Missed diagnosis-a major barrier to patient access to obesity healthcare in the primary care setting.

OBJECTIVE: To investigate whether individuals with an elevated BMI measurement, for whom a diagnosis of overweight or obesity (OW/OB) is not recorded, are less likely to be offered clinical care for obesity compared to those with a recorded diagnosis. SUBJECTS: A retrospective cohort study using the electronic medical record database of Maccabi Healthcare Services (MHS) in Israel. Included were 200,000 adults with BMI ≥ 25 kg/m2 measurement recorded during a primary care visit between 2014 and 2020, and no prior diagnosis of OW/OB or related co-morbidities. METHODS: The relationships between a recorded diagnosis of OW/OB and two composite outcomes: 1. A composite of referrals to screening tests for metabolic complications; 2. A composite of weight loss intervention and follow up, were analyzed using multivariate logistic regression models. RESULTS: In only 18% of individuals, a diagnosis of OW/OB was recorded. After adjusting for multiple potential confounding factors, individuals who received a recorded diagnosis were 18% more likely to be offered an evaluation for obesity-related metabolic complication, (OR 1.18, 95% CI 1.15-1.21, p < 0.001), and almost twice as likely to be offered intervention and follow up for their excess body weight (OR 1.84, 95% CI 1.76-1.94, p < 0.001) compared to individuals with missed diagnosis. These results persisted after adjusting for inter-physician variability. In addition, male sex, older age, and Arab sector were all associated with lower rates of weight loss intervention and follow up, while young individuals were less likely to be screened for metabolic complications. CONCLUSION: Beyond BMI measurement, a recorded diagnosis of OW/OB is associated with statistically and clinically significant higher rates of performance of obesity care and intervention. Undiagnosed OW/OB presents a significant clinical opportunity, as recording a diagnosis of OW/OB would predict improved patient access to obesity healthcare and improved clinical outcomes.

Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

INTRODUCTION: Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. METHODS: This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. RESULTS: Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda = 0.34, F(6,14) = 4.52, p = 0.009), basal insulin (Wilks' Lambda = 0.41, F(6,14) = 3.30, p = 0.031) and bolus insulin (Wilks' Lambda = 0.43, F(6,14) = 3.02, p = 0.041). Total insulin/kg requirements increased by 5.5% from 13-20 weeks to 20-26 weeks, 19% from 20-26 weeks to 26-33 weeks, and 17.4% from 26 to 33 weeks to delivery (p for trend = 0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p < 0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. CONCLUSIONS: There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

The relationship between neonatal hypoglycaemia and cord blood C-peptide levels in neonates of birthing individuals with type 1 diabetes.

INTRODUCTION: Neonates of individuals with type 1 diabetes (T1D) are at increased risk of neonatal hypoglycaemia. It is hypothesised that this is a result of birthing-individual hyperglycaemia and subsequent foetal hyperinsulinemia. AIMS: To test for association between clinically significant neonatal hypoglycaemia (requiring intravenous glucose treatment) and cord-blood c-peptide (CBCP) concentrations in birthing-individuals with T1D. MATERIALS AND METHODS: This is a prospective cohort study of individuals with T1D followed at a single tertiary centre. Clinical variables and glucose control during pregnancy were recorded. Cord-blood was collected and CBCP concentrations determined. The correlation between clinically significant neonatal hypoglycaemia and CBCP concentrations was determined. RESULTS: Fifty-four pregnant individuals and their newborns were included in the study. Individuals to neonates who experienced hypoglycaemia had longer diabetes duration (19 vs. 13 years, respectively, p = 0.023), higher HbA1c at conception (7.3 [6.3-8.8] vs. 6.5 [6.0-7.0], respectively, p = 0.042) and higher rates of caesarian section (73.3% vs. 28.2%, respectively, p = 0.005) than individuals to those who did not. CBCP levels were significantly higher in neonates with clinically significant neonatal hypoglycaemia as compared to those who did not experience hypoglycaemia (3.3 mcg/L vs. 1.9 mcg/L, respectively, p = 0.002). After adjustment for possible confounders, every 1 unit higher in CBCP level was associated with a 1.46 (1.02-2.09, p = 0.035)-fold greater risk for neonatal hypoglycaemia. No significant differences were observed in either birthing individual complications or glucose control indices during pregnancy between the two groups. CONCLUSIONS: In neonates of individuals with T1D, higher CBCP levels are an independent risk factor for clinically significant neonatal hypoglycaemia.

Effect of basal insulin and omega 3 fatty acids on cognitive impairment in dysglycaemia: An exploratory analysis of the ORIGIN trial.

AIM: The outcomes reduction with an initial glargine intervention (ORIGIN) trial reported that, allocation to insulin glargine-mediated normoglycaemia versus standard care, and to omega 3 fatty acids versus placebo had a neutral effect on cognitive test scores when analysed as continuous variables. Analyses of these scores as standardized categorical variables using a previously validated strategy may yield different results. MATERIALS AND METHODS: The ORIGIN trial recruited participants with dysglycaemia and additional cardiovascular risk factors from 573 sites in 40 countries. They completed a mini mental state examination and a subset completed the digit symbol substitution test at baseline and up to three subsequent visits. The effect of the interventions on country-standardized substantive cognitive impairment, defined as the first occurrence of a baseline-adjusted follow-up mini mental state examination or digit symbol substitution test score ≥1.5 standard deviations below the baseline mean score in each participant's country was assessed using Cox proportional hazards models. RESULTS: During a median follow-up of 6.2 years, 2627 of 11 682 people (22.5%) developed country-standardized substantive cognitive impairment. The hazard of this outcome was reduced by 9% (hazard ratio 0.91, 95% confidence interval 0.85, 0.99; p = .023) in participants assigned to insulin glargine (21.6%) versus standard care (23.3%). Conversely, the hazard of this outcome was not affected by assignment to omega 3 fatty acid versus placebo (hazard ratio 0.93, 95% confidence interval 0.86, 1.01; p = .074). CONCLUSIONS: In this post hoc exploratory analysis, insulin glargine-mediated normoglycaemia but not omega 3 fatty acids reduced the hazard of substantive cognitive impairment in people with dysglycaemia and additional cardiovascular risk factors.

Development and first-stage validation of a digital version of the Digit Symbol Substitution test for use in assessing cognitive function in older people with diabetes.

AIMS: To describe the development and report the first-stage validation of a digital version of the digit symbol substitution test (DSST), for assessment of cognitive function in older people with diabetes. MATERIALS AND METHODS: A multidisciplinary team of experts was convened to conceptualize and build a digital version of the DSST and develop a machine-learning (ML) algorithm to analyse the inputs. One hundred individuals with type 2 diabetes (aged ≥ 60 years) were invited to participate in a one-time meeting in which both the digital and the pencil-and-paper (P&P) versions of the DSST were administered. Information pertaining to demographics, laboratory measurements, and diabetes indices was collected. The correlation between the digital and P&P versions of the test was determined. Additionally, as part of the validation process, the performance of the digital version in people with and without known risk factors for cognitive impairment was analysed. RESULTS: The ML model yielded an overall accuracy of 89.1%. A strong correlation was found between the P&P and digital versions (r = 0.76, p < 0.001) of the DSST, as well as between the ML model and the manual reading of the digital DSST (r = 0.99, p < 0.001). CONCLUSIONS: This study describes the development of and provides first-stage validation data for a newly developed digital cognitive assessment tool that may be used for screening and surveillance of cognitive function in older people with diabetes. More studies are needed to further validate this tool, especially when self-administered and in different clinical settings.

The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study.

BACKGROUND: As indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults. METHODS: A retrospective, pharmacovigilance study of the FDA's global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR). RESULTS: We identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51-68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 - 487.3] vs adj.ROR = 250.2 [79.3 - 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 - 58.8] vs adj.ROR = 88.0 [27.0 - 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 - 34.8] vs adj.ROR = 23.3 [19.2 - 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 - 11.2] vs adj.ROR = 8.6 [7.2 - 10.3]), nocturia (adj.ROR = 5.5 [3.7 - 8.2] vs adj.ROR = 6.7 [2.8 - 15.7]), dehydration (adj.ROR = 2.5 [2.3 - 2.8] vs adj.ROR = 2.6 [2.1 - 3.3]), and fractures (adj.ROR = 1.7 [1.4 - 2.1] vs adj.ROR = 1.5 [1.02 - 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteraction threshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 - 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 - 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults. CONCLUSION: In this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.

High BMI and the risk for incident type 1 Diabetes Mellitus: a systematic review and meta-analysis of aggregated cohort studies.

BACKGROUND: There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize evidence regarding BMI and the risk of developing type 1 diabetes. METHODS: A systematic review and meta-analysis were conducted to assess the association between BMI and incident type 1 diabetes. Databases were searched up to June 2022. Cohort studies were included reporting the association between overweight and/or obesity, as measured by BMI after age 2 years, with incident type 1 diabetes. Independent reviewers extracted data and assessed study quality. Risk estimates were pooled using a random-effects model. RESULTS: Ten cohort studies met the inclusion criteria. The seven studies that classified BMI into categories were of high quality and involved 1,690,660 individuals and 1979 incident type 1 diabetes cases. The pooled risk ratio (RR) for type 1 diabetes was 1.35 (95% CI 0.93-1.97) among people with overweight (3 studies); 2.17 (95% CI 1.75-2.69) among people with obesity (5 studies); and 1·87 (95% CI 1.52-2.29) among people with overweight/obesity (two studies merged the categories). These point estimates persisted in sensitivity analyses that addressed the duration of follow-up, variability in baseline risk for incident type 1 diabetes, and potential misclassifications related to exposure or outcome definitions. People with overweight/obesity had a 2.55 (95% CI 1.11-5.86) greater risk for incident type 1 diabetes with positive islet autoantibodies. CONCLUSION: This systematic review and meta-analysis of high-quality observational cohort studies indicated an association between high BMI and the risk of type 1 diabetes, in a graded manner.

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.

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.

Quality of life of patients with thyroid eye disease: 3-year follow-up in a multidisciplinary clinic in Israel.

BACKGROUND: Changes in the quality of life (QOL) of patients with thyroid eye disease (TED) were examined during a 3-year follow-up in a multidisciplinary eye clinic, and factors that may improve QOL were identified. METHODS: A retrospective review of medical records of all patients who attended the TED clinic at Sheba Medical Center, Israel, from May 2016 to May 2019 was performed. The retrieved data included demographics, comprehensive ophthalmic examination findings, clinical activity scores (CAS), laboratory test results, and QOL assessments by the Graves' Orbitopathy QOL (GO-QOL) questionnaire. RESULTS: One hundred thirty-two TED clinic patients were examined. Thirty patients (22.72%) received medical treatment consisting of steroids according to the European Group on Graves' Orbitopathy (EUGOGO) protocol, high-dose steroids, or immunosuppressive drugs. Twenty-eight patients (21.21%) underwent surgical rehabilitation (decompression, strabismus, or eyelid surgery). There was a significant increase in total QOL score after steroid treatment according to the EUGOGO protocol, after decompression surgery, and after strabismus surgery compared to pre-treatment total QOL (p=0.04, p=0.021, and p=0.042, respectively, matched pairs). In addition, there were significant positive correlations between the changes in the total QOL score and the change in thyroid-stimulating immunoglobulin (TSI) as well as the change in CAS among the patients who underwent medical and surgical interventions. CONCLUSIONS: QOL improved significantly after medical/surgical treatments. A change in the CAS and in the TSI may also correlate with change in QOL. Periodic evaluation of TED patients' QOL is recommended for enhanced and more comprehensive management.

Maternal glucose variability during pregnancy & birthweight percentile in women with pre-gestational diabetes.

INTRODUCTION: Pre-gestational diabetes mellitus (PGDM) is a major risk factor for fetal overgrowth. Interestingly, even in relatively well controlled PGDM women, as determined by average glucose indices such HbA1c, there is an increased rate of LGA (large for gestational age). Glucose variability (GV) has emerged as an important independent risk factor for several diabetes complications. The aim of this study was to determine the relationship between maternal GV indices and neonatal birth percentile. METHODS: This was a historical cohort study that included all consecutive PGDM women monitored in a single tertiary care center. Clinical and demographic variables, as well as data regarding glucose control, were prospectively recorded. Mean, standard deviation (SD) and coefficient of variance (CV) of glucose values were calculated. Pearson correlations coefficient was used to determine the correlation between glucose indices and birth percentile. The analysis was repeated after adjustment for several confounders. RESULTS: Mean birthweight and birthweight percentile were 3212 ± 532 g and 66.9%, respectively. There was a statistically significant correlation between birthweight percentile and maternal glucose SD (ß = 0.28, p = .002) and maternal glucose CV (ß = 0.21, p = .019). There was no significant correlation between birthweight percentile and mean glucose values. The association between the maternal glucose SD and birthweight percentile remained statistically significant after adjustment for maternal age, pre-pregnancy BMI and duration of diabetes. CONCLUSION: There is an association between maternal glucose variability indices (SD and CV) during pregnancy and neonatal birth percentile. Larger studies are needed to confirm these results.

Sensorimotor and Cognitive Abilities Associated With Touchscreen Tablet App Performance to Support Self-Management of Type 2 Diabetes.

IMPORTANCE: Self-management programs (facilitated by mobile devices) may improve health and prevent secondary complications for older adults with diabetes. However, older adults may have difficulties using mobile devices because of neuropathy or cognitive dysfunction. OBJECTIVE: To identify sensorimotor and cognitive abilities associated with touchscreen tablet app performance to support self-management of diabetes in older adults. DESIGN: Cross-sectional study. SETTING: Outpatient Center for Successful Aging With Diabetes. PARTICIPANTS: Forty-five older adults with Type 2 diabetes. OUTCOMES AND MEASURES: Dexterity (Purdue Pegboard Test), touch sensation (Semmes-Weinstein monofilaments), pinch strength (pinch gauge), cognition (Montreal Cognitive Assessment), and executive functioning (Trail Making Test) were assessed. Two apps were then used: Dexteria and SuCare. Demographic data, prior mobile device use, and diabetes severity (hemoglobin A1C [HbA1C]) were collected. RESULTS: Age and HbA1C accounted for 29.8% and 9.7%, respectively, of the total variance of Dexteria performance time (dominant hand). Dexterity (dominant hand) accounted for an additional 5.4% of the total variance of 45.1%, F(4, 40) = 10.021, p < .001. Prior mobile device use, age, and diabetes severity accounted for 6.4%, 11.8%, and 26.4%, respectively, of the total variance of SuCare performance time. Executive functioning and dominant-hand dexterity accounted for an additional 9.5% and 9.4%, respectively, of the total variance of 61.0%, F(5, 39) = 14.75, p < .001. CONCLUSIONS AND RELEVANCE: Beyond age and diabetes severity, executive functioning and dominant-hand dexterity contributed to app performance, highlighting the importance of diabetes self-management. These findings may help determine suitable candidates for tablet use for self-management. WHAT THIS ARTICLE ADDS: App performance is explained by the executive functioning and dexterity of older adults with Type 2 diabetes. These factors, in addition to age and diabetes severity, should be taken into consideration by occupational therapy practitioners in future mobile self-management programs.

[THE CHALLENGE OF HEALTHY AGING WITH DIABETES: THE ISRAELI NATIONAL DIABETES COUNCIL GUIDELINES FOR TREATING OLDER PEOPLE].

INTRODUCTION: The prevalence of diabetes increases with age. Diabetes is a risk factor for many complications such as cardiovascular disease, kidney failure, stroke, neuropathy, and retinopathy. Data from recent years indicate that it is also a risk factor for cognitive impairment, dementia, functional disability and frailty. Diabetes is a disease that requires complex self-care capabilities; the individuals with diabetes are required to take medications on time, examine their feet, exercise, maintain a balance diet, preform daily glucose monitoring, cope with hypoglycemia and understand how differing life situations may effect glucose levels. All of these require intact cognitive and functional abilities. Thus, treatment plans should take into consideration the person's cognitive/functional state. Indeed, in the last several years many professional organizations such as the American Diabetes Association, the International Diabetes Federation, and the American Endocrinology Society have published guidelines for treating older people with diabetes. The Israeli National Diabetes Council, headed by Prof. Itamar Raz, in collaboration with other physician unions and other national councils, have recently authorized the Israeli guidelines for treating older people with diabetes. The Israeli guidelines include categorization of older adults with diabetes in relation to their functional status in order to reach determined treatment targets. According to the Israeli guidelines and in accordance with international guidelines, the treatment targets of the elderly person with diabetes should not be determined by the chronological age of the individuals but rather by their risk for functional deterioration. Older people with diabetes are categorized into three groups according to their risk for functional deterioration. Each category has unique glucose, blood pressure and lipid targets. The guidelines offer valid and reliable tools that, in addition to personal acquaintance with the patient, can help determine the level of risk of functional decline.

Adolescent BMI and early-onset type 2 diabetes among Ethiopian immigrants and their descendants: a nationwide study.

BACKGROUND: We assessed in a nationwide cohort the association between adolescent BMI and early-onset (< 40 years) type 2 diabetes among Israelis of Ethiopian origin. METHODS: Normoglycemic adolescents (range 16-20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. RESULTS: 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3-5.1) and 15.8 (8.3-30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7-11.4) and 29.1 (12.9-70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. CONCLUSIONS: Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.

Are large simple trials for dementia prevention possible?

New trials of dementia prevention are needed to test novel strategies and agents. Large, simple, cardiovascular trials have successfully discovered treatments with moderate but worthwhile effects to prevent heart attack and stroke. The design of these trials may hold lessons for the dementia prevention. Here we outline suitable populations, interventions and outcomes for large simple trials in dementia prevention. We consider what features are needed to maximise efficiency. Populations could be selected by age, clinical or genetic risk factors or clinical presentation. Patients and their families prioritise functional and clinical outcomes over cognitive scores and levels of biomarkers. Loss of particular functions or dementia diagnoses therefore are most meaningful to participants and potential patients and can be measured in large trials. The size of the population and duration of follow-up needed for dementia prevention trials will be a major challenge and will need collaboration between many clinical investigators, funders and patient organisations.

The association between novel glucose indices in parturients with type 1 diabetes mellitus and clinically significant neonatal hypoglycemia.

The aim of this study was to determine the association between glucose control indices of parturient with type 1 diabetes (T1DM), treated with an insulin pump and utilizing continuous glucose monitoring (CGM), and clinically significant neonatal hypoglycemia. This was a retrospective cohort study which included 37 pregnant women with T1DM. All women were followed at a single tertiary center and had available CGM data. The association between maternal glucose indices before delivery and the risk for neonatal hypoglycemia requiring IV glucose (clinically significant hypoglycemia) was assessed using logistic regression. Mothers to neonates that experienced clinically significant hypoglycemia had a higher glucose standard deviation (SD) before delivery than did mothers to neonates who did not (25.5 ± 13 mg/dL vs. 14.7 ± 6.7 mg/dl respectively; p = .008). This association persisted after adjustment for maternal age, maternal pregestational body mass index (BMI), gestational age at delivery, neonatal birth weight, large for gestational age (LGA) and gender. This study demonstrates an association between high maternal glucose standard deviation before delivery and the risk for clinically significant neonatal hypoglycemia. Larger studies are needed to confirm these results and further explore the role of intrapartum glucose variability in the prediction and prevention of significant neonatal hypoglycemia.

Towards Implementation of the Saint Vincent Declaration: Outcomes of Women with Pregestational Diabetes.

BACKGROUND: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM. OBJECTIVES: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach. METHODS: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA). RESULTS: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts. CONCLUSIONS: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

Severe obesity and cardio-metabolic comorbidities: a nationwide study of 2.8 million adolescents.

BACKGROUND: Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. METHODS: A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). RESULTS: There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04-2.23) and 2.86 (2.60-3.15) in males, and 2.59 (2.43-2.76) and 3.44 (3.04-3.90) in females, whereas the ORs for T2DM were 19.1 (12.3-29.6) and 38.0 (22.6-64.0) in males, and 15.1 (11.4-20.0) and 24.8 (17.2-35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). CONCLUSIONS: Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

Effect of glycaemic control on cardiovascular disease in individuals with type 2 diabetes with pre-existing cardiovascular disease: A systematic review and meta-analysis.

The role of intensive glucose control in people with type 2 diabetes and pre-existing cardiovascular disease (CVD) is controversial. The aim of this systematic review and meta-analysis was to determine in a subset of people with type 2 diabetes and pre-existing CVD, the CV effect of intensive glucose control versus standard of care. We searched Medline, the Cochrane library, EMBASE and the National Institutes of Health Trial registration database for randomized controlled trials that evaluated the effect of intensive glucose control versus standard glucose control in people with type 2 diabetes on incident CVD. Data were extracted using a structured form. When data were not available in the publications, authors were contacted. Eight trials involving 8339 participants were included. Among adults with type 2 diabetes and pre-existing CVD, there was no difference in the risk of CV events in those allocated to intensive glucose control compared with those in the standard care arm (relative risk 0.98, 95% confidence interval 0.87-1.09). In conclusion, in people with diabetes and pre-existing CVD, intensive glucose control versus standard care had a neutral effect on incident CV events.

Disease Management plus Recommended Care versus Recommended Care Alone for Ambulatory Patients with Chronic Obstructive Pulmonary Disease.

Rationale: The efficacy of disease management programs in the treatment of patients with chronic obstructive pulmonary disease (COPD) remains uncertain.Objectives: To study the effect of disease management (DM) added to recommended care (RC) in ambulatory patients with COPD.Measurements and Main Results: In this trial, 1,202 patients with COPD (age, ≥40 yr), with moderate to very severe airflow limitation were randomly assigned either to DM plus RC (study intervention) or to RC alone (control intervention). RC included follow-up by pulmonologists, inhaled long-acting bronchodilators and corticosteroids, smoking cessation intervention, nutritional advice and psychosocial support when indicated, and supervised physical activity sessions. DM, delivered by trained nurses during patients' visits to the designated COPD centers and by remote contacts with the patients between these visits, included patient self-care education, monitoring patients' symptoms and adherence to treatment, provision of advice in case of acute disease exacerbation, and coordination of care vis-à-vis other healthcare providers. The primary composite endpoint was first hospital admission for respiratory symptoms or death from any cause. During 3,537 patient-years, 284 patients (47.2%) in the control group and 264 (44.0%) in the study intervention group had a primary endpoint event. The median (range) time elapsed until a primary endpoint event was 1.0 (0-4.0) years among patients assigned to the study intervention and 1.1 (0-4.1) years among patients assigned to the control intervention; adjusted hazard ratio, 0.92 (95% confidence interval, 0.77-1.08).Conclusions: DM added to RC was not superior to RC alone in delaying first hospital admission or death among ambulatory patients with COPD.