Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.

Screening for Subclinical Atherosclerosis and the Prediction of Cardiovascular Events in People with Type 1 Diabetes.

People with type 1 diabetes (T1D) have a high cardiovascular disease (CVD) risk, which remains the leading cause of death in this population. Despite the improved control of several classic risk factors, particularly better glycaemic control, cardiovascular morbidity and mortality continue to be significantly higher than in the general population. In routine clinical practice, estimating cardiovascular risk (CVR) in people with T1D using scales or equations is often imprecise because much of the evidence comes from pooled samples of people with type 2 diabetes (T2D) and T1D or from extrapolations of studies performed on people with T2D. Given that T1D onsets at a young age, prolonged exposure to the disease and its consequences (e.g., hyperglycaemia, changes in lipid metabolism or inflammation) have a detrimental impact on cardiovascular health. Therefore, it is critical to have tools that allow for the early identification of those individuals with a higher CVR and thus be able to make the most appropriate management decisions in each case. In this sense, atherosclerosis is the prelude to most cardiovascular events. People with diabetes present pathophysiological alterations that facilitate atherosclerosis development and that may imply a greater vulnerability of atheromatous plaques. Screening for subclinical atherosclerosis using various techniques, mainly imaging, has proven valuable in predicting cardiovascular events. Its use enables the reclassification of CVR and, therefore, an individualised adjustment of therapeutic management. However, the available evidence in people with T1D is scarce. This narrative review provides and updated overview of the main non-invasive tests for detecting atherosclerosis plaques and their association with CVD in people with T1D.

Real-world evidence of off-label use of commercially automated insulin delivery systems compared to multiple daily insulin injections in pregnancies complicated by type 1 diabetes.

AIMS: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) vs. multiple daily insulin injections (MDI) plus continuous glucose monitoring (CGM). METHODS: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR) and above (TAR) the pregnancy-specific glucose range 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes including baseline maternal characteristics and center. RESULTS: 112 women were included (HCL n=59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There were no between-group differences in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12±9.06 vs. -2.16 ±7.42 mmol/mol, p=0.031). No differences in TIR (3.5-7.8 mmol/L) and TAR were observed between HCL and MDI users, but with a higher total insulin dose in the second trimester (+0.13 IU/Kg/d). HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted 3.20 kg, 95%CI 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c were included in the models. CONCLUSIONS: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Adherence to an energy-restricted Mediterranean diet is associated with the presence and burden of carotid atherosclerosis in people with type 1 diabetes.

AIMS: People with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD). The Mediterranean diet is associated with reduced CVD; however, the evidence in T1D is scarce. We aimed to analyse the relationships between adherence to the energy-restricted Mediterranean diet (erMEDd) and carotid atherosclerosis. MATERIALS AND METHODS: We included children with T1D without CVD, with ≥1 of the following: age ≥40 years, diabetic kidney disease, or ≥10 years of disease duration with another risk factor. Plaque presence (intima-media thickness ≥1.5 mm) was determined by ultrasonography. The PREDIMED-Plus 17-item questionnaire (PP-17) was used to assess adherence to the erMEDd. RESULTS: Four hundred one individuals were included (48% males, age 48.3 ± 11 years, diabetes duration 26.8 ± 11.4 years). Those harbouring plaques (42%) showed lower adherence to the erMEDd (PP-17: 8.9 ± 2.3 of a maximum of 17 vs. 9.8 ± 2.5, p < 0.001). Greater adherence to the erMEDd was correlated with an overall better metabolic profile. After adjusting for multiple confounders, adherence to the erMEDd was independently associated with carotid atherosclerosis (OR 0.86 [0.77-0.95] for plaque presence and OR 0.85 [0.75-0.97] for ≥2 plaques). The consumption of fruit and nuts and preference of white over red meat was higher in individuals without atherosclerosis (p < 0.05). Fruit and nut consumption was associated with lower plaque prevalence in the fully adjusted models (OR 0.38 [0.19-0.73] and 0.51 [0.29-0.93]). CONCLUSIONS: Greater adherence to the erMEDd is associated with less carotid atherosclerosis in children with T1D at high risk of CVD. Strategies to improve and implement healthy dietary patterns in this population should be encouraged.

Neutrophil-to-lymphocyte ratio is independently associated with carotid atherosclerosis burden in individuals with type 1 diabetes.

BACKGROUND AND AIMS: Recent studies have identified a relationship between innate versus. Adaptative immunity and cardiovascular disease (CVD) in the general population, but information on type 1 diabetes (T1D) is lacking. We aimed to study the relationship between inflammatory biomarkers and preclinical atherosclerosis in this population. METHODS AND RESULTS: Cross-sectional study in T1D individuals without CVD and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of diabetes duration with classical CVD risk factors. Carotid plaques were evaluated by ultrasonography. C-reactive protein, total leukocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio and systemic immune-inflammation index were assessed as inflammatory markers. Multivariate-adjusted models including age, sex, and other CVD risk factors were constructed to test their independent associations with atherosclerosis burden. We included 602 subjects (52.8% men, 48.7 ± 10.2 years old and 27.0 ± 10.5 years of diabetes duration). Carotid plaques were found in 41.2% of the individuals (12.8%, ≥3 plaques). The number of carotid plaques (none, 1-2, ≥3 plaques), was directly associated with the leukocyte count (6570 [5445-8050], 6640 [5450-8470] and 7310 [5715-8935] per mm3, respectively; p for trend = 0.021) and the NLR (1.63 [1.28-2.13], 1.78 [1.38-2.25] and 2.14 [1.58-2.92], respectively; p for trend <0.001), but only the NLR remained directly associated in fully-adjusted models (presence of plaques; OR 1.285 [1.040-1.587]; ≥3 plaques, OR 1.377 [1.036-1.829]). CONCLUSIONS: The NLR was independently and directly associated with carotid plaque burden in T1D individuals. Our data support the role of innate versus. Adaptative immunity in atherosclerosis also among the T1D population.

Impact of preeclampsia and parity on sex-based discrepancies in subclinical carotid atherosclerosis in type 1 diabetes.

CONTEXT: The excess risk of fatal and non-fatal cardiovascular events is roughly twice as high in women than in men with type 1 diabetes (T1D). OBJECTIVE: To evaluate the impact of preeclampsia and parity on sex-based discrepancies in preclinical atherosclerosis and on the diagnostic performance of a cardiovascular risk scale. DESIGN: Cross-sectional study. SETTING: Single tertiary hospital. PATIENTS: 728 T1D (48.5% women) without cardiovascular disease and age ≥40 years, nephropathy, and/or ≥10 years of diabetes duration with another risk factor. INTERVENTION: Standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Carotid plaque determined by ultrasonography and cardiovascular risk estimated according to the Steno T1 Risk Engine (Steno-Risk). RESULTS: Nulliparous women and parous women without previous preeclampsia had a lower risk for carotid plaque than men (adjusted odds ratio [OR]: 0.48, 95% confidence interval [0.28-0.82]; adjusted OR: 0.51 [0.33-0.79], respectively), without differences in the preeclampsia group. The prevalence of carotid plaque increased as the estimated cardiovascular risk increased in all subgroups except for preeclampsia group. The area under the curve (AUC) of the Steno-Risk for identifying ≥2 carotid plaques was lower in the preeclampsia group (men: 0.7886, nulliparous women: 0.9026, women without preeclampsia: 0.8230, preeclampsia group: 0.7841; p between groups=0.042). Neither the addition of parity nor preeclampsia in the Steno-Risk led to a statistically significant increase in the AUC. CONCLUSIONS: The risk for carotid plaque in women compared to men decreased as exposure to obstetric factors diminished. However, the addition of these factors did not improve the prediction of the Steno-Risk.

Impact of conducting a genetic study on the management of familial hypercholesterolemia.

BACKGROUND: Clinically diagnosed familial hypercholesterolemia (FH) may require a genetic test (GT) to confirm diagnosis. GT availability/accessibility is resource-dependent and usually restricted to specialized clinics. While GT has a diagnostic value, it has not yet defined its impact on long-term management and prognosis of FH. OBJECTIVE: The aim was to identify the clinical characteristics associated with the request for a GT in suspected heterozygous FH. METHODS: Retrospective study including adult patients with clinically suspected to be FH. Positive GT (GT+) was defined as having a pathogenic/likely pathogenic variant. Patients were stratified based on whether they had a genetic study conducted, and among those with a genetic study, according to those who did or did not have a GT+. RESULTS: From 4854 patients included, 3090 were performed a GT (GT+: 2113). Median follow-up: 6.2 years. A younger age, FH-related physical signs, premature coronary disease, higher low-density lipoprotein cholesterol (LDLc) and lower body mass index and triglycerides, associated higher odds of being conducted a genetic study. These patients had higher baseline LDLc (252 mg/dL vs. 211 mg/dL among clinically diagnosed patients) and experienced larger reductions over the follow-up (157.7 mg/dL vs. 113.5 mg/dL, respectively). A similar pattern was observed among patients with GT+ (vs. negative GT). LDLc target attainment was low but increased to 66-95% when a triple combination with statin/ezetimibe/proprotein convertase subtilisin kexin type 9-inhibitor was used. Cardiovascular events occurred in 3.2% and 3.1% of patients who conducted/not conducted a genetic study. Patients conducted a genetic analysis and those with GT+ tended to present the events earlier. CONCLUSIONS: Genetic study, vs. having a clinical-only diagnosis, impacts the management of FH. Cardiovascular prognosis was similar in both groups, perhaps as a result of the more intensive management of patients with a genetic study.

Impaired hypoglycaemia awareness in early pregnancy increases risk of severe hypoglycaemia in the mid-long term postpartum irrespective of breastfeeding status in women with type 1 diabetes.

INTRODUCTION: Information regarding the postpartum period in women with type 1 diabetes (T1D) is scarce. We aim to evaluate the relation of impaired hypoglycaemia awareness (IAH) in early pregnancy and breastfeeding status (its presence and duration) with severe postpartum hypoglycaemia (SH). MATERIALS AND METHODS: Retrospective cohort study of women with T1D followed during pregnancy between 2012 and 2019. Data on SH were recorded before and during pregnancy. IAH was evaluated at the first antenatal visit. Data on breastfeeding and the long-term postpartum period were collected by questionnaire and from medical records. RESULTS: A total of 89 women with T1D were included with a median follow-up after pregnancy of 19.2 [8.7-30.5] months. Twenty-eight (32%) women had IAH at the first antenatal visit. At discharge, 74 (83%) started breastfeeding during a median of 8 [4.4-15] months. A total of 18 (22%) women experienced ≥1 SH during postpartum. The incidence of SH significantly increased from pregestational to the gestational and post-partum period (0.09, 0.15 and 0.25 episodes/patient-year, respectively). Postpartum SH rates were comparable in breastfeeding and non-breastfeeding women (21.4% vs. 25%, respectively, p>0.05). Clarke test score at the first antenatal visit was associated with postpartum SH (for each 1-point increase: OR 1.53; 95% CI, 1.06-2.21) adjusted for confounders. No other diabetes and pregnancy-related variables were identified as predictors of SH in this period. CONCLUSIONS: SH are common in the long-term postpartum period independently of breastfeeding. Assessing IAH in early pregnancy could identify those at an increased risk of SH in the postpartum period.

Role of Muscle Ultrasound for the Study of Frailty in Elderly Patients with Diabetes: A Pilot Study.

BACKGROUND: Sarcopenia and diabetes contribute to the development of frailty. Therefore, accessible methods, such as muscle ultrasounds (MUSs), to screen for sarcopenia should be implemented in clinical practice. METHODS: We conducted a cross-sectional pilot study including 47 patients with diabetes (mean age: 77.72 ± 5.08 years, mean weight: 75.8 kg ± 15.89 kg, and body mass index: 31.19 ± 6.65 kg/m2) categorized as frail by the FRAIL Scale or Clinical Frailty Scale and confirmed by Fried's Frailty Phenotype or Rockwood's 36-item Frailty Index. We used the SARC-F questionnaire to identify sarcopenia. The Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) tests were used to assess physical performance and the risk of falls, respectively. In addition, other variables were measured: fat-free mass (FFM) and Sarcopenia Risk Index (SRI) with the bioimpedance analysis (BIA); thigh muscle thickness (TMT) of the quadriceps with MUS; and hand-grip strength with dynamometry. RESULTS: We observed correlations between the SARC-F and FFM (R = -0.4; p < 0.002) and hand-grip strength (R = -0.5; p < 0.0002), as well as between the TMT and FFM of the right leg (R = 0.4; p < 0.02) and the SRI (R = 0.6; p < 0.0001). We could predict sarcopenia using a logistic regression model with a ROC curve (AUC = 0.78) including FFM, handgrip strength, and TMT. The optimal cut-off point for maximum efficiency was 1.58 cm for TMT (sensitivity = 71.4% and specificity = 51.5%). However, we did not observe differences in the TMT among groups of greater/less frailty based on the SARC-F, SPPB, and TUG (p > 0.05). CONCLUSIONS: MUSs, which correlated with the BIA (R = 0.4; p < 0.02), complemented the diagnosis, identifying regional sarcopenia of the quadriceps in frail patients with diabetes and improving the ROC curve to AUC = 0.78. In addition, a TMT cut-off point for the diagnosis of sarcopenia of 1.58 cm was obtained. Larger studies to validate the MUS technique as a screening strategy are warranted.

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk.

BACKGROUND AND AIMS: People with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D. METHODS AND RESULTS: Cross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (1H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [7-8]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204-0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590-0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495-0.968]; p = 0.032), 1H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026-1.275]; p = 0.015), and 1H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019-1.361], p = 0.026) remained associated with atherosclerosis. CONCLUSIONS: In adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.

The Medtronic 780G advanced hybrid closed-loop system achieves and maintains good glycaemic control in type 1 diabetes adults despite previous treatment.

INTRODUCTION: Improvements in continuous glucose monitoring (CGM) in recent years have changed the treatment of type 1 diabetes (T1D) by permitting the automation of glucose control. The Minimed 780G advanced hybrid closed-loop (ACHL) system adapts basal infusion rates and delivers auto-correction boluses in order to achieve a user-decided glucose target (100, 110 or 120mg/dL). This study set out to evaluate the effectiveness of the Medtronic 780G system in real-life conditions over 6 months. MATERIALS AND METHODS: Prospective study that included T1D subjects previously treated with insulin pump without CGM (pump group) or with sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS group) who started with the Minimed 780G system. Sensor and pump data from baseline, and at 1, 3 and 6 months were downloaded and HbA1c was recorded at baseline and at 6 months. RESULTS: Fifty T1D subjects were included; 25 were previous SAP-PLGS 640G users and 25 used 640G without CGM. 66% were female, 48.6 (40-57) years of age with 20 (12-31.5) years of diabetes duration. Time in range (TIR) improved in the total cohort from baseline to 6 months (69% (57.7-76) vs. 74% (70-82); p=0.01 as did HbA1c (7.6% (7.1-7.8) vs. 7.0% (6.8-7.5); p<0.001), with improvement in times <54, >180 and >250mg/dL. Outcomes at 6 months did not differ between groups, although the SAP-PLGS subjects were prone to hypoglycaemia and the pump group mainly presented suboptimal metabolic control. CONCLUSION: The AHCL Medtronic Minimed 780G system achieves and maintains good glycaemic control over 6 months in real-life conditions in different profiles of T1D subjects.

Nuclear Magnetic Resonance-Based Lipidomics in the Assessment of Cardiometabolic Risk in Type 1 Diabetes: An Exploratory Analysis.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in type 1 diabetes (T1D). However, there is a need for daily practice tools for identifying those more prone to suffer from these events. We aimed to assess the relationships between nuclear magnetic resonance (1H NMR)-based lipidomic analysis and several CVD risk variables (including preclinical carotid atherosclerosis) in individuals with T1D at high risk. METHODS: We included patients with T1D without CVD, with at least one of the following: age ≥ 40 years, diabetic kidney disease, or ≥ 10 years of evolution with another risk factor. The presence of plaque (intima-media thickness > 1.5 mm) was determined by standardized ultrasonography protocol. Lipidomic analysis was performed by 1H NMR. Bivariate and multivariate-adjusted differences in 1H NMR lipidomics were evaluated. RESULTS: We included n = 131 participants (49.6% female, age 46.4 ± 10.3 years, diabetes duration 27.0 ± 9.5 years, 47.3% on statins). Carotid plaques were present in 28.2% of the individuals (n = 12, with ≥ 3 plaques). Glucose (HbA1c), anthropometric (body mass index and waist circumference), and insulin resistance-related (fatty liver index and estimated glucose disposal rate) variables were those most associated with 1H NMR-derived lipidomic analysis (p < 0.01 for all). Regarding preclinical atherosclerosis, sphingomyelin was independently associated with carotid plaque presence (for 0.1 mmol/L increase, OR 0.50 [0.28-0.86]; p = 0.013), even after adjusting for age, sex, hypertension, statin use, mean 5-year HbA1c and diabetes duration. Furthermore, linoleic acid and ω-6 fatty acids remained independently associated with higher plaque burden (≥ 3 plaques) in multivariate models (0.17 [0.03-0.93] and 0.27 [0.07-0.97], respectively; p < 0.05 for both). CONCLUSION: In our preliminary study of individuals with T1D at high risk, several 1H NMR-derived lipidomic parameters were independently associated with preclinical atherosclerosis. Specifically, ω-6 fatty acids and linoleic acid seem promising for identifying those with higher plaque burden.

Role of Excessive Weight Gain During Gestation in the Risk of ADHD in Offspring of Women With Gestational Diabetes.

CONTEXT: Although attention-deficit/hyperactivity disorder (ADHD) has been associated with gestational diabetes mellitus (GDM) and maternal obesity, excessive weight gain (EWG) during pregnancy has scarcely been evaluated. OBJECTIVE: This study aimed to assess the joint effect of maternal weight and EWG on the risk of ADHD in offspring of GDM pregnancies. METHODS: In this cohort study of singleton births >22 weeks of gestation of women with GDM between 1991 and 2008, gestational weight gain above the National Academy of Medicine (NAM) recommendations was classified into EWG. Cox-regression models estimated the effect of maternal pregestational weight and EWG on the risk of ADHD (identified from medical records), adjusted for pregnancy outcomes and GDM-related variables. RESULTS: Of 1036 children who were included, with a median follow-up of 17.7 years, 135 (13%) were diagnosed with ADHD. ADHD rates according to pregestational maternal weight were 1/14 (7.1%) for underweight, 62/546 (11.4%) for normal weight, 40/281 (14.2%) for overweight, and 32/195 (16.4%) for obesity. Only maternal obesity was independently associated with ADHD (HRadjusted 1.66 [95% CI, 1.07-2.60]), but not maternal overweight or EWG. On evaluating the joint contribution of maternal weight and EWG, maternal obesity with EWG was associated with the highest risk of ADHD (vs normal weight without EWG; HRadjusted 2.13 [95% CI, 1.14-4.01]). Pregestational obesity without EWG was no longer associated (HRadjusted 1.36 [95% CI, 0.78-2.36]). CONCLUSION: Among GDM pregnancies, pregestational obesity was associated with a higher risk of ADHD in offspring. Nonetheless, when gestational weight gain was taken into account, only the joint association of obesity and EWG remained significant.

Use of the Steno T1 Risk Engine Identifies Preclinical Atherosclerosis Better Than Use of ESC/EASD-2019 in Adult Subjects With Type 1 Diabetes at High Risk.

OBJECTIVE: To evaluate the concordance between the 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD (ESC/EASD-2019) and the Steno T1 Risk Engine (Steno-Risk) cardiovascular risk scales for individuals with type 1 diabetes (T1D) without cardiovascular disease (CVD) and to analyze the relationships of their use with identification of preclinical atherosclerosis. RESEARCH DESIGN AND METHODS: We consecutively selected patients with T1D, without CVD, age ≥40 years, with nephropathy, and/or with ≥10 years of T1D evolution with another risk factor. The presence of plaque at different carotid segments was determined by ultrasonography. Cardiovascular risk was estimated in accord with ESC/EASD-2019 risk groups (moderate/high/very high) and the Steno-Risk (<10%, low; 10-20%, moderate; ≥20%, high), as T1D-specific scores. In an exploratory analysis, we also evaluated the non-T1D-specific 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk (ACC/AHA-2013) pooled cohort equation for individuals between 40 and 79 years of age. RESULTS: We included 501 patients (53% men, mean age 48.8 years, median T1D duration 26.5 years, 41.3% harboring plaques). Concordance between T1D-specific scales was poor (κ = 0.19). A stepped increase in the presence of plaques according to Steno-Risk category was seen (18.4%, 38.2%, and 64.1%, for low, moderate, and high risk, respectively; P for trend <0.001), with no differences according to ESC/EASD-2019 (P = 0.130). Steno-Risk identified individuals with plaques, unlike ESC/EASD-2019 (area under the curve [AUC] 0.691, P < 0.001, vs. AUC 0.538, P = 0.149). Finally, in polynomial regression models (with adjustment for lipid parameters and cardioprotective treatment), irrespective of the ESC/EASD-2019 category, high risk by Steno-Risk was directly associated with atherosclerosis (in moderate/high-risk by ESC/EASD-2019 odds ratio 2.91 [95% CI 1.27-6.72] and 4.94 [2.35-10.40] for the presence of plaque and two or more plaques). Similar results were obtained with discordant higher Steno-Risk versus ACC/AHA-2013 (P < 0.001). CONCLUSIONS: Among T1D patients undergoing primary prevention, use of Steno-Risk seems to result in better recognition of individuals with atherosclerosis in comparison with ESC/EASD-2019. Notwithstanding, carotid ultrasound could improve the categorization of cardiovascular risk.

Carotid ultrasonography as a strategy to optimize cardiovascular risk management in type 1 diabetes: a cohort study.

BACKGROUND AND AIMS: Although cardiovascular disease (CVD) remains the leading cause of mortality in type 1 diabetes (T1D), the use of cardioprotective drugs is scarce. We aimed to evaluate the impact of carotid ultrasonography (US) on the improvement in cardiovascular risk factors (CVRFs) in T1D. METHODS AND RESULTS: T1D patients without CVD meeting criteria for lipid treatment according to guidelines (age ≥ 40 years, nephropathy and/or ≥ 10 years of diabetes duration with ≥ 1 additional CVRFs) were included. The carotid-US group (US-G) underwent a standardized US protocol and CVRF assessment; recommendations were made according to subclinical atherosclerosis status. The control group (CG) followed usual clinical practice. Changes in CVRFs, specially statin use and LDL cholesterol levels, at 1 year were analysed. A total of 318 patients were included (51.3% female, mean age of 49.1 years and 25.5 years of diabetes duration): 211 in the US-G and 107 in the CG. Participants in the US-G had a higher baseline LDL cholesterol than controls (114 vs. 102 mg/dL; p < 0.001). Lipid-lowering treatment was modified in 38.9% in the US-G and 6.5% in the CG (p < 0.001). At 1 year, the US-G was more frequently on statins, had lower LDL cholesterol and 27% had stopped smoking (p < 0.001 for all). Changes were more pronounced in those with plaques (p < 0.001). In multivariate analyses adjusted for age, sex and other CVRFs, belonging to the US-G was independently associated with the intensification of lipid-lowering treatment (OR 10.47 [4.06-27.01]). Propensity score-matching analysis yielded similar results (OR 20.09 [7.86-51.37]). CONCLUSION: Carotid-US is independently associated with an intensification of lipid-lowering therapy in a high-risk T1D population.

Hyperglycemia and hypoglycemia exposure are differentially associated with micro- and macrovascular complications in adults with Type 1 Diabetes.

AIMS: Evaluate the relationship between high and low exposure continuous glucose monitoring (CGM)-derived glucometrics and micro- and macrovascular complications in type 1 diabetes (T1D). METHODS: Cross-sectional study in T1D without cardiovascular disease (CVD) and with ≥ 1 of the following: ≥40 years, diabetic nephropathy, or ≥ 10 years of diabetes duration with CVD risk factors. Glucometrics were obtained over 14 consecutive days: glucose management indicator (GMI) and proportion of time < 54 (TBR < 54), <70, 70-180 (TIR), >180 (TAR). Carotid plaque was evaluated by ultrasonography. Logistic regression models adjusted for age, sex, and other risk factors were constructed to test the independent associations with chronic complications. RESULTS: We included 152 patients (54.6% men, 48.7 ± 10.0 years-old). Sixty-seven patients had plaque and n = 71 microvascular complications. TAR (OR 1.28 [1.09-1.51]) and GMI (OR 3.05 [1.46-6.36]) were directly associated with the presence of microvascular complications, while TIR had an inverse relationship (OR 0.79 [0.66-0.93]). TBR < 54 was directly associated with the presence of plaque, even after adjusting for 5-year mean HbA1c (OR 1.51 [1.07-2.13]). CONCLUSIONS: High-glucose glucometrics were independently associated with microvascular complications. Only low-glucose exposure glucometrics was significantly associated with preclinical atherosclerosis. Our data support the role of hypoglycemia in the development of CVD in this population.

Addition of intermittently scanned continuous glucose monitoring to standard care in a cohort of pregnant women with type 1 diabetes: effect on glycaemic control and pregnancy outcomes.

AIMS/HYPOTHESIS: The aim of this study was to assess whether the addition of intermittently scanned continuous glucose monitoring (isCGM) to standard care (self-monitoring of blood glucose [SMBG] alone) improves glycaemic control and pregnancy outcomes in women with type 1 diabetes and multiple daily injections. METHODS: This was a multicentre observational cohort study of 300 pregnant women with type 1 diabetes in Spain, including 168 women using SMBG (standard care) and 132 women using isCGM in addition to standard care. In addition to HbA1c, the time in range (TIR), time below range (TBR) and time above range (TAR) with regard to the pregnancy glucose target range (3.5-7.8 mmol/l) were also evaluated in women using isCGM. Logistic regression models were performed for adverse pregnancy outcomes adjusted for baseline maternal characteristics and centre. RESULTS: The isCGM group had a lower median HbA1c in the second trimester than the SMBG group (41.0 [IQR 35.5-46.4] vs 43.2 [IQR 37.7-47.5] mmol/mol, 5.9% [IQR 5.4-6.4%] vs 6.1% [IQR 5.6-6.5%]; p=0.034), with no differences between the groups in the other trimesters (SMBG vs isCGM: first trimester 47.5 [IQR 42.1-54.1] vs 45.9 [IQR 39.9-51.9] mmol/mol, 6.5% [IQR 6.0-7.1%] vs 6.4% [IQR 5.8-6.9%]; third trimester 43.2 [IQR 39.9-47.5] vs 43.2 [IQR 39.9-47.5] mmol/mol, 6.1% [IQR 5.8-6.5%] vs 6.1% [IQR 5.7-6.5%]). The whole cohort showed a slight increase in HbA1c from the second to the third trimester, with a significantly higher rise in the isCGM group than in the SMBG group (median difference 2.2 vs 1.1 mmol/mol [0.2% vs 0.1%]; p=0.033). Regarding neonatal outcomes, newborns of women using isCGM were more likely to have neonatal hypoglycaemia than newborns of non-sensor users (27.4% vs 19.1%; ORadjusted 2.20 [95% CI 1.14, 4.30]), whereas there were no differences between the groups in large-for-gestational-age (LGA) infants (40.6% vs 45.1%; ORadjusted 0.73 [95% CI 0.42, 1.25]), Caesarean section (57.6% vs 48.8%; ORadjusted 1.33 [95% CI 0.78, 2.27]) or prematurity (27.3% vs 24.8%; ORadjusted 1.05 [95% CI 0.55, 1.99]) in the adjusted models. A sensitivity analysis in pregnancies without LGA infants or prematurity also showed that the use of isCGM was associated with a higher risk of neonatal hypoglycaemia (non-LGA: ORadjusted 2.63 [95% CI 1.01, 6.91]; non-prematurity: ORadjusted 2.52 [95% CI 1.12, 5.67]). For isCGM users, the risk of delivering an LGA infant was associated with TIR, TAR and TBR in the second trimester in the logistic regression analysis. CONCLUSIONS/INTERPRETATION: isCGM use provided an initial improvement in glycaemic control that was not sustained. Furthermore, offspring of isCGM users were more likely to have neonatal hypoglycaemia, with similar rates of macrosomia and prematurity to those of women receiving standard care.

Usefulness of Muscle Ultrasound to Study Sarcopenic Obesity: A Pilot Case-Control Study.

Background and objectives: Sarcopenic obesity (SO) is an emerging problem, especially in candidates for bariatric surgery (BS). We hypothesized that musculoskeletal ultrasound (MUS), a simple and accessible method, could be a reliable index of SO. Materials and Methods: A cross-sectional pilot study including 122 subjects (90 cases and 32 controls, 73% female, mean age: 51.2 years) who underwent BS was conducted at University Hospital Mútua Terrassa. The lean mass (LM) was calculated by bioelectrical impedance analysis (BIA) and the thigh muscle thickness (TMT) by MUS. To identify the subjects with SO by BIA, we used skeletal muscle index (SMI). The validity of MUS was determined using the ROC curve. Results: The mean BMI in the obesity group was 44.22 kg/m2. We observed a correlation between the LM and SMI assessed by BIA and the TMT assessed by MUS (R = 0.46, p < 0.001). This correlation was maintained at significant levels in the SO group (n = 40): R = 0.79; p = 0.003). The TMT assessed by MUS was able to predict SMI using BIA (AUC 0.77; 95% CI: 0.68242 to 0.84281). The optimal cut-off point for maximum efficiency was 1.57 cm in TMT (sensitivity = 75.6% and specificity = 71.1%). Conclusions: The TMT of the quadriceps assessed by US is a useful tool for identifying subjects with SO. Larger studies to validate this simple low-cost screening strategy are warranted.