were 1:1.6 (p<0.0001) (T1D) and 1:1.4 (p<0.01) respectively. T1D cases by age-group were 7.3% (0-4 y), 19.9% (5-9 y), 43.6% (10-14 y) and 29.3% (15-19 y). Mean ± SD ages of onset were 12.3 ± 4.2 y (T1D) and 13.1 ± 2.4 y (T2D). Annual T1D mean incidences/100,000 were 1.22 [95%CI: 0.85-1.58] (<15 y) and 1.25 [0.94-1.57] (<20 y), and for T2D 0.52 [0.33-0.73] (<20 y). T1D incidence <15 y was 1.04 [0.69-1.39] in 2011 and 1.42 [1.04-1.80] in 2018 (p=0.08). T2D incidence rose from 0.22 [0.80-0.36] (2011) to 0.57 [0.36-0.77] (2018), an annualized increase of 12% [8-22%] (p=0.001). Ascertainment was estimated as 95%. CONCLUSIONS: T1D was most common, but T2D, FCPD and other forms also occur. T2D incidence increased during the study period.

High incidence of type 1 diabetes in adolescents and young adults in Eritrea.

BACKGROUND: Eritrea has no data on type 1 diabetes incidence in children and youth; therefore, a study was undertaken to determine this in persons aged <25 years. METHODS: Data were collected on new type 1 diabetes diagnoses during 2019, from district, provincial and national hospitals. Type 1 diabetes was diagnosed according to standard WHO criteria. No secondary ascertainment source was available. 95% confidence intervals were computed based on approximation to the Poisson distribution, and age and gender effects were analysed with Poisson regression. RESULTS: There were 532 new cases of type 1 diabetes. Mean ± standard deviation (range) age of diagnosis was 16.2 ± 5.7 (1.5-24.9) years, and peak age group was 15-19 years (n = 200, 37.6%), with mode at 18 years. Incidence <15 years was 11.5/100,000 individuals [9.9-13.2], with the highest incidence in the 10-14 years group (19.0/100,000 [15.5-23.1]). Incidence then peaked in the 15-19 years age group (50.2/100,000 [43.5-57.7]) and remained high in the 20-24 years group (46.2/100,000 [39.0-54.3]). There was a male:female ratio of 1.37 (p = 0.001). Two hundred and thirty-eight (44.7%) presented in diabetic ketoacidosis. CONCLUSION: Type 1 diabetes incidence in Eritrea is moderate <15 years, and high 15-24 years. The 15-19 and 20-24 years rates appear to be the highest published to date. Given the study was only for one year, further confirmatory prospective information will clarify the situation and document trends. Assessment of the type 1 diabetes phenotypes that are occurring in Eritrea is also indicated.

Perceived impact of the COVID-19 pandemic on young adults with type 1 diabetes in Rwanda.

INTRODUCTION: data on the impact of COVID-19 on people with type 1 diabetes (T1D) in less resourced countries are limited. Our study was undertaken in Kigali, Rwanda, and aimed to investigate and describe the problems and challenges experienced by young adults with T1D resulting from the early phase of the pandemic. The study further aimed to understand the mechanisms being used to solve problems and overcome challenges, and perceived support needs. METHODS: this was a cross-sectional study, with anonymous data (n=52) collected through use of questionnaire. Participants were registered, and attending or receiving diabetes-related healthcare through the Rwanda Diabetes Association clinic. RESULTS: mean+standard deviation age and T1D duration were 24.0±2.1 and 7.4±3.4 years respectively, with sex distribution unequal (male n=22, 42.3%). Of 43 participants, the COVID-19 pandemic did not significantly affect participants´ access to diabetes management supplies and care. Eight (18.6%) participants experienced difficulties accessing blood glucose testing strips, 13 (30.2%) insulin, and three (7.0%) syringes and pen devices. Thirty-two (74.4%) experienced difficulty in attending standard diabetes healthcare reviews at the clinic setting. Some participants experienced hardship, through a decrease in personal or family income (n=42, 80.8%) and challenges in accessing food (n=34, 65.4%), with thirty (57.7%) participants having decreased meal frequency (p<0.001). CONCLUSION: our research illustrates the indirect effects of measures undertaken to curb the spread of COVID-19 on young adults with T1D in Rwanda. Study findings may help inform actions to mitigate negative impacts on T1D care in other crises.

NAD+ Repletion Rescues Female Fertility during Reproductive Aging.

Reproductive aging in female mammals is an irreversible process associated with declining oocyte quality, which is the rate-limiting factor to fertility. Here, we show that this loss of oocyte quality with age accompanies declining levels of the prominent metabolic cofactor nicotinamide adenine dinucleotide (NAD+). Treatment with the NAD+ metabolic precursor nicotinamide mononucleotide (NMN) rejuvenates oocyte quality in aged animals, leading to restoration in fertility, and this can be recapitulated by transgenic overexpression of the NAD+-dependent deacylase SIRT2, though deletion of this enzyme does not impair oocyte quality. These benefits of NMN extend to the developing embryo, where supplementation reverses the adverse effect of maternal age on developmental milestones. These findings suggest that late-life restoration of NAD+ levels represents an opportunity to rescue female reproductive function in mammals.

Incidence, prevalence and mortality of diabetes in children and adolescents aged under 20 years in the Republic of Maldives.

AIM: There is little published data on diabetes in youth in the Maldives. This study aimed to determine incidence, prevalence and mortality of diabetes in children and adolescents <20 years. METHODS: Data on all known existing cases in 2009 and all new cases from 2009 to 2018 was collected from the Diabetes Society of the Maldives registry. RESULTS: Thirty-nine subjects <20 years were known to have diabetes at the start of 2009 and 92 new cases were diagnosed from 2009 to 2018. Of the 92 new cases, 76 had type 1 diabetes (T1D), 15 type 2 diabetes (T2D) and one secondary diabetes. Of the 76 new T1D cases, 64 were diagnosed <15 years. Mean age of onset for T1D <20 years was 10 ± 4.6 years, with 42 (55.3%) female. Ten (13.2%) were diagnosed 0-4 years, 27 (35.5%) 5-9 years, 27 (35.5%) 10-14 years and 12 (15.8%) 15-19 years. Annual T1D mean incidence rates/per 100 000 subjects for <15/<20 years, respectively, increased from 3.6/2.7 in 2009 to 11.0/9.1 in 2018, representing 12.0%/13.0% annualised increases (P = 0.01 for both). T1D prevalence in 2018 for <15 and <20 years was 47.1/100 000 and 52.0/100 000, respectively. No young person with T1D died during this period, with a total of 262 patient-years of follow-up for T1D cases. The child with secondary diabetes died of other causes. CONCLUSION: T1D incidence in Maldives is higher than that reported from other South Asian countries, and an increasing trend was observed. T2D also occurs relatively frequently. A zero mortality rate was observed for children and young adults with T1D and T2D from 2009 to 2018.

Relationship of Lipids and Lipid-Lowering Medications With Cognitive Function: The Multi-Ethnic Study of Atherosclerosis.

Studies on the relationship of cholesterol concentrations and lipid-lowering medications with dementia risk have yielded inconsistent findings. Therefore, we investigated the association of lipid concentrations and lipid-lowering medications with cognitive function in the Multi-Ethnic Study of Atherosclerosis across 3 different cognitive domains assessed by means of the Cognitive Abilities Screening Instrument (CASI; version 2), the Digit Symbol Coding (DSC) Test, and the Digit Span (DS) Test in 2010-2012. After adjustment for sociodemographic and confounding factors, including concentrations of other lipids and use of lipid-lowering medication, higher total cholesterol, low-density lipoprotein cholesterol, and non-high-density-lipoprotein cholesterol concentrations were modestly associated with higher DS Test scores. None of the lipid parameters were associated with CASI or DSC Test scores. Similarly, changes in lipid concentrations were not associated with any cognitive function test score. Using treatment effects model analysis and after adjusting for confounding factors, including lipid concentrations, the use of any lipid-lowering medication, especially statins, was associated with higher scores on the CASI and backward DS tests but not on the DSC and forward DS tests. Our study does not support a robust association between lipid concentrations and cognitive function or between the use of lipid-lowering medication, especially statins, and worse cognitive function.

The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity.

Short-term exposure to high-energy diets impairs memory but there is little data on the relative contributions of fat and sugar to these deficits or the mechanisms responsible. Here, we investigated how these different macronutrients affect memory, neuroinflammation and neuroplasticity markers and the gut microbiota. Rats were fed matched purified diets for 2weeks; Control, Sugar, Saturated Fatty Acid (SFA) or Polyunsaturated Fatty Acid (PUFA), which varied only in the percentage of energy available from sugar and the amount and type of fat. Rats consuming SFA and Sugar were impaired on hippocampal-dependent place recognition memory compared to Controls and PUFA rats, despite all rats consuming similar amounts of energy. All rats performed comparably on the object recognition task. Hippocampal and hypothalamic inflammatory markers were not substantially affected by the diets and there was no change in the neuroplasticity marker, brain-derived neurotrophic factor. Each of the diets significantly altered the microbial composition in distinct ways. Specifically, the relative abundance of 89 taxa differed significantly between groups with the majority of these changes accounted for by the Clostridiales order and within that, Lachnospiraceae and Ruminococcaceae. These taxa showed a range of macronutrient specific correlations with place memory. In addition, Distance based Linear Models found relationships between memory, inflammation-related hippocampal genes and the gut microbiota. In conclusion, our study shows that the macronutrient profile of the diet is crucial for diet-induced memory deficits and suggests a possible link between diet, the gut microbiota and hippocampal inflammatory genes.

A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers.

Stress exposure during early development is known to produce long-term mental health deficits. Stress promotes poor lifestyle choices such as poor diet. Early life adversity and diets high in fat and sugar (HFHS) are known to affect anxiety and memory. However additive effects of HFHS and stress during early development are less explored. Here, we examined whether early life stress (ELS) simulated by limited nesting (LN) induces anxiety-like behaviour and cognitive deficits that are modulated by HFHS diet. We examined key hippocampal markers involved in anxiety and cognition, testing the hypothesis that post-weaning HFHS following ELS would ameliorate anxiety-like behaviour but worsen memory and associated hippocampal changes. Sprague-Dawley rats were exposed to LN, postnatal days 2-9, and at weaning, male siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, LN-HFHS, n=11-15/group). Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM) at 10 weeks and spatial and object recognition tested at 11 weeks of age. Rats were culled at 13 weeks. Hippocampal mRNA expression was measured using TaqMan(®) Array Micro Fluidic cards (Life Technologies). As expected HFHS diet increased body weight; LN and control rats had similar weights at 13 weeks, energy intake was also similar across groups. LN-Chow rats showed increased anxiety-like behaviour relative to control rats, but this was reversed by HFHS diet. Spatial and object recognition memory were unaltered by LN exposure or consumption of HFHS diet. Hippocampal glucocorticoid receptor (GR) protein was not affected by LN exposure in chow rats, but was increased by 45% in HFHS rats relative to controls. Hippocampal genes involved in plasticity and mood regulation, GSKα and GSKß were affected, with reductions in GSKß under both diet conditions, and reduced GSKα only in LN-HFHS versus Con-HFHS. Interestingly, HFHS diet and LN exposure independently reduced expression of Akt3 mRNA, a key gene involved post-natal brain development. In summary, while an energy rich diet ameliorated anxiety-like behaviour induced by LN exposure, it significantly altered key genes that are essential for hippocampal development.

Early Life Stress Induced by Limited Nesting Material Produces Metabolic Resilience in Response to a High-Fat and High-Sugar Diet in Male Rats.

Environmental conditions experienced in early life can profoundly influence long-term metabolic health, but the additive impact of poor nutrition is poorly understood. Here, we tested the hypothesis that early life stress (ELS) induced by limited nesting material (LN) combined with high-fat and high-sugar diet (HFHS) post-weaning would worsen diet-related metabolic risk. Sprague-Dawley male rats were exposed to LN, postnatal days 2-9, and at weaning (3 weeks), siblings were given unlimited access to chow or HFHS resulting in (Con-Chow, Con-HFHS, LN-Chow, and LN-HFHS, n = 11-15/group). Glucose and insulin tolerance were tested and rats were killed at 13 weeks. LN rats weighed less at weaning but were not different to control at 13 weeks; HFHS diet led to similar increases in body weight. LN-chow rats had improved glucose and insulin tolerance relative to Con-Chow, whereas LN-HFHS improved insulin sensitivity versus Con-HFHS, associated with increased peroxisome proliferator-activated receptor gamma co-activator-1-alpha (Pgc-1α) mRNA in muscle. No effect of LN on plasma or liver triglycerides was observed, and hepatic gluconeogenic regulatory genes were unaltered. In summary, this study demonstrates that ELS induced by LN conferred some metabolic protection against insulin and/or glucose intolerance in a diet-dependent manner during adulthood.

The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11ßHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11ßHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.