The effect of poor glycemic control on cognitive function in children and adolescents with type 1 diabetes mellitus: A single-center cross-sectional study (2019-2020).

OBJECTIVES: To investigate the effect of chronic hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA) on the cognitive function of children and adolescents with type 1 diabetes mellitus (T1DM), and explore whether early disease onset correlated with cognitive impairment. METHODS: Children and adolescents with T1DM who attended the Pediatric Diabetes Clinic between January 2019 and 2020, aged between 5-14 years, with a mean of 3 glycated hemoglobin (HbA1c) readings ≥7% (53 mmol/mol) during the study period reflecting a hyperglycemic status and who agreed to participate were interviewed about their history of hypoglycemia and DKA. Participants were personally interviewed by a clinical psychologist to assess their cognitive function using a validated Arabic version of the Stanford-Binet test. RESULTS: Higher mean HbA1c levels were associated with cognitive dysfunction in three verbal domains: fluid reasoning, quantitative reasoning, and working memory. Frequent hypoglycemia negatively affected verbal knowledge. In contrast, significant hypoglycemia affected both verbal and nonverbal domains of cognition, specifically verbal and nonverbal fluid reasoning, knowledge, and working memory. Children with recurrent DKA performed below average in nonverbal fluid reasoning tasks. Additionally, moderate or severe DKA, regardless of its frequency, affected children's overall intelligence quotient. CONCLUSION: Regardless of disease onset, exposure to glycemic variability subjects children and adolescents to subtle and measurable cognitive dysfunction resulting in significant morbidity.

Behavioral changes and hyperglycemia in NODEF mice following bisphenol S exposure are affected by diets.

Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 µg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 µg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L-cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 µg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.

The Relationship of Functional Status of Cortisol, Testosterone, and Parameters of Metabolic Syndrome in Male Schizophrenics.

BACKGROUND: The cross-sectional study is aimed at investigating the relationship between cortisol, testosterone, and metabolic characteristics among male schizophrenics. METHODS: 174 patients were grouped based on their risk of metabolic syndrome (MetS) into the non-MetS, high-risk-MetS (HR-MetS), or MetS groups. Metabolic indices (body mass index (BMI), mean arterial pressure (MAP), cholesterol, triglyceride, and fasting blood glucose (FBG)) were associated with cortisol and testosterone levels using correlation analysis. Multiple linear regression analysis was used to associate the correlations between the WHO Quality of Life-BREF (WHOQOL-BREF) score and the five metabolic indices. RESULTS: The WHOQOL-BREF score for the non-MetS group significantly differed from the scores of the HR-MetS and MetS groups. The triglyceride level was positively correlated with the cortisol level, while all five metabolic indices were negatively correlated with testosterone level. Stepwise regression analysis produced a model predicting WHOQOL-BREF scores with four variables including MAP, intelligence quotient (IQ), FBG, and age. The correlation analysis then showed that there was a weak linear correlation between the testosterone level and all five metabolic indices. CONCLUSIONS: Among the five metabolic indices, the risks of hypertension and hyperglycemia are correlated with the quality of life in male schizophrenics rather than those of obesity or hyperlipidemia.

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.

OBJECTIVE: This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. RESEARCH DESIGN AND METHODS: We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. RESULTS: Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (ß = -0.12, P < 0.001), item-color recall (ß = -0.08, P = 0.010), and forward digit span (ß = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (ß = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (ß = -0.10 and ß = -0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (ß = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. CONCLUSIONS: A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

Effect of Flash Glucose Monitoring on Glycemic Control, Hypoglycemia, Diabetes-Related Distress, and Resource Utilization in the Association of British Clinical Diabetologists (ABCD) Nationwide Audit.

OBJECTIVE: The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions. RESEARCH DESIGN AND METHODS: Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The t and Mann-Whitney U tests were used to compare the baseline and follow-up HbA1c and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA1c following the use of FSL. Within-person variations of HbA1c were calculated using [Formula: see text]. RESULTS: Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m2 (mean [±SD]). FSL users demonstrated a -5.2 mmol/mol change in HbA1c, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4-7.8) months of follow-up (n = 3,182) (P < 0.0001). HbA1c reduction was greater in those with initial HbA1c ≥69.5 mmol/mol (>8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (P < 0.0001). The baseline Gold score (score for hypoglycemic unawareness) was 2.7 (±1.8) and reduced to 2.4 (±1.7) (P < 0.0001) at follow-up. A total of 53% of those with a Gold score of ≥4 at baseline had a score <4 at follow-up. FSL use was also associated with a reduction in diabetes distress (P < 0.0001). FSL use was associated with a significant reduction in paramedic callouts and hospital admissions due to hypoglycemia and hyperglycemia/diabetic ketoacidosis. CONCLUSIONS: We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.

Acclimation Prior to an Intraperitoneal Insulin Tolerance Test to Mitigate Stress-Induced Hyperglycemia in Conscious Mice.

The insulin tolerance test is commonly used in metabolic studies to assess whole body insulin sensitivity in rodents. It is a relatively simple test that involves measurement of blood glucose levels over time following a single intraperitoneal injection of insulin. Given that it is performed in the conscious state and blood is often collected via a tail snip, it has the potential to elicit a stress response from animals due to anxiety associated with handling and blood collection. As such, a stress-induced rise in blood glucose can occur, making it difficult to detect and interpret the primary endpoint measure, namely an insulin-mediated reduction in blood glucose. This has been seen in many mouse strains, and is quite common in diabetic db/db mice, where glucose levels can increase, rather than decrease, after insulin administration. Here, we describe a method of acclimating mice to handling, injections and blood sampling prior to performing the insulin tolerance test. We find that this lowers stress-induced hyperglycemia and results in data that more accurately reflects whole body insulin sensitivity.

Acute Hyperglycemia and Spatial Working Memory in Adolescents With Type 1 Diabetes.

OBJECTIVE: To investigate the effect of acute hyperglycemia on brain function in adolescents with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Twenty participants with T1D (aged 14.64 ± 1.78 years) and 20 age-matched healthy control subjects (aged 14.40 ± 2.82 years) performed two functional MRI sessions. Participants with T1D performed the first scanning session under euglycemic and the second under hyperglycemic clamp (20 mmol/L [360 mg/dL]). RESULTS: Lower spatial working memory (sWM) capacity during acute hyperglycemia and significant differences in activation of regions of interest during different stages of the sWM task (P = 0.014) were observed. CONCLUSIONS: Acute hyperglycemia negatively affected sWM capacity in adolescents with T1D, which is relevant for daily functioning and academic performance.

Automated Insulin Delivery in Adults.

Hybrid closed-loop (artificial pancreas) systems have recently been introduced into clinical practice for adults with type 1 diabetes. This reflects successful translation from research studies in highly supervised settings to evaluation of the technology in free-living home settings. We review the different closed-loop approaches and the key clinical evidence supporting adoption of hybrid closed-loop systems for adults with type 1 diabetes. We also discuss the growing evidence for automated insulin delivery in pregnant women and in hospitalized patients with hyperglycemia. We consider the psychosocial impact of closed-loop systems and the challenges and potential future advancements for automated insulin delivery.

Quality of Life, Social Support, Acceptance of Illness, and Self-Efficacy among Pregnant Women with Hyperglycemia.

Carbohydrate metabolism disorders resulting in hyperglycemia are among the most common metabolic complications of pregnancy. According to 2017 data from the International Diabetes Federation (IDF), 16.2% of pregnancies are complicated with hyperglycemia, of which gestational diabetes mellitus (GDM) accounts for 86.4% of cases. Carbohydrate metabolism disorders developing during pregnancy require the patient to change her lifestyle or, in some cases, to undergo pharmaceutical treatment, which may affect various aspects of the patient's life, including her perceived quality of life (QoL). The purpose of the present study was to evaluate levels of QoL, social support, acceptance of illness, and self-efficacy among pregnant patients with hyperglycemia. The study was performed between July 2016 and September 2017 in a group of hyperglycemic pregnant women. The following instruments were used: the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Berlin Social Support Scales (BSSS), the Acceptance of Illness Scale (AIS), the Generalized Self-Efficacy Scale (GSES) and a standardized interview questionnaire. Participants rated their overall QoL (3.64 points) higher than their overall perceived health (3.43). In terms of social support, the highest scores were obtained in terms of actually received support (3.53) and perceived available instrumental support (3.52), while the lowest in terms of support seeking (2.99) and the need for support (2.95). The mean acceptance of illness score among the hyperglycemic pregnant women that were studied was 31.37, and the mean generalized self-efficacy score was 31.58. Participants' reported QoL in the various WHOQOL-BREF domains was associated with specific social support scales, acceptance of illness, and generalized self-efficacy.

Evaluation of illness perceptions and their associations with glycaemic control, medication adherence and chronic kidney disease in type 2 diabetes mellitus patients in Malaysia.

BACKGROUND: Illness perceptions (IP) involve coping strategies and behavioural responses that can influence glycaemic control. Despite the importance of good glycaemic control, the majority of patients in Asia are not achieving glycaemic targets. An evaluation of IP in association with glycaemic control, medication adherence and chronic kidney disease (CKD) in Type 2 diabetes mellitus patients (T2DM) was carried out in an outpatient setting in Malaysia METHOD: A cross-sectional study was conducted using the Revised Illness Perception Questionnaire in a purposive sample of 384 T2DM patients. RESULTS: There were 55.7% females, median age was 58.2 years and median duration of diabetes was 13 years. The majority (79.4%) of patients had poor diabetes control (HbA1c ≥ 7.0%) and 39.6% of patients had low medication adherence. Patients with good glycaemic control had a higher Timeline Acute/Chronic and Emotional Representations score, hence they held the correct belief that diabetes is chronic and experienced negative emotions. Highly adherent patients had a higher Illness Coherence (χ2 = 21.385, p < 0.001) score but a lower Consequences (χ2 = 17.592, p < 0.001) and Emotional Representations (χ2 = 16.849, p < 0.001) score indicating good understanding and less negative perceptions of disease burden. Patients in a more advanced stage of CKD had a significantly higher Timeline Cyclical score (χ2 = 18.718, p = 0.001), believing that diabetes was unpredictable. CONCLUSION: Dimensions of IP have been shown to be significantly associated with the assessed variables, therefore intervention studies with education, support and counselling should be conducted in Asia with the ultimate aim of empowering patients through IP-targeted management.

Cognitions Associated With Hypoglycemia Awareness Status and Severe Hypoglycemia Experience in Adults With Type 1 Diabetes.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and recurrent severe hypoglycemia (RSH) remain problematic for people with type 1 diabetes (T1D), despite major therapeutic advances. We explored beliefs around hypo- and hyperglycemia in adults with T1D with, and without, IAH and RSH. RESEARCH DESIGN AND METHODS: A cross-sectional U.S. multicenter survey included Attitudes to Awareness of Hypoglycemia (A2A; a 19-item questionnaire concerning beliefs about hypoglycemia), the Gold score (single item: awareness of hypoglycemia), and a question about severe hypoglycemia over the preceding year. The survey was emailed to 6,200 adult participants of the annual T1D Exchange clinic registry data collection. A2A data were subjected to principal component analysis with varimax rotation. RESULTS: Among 1,978 respondents (response rate 32%), 61.7% were women, mean ± SD age was 39.6 ± 16.3 years, and T1D duration was 23.1 ± 13.8 years. Thirty-seven percent reported IAH, 16% RSH, and 9% both. A2A items segregated into three factors, differently distributed by hypoglycemia experience. Respondents with IAH or RSH expressed appropriate concern about hypoglycemia, but those with IAH were more likely to prioritize hyperglycemia concerns than those with intact awareness (P = 0.002). Those with RSH showed greater normalization of asymptomatic hypoglycemia than those without (P = 0.019) and trended toward prioritizing hyperglycemia concerns (P = 0.097), driven by those with both IAH and RSH. CONCLUSIONS: Adults with T1D with IAH and RSH report specific cognitions about hypoglycemia and hyperglycemia, which may act as barriers to hypoglycemia avoidance and recovery of awareness. These may be modifiable and present a target for enhancing engagement of vulnerable people with strategies to avoid future hypoglycemia.

Benefits and Barriers of Continuous Glucose Monitoring in Young Children with Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) has potential to address challenges of type 1 diabetes (T1D) management for young children. CGM use is increasing, yet remains underutilized. Characterizing parents' experiences with CGM can inform clinical strategies to help parents make decisions about diabetes management, overcome obstacles to initiating and sustaining CGM use, and maximize benefits of CGM use in their children's diabetes care. Methods: Transcripts from semistructured qualitative interviews with 55 parents of children aged 1 to <8 years, with T1D duration ≥6 months, and whose child currently or previously used CGM were coded and analyzed to derive themes about their experiences with CGM. Results: Participants were 88% mothers and the mean child age was 5.0 ± 1.5 years. Parents described benefits of CGM use: decreased worry about glucose excursions, improved sleep, increased sense of safety with children who cannot recognize or express symptoms of hypo- or hyperglycemia, and greater comfort with other caregivers, especially using remote monitoring functionality when away from children. Challenges included painful insertions, wearing multiple devices on small bodies, disruptive alerts, data gaps due to lost signals, skin/adhesive problems, and difficulty interpreting the amount of information generated by CGM. For some, the challenges outweighed potential benefits and they stopped CGM use. Conclusions: CGM may address unique challenges of T1D in young children and increase parental comfort with diabetes management, yet there are multiple barriers to initiating or maintaining CGM use. Education and behavioral support to address these benefits and barriers may equip caregivers with skills to address challenges of CGM use.

Predictors of Health-Protective Behavior and Glycemia After Gestational Diabetes, NHANES 2007-2014.

PURPOSE: This study examined weight loss behavior and the prevalence of hyperglycemia unawareness (unknown high blood glucose) after gestational diabetes mellitus (GDM), within a nationally, representative sample. This study also examined social-demographic, psychosocial, provider communication, and health care access/utilization factors as predictors of A1C and health-protective behavior after GDM. METHODS: A secondary analysis of 2007-2014 National Health and Nutrition Examination Surveys (NHANES) data was conducted, including 205 women, aged 20 to 44 years, with a history of GDM, whose last live birth was in the past 10 years, excluding pregnant women and those with diabetes. Weighted bivariate, stepwise linear, and binary logistic regression analyses were conducted to examine correlates of A1C, weight change, weight loss attempt and behavior, diabetes screening, and physical activity. RESULTS: Hyperglycemia unawareness was associated with increased A1C and weight gain in the past year. Personal weight loss goal and perception of overweight increased the odds of weight loss attempt. Depressive symptoms were associated with weight gain over the past year. A third of the sample failed to have their glucose tested in the past 3 years. Two-thirds were never told about their personal risk for diabetes, but provider communication increased the odds of meeting weekly activity recommendations and glucose screening. Hispanic women and non-Hispanic black women were less likely to have had glucose screening than non-Hispanic white women. CONCLUSION: Diabetes educators should address gaps in provider communication, while supporting psychosocial needs and reducing disparities to encourage health-protective behavior after GDM. The American Association of Diabetes Educators, 7 Self-Care Behaviors (AADE-7TM) provides an excellent framework for interventions to support health-protective behavior after GDM.

Hemoglobin A1c and 10-year information processing speed in Japanese community dwellers.

BACKGROUND: Hyperglycemia is believed to be a risk factor for cognitive decline, but the longitudinal relationship between hyperglycemia and cognitive decline in the Japanese population is unclear. The present study aimed to clarify the association between blood glucose levels and information processing ability in middle-aged and older adults. METHODS: The subjects were 866 men and 815 women aged 40-79 years not taking medication for diabetes who participated in the first study wave (1997-2000) and then participated at least once in the subsequent six study waves (2000-2012) of the National Institute for Longevity Sciences-Longitudinal Study of Aging, Japan. Hemoglobin A1c (HbA1c) levels were categorized into four groups (< 5.6, 5.6 to < 6.0, 6.0 to < 6.5, ≥ 6.5%), and a mixed-effects model was used to evaluate the effects of the HbA1c level (four groups) on repeated measures of information processing speed. The models also included baseline age, body mass index, ethanol intake, smoking status, educational level, family income, and history of stroke, hypertension, heart disease, and dyslipidemia as covariates. RESULTS: Mean (standard deviation) HbA1c and follow-up time in participants were 5.2 (0.5) % and 10.0 (3.6) years, respectively. A linear mixed model showed that the main effect of the four HbA1c groups on information processing ability was not significant in either men or women, but the interaction of HbA1c and time with information processing speed in the higher HbA1c level groups (≥ 6.5% group in men, 6.0 to < 6.5% and ≥ 6.5% groups in women) was significant compared to the lower HbA1c level (< 5.6%) group (P < 0.05). When the slope of information processing speed by HbA1c level at baseline was examined, the slope of information processing speed in the higher HbA1c level (≥ 6.5%) group was higher than in the lower HbA1c level (< 5.6%) group, both in men (- 0.31/year) and in women (- 0.30/year), as well as in women with an HbA1c level of 6.0 to < 6.5% (- 0.40/year). CONCLUSIONS: Higher baseline HbA1c was associated with greater subsequent decline in information processing ability in Japanese community dwellers, even with the pre-clinical HbA1c level (6.0 to < 6.5%) in women. The results suggest that good glycemic control or prevention of hyperglycemia may contribute to maintaining information processing ability.

Acute effects of hyperglycemia on the peripheral nervous system in zebrafish ( Danio rerio) following nitroreductase-mediated ß-cell ablation.

Diabetic peripheral neuropathy (DPN) is estimated to affect 50% of diabetic patients. Although DPN is highly prevalent, molecular mechanisms remain unknown and treatment is limited to pain relief and glycemic control. We provide a novel model of acute DPN in zebrafish ( Danio rerio) larvae. Beginning 5 days postfertilization (dpf), zebrafish expressing nitroreductase in their pancreatic ß-cells were treated with metronidazole (MTZ) for 48 h and checked for ß-cell ablation 7 dpf. In experimental design, this was meant to serve as proof of concept that ß-cell ablation and hyperglycemia are possible at this time point, but we were surprised to find changes in both sensory and motor nerve components. Compared with controls, neurod+ sensory neurons were often observed outside the dorsal root ganglia in MTZ-treated fish. Fewer motor nerves were properly ensheathed by nkx2.2a+ perineurial cells, and tight junctions were disrupted along the motor nerve in MTZ-treated fish compared with controls. Not surprisingly, the motor axons of the MTZ-treated group were defasciculated compared with the control group, myelination was attenuated, and there was a subtle difference in Schwann cell number between the MTZ-treated and control group. All structural changes occurred in the absence of behavioral changes in the larvae at this time point, suggesting that peripheral nerves are influenced by acute hyperglycemia before becoming symptomatic. Moving forward, this novel animal model of DPN will allow us to access the molecular mechanisms associated with the acute changes in the hyperglycemic peripheral nervous system, which may help direct therapeutic approaches.

Diabetes Distress, Intentional Hyperglycemia at Work, and Glycemic Control Among Workers With Type 1 Diabetes.

OBJECTIVE: The aim was to explore relationships between work-related factors, work-related diabetes distress (WRDD), diabetes distress (measured by Problem Areas in Diabetes [PAID]-5 scale), intentional hyperglycemia at work (IHW), and glycemic control. RESEARCH DESIGN AND METHODS: A cross-sectional survey was conducted with 1,030 working adults with type 1 diabetes and linked with electronic health record data from a specialist diabetes clinic in Denmark. With use of structural equation modeling, two alternative models were compared, based on fit indices, statistical significance, and theoretical meaningfulness. RESULTS: A combined model provided the best fit to the data. WRDD was more strongly affected by work ability, opportunity to self-manage at work, being treated differently, and job demands. PAID-5 was more strongly affected by identity concern and blame and judgment. Both PAID-5 and WRDD were associated with more frequent IHW, which was associated in turn with worse glycemic control. CONCLUSIONS: Work-related factors are associated with WRDD and PAID-5. Distress increases the frequency of IHW, which is, in turn, associated with worse glycemic control. Future studies should investigate ways to balance diabetes management and work life without compromising diabetes care.

Community groups or mobile phone messaging to prevent and control type 2 diabetes and intermediate hyperglycaemia in Bangladesh (DMagic): a cluster-randomised controlled trial.

BACKGROUND: Strategies are needed to prevent and control type 2 diabetes and intermediate hyperglycaemia, which together affect roughly a third of adults in Bangladesh. We aimed to assess the effects of mHealth and community mobilisation on the prevalence of intermediate hyperglycaemia and diabetes among the general adult population in rural Bangladesh, and to assess the effect of these interventions on the incidence of type 2 diabetes among people with intermediate hyperglycaemia within the study population. METHODS: DMagic was a three-arm, cluster-randomised trial of participatory community mobilisation, mHealth mobile phone messaging, and usual care (control) in 96 villages (population roughly 125 000) in Bangladesh. Community mobilisation involved 18 monthly group meetings, led by lay facilitators, applying a participatory learning and action (PLA) cycle focused on diabetes prevention and control. mHealth involved twice-weekly voice messages over 14 months promoting behaviour change to reduce diabetes risk. The primary outcomes were the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the overall population at the end of the intervention implementation period, and 2-year cumulative incidence of type 2 diabetes in a cohort with intermediate hyperglycaemia at baseline. Primary outcomes were assessed through fasting blood glucose concentrations and 2-h oral glucose tolerance tests among a cross-section of adults aged 30 years and older and a cohort of individuals identified with intermediate hyperglycaemia. Prevalence findings are based on a cross-sectional survey at the end of the study; incidence findings are based on 2-year follow-up survey of a cohort of individuals identified with intermediate hyperglycaemia through a cross-sectional survey at baseline. We also assessed the cost-effectiveness of the interventions. This trial is registered with the ISRCTN registry, number ISRCTN41083256, and is completed. FINDINGS: The study took place between June 27, 2015, and June 28, 2018, with the PLA intervention running in 32 villages from June, 2016, to December, 2017, and the mHealth intervention running in 32 villages from Oct 21, 2016, to Dec 24, 2017. End-of study prevalence was assessed in 11 454 individuals and incidence in 2100 individuals. There was a large reduction in the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the PLA group compared with the control group at the end of the study (adjusted [for stratification, clustering, and wealth] odds ratio [aOR] 0·36 [0·27-0·48]), with an absolute reduction of 20·7% (95% CI 14·6-26·7). Among 2470 adults with intermediate hyperglycaemia at baseline, 2100 (85%) were followed-up at 2 years. The 2-year cumulative incidence of diabetes in this cohort was significantly lower in the PLA group compared with control (aOR 0·39, 0·24-0·65), representing an absolute incidence reduction of 8·7% (3·5-14·0). There was no evidence of effect of mHealth on combined prevalence of intermediate hyperglycaemia and diabetes (aOR 0·93, 0·74-1·16) or the incidence of diabetes (1·02, 0·73-1·43). The incremental cost-effectiveness ratios for PLA were INT$316 per case of intermediate hyperglycaemia or type 2 diabetes prevented and $6518 per case of type 2 diabetes prevented among individuals with intermediate hyperglycaemia. INTERPRETATION: Our data provide strong evidence to support the use of community mobilisation based on PLA to prevent type 2 diabetes in this rural Bangladeshi population. Despite raising knowledge and awareness of diabetes, the mHealth intervention did not change disease outcomes in our population. Replication studies in other populations should be a priority. FUNDING: UK Medical Research Council.

Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory.

Stringent glucose demands render the brain susceptible to disturbances in the supply of this main source of energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments may arise from disturbed glucose regulation remains unclear. Here we show that chronic social defeat (CSD) stress in adult male mice induces hyperglycemia and directly affects spatial memory performance. Stressed mice developed hyperglycemia and impaired glucose metabolism peripherally as well as in the brain (demonstrated by PET and induced metabolic bioluminescence imaging), which was accompanied by hippocampus-related spatial memory impairments. Importantly, the cognitive and metabolic phenotype pertained to a subset of stressed mice and could be linked to early hyperglycemia 2 days post-CSD. Based on this criterion, ∼40% of the stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance of this biomarker emerges from the effects of the glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because upon dietary treatment, mice identified as having high glucose demonstrated restored spatial memory and normalized glucose metabolism. Conversely, reducing glucose levels by empagliflozin in mice that did not display stress-induced hyperglycemia (resilient mice) impaired their default-intact spatial memory performance. We conclude that hyperglycemia developing early after chronic stress threatens long-term glucose homeostasis and causes spatial memory dysfunction. Our findings may explain the comorbidity between stress-related and metabolic disorders, such as depression and diabetes, and suggest that cognitive impairments in both types of disorders could originate from excessive cerebral glucose accumulation.

Prevalence and predictors of depression and anxiety in adult patients with type 1 diabetes in tertiary care setting.

AIMS: To determine gender and age differences in the prevalence of depression and anxiety and their predictive factors in adult patients with type 1 diabetes (DM1). METHODS: Random sample of DM1 adult patients from a tertiary care hospital cohort. To evaluate the presence of depression and anxiety, psychological evaluation was performed using structured clinical interview (MINI). For the specific evaluation of fear of hypoglycemia (FH), FH-15 questionnaire was used. RESULTS: 339 patients [51.6% male; 38.5 ± 12.9 years; HbA1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.1 ± 12.0 years of DM1] met the inclusion criteria. Prevalence of depression, anxiety, and FH in men vs. women was as follows (%): depression: 15.4 vs. 33.5 (p < 0.05); anxiety: 13.7 vs. 26.2 (p < 0.05); and FH: 42.8 vs. 46.0 (p = NS). Among midlife female patients, prevalence of depression and anxiety was higher compared to male. Moreover, comorbid depressive and anxious symptoms were also higher in midlife female patients compared to age-matched male patients (3.5 vs. 14%, p < 0.05). Apart from age-related vulnerability, female gender, poor glycemic control, and microvascular and macrovascular complications were predictive factors for depressive and anxious symptomatology. Unawareness hypoglycemia and anxiety-prone personality were predictor factors for FH. CONCLUSIONS: In adults with DM1, prevalence of depression and anxiety is higher in women. Midlife patients, in particular women, show a significantly higher prevalence of anxiety symptoms and comorbid depression and anxiety. The presence of secondary complications and sustained poor glycemic control should alert to the possibility of these mental disorders, especially in the most vulnerable age population; clinical, gender and age-related patterns could help to design more effective psychological assessment and support in adult patients with DM1.

Intermittent streptozotocin administration induces behavioral and pathological features relevant to Alzheimer's disease and vascular dementia.

RATIONALE: Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, on vascular and inflammatory changes within the brain. OBJECTIVE AND METHODS: The present study was designed to evaluate the effect of staggered, low-dose administration of STZ on behavioral and cognitive deficits, neuroinflammation, tau pathology, and histopathological alterations related to dementia. RESULTS: Staggered administration (Days 1, 2, 3, 14, 15) of streptozotocin (40 mg/kg/mL) induced a diabetic-like state in mice, resulting in sustained hyperglycemia. STZ-treated animals displayed memory deficits in the novel object recognition task as well as increased tau phosphorylation and increased neuroinflammation. Additionally, STZ led to altered insulin signaling, exhibited by decreased plasma insulin and decreased levels of insulin degrading enzyme and pAKT within the hippocampus. CONCLUSIONS: STZ-treated animals exhibit cognitive deficits and histopathological changes seen in dementia. This model of dementia warrants continued investigation to better understand the role that DM plays in dementia-related alterations.