Is stimulation of browning of human adipose tissue a relevant therapeutic target?

Brown adipose tissue (BAT) and beige adipose tissues are important contributors to cold-induced whole body thermogenesis in rodents. The documentation in humans of cold- and ß-adrenergic receptor agonist-stimulated BAT glucose uptake using positron emission tomography (PET) and of a decrease of this response in individuals with cardiometabolic disorders led to the suggestion that BAT/beige adipose tissues could be relevant targets for prevention and treatment of these conditions. In this brief review, we will critically assess this question by first describing the basic rationale for this affirmation, second by examining the evidence in human studies, and third by discussing the possible means to activate the thermogenic response of these tissues in humans.

Basal Insulin Initiation in Adults With Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using Administrative Health Data in Alberta, Canada.

OBJECTIVES: Pharmacologic treatment of type 2 diabetes mellitus (T2DM) follows a stepwise approach. Typically, metformin monotherapy is first-line treatment, followed by other noninsulin antihyperglycemic agents (NIAHAs) or progression to insulin if glycated hemoglobin (A1C) targets are not achieved. We aimed to describe real-world patterns of basal insulin initiation in people with T2DM, and A1C not at target despite treatment with at least 2 NIAHAs. METHODS: A retrospective cohort study was conducted using administrative health data from Alberta, Canada, among adults with T2DM, indexed on the first test with 7.0% < A1C < 9.5% (April 1, 2011 to March 31, 2019), with at least 2 previous NIAHAs but no insulin. Kaplan-Meier (KM) methodology was used to analyze time to basal insulin initiation, with stratification by index A1C. Annual patient status was categorized into 5 groups: basal insulin initiation, death, NIAHA intensification, no change in therapy (subgroups of A1C <7.1% and A1C ≥7.1% [clinical inertia]), or discontinuance. RESULTS: The cohort included 14,083 individuals. The KM cumulative probability of initiating basal insulin was 7.7% (95% confidence interval [CI] 7.3% to 8.2%) at 1 year, increasing to 43.1% (95% CI 42.1% to 44.1%) at 8 years of follow-up. Higher A1C levels were associated with greater proportions of basal insulin initiation. By year 8, proportions with NIAHA intensification and clinical inertia were 12.1% and 19.3%, respectively, relative to year 7. CONCLUSIONS: Despite current clinical practice guidelines recommending achieving A1C targets within 6 months, less than half of the individuals with T2DM and clear indications for basal insulin initiated treatment within 8 years. Efforts to reduce delays in basal insulin initiation are needed.

Glycemic Control Among Adults With Type 1 Diabetes During Passover: A Pre-Post Single-center Study.

OBJECTIVES: No data are available regarding glycemic control of patients with type 1 diabetes (T1D) during Passover. Our aim in this study was to assess the effect of Passover on diabetes management and glycemic control in adult patients with T1D with nutritional changes during Passover (observant) compared with patients who did not change their dietary habits during Passover (nonobservant). METHODS: Observational pre-post study of adult patients with T1D, followed in a diabetes clinic in Israel. Data were downloaded from insulin pumps and continuous glucose monitoring for 37 days: 2 weeks before Passover; 9 days of Passover; and 2 weeks thereafter. Differences in percentage of time spent above target (>10.0 to >13.9 mmol/L), at target (3.9 to 10.0 mmol/L) and below target (<3.9 to <3.0 mmol/L), were compared using paired t tests or paired signed rank tests. RESULTS: The study cohort included 43 patients (23 observant, 20 nonobservant). The average blood glucose was significantly higher during Passover compared with the period before Passover---in nonobservant patients 8.2±1.5 mmol/L and 7.9±1.3 mmol/L (p=0.043), respectively, and in observant patients 8.7±1.6 mmol/L and 8.4±1.6 mmol/L (p=0.048), respectively. Time above range 10 to 13.9 mmol/L was increased in observant patients during Passover, as compared with the period before Passover, was 24.9±16.2% and 20.6±12.4% (p=0.04), respectively. The dose of bolus insulin had increased significantly in observant patients: 27.4±13.9 units during Passover, as compared with 24.2±11.2 units before Passover (p=0.02). CONCLUSIONS: Passover alters glycemic control and insulin needs in Jewish patients with T1D. It is advisable to make specific adjustments to maintain the recommended glycemic control.

Glycoprotein Acetyls Associate With Intraglomerular Hemodynamic Dysfunction, Albuminuria, Central Adiposity, and Insulin Resistance in Youth With Type 1 Diabetes.

OBJECTIVES: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D. METHODS: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.0 years of age, 50% female, glycated hemoglobin 8.7%±1.3%, T1D duration 5.7±2.6 years). Concentrations of GlycA were quantified by targeted nuclear magnetic resonance spectroscopy. Correlation and multivariable linear regression analyses were performed. RESULTS: GlycA's were higher in girls vs boys (1.05±0.26 vs 0.84±0.15 mmol/L, p=0.001) and in participants living with overweight/obesity vs normal weight (1.12±0.23 vs 0.87±0.20 mmol/L, p=0.0004). GlycA's correlated positively with estimated intraglomerular pressure (r=0.52, p=0.001), UACR (r=0.53, p<0.0001), and trunk mass (r=0.45, p=0.001), and inversely with estimated insulin sensitivity (r=-0.36, p=0.01). All relationships remained significant after adjustment for age, sex, and glycated hemoglobin. CONCLUSIONS: As biomarkers of inflammation, GlycA's were higher in girls and those with overweight or obese body habitus in T1D. GlycA's associated with parameters of early kidney dysfunction, central adiposity, and insulin resistance.

Fasted C-Peptide Distribution and Associated Clinical Factors in Adults With Longstanding Type 1 Diabetes: Analysis of the Canadian Study of Longevity in Type 1 Diabetes.

OBJECTIVE: Although insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors. METHODS: In a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration ≥50 years) and 75 age- and sex-matched controls. Extensive phenotyping for complications was performed and patient-reported variables were included. C-peptide distributions were analyzed, and multivariable logistic regression was used to assess the variable association in participants with T1D. RESULTS: The 74 participants with T1D had a mean age of 66±8 years, a disease duration of 54 (interquartile range 52 to 58) years, and a glycated hemoglobin (A1C) of 7.4%±0.8% (56.8±9.15 mmol/mol). The 75 controls had a mean age of 65±8 years and an A1C of 5.7%±0.4% (38.4±4.05 mmol/mol). Participants with T1D had lower fasted serum C-peptide than controls (0.013±0.022 vs 1.595±1.099 nmol/L, p<0.001). Of the participants with T1D, C-peptide was detectable in 30 of 73 (41%) serum samples, 32 of 74 (43%) urine samples, and 48 of 74 (65%) for either serum or urine. The variables independently associated with detectable serum or urinary C-peptide were lower total daily insulin requirement (odds ratio 2.351 [for 1 lower unit/kg], p=0.013) and lower hypoglycemia worry score (odds ratio 1.059 [for 1 point lower on the worry subscore of the Hypoglycemia Fear Survey], p=0.030). CONCLUSIONS: Although detectable C-peptide in longstanding diabetes was common, the magnitude of concentration was extremely low when compared with age- and sex-matched controls. Despite minimal detectability, its presence is validated by lower insulin requirements and strongly associated with lower hypoglycemia worry.

Falciparum malaria is associated with risk markers of type 2 diabetes mellitus in individuals with or without COVID-19 exposure

Background: Scientific information on the impact of malaria on the risk of developing type 2 diabetes mellitus (T2DM) after recovery from the coronavirus disease 2019 (COVID-19) is limited in the Ghanaian context. The purpose of this study was to examine the association between selected risk markers of T2DM in falciparum malaria patients post-COVID-19 or not at a tertiary hospital in Ghana. Methodology: This was a descriptive cross-sectional comparative study of 38-recovered COVID-19 adult participants with malaria and 40 unexposed COVID-19 adults with malaria at the Tamale Teaching Hospital, Ghana. Demographic, anthropometric and levels of glucose, insulin, C-reactive protein and lipid profiles were measured in the two groups of participants under fasting conditions. Parasitaemia was assessed microscopically but insulin resistance and beta-cell function were assessed by the homeostatic model. Results: The COVID-19 exposed participants were older (p=0.035) with lower parasitaemia (p=0.025) but higher mean levels of insulin, insulin resistance, and beta-cell function compared with their unexposed counterparts (p<0.05). Parasitaemia correlated positively with a number of the measured indices of diabetogenic risk markers in the COVID-19 exposed group only, and predicted (Adjusted R2=0.751; p=0.031) by beta-cell function, C-reactive protein and triglycerides with the model explaining about 75% of the observed variation. Parasitaemia could only be predicted (Adjusted R2=0.245; p=0.002) by C-reactive protein with the model explaining just about a quarter of the observed variation in the COVID-19 unexposed group. Insulin resistance and sub-optimal beta-cell function were detected in both groups of participants. Conclusion: Falciparum malaria is associated with risk markers for development of T2DM irrespective of COVID-19 exposure. Insulin resistance, inflammation and sub-optimal beta-cell secretory function may drive the risk. The observed diabetogenic risk is higher in the recovered COVID-19 participants.

[Closed-loop insulin therapy in type 1 diabetes after age 60]. / Insulinothérapie en boucle fermée au cours du diabètede type 1 après 60 ans.

The closed-loop insulin therapy system has become an indispensable tool in the management of type 1 diabetes. This technological feat improves glycemic control while reducing the mental burden on patients. In an exploratory study, we sought to determine whether older patients, who may be less familiar with new technologies, derive the same benefits as others. Is a lack of digital skills an obstacle to improving patients' daily lives?

[Antidiabetic treatments for the elderly]. / Les traitements antidiabétiques chez le sujet âgé.

Diabetes is very common in people over 75. A broad arsenal of treatments is now available. It is important, however, to choose the right treatment regimen to suit the patient's specific glycemic targets.

A Case of Malignant Myxofibrosarcoma With Hypoglycemia Attacks.

Myxofibrosarcoma is a malignant mesenchymal tumor and a fibroblastic sarcoma of the elderly. Myxofibrosarcoma can be low-grade or high-grade depending on the cell characteristics. Wide surgical resection with or without radiotherapy and chemotherapy is the basis of its treatment. Sometimes, tumor cells secrete insulin or insulin-like substances and cause hypoglycemia attacks. Here, we intend to demonstrate the role of early surgery to end hypoglycemia attacks and prevent recurrence and metastases. We also intend to show the insufficiency of tru-cut biopsy to distinguish between low- and high-grade myxofibrosarcoma. An 82-year-old male patient visited our clinic with a rapidly growing giant mass in the left retroscapular area and suffered from hypoglycemic attacks several times a day. After imaging and initial biopsy, the tumor grade was indeterminate on histopathological examination; hence, the mass was removed surgically. The pathological examination resulted in high-grade myxofibrosarcoma whereas the initial biopsy could not elaborate on the grade. The hypoglycemia attacks ceased after the surgery. Adjuvant local radiotherapy at a total dose of 60 Gy was administered in 30 fractions to the surgery area with no complications after the surgery. No new mass, recurrence, or hypoglycemia attack was detected in the three-year follow-up. In conclusion, hypoglycemia attacks may be a marker of malignant tumor presence and may be a clue at the beginning and in the follow-up period both for recurrence and the aggressiveness of the tumoral mass. Because a biopsy may show the diagnosis but not the grade of the tumor, early surgical intervention is needed.

IGF1 synthesis after CO2 fractional laser resurfacing (FLR): New insights in the treatment of scalp actinic keratoses.

OBJECTIVES: Actinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin-like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet-induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin-like growth factor 1 (IGF-1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing. METHODS: We enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm2 , treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real-time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients. RESULTS: IGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow-up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four- and six-follow-up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment. DISCUSSION: Taken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma.

Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon.

OBJECTIVES: Self-management guidelines for nonsevere hypoglycemia (NS-H) in type 1 diabetes recommend 15 g of simple carbohydrates (CHO) at 15-minute intervals. Because automated insulin delivery (AID) preventively reduces or suspends insulin infusion for imminent hypoglycemia, we aimed to determine whether guidelines were excessive during AID. METHODS: This work was a secondary analysis of NS-H episodes during inpatient single-hormone (insulin) or dual-hormone (insulin and glucagon) AID trials with standardized CHO treatment protocols. RESULTS: Forty NS-H episodes occurred: 15 during single-hormone arms (2 trials) and 25 during dual-hormone arms (5 trials). At NS-H treatment T0min, plasma glucose (PG) level was 3.1±0.6 mmol/L, corresponding to a sensor value of 3.6±0.6 mmol/L. Fifteen minutes after CHO consumption, PG increased by 0.9±0.8 mmol/L, recovering 45% of episodes to a safe PG of ≥4.0 mmol/L. With repeated CHO consumption, time to recovery was 21.4±15.7 minutes without rebound hyperglycemia; PG 1 hour after initial CHO was 5.9±2.0 mmol/L. Outcome differences between single-hormone and dual-hormone systems were not statistically significant, except for higher insulin and glucagon levels and less repeated treatments in dual-hormone AID. PG and glucagon levels at T0min were positively associated with increase in PG at T15min and negatively associated with time to recovery. CONCLUSIONS: NS-H self-management CHO 15-g/15-minute guidelines were neither excessive nor optimal during AID. There is a need to examine data with different AID systems to optimize treatment recommendations.

Barriers to Exercise in Adults With Type 1 Diabetes and Insulin Resistance.

OBJECTIVE: Our aim in this study was to assess attitudes toward exercise and quality of life (QoL) in adults with type 1 diabetes (T1D) with and without insulin resistance (IR). METHODS: We pooled baseline pretreatment data from a subset of individuals with T1D from 2 randomized controlled trials. Estimated glucose disposal rate (eGDR), a validated surrogate marker of IR, was calculated using an established formula to classify individuals according to IR status with a cutpoint of <6 mg/kg/min for the determination of IR. Self-reported barriers to exercise were obtained using a validated questionnaire, the Barriers to Physical Activity in T1D (BAPAD-1). In addition, QoL was determined using the 36-item Short Form (SF-36) questionnaire. Differences between dichotomized variables were assessed using the independent t test, Mann-Whitney U test, or Fisher exact test. Linear regression was employed to explore the association of eGDR with BAPAD-1 and QoL scores, with sequential adjustment for potential confounders. RESULTS: Of the 85 individuals included in our study, 39 were classified as having IR. The mean BAPAD-1 total score was higher for individuals with IR (IR: 3.87±0.61; non-IR: 2.83±0.55; p<0.001). The highest exercise barrier scores for individuals with IR were risk of hypoglycemia (5.67±1.26) and risk of hyperglycemia (5.23±1.20), whereas the highest scoring exercise barrier scores for non-IR individuals were not diabetes-related, with low level of fitness (3.91±1.26) and physical health status, excluding diabetes (3.67±1.48), ranked highest. QoL scores were comparable between groups (p>0.05). CONCLUSIONS: Risk of hypoglycemia was the greatest barrier to exercise in individuals with T1D with IR, whereas non-diabetes-related barriers to exercise were more salient in individuals with T1D without IR.

Association Between Insulin Resistance and the Inflammatory Marker C-reactive Protein in a Representative Healthy Adult Canadian Population: Results From the Canadian Health Measures Survey.

OBJECTIVES: Insulin resistance (IR) leads to type 2 diabetes mellitus. Multiple IR causes have been identified, including inflammation. This study determines the association between IR and the inflammatory marker C-reactive protein (CRP) in a healthy Canadian population and examines potential differences by sex and age. METHODS: Participants were adults with no self-reported history of diabetes, a glycated hemoglobin (A1C) of <6.5%, and a fasting blood glucose of <7 mmol/L, and who had participated in the Canadian Health Measures Survey, cycles 1 to 4 (2007-2015). IR was calculated using the Homeostasis Model of Insulin Resistance (HOMA-IR) assessment. The crude geometric mean HOMA-IR was calculated using a one-way analysis of variance. The association between CRP levels and HOMA-IR was examined using multivariate linear regression. RESULTS: A total of 4,024 eligible nondiabetic adults (1,994 [49.5%] men and 2,030 [50.4%] women) were identified. Eighty percent of the subjects were Caucasian. Among all subjects, 36% had a CRP of ≥2 mg/L. The crude geometric mean HOMA-IR was 1.33 in men and 1.24 in women. Participants with a CRP of <0.7 mg/L had a crude geometric mean HOMA-IR of 1.15 (1.13 to 1.16), compared with 1.41 (1.39 to 1.43) for those with a CRP of ≥2 mg/L. After adjusting for sex, age, race, high-density lipoprotein cholesterol, triglycerides, body mass index, smoking, and diastolic blood pressure, the HOMA-IR-CRP association remained significant. A positive trend for CRP values in men with increasing values of HOMA-IR was observed. However, this trend was not consistent with the increase in women's CRP levels. CONCLUSIONS: Elevated CPR levels are independently associated with IR in men. Prospective cohort studies can confirm the causal relationship between high CRP levels and IR and identify the underlying mechanisms.

Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis.

OBJECTIVES: Our aim in this study was to compare the efficacy and safety of commercially available fixed-ratio combinations (FRCs) of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and basal insulins by a network meta-analysis of randomized controlled trials (RCTs) of people with type 2 diabetes. METHODS: We present a systematic review and network meta-analyses of RCTs of individuals with type 2 diabetes randomized to FRCs or to their components for ≥24 weeks. All reports were obtained from PubMed or ClinicalTrials.gov up to February 28, 2022. The primary outcome was glycated hemoglobin (A1C) level attained. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycemia. Treatment effects were estimated as mean difference (MD) and standard error (SE), or as odds ratio (OR) with 95% confidence interval (CI) using the fixed combination of insulin glargine 100 IU/mL and lixisenatide (iGlarLixi) as reference. RESULTS: We included 29 RCTs from among the 1,404 articles identified. No direct comparisons between FRCs were found. After excluding some insulin-capped trials to reach model consistency, both FRCs were more efficacious regarding A1C than their components, but no difference between FRCs was found (MD, -0.10%; SE, 0.10%). The effect of the fixed combination of insulin degludec and liraglutide (IDegLira) (MD, -0.47 mmol/L; SE, 0.24 mmol/L) and basal insulins was similar to that of iGlarLixi (reference) on fasting glucose, whereas GLP-1RAs had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (MD, -0.72 kg; SE, 0.32 kg) than with iGlarLixi (reference) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs, followed by IDegLira (OR, 0.78; 95% CI, 0.39 to 1.57), iGlarLixi (reference), and basal insulins. CONCLUSIONS: For A1C, both FRCs were more efficacious over their individual components, with similar efficacies of the 2 FRCs.

Health Professionals' Experiences Supporting People With Type 1 Diabetes Mellitus Who Deliberately Restrict and/or Omit Insulin for Weight, Shape, and/or Appearance: A Meta-synthesis.

OBJECTIVES: It has been reported that health professionals currently lack the required empathy, understanding, and knowledge about the deliberate restriction and/or omission of insulin to influence weight and/or shape, which may impact the quality of care provided. We sought to synthesize existing qualitative research pertaining to health professionals' experiences supporting individuals within this unique population. METHODS: We conducted a meta-synthesis using a meta-aggregative approach. We searched 5 electronic databases. Eligible articles were qualitative or mixed-methods empirical studies with primary data reporting health professionals' experiences supporting people with type 1 diabetes restricting and/or omitting insulin for weight and/or shape control, written in English, from database inception to March 2022. RESULTS: A final sample of 4 primary studies were included. The analysis indicated that in the absence of standardized screening and diagnostic tools, health professionals found it challenging to decide when behaviour became clinically significant. Health professionals were also challenged by complex perceptions and behaviours relating to their illness management and features of broader health-care systems and organizational factors. CONCLUSIONS: Our findings have widespread multidisciplinary implications for health professionals and the broader health-care systems in which they work. We provide evidence-based clinical recommendations and suggestions for vital future research.

Factors Associated With Initiation of Antidepressant Medication in Adults With Type 1 and Type 2 Diabetes: A Primary Care Retrospective Cohort Study in Ontario, Canada.

OBJECTIVES: Depression in patients with diabetes mellitus is common and associated with poorer outcomes. This study aims to identify demographic, socioeconomic and medical factors associated with the initiation of antidepressant medication after a diagnosis of diabetes in adult patients without a previous prescription for antidepressants. We also examined frequency of primary care visits in the year after antidepressant initiation compared with the year before treatment began. METHODS: This was a retrospective cohort study using routinely collected electronic medical record data spanning January 2011 to December 2019 from the University of Toronto Practice-based Research Network (UTOPIAN) Data Safe Haven. Our primary outcome was a first prescription for an antidepressant in patients with diabetes. We used a mixed-effects logistic regression model to identify sociodemographic and medical factors associated with this event. RESULTS: Among 22,750 patients with diabetes mellitus, 3,055 patients (13.4%) began taking an antidepressant medication. Increased odds of antidepressant initiation were observed in younger patients (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.39 to 2.26), females (OR, 1.60; 95% CI, 1.46 to 1.7), those receiving insulin treatment (OR, 1.59; 95% CI, 1.43 to 1.78) and cases of polypharmacy (OR, 3.67; 95% CI, 3.29 to 4.11). There was an increase in the mean number of primary care visits from 4.6 to 5.9 per year after antidepressant initiation. CONCLUSIONS: In patients with diabetes, age, sex and medical characteristics were associated with the initiation of antidepressants. These patients accessed primary care more frequently. Screening and prevention of depression, particularly in these subgroups, could reduce its personal and systemic burdens.

Recent Developments in Islet Biology: A Review With Patient Perspectives.

Navigating the coronavirus disease-2019 (COVID-19, now COVID) pandemic has required resilience and creativity worldwide. Despite early challenges to productivity, more than 2,000 peer-reviewed articles on islet biology were published in 2021. Herein, we highlight noteworthy advances in islet research between January 2021 and April 2022, focussing on 5 areas. First, we discuss new insights into the role of glucokinase, mitogen-activated protein kinase-kinase/extracellular signal-regulated kinase and mitochondrial function on insulin secretion from the pancreatic ß cell, provided by new genetically modified mouse models and live imaging. We then discuss a new connection between lipid handling and improved insulin secretion in the context of glucotoxicity, focussing on fatty acid-binding protein 4 and fetuin-A. Advances in high-throughput "omic" analysis evolved to where one can generate more finely tuned genetic and molecular profiles within broad classifications of type 1 diabetes and type 2 diabetes. Next, we highlight breakthroughs in diabetes treatment using stem cell-derived ß cells and innovative strategies to improve islet survival posttransplantation. Last, we update our understanding of the impact of severe acute respiratory syndrome-coronavirus-2 infection on pancreatic islet function and discuss current evidence regarding proposed links between COVID and new-onset diabetes. We address these breakthroughs in 2 settings: one for a scientific audience and the other for the public, particularly those living with or affected by diabetes. Bridging biomedical research in diabetes to the community living with or affected by diabetes, our partners living with type 1 diabetes or type 2 diabetes also provide their perspectives on these latest advances in islet biology.

Effects of High-dose Folic Acid Supplementation on Maternal/Child Health Outcomes: Gestational Diabetes Mellitus in Pregnancy and Insulin Resistance in Offspring.

OBJECTIVES: The purpose of this study was to evaluate the effects of maternal high folic acid (FA) supplementation during pregnancy on glucose intolerance in dams and insulin resistance in offspring. METHODS: Wistar female rats (n=18) were mated and randomly divided into 3 groups: a control group and 2 experimental groups. Three different feeding protocols were administered during pregnancy: control group, 2 mg/kg FA (recommended level FA supplementation); experimental 1 group, 5 mg/kg FA (tolerable upper intake level of FA supplementation [ULFolS]); and experimental 2 group, 40 mg/kg FA (high FA supplementation [HfolS]). All dams were fed the same FA content diet (2 mg/kg FA) during the lactation period. An oral glucose tolerance test was performed on day 16 of pregnancy. After the lactation period, body weight and food intake of 36 pups were monitored. Dams were euthanized at the end of the lactation period and half of the pups were euthanized at the end of week 7 and the others at the end of week 12. Serum FA, homocysteine, vitamin B12, insulin, glucose, interleukin-6, tumor necrosis factor-alpha, glycated hemoglobin (A1C), and adiponectin levels of mothers and pups were evaluated. The homeostatic model of insulin resistance (HOMA-IR) was used to determine insulin resistance in dams and offspring. RESULTS: According to glucose tolerance test results of dams, blood glucose values at minutes 0, 60, 90, and 120 for the HFolS group were significantly higher compared with the control group (p<0.05). The A1C level in HFolS dams was significantly higher than in the control group (p<0.05). The mean birthweight of the pups in the HFolS group was significantly higher than that of control pups (p<0.05). HOMA-IR values for control and HFolS offspring were similar at weeks 7 and 12 and higher than in ULFolS offspring (p>0.05). CONCLUSIONS: It was determined that high doses of FA exposure during pregnancy might be effective in the development of glucose intolerance in dams and insulin resistance in offspring in this study.

Androgen dysfunction in non-alcoholic fatty liver disease: Role of sex hormone binding globulin.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the world. It is linked mainly to insulin resistance and metabolic syndrome including obesity and dyslipidemia. In addition, various endocrine dysfunctions including polycystic ovary syndrome (PCOS) and hypogonadism are involved in the development and progression of NAFLD. We need to know the disease pathophysiology more accurately due to the heterogeneity of clinical presentation of fatty liver disease. The liver is the major metabolic organ with sexual dimorphism. Sexual dimorphism is associated not only with behavioral differences between men and women, but also with physiological differences reflected in liver metabolism. In men, normal androgen levels prevent hepatic fat accumulation, whereas androgen deficiency induce hepatic steatosis. In women, higher androgens can increase the risk of NAFLD in PCOS. Sex hormone binding globulin (SHBG) is involved in androgen regulation. Recently, SHBG may be reported as a surrogate marker for NAFLD. Therefore, this review will focus on the mechanism of androgen dysfunction in the regulation of hepatic metabolism, the risk of developing NAFLD, and the potential role of SHBG in the course of NAFLD.; Keywords: Non-alcoholic fatty liver disease, insulin resistance, sexual dimorphism, androgen, sex hormone binding globulin.