From liver to hormones: The endocrine consequences of cirrhosis.

Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.

Relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes using continuous glucose monitoring systems.

AIMS: To evaluate relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring (CGM) glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes (T1D) who use CGM. METHODS: A cross-sectional survey and data collections were completed with 196 T1D adults who used CGM (59% also used automated insulin delivery devices (AIDs)). We assessed hypoglycemia awareness (Gold instrument), hypoglycemia beliefs (Attitudes to Awareness of Hypoglycemia instrument), CGM glycemic profiles, demographics, and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Analysis included simple and multiple linear regression analyses. RESULTS: Lower hypoglycemia awareness, weaker "hypoglycemia concerns minimized" beliefs, stronger "hyperglycemia avoidance prioritized" beliefs were independently associated with higher anxiety symptoms (P < 0.05), with similar trends in both subgroups using and not using AIDs. Lower hypoglycemia awareness were independently associated with greater depression symptoms (P < 0.05). In participants not using AIDs, more time in hypoglycemia was related to less anxiety and depression symptoms (P < 0.05). Being female and younger were independently associated with higher anxiety symptoms, while being younger was also independently associated with greater depression symptoms (P < 0.05). CONCLUSION: Our findings revealed relationships of impaired hypoglycemia awareness, hypoglycemia beliefs, CGM-detected hypoglycemia with anxiety and depression symptoms in T1D adults who use CGMs.

Binge eating symptomatology in adolescents with polycystic ovary syndrome.

Several factors may contribute to binge eating behaviors in PCOS. However, findings are contradictory and studies in the adolescence are limited. We aimed to evaluate the eating attitudes of adolescents with PCOS and the possible etiological factors underlying the association between PCOS and binge eating symptomology. Between 2019 and 2022, 46 newly diagnosed adolescents with PCOS and 56 controls matched for age and BMI z-score were included. The Eating Disorder Examination Questionnaire, Three Factor Eating Questionnaire-R18, and a questionnaire assessing postprandial reactive hypoglycemia symptom severity were given. Binge eating symptomology, in terms of over, uncontrolled, and emotional eating, were more prevalent in the PCOS group. Uncontrolled, emotional, and binge eating were positively correlated with postprandial reactive hypoglycemia symptom score. Overeating was also associated with clinical hyperandrogenism. Improving the disease outcome and reducing the future complications requires early recognition and management of emotional and uncontrolled eating behaviors in adolescents with PCOS.

Continuous moderate and intermittent high-intensity exercise in youth with type 1 diabetes: Which protection for dysglycemia?

AIM: From an early age, exercise is key to managing type 1 diabetes (T1D). However, hypoglycemia around aerobic exercise is a major barrier to physical activity in children. We explore whether intermittent high-intensity aerobic exercise (IHE), designed to mimic spontaneous childhood physical activity patterns, offers better protection against glycemic drop than continuous moderate-intensity exercise (CME). METHODS: Five boys and 7 girls with T1D (9.8 ± 1.4y) performed ergo cycle-based randomized CME and IHE of identical duration and total mechanical load [50 %PWC170vs. 15sec(150 %PWC170)/30 sec passive recovery; both during two 10-min sets, 5 min in-between]. Capillary glycemia during exercise and interstitial glucose during recovery were compared between exercises and an inactive condition, controlling for baseline glycemia, carbohydrate and insulin. RESULTS: The exercise-induced decrease in capillary glycemia was attenuated by 1.47 mmol·L-1 for IHE vs. CME (P < 0.05). No symptomatic hypoglycemic episodes occurred during exercises. Post-exercise time in hypoglycemia did not differ between conditions. During early recovery, CME reduced time spent > 16.7 mmol·L-1 compared with inactive days (P < 0.05; CME: 0 %; IHE: 16,7 %; INACTIVE: 41,7 %). CONCLUSION: IHE appeared to limit the glycemic drop compared to CME. Performing 20-min CME or IHE was not associated with increased hypoglycemic risk compared to being inactive. CME appeared even transiently protective against serious hyperglycemia.

Effects of ADHD and ADHD treatment on glycemic management in type 1 diabetes: A systematic review and meta-analysis of observational studies.

AIMS: Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how ADHD impacts glycemia and diabetes-related complications. This systematic review and meta-analysis aimed to investigate the effect of ADHD and ADHD medications on HbA1c and acute complications in T1D. METHODS: A literature search was conducted in PubMed, EMBASE, CINAHL, Scopus, PsycINFO, CENTRAL, and Web of Science collections up to November 22, 2023. Seventeen studies were selected for the systematic review by independent reviewers, with twelve included in the meta-analysis. RESULTS: Mean HbA1c levels were significantly higher in T1D individuals with ADHD compared to those without ADHD (MD = 0.60; 95 % CI: 0.41, 0.79; I2 = 90.1 %; p-value < 0.001). The rates of suboptimal HbA1c levels, hospitalization, diabetic ketoacidosis, and hypoglycemia were all substantially higher in T1D individuals with ADHD than those without ADHD. No difference was found in mean HbA1c between those who received ADHD treatment and those who did not (mean difference = -0.52; 95 % confidence interval: -1.16, 0.13; I2 = 78.6 %; p-value = 0.12). CONCLUSIONS: ADHD is associated with higher HbA1c and increased acute diabetes-related complications. More research is needed to assess the effects of ADHD treatments on T1D management.

Association of hypoglycemic events with cognitive impairment in patients with type 2 diabetes mellitus: Protocol for a dose-response meta-analysis.

INTRODUCTION: With an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations. METHOD AND ANALYSIS: This work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed. DISCUSSION AND CONCLUSION: Hypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions. TRIAL REGISTRATION: Prospero registration number: CRD42023432352.

Remission of type 2 diabetes: always more questions, but enough answers for action.

The concept of type 2 diabetes remission is evolving rapidly, and gaining wide public and professional interest, following demonstration that with substantial intentional weight loss almost nine in ten people with type 2 diabetes can reduce their HbA1c level below the diagnostic criterion (48 mmol/mol [6.5%]) without glucose-lowering medications, and improve all features of the metabolic syndrome. Pursuing nomoglycaemia with older drugs was dangerous because of the risk of side effects and hypoglycaemia, so the conventional treatment target was an HbA1c concentration of 53 mmol/mol (7%), meaning that diabetes was still present and allowing disease progression. Newer agents may achieve a normal HbA1c safely and, by analogy with treatments that send cancers or inflammatory diseases into remission, this might also be considered remission. However, although modern glucagon-like peptide-1 receptor agonists and related medications are highly effective for weight loss and glycaemic improvement, and generally safe, many people do not want to take drugs indefinitely, and their cost means that they are not available across much of the world. Therefore, there are strong reasons to explore and research dietary approaches for the treatment of type 2 diabetes. All interventions that achieve sustained weight loss of >10-15 kg improve HbA1c, potentially resulting in remission if sufficient beta cell capacity can be preserved or restored, which occurs with loss of the ectopic fat in liver and pancreas that is found with type 2 diabetes. Remission is most likely with type 2 diabetes of short duration, lower HbA1c and a low requirement for glucose-lowering medications. Relapse is likely with weight regain and among those with a poor beta cell reserve. On current evidence, effective weight management should be provided to all people with type 2 diabetes as soon as possible after diagnosis (or even earlier, at the stage of prediabetes, defined in Europe, Australasia, Canada [and most of the world] as ≥42 and <48 mmol/mol [≥6.0 and <6.5%], and in the USA as HbA1c ≥39 and <48 mmol/mol [≥5.7 and <6.5%]). Raising awareness among people with type 2 diabetes and their healthcare providers that remission is possible will enable earlier intervention. Weight loss of >10 kg and remission lasting 1-2 years may also delay vascular complications, although more evidence is needed. The greatest challenge for research is to improve long-term weight loss maintenance, defining cost-effective approaches tailored to the preferences and needs of people living with type 2 diabetes.

The role of basal insulins in the treatment of people with type 2 diabetes and chronic kidney disease: A narrative review.

The majority of cases of chronic kidney disease (CKD) worldwide are driven by the presence of type 2 diabetes (T2D), resulting in an increase in CKD rates over the past few decades. The existence of CKD alongside diabetes is associated with increased burden of cardiovascular disease and increased risk of death. Optimal glycaemic control is essential to prevent progression of CKD, but achieving glycaemic targets in people with CKD and diabetes can be challenging because of increased risk of hypoglycaemia and limitations on glucose-lowering therapeutic options. This review considers the challenges in management of T2D in people with impaired kidney function and assesses evidence for use of basal insulin analogues in people with CKD.

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management.

Factors associated with neonatal hyperinsulinemic hypoglycemia, a case-control study.

OBJECTIVES: We aimed to identify perinatal risk factors associated with hyperinsulinemic hypoglycemia in neonates. Secondary objectives included an examination of clinical and biochemical characteristics at the time of diagnosis and an exploration of the duration of diazoxide therapy. METHODS: A case-control study was conducted, involving individual chart reviews of inborn infants diagnosed with hyperinsulinemic hypoglycemia (the HH group) between 2014 and 2021. These cases were paired with controls (the non-HH group) belonging to the same gestational age (GA) strata who did not exhibit HH or only had transient postnatal hypoglycemia. RESULTS: A total of 52 infants with HH were matched with corresponding controls. The mean GA in the HH group was 34.4 ± 3.1 weeks. Notably, the HH group exhibited lower mean minimum plasma glucose (PG) levels and required higher glucose infusion rates in comparison to the non-HH group (26.5 ± 15.6 vs. 49.1 ± 37.7 mg/dL and 12.9 ± 3.8 vs. 5.7 ± 2.1 mg/kg/min, respectively; p<0.001 for both). After adjusting for potential confounding factors, only two variables, fetal growth restriction (FGR) and neonatal sepsis, demonstrated significant associations with HH (adjusted odds ratio [95 % confidence interval]: 8.1 [2.1-31.0], p=0.002 and 6.3 [1.9-21.4], p=0.003, respectively). The median duration of diazoxide therapy for the HH group was 4 months. CONCLUSIONS: FGR and neonatal sepsis emerged as notable risk factors for HH. These infants exhibited lower PG levels and necessitated higher glucose infusion rates compared to their non-HH counterparts. Importantly, a substantial proportion of the HH group received diazoxide therapy, with a median treatment duration of 4 months.

S100A9 exerts insulin-independent antidiabetic and anti-inflammatory effects.

Type 1 diabetes mellitus (T1DM) is characterized by insulin deficiency leading to hyperglycemia and several metabolic defects. Insulin therapy remains the cornerstone of T1DM management, yet it increases the risk of life-threatening hypoglycemia and the development of major comorbidities. Here, we report an insulin signaling-independent pathway able to improve glycemic control in T1DM rodents. Co-treatment with recombinant S100 calcium-binding protein A9 (S100A9) enabled increased adherence to glycemic targets with half as much insulin and without causing hypoglycemia. Mechanistically, we demonstrate that the hyperglycemia-suppressing action of S100A9 is due to a Toll-like receptor 4-dependent increase in glucose uptake in specific skeletal muscles (i.e., soleus and diaphragm). In addition, we found that T1DM mice have abnormal systemic inflammation, which is resolved by S100A9 therapy alone (or in combination with low insulin), hence uncovering a potent anti-inflammatory action of S100A9 in T1DM. In summary, our findings reveal the S100A9-TLR4 skeletal muscle axis as a promising therapeutic target for improving T1DM treatment.

Acute and Chronic Adverse Outcomes of Type 1 Diabetes.

Type 1 diabetes is associated with both acute and chronic complications. Acute complications include diabetic ketoacidosis and severe hypoglycemia. Chronic complications can be microvascular or macrovascular. Microvascular complications include retinopathy, nephropathy, and neuropathy. The pathophysiology of microvascular complications is complex. Hyperglycemia is a common underlying risk factor, underscoring the importance of optimizing glycemic management. Patients with type 1 diabetes are also at increased risk of macrovascular complications including coronary artery disease and vascular disease. The American Diabetes Association provides screening guidelines for chronic complications of diabetes. Adherence to these guidelines is an important aspect of diabetes care.

Hypoglycemia and Cardiovascular Outcomes in the CARMELINA and CAROLINA Trials of Linagliptin: A Secondary Analysis of Randomized Clinical Trials.

Importance: Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype. Objective: To evaluate the associations between hypoglycemia and CV outcomes. Design, Setting, and Participants: This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023. Intervention: Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial. Main Outcomes and Measures: The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode. Results: In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze. Conclusions and Relevance: This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both. Trial Registration: ClinicalTrials.gov Identifier: NCT01897532 (CARMELINA) and NCT01243424 (CAROLINA).

The Relationship Between Parent Fear of Hypoglycemia and Youth Glycemic Control Across the Recent-Onset Period in Families of Youth with Type 1 Diabetes.

BACKGROUND: This study aims to examine the relationship between parents' fear of hypoglycemia (FH) over a 1-year period and child glucose metrics in 126 families of youth recently diagnosed with type 1 diabetes (T1D). METHODS: Parents completed the Hypoglycemia Fear Survey for Parents (HFS-P) and uploaded 14 days of glucose data at a baseline, 6-month, and 12-month assessment. RESULTS: Parents' HFS-P total and worry scores increased to a clinically meaningful degree from baseline to 6-month assessment, while multilevel models revealed within- and between-person variability in parents' HFS-P worry and behavior scores over time associated with child glycemia. Specifically, a significant negative relationship for within-person worry scores suggested that when parents reported higher than their average worry scores, their children recorded fewer glucose values in the target range, while within-person behavior scores suggested that when parents reported lower than their average behavior scores, their children recorded more values above the target range. There was also a negative relationship for between-person behavior scores with child glycated hemoglobin and a positive relationship for between-person behavior scores with child glucose values in the target range. CONCLUSIONS: In the recent-onset period of T1D, parental FH worry and behavior associated with child glycemia possibly due to changes in parents' perceptions of their child's hypoglycemia risk. The clinically meaningful increases in parent FH in the recent-onset period and the negative association for between-person behavior scores with child glycated hemoglobin suggest that clinics should consider screening parents for FH, especially among parents of children with lower glycemic levels.

Potential risk factors for mild cognitive impairment among patients with type 2 diabetes experiencing hypoglycemia.

AIMS: This study examined the association between hypoglycemia and mild cognitive impairment (MCI) among patients with type 2 diabetes mellitus (T2DM) and identified risk factors for MCI in patients with hypoglycemia. METHODS: In this retrospective study, 328 patients with T2DM were screened in 2019 and followed up in 2022. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). The diagnosis of MCI was based on established criteria. Risk ratio (RR) with 95 % confidence intervals (CI) was calculated to estimate the risk of MCI. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for MCI in those with hypoglycemia. RESULTS: Patients with hypoglycemia had lower cognitive performance 3 years later. The RR of MCI was 2.221 (95 % CI 1.269-3.885). Multivariate logistic analysis showed that low grip strength, existing diabetic retinopathy (DR), and multiple hypoglycemia episodes were associated with higher odds of MCI in patients with hypoglycemia (adjusted odds ratio [OR] 0.909 [95 % CI 0.859-0.963]), 3.078 [95 % CI 1.158-12.358], and 4.642 [95 % CI 1.284-16.776], respectively, all P < 0.05). CONCLUSIONS: Hypoglycemia increased MCI risk among patients with T2DM. Low grip strength, DR, and multiple hypoglycemia episodes may be potential risk factors for hypoglycemia-associated MCI.

Activation of mitophagy improves cognitive dysfunction in diabetic mice with recurrent non-severe hypoglycemia.

Recurrent non-severe hypoglycemia (RH) in patients with diabetes might be associated with cognitive impairment. Previously, we found that mitochondrial dysfunction plays an important role in this pathological process; however, the mechanism remains unclear. The objective of this study was to determine the molecular mechanisms of mitochondrial damage associated with RH in diabetes mellitus (DM). We found that RH is associated with reduced hippocampal mitophagy in diabetic mice, mainly manifested by reduced autophagosome formation and impaired recognition of impaired mitochondria, mediated by the PINK1/Parkin pathway. The same impaired mitophagy initiation was observed in an in vitro high-glucose cultured astrocyte model with recurrent low-glucose interventions. Promoting autophagosome formation and activating PINK1/Parkin-mediated mitophagy protected mitochondrial function and cognitive function in mice. The results showed that impaired mitophagy is involved in the occurrence of mitochondrial dysfunction, mediating the neurological impairment associated with recurrent low glucose under high glucose conditions.

Perioperative Glycemic Management in Cardiac Surgery: A Narrative Review.

Diabetes and hyperglycemic events in cardiac surgical patients are associated with postoperative morbidity and mortality. The causes of dysglycemia, the abnormal fluctuations in blood glucose concentrations, in the perioperative period include surgical stress, surgical techniques, medications administered perioperatively, and patient factors. Both hyperglycemia and hypoglycemia lead to poor outcomes after cardiac surgery. While trying to control blood glucose concentration tightly for better postoperative outcomes, hypoglycemia is the main adverse event. Currently, there is no definite consensus on the optimum perioperative blood glucose concentration to be maintained in cardiac surgical patients. This review provides an overview of perioperative glucose homeostasis, the pathophysiology of dysglycemia, factors that affect glycemic control in cardiac surgery, and current practices for glycemic control in cardiac surgery.

Hyperglycaemia aversion in type 1 diabetes: A grounded theory study.

OBJECTIVE: Very little is known about the circumstances under which hyperglycaemia aversion develops and is maintained. The present study aimed to identify psychological factors involved in the process of hyperglycaemia aversion and to understand how it affects people's self-management of type 1 diabetes. DESIGN: Qualitative, in-depth interviews were used. METHODS: A constructivist grounded theory study, using semi-structured participant interviews, was undertaken to build a theoretical model of the process of hyperglycaemia aversion. RESULTS: Eighteen participants were interviewed. Fifteen were considered hyperglycaemia averse and included in the analysis. A theoretical model was developed to describe and explain processes involved in hyperglycaemia aversion. Many participants held very high standards for themselves and often had a strong preference for control. While some participants described anxiety associated with higher blood glucose, the most proximal driver of their approach was self-criticism and frustration associated with not meeting their own high standards for blood glucose. A number of attentional processes and beliefs, mostly related to hypoglycaemia, maintained and reinforced their blood glucose preference. Diabetes technology served as an enabler, raiser of standards, and additional critical judge of participants' hyperglycaemia aversion. CONCLUSIONS: The trans-diagnostic concept of emotional over-control is used to understand the proposed model of processes of hyperglycaemia aversion. The present study offers new insight which will aid clinicians in identifying and supporting those who may be at risk of psychological distress and harm associated with a preference for avoidance of higher blood glucose levels.

Open-source Artificial Pancreas Systems Are Safe and Effective When Supported In-clinic: Outcomes in 248 Consecutive Type 1 Diabetes Clients.

OBJECTIVE: Our aim in this study was to determine the safety, glycemia, and quality of life (QoL) associated with in-clinic installation and management of supported open-source artificial pancreas systems (SOSAPS) in type 1 diabetes (T1D). METHODS: This investigation is a retrospective cohort study of consecutive SOSAPS users at a Canadian diabetes centre. SOSAPS were offered to all moderately tech-savvy T1D clients on sensor-augmented multiple daily injection or pump, able to pay for hardware, and willing to sign a consent and waiver document. SOSAPS were installed and maintained by clinic staff at no cost to clients. iPhone users were assigned to either Loop (n=108) or iPhone artificial pancreas systems (iAPS; n=114) and Android users to Android-type APS (n=24). Outcomes included severe hypoglycemia and diabetic ketoacidosis (DKA), time in range (TIR) 4.0 to 10.0 mmol/L, time below range (TBR) <4 mmol/L, glucose management indicator (GMI), mean sensor glucose (MSG), change in glycated hemoglobin (A1C), and QoL. RESULTS: Two hundred forty-eight subjects (131 males, 117 females), with a mean age of 36 years and diabetes duration of 21 years, experienced 3 episodes of severe hypoglycemia and no DKA over a follow-up of 17 months. TIR rose by 16%, from 64% to 80% (p<0.0001); TBR fell by 1.0%, from 3.5% to 2.5% (p=0.001); MSG fell from 9.0 to 8.1 mmol/L (p<0.001); GMI fell from 7.3% to 6.7% (p<0.001); and A1C fell from 7.2% to 6.7% (p<0.0001). QoL scores were healthy before and improved after SOSAPS. CONCLUSIONS: Clients with T1D using SOSAPS and supported with no-cost care to the client (software, technology, and physician/physician assistant) safely achieved improved TIR, GMI, A1C, and QoL.

Fracture patterns and associated risk factors in pediatric and early adulthood type 1 diabetes: Findings from a nationwide retrospective cohort study.

PURPOSE: People with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D. METHODS: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls. RESULTS: The crude HRs for any fracture (HR: 1.30, CI95%: 1.11-1.51), lower-arm (HR: 1.22, CI95%: 1.00-1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11-2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70-2.36; MOFs: HR: 1.89, CI95%: 1.44-2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53-2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34-3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20-1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21-1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47-3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10-2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67-0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38-0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0-4 years: HR: 1.20, CI95%: 1.00-1.44; 5-9 years: HR: 1.17, CI95%: 0.91-1.50; <10 years: HR: 0.83, CI95%: 0.54-1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04-1.95). CONCLUSION: The overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones.