Glycemic outcomes and patient satisfaction and self-management improves in transition from standard to virtual multidisciplinary care.

AIMS: With advances in cloud-based technologies, there has been a rise in remote T1D care. We hypothesized that transitioning T1DM care to a virtual, multidisciplinary clinic could improve measures beyond HbA1c. METHODS: To assess the impact of transitioning from standard to virtual T1DM care, we evaluated glycemic measures and patient reported outcomes. RESULTS: Sixty-one adults with T1DM were included, with mean age 40.2 ± 13.5 years and diabetes duration 16.9 ± 9.0 years. Most patients were treated with insulin pumps and CGM. The number of annual diabetes care encounters rose from 2.1 ± 4.2 to 12.8 ± 5.5. Baseline HbA1c was 7.9 ± 1.6 %(63 ± 16.9 mmol/mol), declining to 7.3 ± 1.1 %(56 ± 8.5 mmol/mol) and 7.1 ± 1.0 %(54 ± 7.7 mmol/mol) at 6 and 12 months respectively (p < 0.001 for both). In parallel, TIR improved from 63.1 ± 19.3 % to 69.2 ± 13.8 % (p < 0.001) and 67.5 ± 19.4 % (p = 0.03) at 6 and 12 months respectively, while TBR declined. Scores from validated diabetes treatment and self-management questionnaires rose significantly and these rises were associated with a reduction in HbA1c, the latter score was also associated with increased TIR. There was a trend toward a correlation between encounter frequency and improvement in HbA1c and TIR. CONCLUSIONS: Transitioning from standard to virtual, coordinated, multidisciplinary T1DM care is associated with increased visit frequency, improving glycemic control, treatment satisfaction and self-care behaviors.

An Automated Insulin Delivery System with Automatic Meal Bolus Based on a Hand-Gesturing Algorithm.

Background: Carbohydrate counting (CC) and meal announcements, before eating, introduce a significant burden for individuals managing type 1 diabetes (T1D). An automated insulin delivery system with automatic bolusing that eliminates the need for CC and premeal bolusing (i.e., a hands-free closed-loop [HFCL] system) was assessed in a feasibility trial of adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the Klue application (Klue, Inc.) that detects eating and drinking gestures. A smartphone algorithm converted gestures into carb amounts that were transmitted to the pump for automatic bolusing. For 5 days, participants (N = 17, 18-75 years of age) used the system at home with meal announcements based on traditional CC, with the Klue application disabled (Home-stay phase). Thereafter, participants moved to a supervised hotel setting, where the Klue application was enabled for 5 days and meals were not announced (Hotel-stay phase). Participants consumed the same eight test meals (six solid and two liquid) of varying caloric and carb size at the same time and day of the week for both phases, and glycemic metrics were compared. Otherwise, there were no other meal restrictions. Results: The overall time in range (70-180 mg/dL) was 83.4% ± 7.0% and 80.6% ± 6.7% for the Home-stay and Hotel-stay, respectively (P = 0.08). The average time at <70 mg/dL was 3.1% and 3.0% (P = 0.9144), respectively, and the average time at >180 mg/dL was 13.5% and 16.3% (P = 0.1046), respectively. Postprandial glycemia following low-carb test meals was similar between the two phases. The system's ability to accommodate high-carb meals was somewhat limited. There were no episodes of severe hypoglycemia or diabetic ketoacidosis. Conclusion: Preliminary findings show that a HFCL system was safe and maintained overall glycemic control, similar to that observed with traditional CC and manual meal bolusing. By eliminating these daily T1D burdens, a HFCL system may improve quality of life for individuals with T1D. ClinicalTrials.gov number: NCT04964128.

Non-invasive, Real-time, Glucose Monitoring is in the Near Future.

OBJECTIVE: Since the introduction of continuous glucose monitoring technology, developers have rigorously researched the feasibility of creating a noninvasive glucose monitoring device. In a recent pilot study, investigators reported a strong correlation between glucose values obtained from novel, noninvasive monitoring device (GWave) values to venous and capillary glucose measurements. RESEARCH DESIGN AND METHODS: We investigated if the level of accuracy observed in the pilot study could be reproduced in a larger cohort, using a smaller third-generation, manufacturable device (Gen III GWave) containing a standardized sensor chip that can be mass produced for commercial use. The evaluation assessed concordance with capillary blood glucose, reproducibility between two gen III devices, and accuracy during insulin-induced hypoglycemia. RESULTS: Assessment of samples from 75 subjects (T2D, n=6; T1D, n=28; nondiabetic pregnant subjects, n=10; and nondiabetic, n=31) showed that 97% of values were in Zone A with 3% in Zone B of the Clarke Error Grid, with a mean absolute relative difference (MARD) of 6.7% from reference blood glucose. Comparison between two independent Gen III GWave devices demonstrated reproducibility between the sensors (R2=0.95), with 100% of values within Zone A. In the hypoglycemia assessment, measurements from the Gen III sensor tightly followed the capillary glucose measurements down to 42 mg/dL (2.3 mmol/L), whereas the CGM measurements from two different CGM only converged with the GWave and capillary glucose readings after 90 minutes of decreasing glucose levels. CONCLUSION: Our results show promise as potentially the first noninvasive technology. Future studies will focus on larger numbers of people in all glucose ranges. Real-time noninvasive blood glucose monitoring is possible using GWave technology.

Adipose tissue-derived FABP4 mediates glucagon-stimulated hepatic glucose production in gestational diabetes.

AIMS: One of the most common complications of pregnancy is gestational diabetes mellitus (GDM), which may result in significant health threats of the mother, fetus and the newborn. Fatty acid-binding protein 4 (FABP4) is an adipokine that regulates glucose homeostasis by promoting glucose production and liver insulin resistance in mouse models. FABP4 levels are increased in GDM and correlates with maternal indices of insulin resistance, with a rapid decline post-partum. We therefore aimed to determine the tissue origin of elevated circulating FABP4 levels in GDM and to assess its potential contribution in promoting glucagon-induced hepatic glucose production. MATERIALS AND METHODS: FABP4 protein and gene expression was determined in biopsies from placenta, subcutaneous (sWAT) and visceral (vWAT) white adipose tissues from GDM and normoglycaemic pregnant women. FABP4 differential contribution in glucagon-stimulated hepatic glucose production was tested in conditioned media before and after its immune clearance. RESULTS: We showed that FABP4 is expressed in placenta, sWAT and vWAT of pregnant women at term, with a significant increase in its secretion from vWAT of women with GDM compared with normoglycaemic pregnant women. Neutralizing FABP4 from both normoglycaemic pregnant women and GDM vWAT secretome, resulted in a decrease in glucagon-stimulated hepatic glucose production. CONCLUSIONS: This study provides new insights into the role of adipose tissue-derived FABP4 in GDM, highlighting this adipokine, as a potential co-activator of glucagon-stimulated hepatic glucose production during pregnancy.

Expectations from a Home Cooking Program: Qualitative Analyses of Perceptions from Participants in "Action" and "Contemplation" Stages of Change, before Entering a Bi-Center Randomized Controlled Trial.

Home cooking is an emerging strategy to improve nutrition; however, the literature lacks reports about patient expectations from culinary interventions. Personalized medicine utilizes knowledge about a person's genes; yet, behavioral factors, such as participant "readiness" to make a change, may also impact treatment preferences and outcomes. The purpose is to explore the expectations of participants in different stages of change from a home cooking intervention. Participants were recruited to a randomized controlled trial evaluating the impact of a home cooking intervention on weight. Stage of change assessed by a validated University of Rhode Island Change Assessment scale and expectations through an open-ended questionnaire. Sixteen (21%) participants were in the action stage of change, and 59 (79%) were in the contemplation stage. Participants from both groups shared similar expectations to achieve healthy eating and lifestyle goals and to adopt sustainable change. However, action group expectations also included expanding existing culinary knowledge and change of habits; the contemplation group expectations also included acquiring culinary knowledge, improving self-regulatory skills, and obtaining guidance and support. While action group participants were looking to expand existing knowledge and techniques, contemplation group participants were focusing on acquiring culinary knowledge and skills. This can potentially contribute to developing effective, personalized nutrition interventions.

Unannounced Meal Challenges Using an Advanced Hybrid Closed-Loop System.

Background: The advanced hybrid closed-loop (AHCL) algorithm combines automated basal rates and corrections yet requires meal announcement for optimal outcomes. We aimed to compare the performance of the MiniMed™ 780G AHCL algorithm with and without meal announcement. Methods: In a single-arm study involving 14 adults with type 1 diabetes, we evaluated the safety and efficacy of AHCL when meals were not announced. Participants stayed at a supervised environment for 5 days, during which the outcomes of not announcing meals (≤80 g of carbohydrate) were assessed. Next, participants entered a 90-day at-home "unannounced" phase, during which all meals (≤80 g of carbohydrate) were unannounced, followed by a 90-day at-home phase in which all meals were announced. Results: Time in range (TIR 70-180 mg/dL) was lower in the unannounced versus announced periods (67.5% ± 12.5% vs. 77.7% ± 9.5%; P < 0.01, respectively), with more time spent in hyperglycemia range 180-250 mg/dL (22.7% ± 7.7% vs. 15.7% ± 7.2%) and >250 mg/dL (7.9% ± 6.4% vs. 3.6% ± 2.7%), but less time in hypoglycemia range 54-70 mg/dL (1.6% ± 1% vs. 2.8% ± 1.8%) and <54 mg/dL (0.3% ± 0.4% vs. 0.7% ± 0.9%). Not announcing meals containing up to 60 g of carbohydrate did not lead to increase in postprandial extreme dysglycemia >250 mg/dL, and up to 20 g of unannounced carbohydrates did not significantly change the TIR 70-180 mg/dL compared with full announcement. Conclusion: The AHCL system is optimized for use with meal announcement. While not announcing meals of ≤80 g carbohydrates appears to be safe, it results in suboptimal postprandial glycemic control, especially with high-carbohydrate meals. Not announcing small meals (≤20 g carbohydrate) does not deteriorate glycemic control. Clinical Trial Registration number: NCT04479826.

Glucose intolerance in pregnancy and risk of early-onset type 2 diabetes: a population-based cohort study.

BACKGROUND: The risk of type 2 diabetes among women with glucose intolerance during pregnancy that does not meet gestational diabetes criteria requires further investigation. We aimed to explore the associations between various degrees of gestational glucose intolerance and the risk of type 2 diabetes in young adulthood. METHODS: For this population-based cohort study, the national Israeli conscription database was linked to Maccabi Healthcare Services (MHS), the second-largest state-mandated health provider in Israel. We included 177 241 women who underwent a pre-recruitment evaluation at adolescence (age 16-20 years), 1 year before mandatory military service, and later underwent, from Jan 1, 2001, to Dec 31, 2019, two-step gestational diabetes screening with a 50 g glucose challenge test (GCT) based on a threshold of 140 mg/dL (7·8 mmol/L), followed as needed by a 100 g oral glucose tolerance test (OGTT). Abnormal OGTT values were defined according to the Carpenter-Coustan thresholds: 95 mg/dL (5·3 mmol/L) or higher in the fasting state; 180 mg/dL (10·0 mmol/L) or higher at 1 h; 155 mg/dL (8·6 mmol/L) or higher at 2 h; and 140 mg/dL (7·8 mmol/L) or higher at 3 h. The primary outcome was incident type 2 diabetes in the MHS diabetes registry. Cox proportional hazards models were applied to estimate adjusted hazard ratios (HRs) with 95% CIs for incident type 2 diabetes. FINDINGS: During a cumulative follow-up of 1 882 647 person-years, and with a median follow-up of 10·8 (IQR 5·2-16·4) years, 1262 women were diagnosed with type 2 diabetes. Crude incidence rates of type 2 diabetes were 2·6 (95% CI 2·4-2·9) per 10 000 person-years in women with gestational normoglycaemia, 8·9 (7·4-10·6) per 10 000 person-years in women with an abnormal GCT and normal OGTT, 26·1 (22·4-30·1) per 10 000 person-years in women with one abnormal OGTT value (in the fasting state or 1 h, 2 h, or 3 h post-challenge), and 71·9 (66·0-78·3) per 10 000 person-years in women with gestational diabetes. After adjustment for sociodemographic characteristics, adolescent BMI, and age at gestational screening, the risk of type 2 diabetes was higher, compared to the gestational normoglycaemia group, in women with an abnormal GCT and normal OGTT (adjusted hazard ratio [HR] 3·39 [95% CI 2·77-4·16]; p<0·0001), in women with one abnormal OGTT value (9·11 [7·64-10·86]; p<0·0001), and in women with gestational diabetes (24·84 [21·78-28·34]; p<0·0001). The risk of type 2 diabetes was modestly increased in women with isolated elevated fasting glucose (adjusted HR 11·81 [95% CI 8·58-16·25]; p<0·0001), and in women with gestational diabetes and an abnormal fasting glucose (38·02 [32·41-44·61]; p<0·0001). INTERPRETATION: Gestational glucose intolerance, including conditions not meeting gestational diabetes criteria of the two-step strategy, confers a high risk of type 2 diabetes in young adulthood. These conditions should be recognised as risk factors for type 2 diabetes, especially among women with abnormal fasting glucose concentrations during pregnancy. FUNDING: None.

A Multidisciplinary Thyroid Eye Clinic: A One-stop Shop.

BACKGROUND: Little is known about the success of multidisciplinary thyroid eye disease (TED) clinic. OBJECTIVES: To present the characteristics, treatments, and outcomes of patients treated in a multidisciplinary TED clinic. METHODS: A medical record review of all patients who attended a TED clinic was performed. Data included demographics, medical history, laboratory tests, visual function tests, ocular examinations, clinical activity score (CAS), and assessment of quality-of-life (QOL). RESULTS: Clinic visits included 132 patients seen during 385 appointments at a TED clinic (mean 12 appointments per patient). Management of TED included medical treatments for 48 patients (36.3%) and surgical treatment for 56 (42.4%). There was a positive significant correlation between the CAS and thyroid-stimulating immunoglobulin (TSI) activity at the first visit and at the last follow-up visit (P < 0.01 and P < 0.02, respectively). However, no correlation was found between the CAS and the thyroid-stimulating hormone levels or between the free triiodothyronine (fT3) and fT4 levels at the first or last visit. There was a significant negative correlation between the CAS and color vision (-0.347, P < 0.01, Pearson correlation) at the first visit, but not between the CAS and visual acuity and visual field at either the first or last visit. Changes in the QOL and the CAS scores were significantly negatively correlated (-0.240, P < 0.01). CONCLUSIONS: Treatment and management decisions for TED should be based on multiple parameters including clinical examinations by ophthalmologists and endocrinologists, laboratory tests, and CAS and QOL scores.

Obesity in late adolescence and incident type 1 diabetes in young adulthood.

AIMS/HYPOTHESIS: Studies in children have reported an association between increased BMI and risk for developing type 1 diabetes, but evidence in late adolescence is limited. We studied the association between BMI in late adolescence and incident type 1 diabetes in young adulthood. METHODS: All Israeli adolescents, ages 16-19 years, undergoing medical evaluation in preparation for mandatory military conscription between January 1996 and December 2016 were included for analysis unless they had a history of dysglycaemia. Data were linked with information about adult onset of type 1 diabetes in the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied, with BMI being analysed both as a categorical and as a continuous variable. RESULTS: There were 777 incident cases of type 1 diabetes during 15,819,750 person-years (mean age at diagnosis 25.2±3.9 years). BMI was associated with incident type 1 diabetes. In a multivariable model adjusted for age, sex and sociodemographic variables, the HRs for type 1 diabetes were 1.05 (95% CI 0.87, 1.27) for the 50th-74th BMI percentiles, 1.41 (95% CI 1.11, 1.78) for the 75th-84th BMI percentiles, 1.54 (95% CI 1.23, 1.94) for adolescents who were overweight (85th-94th percentiles), and 2.05 (95% CI 1.58, 2.66) for adolescents with obesity (≥95th percentile) (reference group: 5th-49th BMI percentiles). One increment in BMI SD was associated with a 25% greater risk for incidence of type 1 diabetes (HR 1.25, 95% CI 1.17, 1.32). CONCLUSIONS: Excessively high BMI in otherwise healthy adolescents is associated with increased risk for incident type 1 diabetes in early adulthood.

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Insulin-Naïve People with Type 2 Diabetes: the ATOS Study.

INTRODUCTION: The clinical benefits of insulin glargine 300 U/mL (Gla-300) have been confirmed in randomised clinical trials (EDITION programme and BRIGHT) and real-world studies in the USA and Western Europe. ATOS evaluated the real-world effectiveness and safety of Gla-300 in wider geographic regions (Asia, the Middle East, North Africa, Latin America and Eastern Europe). METHODS: This prospective observational, international study enrolled adults (≥ 18 years) with type 2 diabetes mellitus (T2DM) uncontrolled [haemoglobin A1c (HbA1c) > 7% to ≤ 11%] on one or more oral anti-hyperglycaemic drugs (OADs) who had been advised by their treating physician to add Gla-300 to their existing treatment. The primary endpoint was achievement of a pre-defined individualised HbA1c target at month 6. RESULTS: Of the 4550 participants included, 4422 (51.8% female) were eligible for assessment. The mean ± standard deviation (SD) age was 57.2 ± 10.8 years, duration of diabetes was 10.2 ± 6.2 years and baseline HbA1c was 9.28 ± 1.0%. The proportion of participants reaching their individualised glycaemic target was 25.2% [95% confidence interval (CI) 23.8-26.6%] at month 6 and 44.5% (95% CI 42.9-46.1%) at month 12. At months 6 and 12, reductions were observed in HbA1c (-1.50% and -1.87%) and fasting plasma glucose (-3.42 and -3.94 mmol/L). Hypoglycaemia incidence was low, and body weight change was minimal. Adverse events were reported in 283 (6.4%) participants, with 57 (1.3%) experiencing serious adverse events. CONCLUSION: In a real-world setting, initiation of Gla-300 in people with T2DM uncontrolled on OADs resulted in improved glycaemic control and low rates of hypoglycaemia with minimal weight change. TRIAL REGISTRATION: Clinicaltrials.gov number NCT03703869.

Effects of imatinib on glycemic and lipid profiles: a retrospective cohort study.

Despite a favorable effect of imatinib on glucose metabolism in animal models, human reports are inconsistent. We retrospectively studied the long-term effect of imatinib on fasting plasma glucose (FPG), glycated hemoglobin (HbA1C), LDL-cholesterol (LDL), and triglycerides (TGs) in a large HMO cohort of patients initiating therapy. In patients with diabetes (n = 118), significant reductions in HbA1c (0.53%, IQR 0.09, 1.19; p < .001) and FPG (10.2 mg/dL, IQR -3.5, 32.2; p < .001), independent of demographics and of glucose-lowering drugs utilization, were observed during the first year of imatinib treatment. Significant reductions in LDL (17.8 mg/dL, IQR -1.3, 34.0; p < .001) and TG (25.0 mg/dL, IQR -2.3, 58.3; p < .001), also independent of demographics and of statin utilization, were evident in the entire cohort (n = 611) during the first imatinib year. All reductions persisted during the second treatment year. To conclude, imatinib is associated with durable metabolic benefits, which may guide TKI choice in patients with cardiovascular co-morbidities.

Comparison of Insulin Dose Adjustments Made by Artificial Intelligence-Based Decision Support Systems and by Physicians in People with Type 1 Diabetes Using Multiple Daily Injections Therapy.

Objective: Artificial intelligence-based decision support systems (DSS) need to provide decisions that are not inferior to those given by experts in the field. Recommended insulin dose adjustments on the same individual data set were compared among multinational physicians, and with recommendations made by automated Endo.Digital DSS (ED-DSS). Research Design and Methods: This was a noninterventional study surveying 20 physicians from multinational academic centers. The survey included 17 data cases of individuals with type 1 diabetes who are treated with multiple daily insulin injections. Participating physicians were asked to recommend insulin dose adjustments based on glucose and insulin data. Insulin dose adjustments recommendations were compared among physicians and with the automated ED-DSS. The primary endpoints were the percentage of comparison points for which there was agreement on the trend of insulin dose adjustments. Results: The proportion of agreement and disagreement in the direction of insulin dose adjustment among physicians was statistically noninferior to the proportion of agreement and disagreement observed between ED-DSS and physicians for basal rate, carbohydrate-to insulin ratio, and correction factor (P < 0.001 and P ≤ 0.004 for all three parameters for agreement and disagreement, respectively). The ED-DSS magnitude of insulin dose change was consistently lower than that proposed by the physicians. Conclusions: Recommendations for insulin dose adjustments made by automatization did not differ significantly from recommendations given by expert physicians regarding the direction of change. These results highlight the potential utilization of ED-DSS as a useful clinical tool to manage insulin titration and dose adjustments.

Stability in BMI over time is associated with a better cognitive trajectory in older adults.

OBJECTIVE: Evidence on simultaneous changes in body mass index (BMI) and cognitive decline, which better reflect the natural course of both health phenomena, is limited. METHODS: We capitalized on longitudinal data from 15,977 initially non-demented elderly from the Alzheimer's Disease Centers followed for 5 years on average. Changes in BMI were defined as (1) last minus first BMI, (2) mean of all follow-up BMIs minus first BMI, and (3) standard deviation of BMI change from baseline and all follow-up visits (representing variability). RESULTS: Participants with significant changes in BMI (increase or decrease of ≥5%), or who had greater variability in BMI, had faster cognitive decline. This pattern was consistent irrespective of normal (BMI < 25; N = 5747), overweight (25 ≤ BMI < 30; N = 6302), or obese (BMI ≥ 30; N = 3928) BMI at baseline. CONCLUSIONS: Stability in BMI predicts better cognitive trajectories suggesting clinical value in tracking BMI change, which is simple to measure, and may point to individuals whose cognition is declining.

Personality disorders and cause-specific mortality: a nationwide study of 2 million adolescents.

BACKGROUND: Personality disorders are prevalent in 6-10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality. METHODS: We performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16-19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011. RESULTS: The study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03-1.74), 1.82 (1.20-2.76), 1.45 (1.23-1.71), 1.41 (1.30-1.53) and 1.44 (1.36-1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87-4.00) and 2.01 (1.56-2.58). Associations were already evident within 10 years of follow-up. CONCLUSIONS: Personality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

Myopia and Early-Onset Type 2 Diabetes: A Nationwide Cohort Study.

CONTEXT: A correlation between myopia and insulin resistance has been suggested. OBJECTIVE: We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood. METHODS: This population-based, retrospective, cohort study comprised 1 329 705 adolescents (579 543 women, 43.6%) aged 16 to 19 years, who were medically examined before mandatory military service during 1993 to 2012, and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right-eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up. RESULTS: There was an interaction between myopia and sex with T2D (P < .001). For women, T2D incidence rates (per 100 000 person-years) were 16.6, 19.2, and 25.1 for those without myopia, and with mild-to-moderate and high myopia, respectively. These corresponded to HRs of 1.29 (95% CI, 1.14-1.45) and 1.63 (1.21-2.18) for women with mild-to-moderate and high myopia, respectively, compared to those without myopia, after adjustment for age at study entry, birth year, adolescent body mass index, cognitive performance, socioeconomic status, and immigration status. Results persisted in extensive sensitivity and subgroup analyses. When managed as a continuous variable, every 1-diopter lower spherical equivalent yielded a 6.5% higher adjusted HR for T2D incidence (P = .003). There was no significant association among men. CONCLUSION: For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis.

Fatty acid-binding protein 4: a key regulator of ketoacidosis in new-onset type 1 diabetes.

AIMS/HYPOTHESIS: Fatty acid-binding protein 4 (FABP4) is an adipokine with a key regulatory role in glucose and lipid metabolism. We prospectively evaluated the role of FABP4 in the pathophysiology of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes. METHODS: Clinical and laboratory data were prospectively collected from consecutive children presenting with new-onset type 1 diabetes. In addition to blood chemistry and gases, insulin, C-peptide, serum FABP4 and NEFA were collected upon presentation and 48 h after initiation of insulin treatment. In a mouse model of type 1 diabetes, glucose, insulin, ß-hydroxybutyrate and weight were compared between FABP4 knockout (Fabp4-/-) and wild-type (WT) mice. RESULTS: Included were 33 children (mean age 9.3 ± 3.5 years, 52% male), of whom 14 (42%) presented with DKA. FABP4 levels were higher in the DKA group compared with the non-DKA group (median [IQR] 10.1 [7.9-14.2] ng/ml vs 6.3 [3.9-7] ng/ml, respectively; p = 0.005). The FABP4 level was positively correlated with HbA1c at presentation and inversely correlated with venous blood pH and bicarbonate levels (p < 0.05 for all). Following initiation of insulin therapy, a marked reduction in FABP4 was observed in all children. An FABP4 level of 7.22 ng/ml had a sensitivity of 86% and a specificity of 78% for the diagnosis of DKA, with an area under the receiver operating characteristic curve of 0.78 (95% CI 0.6, 0.95; p = 0.008). In a streptozotocin-induced diabetes mouse model, Fabp4-/- mice exhibited marked hypoinsulinaemia and hyperglycaemia similar to WT mice but displayed no significant increase in ß-hydroxybutyrate and were protected from ketoacidosis. CONCLUSIONS/INTERPRETATION: FABP4 is suggested to be a necessary regulator of ketogenesis in insulin-deficient states.

The association between adrenal adenoma size, autonomous cortisol secretion and metabolic derangements.

OBJECTIVE: Autonomous cortisol secretion (ACS) is common in patients with adrenal incidentalomas (AI). ACS is associated with increased cardiovascular morbidity and mortality. Data regarding the association between radiological characteristics of adrenal adenomas, their hormonal functionality and metabolic outcomes, are scarce and inconclusive. In this study, we aim to delineate the association between radiological characteristics of AI, ACS and metabolic status. METHODS: A cross-sectional study of 77 patients with AI who underwent a comprehensive hormonal evaluation. Radiological assessments were performed by an independent radiologist blinded to the clinical and hormonal phenotype of each case. Linear regression models were used to evaluate the association between post dexamethasone suppression test (DST) cortisol levels, metabolic indices and radiological measurements. RESULTS: Mean maximal adenoma diameter was greater in patients with versus without ACS (20.35 ± 6 vs. 27.09 ± 9.3 mm, respectively, p < .01). Maximal adenoma diameter was found to be positively and linearly correlated with post-DST morning cortisol levels across their entire range (R = .474, p < .01). Linear correlations between maximal adenoma diameter and indices of glycemic control showed a correlation coefficient (R) of .481 and .463 for fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c), respectively, p < .01. When analysis included only patients with ACS, an R = .584 and R = .565 was observed for FPG and HbA1c, respectively (p < .01 for both). The association between maximal adenoma diameter and both FPG and post-DST morning cortisol intensified in patients with metabolic syndrome. CONCLUSION: There is a quantitative positive mild correlation between AI size and both cortisol autonomy and metabolic parameters.

Adolescent body mass index and changes in pre-pregnancy body mass index in relation to risk of gestational diabetes.

BACKGROUND: Pregestational excessive body mass index (BMI) is linked to an increased risk for gestational diabetes mellitus (GDM), but less is known on the effect of adolescent BMI on GDM occurrence. The study aimed to investigate possible associations of adolescent BMI and changes in BMI experienced before first pregnancy, with gestational diabetes risk. METHODS: This retrospective study was based on linkage of a military screening database of adolescent health status (Israel Defence Forces) including measured height and weight, with medical records (Maccabi Healthcare Services, MHS) of a state-mandated health provider. The latter covers about 25% of the Israeli population; about 90% of pregnant women undergo screening by the two-step Carpenter-Coustan method. Adolescent BMI was categorized according to Center of Disease Control and Prevention percentiles. Only first documented pregnanies were analyzed and GDM was the outcome. FINDINGS: Of 190,905 nulliparous women, 10,265 (5.4%) developed GDM. Incidence proportions of GDM were 5.1%, 6.1%, 7.3%, and 8.9% among women with adolescent normal BMI, underweight, overweight, and obesity (p<0.001), respectively. In models that accounted for age at pregnancy, birth year, and sociodemographic variables, the adjusted odd ratios (aORs) for developing GDM were: 1.2 (95%CI, 1.1-1.3), 1.5 (1.4-1.6), and 1.9 (1.7-2.1) for adolescent underweight, overweight, and obesity (reference group, normal BMI). Adolescent BMI tracked with BMI notes in the pre-pregnancy period (r=63%). Resuming normal pre-pregnancy BMI from overweight or obesity in adolescence diminished GDM risk, but this diminished risk was not observed among those who returned to a normal per-pre-pregnancy BMI from being underweight in adolescence. Sustained overweight or obesity conferred an aOR for developing GDM of 2.5 (2.2-2.7); weight gain from adolescent underweight and normal BMI to pre-pregnancy excessive BMI conferred aORs of 3.1 (1.6-6.2) and 2.6 (2.2-2.7), respectively. INTERPRETATION: Change in BMI status from adolescence to pre-pregnancy may contribute to GDM risk. Identifying at-risk populations is important for early preventive interventions. FUNDING: None.

The adipokine FABP4 is a key regulator of neonatal glucose homeostasis.

During pregnancy, fetal glucose production is suppressed, with rapid activation immediately postpartum. Fatty acid-binding protein 4 (FABP4) was recently demonstrated as a regulator of hepatic glucose production and systemic metabolism in animal models. Here, we studied the role of FABP4 in regulating neonatal glucose hemostasis. Serum samples were collected from pregnant women with normoglycemia or gestational diabetes at term, from the umbilical circulation, and from the newborns within 6 hours of life. The level of FABP4 was higher in the fetal versus maternal circulation, with a further rise in neonates after birth of approximately 3-fold. Neonatal FABP4 inversely correlated with blood glucose, with an approximately 10-fold increase of FABP4 in hypoglycemic neonates. When studied in mice, blood glucose of 12-hour-old WT, Fabp4-/+, and Fabp4-/- littermate mice was 59 ± 13 mg/dL, 50 ± 11 mg/dL, and 43 ± 11 mg/dL, respectively. Similar to our observations in humans, FABP4 levels in WT mouse neonates were approximately 8-fold higher compared with those in adult mice. RNA sequencing of the neonatal liver suggested altered expression of multiple glucagon-regulated pathways in Fabp4-/- mice. Indeed, Fabp4-/- liver glycogen was inappropriately intact, despite a marked hypoglycemia, with rapid restoration of normoglycemia upon injection of recombinant FABP4. Our data suggest an important biological role for the adipokine FABP4 in the orchestrated regulation of postnatal glucose metabolism.

A Pilot Trial to Evaluate the Accuracy of a Novel Non-Invasive Glucose Meter.

The non-invasive self-monitoring of blood glucose (SMBG) has been the subject of intense investigation over recent decades. We conducted a pilot study designed to examine a novel non-invasive glucometer, the HGR GWave, utilizing radiofrequency (RF) sensing. Blood glucose levels assessed by this HGR prototype were compared to measurements performed by a hexokinase core laboratory assay during an oral glucose tolerance test (oGTT) for 5 subjects with type 2 diabetes. The HGR glucose meter readings were also compared to two Abbot Freestyle® glucose meters, which were also used for calibration. The accuracy of the results was evaluated through the calculation of relative absolute difference (RAD), specified percentage differences between 43 reference glucose measurements, and using comparator measurements. The median RAD was -4.787. We detected 79.04%, 92.99% and 97.64% of HGR readings within ±10%, ±15% and ±20% of the reference glucose measurements. The HGR readings had a high correlation with reference lab glucose measurements with R2 = 0.924 (95% CI 0.929-0.979; p < 0.0001). When compared to the Freestyle® glucose meters 94.3% and 100% of the readings were within ±5% and ±10%, with R2 = 0.975 (0.975-0.994; p < 0.0001). The HGR prototype glucose meter was found to be accurate in detecting real-time blood glucose during an oGTT in this small pilot study. A study with a broader range of blood glucose levels is needed to further assess its accuracy and its suitability for clinical use.