Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes.

BACKGROUND: Diabetes is a major risk factor for atherosclerotic cardiovascular diseases with a 2-fold higher risk of cardiovascular events in people with diabetes compared with those without. Circulating monocytes are inflammatory effector cells involved in both type 2 diabetes (T2D) and atherogenesis. METHODS: We investigated the relationship between circulating monocytes and cardiovascular risk progression in people with T2D, using phenotypic, transcriptomic, and metabolomic analyses. cardiovascular risk progression was estimated with coronary artery calcium score in a cohort of 672 people with T2D. RESULTS: Coronary artery calcium score was positively correlated with blood monocyte count and frequency of the classical monocyte subtype. Unsupervised k-means clustering based on monocyte subtype profiles revealed 3 main endotypes of people with T2D at varying risk of cardiovascular events. These observations were confirmed in a validation cohort of 279 T2D participants. The predictive association between monocyte count and major adverse cardiovascular events was validated through an independent prospective cohort of 757 patients with T2D. Integration of monocyte transcriptome analyses and plasma metabolomes showed a disruption of mitochondrial pathways (tricarboxylic acid cycle, oxidative phosphorylation pathway) that underlined a proatherogenic phenotype. CONCLUSIONS: In this study, we provide evidence that frequency and monocyte phenotypic profile are closely linked to cardiovascular risk in patients with T2D. The assessment of monocyte frequency and count is a valuable predictive marker for risk of cardiovascular events in patients with T2D. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04353869.

Heterogeneity of glycaemic phenotypes in type 1 diabetes.

AIMS/HYPOTHESIS: Our study aims to uncover glycaemic phenotype heterogeneity in type 1 diabetes. METHODS: In the Study of the French-speaking Society of Type 1 Diabetes (SFDT1), we characterised glycaemic heterogeneity thanks to a set of complementary metrics: HbA1c, time in range (TIR), time below range (TBR), CV, Gold score and glycaemia risk index (GRI). Applying the Discriminative Dimensionality Reduction with Trees (DDRTree) algorithm, we created a phenotypic tree, i.e. a 2D visual mapping. We also carried out a clustering analysis for comparison. RESULTS: We included 618 participants with type 1 diabetes (52.9% men, mean age 40.6 years [SD 14.1]). Our phenotypic tree identified seven glycaemic phenotypes. The 2D phenotypic tree comprised a main branch in the proximal region and glycaemic phenotypes in the distal areas. Dimension 1, the horizontal dimension, was positively associated with GRI (coefficient [95% CI]) (0.54 [0.52, 0.57]), HbA1c (0.39 [0.35, 0.42]), CV (0.24 [0.19, 0.28]) and TBR (0.11 [0.06, 0.15]), and negatively with TIR (-0.52 [-0.54, -0.49]). The vertical dimension was positively associated with TBR (0.41 [0.38, 0.44]), CV (0.40 [0.37, 0.43]), TIR (0.16 [0.12, 0.20]), Gold score (0.10 [0.06, 0.15]) and GRI (0.06 [0.02, 0.11]), and negatively with HbA1c (-0.21 [-0.25, -0.17]). Notably, socioeconomic factors, cardiovascular risk indicators, retinopathy and treatment strategy were significant determinants of glycaemic phenotype diversity. The phenotypic tree enabled more granularity than traditional clustering in revealing clinically relevant subgroups of people with type 1 diabetes. CONCLUSIONS/INTERPRETATION: Our study advances the current understanding of the complex glycaemic profile in people with type 1 diabetes and suggests that strategies based on isolated glycaemic metrics might not capture the complexity of the glycaemic phenotypes in real life. Relying on these phenotypes could improve patient stratification in type 1 diabetes care and personalise disease management.

Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1.

INTRODUCTION & OBJECTIVES: To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020-2022 and sex inequalities in achievement of standards of care in diabetes. METHODS: We used 2020-2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète- Cohorte Diabète de Type 1 cohort (SFDT1), in France. RESULTS: We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). CONCLUSION: In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies.

Should people with type 2 diabetes treated by multiple daily insulin injections with home health care support be switched to hybrid closed-loop? The CLOSE AP+ randomized controlled trial.

AIM: The study aim was to evaluate the feasibility, safety and efficacy of automated insulin delivery (AID) assisted by home health care (HHC) services in people with type 2 diabetes unable to manage multiple daily insulin injections (MDI) at home on their own. PATIENTS AND METHODS: This was an open label, multicentre, randomized, parallel group trial. In total, 30 adults with type 2 diabetes using MDI and requiring nursing support were randomly allocated to AID or kept their usual therapy over a 12-week period. Both treatments were managed with the support of HHC services. The primary outcome was the percentage time in the target glucose range of 70-180 mg/dl (TIR). Secondary outcomes included other continuous glucose monitoring metrics, glycated haemoglobin (HbA1c) levels, daily insulin doses, body weight, and of quality of life scores, fear of hypoglycaemia and satisfaction questionnaires. RESULTS: Age (69.7 vs. 69.3 years) and HbA1c (9.25 vs. 9.0) did not differ in MDI and AID at baseline. Compared with MDI, AID resulted in a significant increase in TIR by 27.4% [95% CI (15.0-39.8); p < .001], a decrease in time above range by 27.7% and an unchanged time below range of <1%. A between-group difference in HbA1c was 1.3% favouring AID. Neither severe hypoglycaemia nor ketoacidosis occurred in either group. Patient and caregiver satisfaction with AID was high. CONCLUSIONS: AID combined with tailored HHC services significantly improved glycaemic control with no safety issues in people with type 2 diabetes previously under an MDI regimen with HHC. AID should be considered a safe option in these people when lacking acceptable glucose control.

Reduction of clinically important low glucose excursions with a long-term implantable continuous glucose monitoring system in adults with type 1 diabetes prone to hypoglycaemia: the France Adoption Randomized Clinical Trial.

AIM: To assess the glucose control outcomes of the implantable Eversense real-time continuous glucose monitoring (CGM) system compared to self-monitoring of blood glucose or intermittently scanned CGM in patients with type 1 (T1D) or type 2 diabetes (T2D). PATIENTS AND METHODS: This was a randomized (2:1), prospective, national, multicentre study. All participants, aged >18 years and on multiple daily insulin injections or insulin pump treatment, had a sensor inserted, which was activated only in the "enabled" group. Included patients had T1D or T2D with a glycated haemoglobin (HbA1c) level > 8% (64 mmol/mol) (Cohort 1) or T1D with a time spent with glucose values below 70 mg/dL (3.8 mmol/l) (TBR<70 ) for >1.5 h/d during the previous 28 days (Cohort 2). The primary outcomes were HbA1c change at D180 (Cohort 1) or change in time spent with glucose values below 54 mg/dL (TBR<54 ) during the period of Day (D)90 to D120 (Cohort 2). A covariance model (analyses of covariance) was used for endpoint analyses. RESULTS: Overall, 149 patients were included in Cohort 1 and 90 in Cohort 2. In Cohort 1, the adjusted mean difference (enabled - control) in HbA1c at D180 was -0.1% (95% confidence interval [CI] -0.4; 0.1; P = 0.341). No significant difference in time with values in the range 70 to 180 mg/dL or time with values above range (>180 mg/dL) was observed. In Cohort 2, the mean adjusted difference in TBR<54 was -1.6% (95% CI -3.1; -0.1; P = 0.039) during D90 to D120 and remained at -2.6% (95% CI -4.5; -0.6; P = 0.011) during D150 to D180 (prespecified secondary outcome). The CGM system was found to be safe. CONCLUSION: This study shows that the Eversense CGM system can significantly decrease TBR<54 in patients with T1D prone to hypoglycaemia.

Real world hypoglycaemia related to glucose variability and Flash glucose scan frequency assessed from global FreeStyle Libre data.

AIM: Flash glucose monitoring provides a range of glucose metrics. In the current study, we aim to identify those that indicate that glycaemic targets can be consistently met and contrast the total (t-CV) and within-day coefficient of variation (wd-CV) to guide the assessment of glucose variability and hypoglycaemia exposure. METHODS: De-identified data from Flash readers were collected. The readers were sorted into 10 equally sized groups of scan frequency followed by quartiles of estimated A1c (eA1c). A similar grouping was performed for the total coefficient of variation (t-CV) and within-day coefficient of variation (wd-CV). In addition, analysis of the association of time below 54 mg/dl and glucose variability measured by t-CV and wd-CV was performed. RESULTS: The dataset included 1 002 946 readers. Readers sorted by 10 equal groups of scan rate and quartiles by eA1c, t-CV and wd-CV represented 25 074 readers per group. The association of lower eA1c with higher time in range and reduced time above range was clear. The correlation of eA1c quartiles and time below range was not consistent. An association between glucose variability and hypoglycaemia was found. Both wd-CV and t-CV were associated with time below range. For achieving the consensus target of <1% time below 54 mg/dl, the associated wd-CV and t-CV values were 33.5% and 39.5%, respectively. CONCLUSIONS: The type of CV reported by the different continuous glucose monitoring systems should be acknowledged. CV <36% might not be adequate to ensure low hypoglycaemia exposure. To our knowledge, the majority of continuous glucose monitoring reports the t-CV. Appropriate thresholds should be used to identify patients that would probably meet time below range targets (t-CV <40% or wd-CV <34%).

The COVID-19 lockdown as an opportunity to change lifestyle and body weight in people with overweight/obesity and diabetes: Results from the national French COVIDIAB cohort.

BACKGROUND AND AIMS: To analyze lifestyle habits and weight evolution during the COVID-19 pandemic-associated lockdown, in diabetes and overweight/obesity patients (body mass index (BMI) [25-29.9] and ≥30 kg/m2, respectively). METHODS AND RESULTS: We collected information on participants' characteristics and behavior regarding lifestyle before and during the lockdown, through the CoviDIAB web application, which is available freely for people with diabetes in France. We stratified the cohort according to BMI (≥25 kg/m2vs < 25 kg/m2) and examined the determinants of weight loss (WL), WL > 1 kg vs no-WL) in participants with a BMI ≥25 kg/m2, in both univariate and multivariate analyses. Of the 5280 participants (mean age, 52.5 years; men, 49%; diabetes, 100% by design), 69.5% were overweight or obese (mean BMI, 28.6 kg/m2 (6.1)). During the lockdown, patients often quit or decreased smoking; overweight/obese participants increased alcohol consumption less frequently as compared with normal BMI patients. In addition, overweight/obese patients were more likely to improve other healthy behaviors on a larger scale than patients with normal BMI: increased intake of fruits and vegetables, reduction of snacks intake, and reduction of total dietary intake. WL was observed in 18.9% of people with a BMI ≥25 kg/m2, whereas 28.6% of them gained weight. Lifestyle favorable changes characterized patients with WL. CONCLUSIONS: A significant proportion of overweight/obese patients with diabetes seized the opportunity of lockdown to improve their lifestyle and to lose weight. Identifying those people may help clinicians to personalize practical advice in the case of a recurrent lockdown.

Prevalence, severity stages, and risk factors of diabetic retinopathy in 1464 adult patients with type 1 diabetes.

PURPOSE: To determine the prevalence of diabetic retinopathy (DR) and its risk factors in adult type 1 diabetes (T1D) patients METHODS: In this cross-sectional study, all T1D patients followed in the University Center for Diabetes and its Complications of Lariboisière Hospital (Paris, France) between January 2017 and February 2019 were included. Ophthalmologic and systemic data were collected from electronic records. The association between DR (and each grade) and associated factors were estimated by univariate and multivariate analyses using logistic regression models. RESULTS: A total of 1464 patients (46.2% of women, mean age: 42.2 ± 15.8 years) were included. The mean hemoglobin A1c (HbA1c) was 7.8 ± 1.7% and the mean diabetes duration was 20.5 ± 13.5 years. DR prevalence was 50.1% (47.4-52.6) and the prevalence of mild, moderate, and severe non-proliferative DR and proliferative DR was 19.1%, 9.4%, 3.9%, and 17.6%, respectively. DR was significantly associated with male gender, an older age, former and current smoking status, a higher BMI, the presence of nephropathy and neuropathy, higher HBA1c, and longer diabetes duration. Patients with HbA1c > 10% had an adjusted odds ratio (OR) of 3.25 (1.77-6.01) of having DR compared to patients with HbA1c < 6.5%. Patients with a diabetes duration > 30 years had an adjusted OR of 24.87 (14.82-42.67) higher of having DR compared to patients with a diabetes duration < 10 years. CONCLUSION: In this study, 50.1% of adult T1D patients had DR and 17.6% had proliferative DR. Diabetes duration and HbA1c were major risk factors.

Correction to: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

The authors regret a mistake in Table 1.

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.

Gout and pseudo-gout-related crystals promote GLUT1-mediated glycolysis that governs NLRP3 and interleukin-1ß activation on macrophages.

OBJECTIVE: Macrophage activation by monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals mediates an interleukin (IL)-1ß-dependent inflammation during gout and pseudo-gout flare, respectively. Since metabolic reprogramming of macrophages goes along with inflammatory responses dependently on stimuli and tissue environment, we aimed to decipher the role of glycolysis and oxidative phosphorylation in the IL-1ß-induced microcrystal response. METHODS: Briefly, an in vitro study (metabolomics and real-time extracellular flux analysis) on MSU and CPP crystal-stimulated macrophages was performed to demonstrate the metabolic phenotype of macrophages. Then, the role of aerobic glycolysis in IL-1ß production was evaluated, as well in vitro as in vivo using 18F-fluorodeoxyglucose positron emission tomography imaging and glucose uptake assay, and molecular approach of glucose transporter 1 (GLUT1) inhibition. RESULTS: We observed that MSU and CPP crystals led to a metabolic rewiring toward the aerobic glycolysis pathway explained by an increase in GLUT1 plasma membrane expression and glucose uptake on macrophages. Also, neutrophils isolated from human synovial fluid during gout flare expressed GLUT1 at their plasma membrane more frequently than neutrophils isolated from bloodstream. Both glucose deprivation and treatment with either 2-deoxyglucose or GLUT1 inhibitor suppressed crystal-induced NLRP3 activation and IL-1ß production, and microcrystal inflammation in vivo. CONCLUSION: In conclusion, we demonstrated that GLUT1-mediated glucose uptake is instrumental during the inflammatory IL-1ß response induced by MSU and CPP crystals. These findings open new therapeutic paths to modulate crystal-related inflammation.

Non-severe hypoglycaemia is associated with weight gain in patients with type 1 diabetes: Results from the Diabetes Control and Complication Trial.

It is unclear whether the frequent non-severe episodes of hypoglycaemia observed during intensive glucose control in individuals with type 1 diabetes (T1D) are associated with subsequent weight gain. We analysed the association between non-severe hypoglycaemia and weight gain in 1441 Diabetes Control and Complication Trial (DCCT) participants. Non-severe hypoglycaemia was assessed by hypo-score (ie, number of blood glucose values <70 mg/dL divided by the total number of measurements during the DCCT quarterly visits). Significant associations were observed between the hypo-score and annual and total weight gain. The annual weight gain by hypo-score tertiles was 0.8 ± 1.2 (T1), 1.3 ± 1.5 (T2) and 1.4 ± 1.3 kg/y (T3), P < .001 for T2 and T3 vs T1, and for T3 vs T2. The odds ratio for a weight gain of 1.8 kg/y was 2.14 (95% CI, 1.56-2.93) for T2, and 2.53 (95%CI, 1.85-3.45) for T3 vs T1. These differences in weight gain and in risk of weight gain remained significant after adjustment for sex, age, duration of diabetes, HbA1c at baseline and treatment arms. In conclusion, our analysis shows a significant association between non-severe hypoglycaemia and weight gain in individuals with T1D from the DCCT.

Real-time continuous glucose monitoring in type 1 diabetes: a systematic review and individual patient data meta-analysis.

BACKGROUND: Real-time continuous glucose monitoring (RTCGM) may help in the management of individuals with type 1 diabetes mellitus (T1DM); however, the evidence supporting its use is unclear. The available meta-analyses on this topic use aggregate data which weaken inference. OBJECTIVE: Individual patient data were obtained from randomized controlled trials (RCTs) to conduct a meta-analysis and synthesize evidence about the effect of RTCGM on glycosylated haemoglobin (HbA1c), hypoglycaemic events and time spent in hypoglycaemia in T1DM. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus through January 2015. We included RCTs that enrolled individuals with T1DM and compared RTCGM vs control group. A two-step regression model was used to pool individual patient data. RESULTS: We included 11 RCTs at moderate risk of bias. Meta-analysis suggests that the use of RTCGM is associated with a statistically significant but modest reduction in HbA1c (-0·276; 95% confidence interval -0·465 to -0·087). The improvements in HbA1c were primarily seen in individuals over age 15 years. We were unable to identify a statistically significant difference in time spent in hypoglycaemia or the number of hypoglycaemic episodes although these analyses were imprecise and warrant lower confidence. There was no difference between males and females. CONCLUSION: RTCGM in T1DM is associated with a reduction in HbA1c primarily in individuals over 15 years of age. We were unable to identify a statistically significant difference in the time spent in hypoglycaemia or the incidence of hypoglycaemic episodes.

Reduced Rate of Hospitalizations for Acute Diabetes Events Before and After FreeStyle Libre® System Initiation in Some People With Type 2 Diabetes on Insulin-Secretagogue Oral Drug Therapy Without Insulin in France.

Objective: Glycemic management in people with type 2 diabetes mellitus (T2DM) on insulin-secretagogue regimens without insulin is of importance, as this group still represents a significant proportion of patients. Risks for acute diabetes events (ADEs), including diabetic ketoacidosis (DKA) or hypoglycemia, using insulin-secretagogue drugs are well established. Few studies have suggested that continuous glucose monitoring (CGM) could be useful for monitoring glucose dynamics associated with the use of such therapies. To document this point an exploratory analysis was conducted in a group of individuals with noninsulin treated T2DM in France who are managed with oral insulin-secretagogues and initiating the FreeStyle Libre® system (FSL). Methods: A retrospective study of the French national SNDS reimbursement claims database (≈66 million French people) was conducted to identify people with T2DM on oral insulin-secretagogues and receiving a first reimbursement of FSL between August 1, 2017 and December 31, 2018. The analysis included data for the 12 months before and up to 24 months after FSL initiation. Hospitalizations for diabetes-related acute events were identified using ICD-10 codes as main or related diagnosis, for: hypoglycemic events; DKA events; comas; and hyperglycemia-related admissions. Results: A total of 1272 people with T2DM on insulin-secretagogues without insulin initiated FSL during the selection period. Of these, 7.15% had at least one hospitalization for any ADE in the year before FSL initiation, compared with 2.52% at 12 months and 2.83% at 24 months following FSL initiation. Reductions in ADEs were driven by -73% fewer admissions for ADEs related to diabetic ketoacidosis (DKA) or other hyperglycemia-related events. These patterns of reduced ADEs persisted after 2 years. Conclusions: This study suggests the value of the FSL system in reducing ADEs in some people with T2DM in France being treated with insulin-secretagogues without insulin. Characteristics of these patients remain to be documented.

Assessment of the Impact of Subcutaneous Catheter Change on Glucose Control in Patients with Type 1 Diabetes Treated by Insulin Pump in Open- and Closed-Loop Modes.

Introduction: Most continuous subcutaneous insulin infusion (CSII) catheters (KT) are changed every 3 days. This study aims at evaluating whether KT changes impact glucose control while under open-loop (OL) or automated insulin delivery (AID) modes. Methods: We included patients with type 1 diabetes who used Tandem t:slim x2 insulin pump and Dexcom G6 glucose sensor for 20 days in OL, then as AID. CSII and sensor glucose data in OL and for the past 20 days of 3-month AID were retrospectively analyzed. The percentage of time spent with sensor glucose above 180 mg/dL (%TAR180) was compared between the calendar day of KT change (D0), the next day (D1), and 2 days later (D2). Values were adjusted for age, gender, body mass index (BMI), hemoglobin A1c (HbA1c) at inclusion, and %TAR180 for the 2 h before KT change. Results: A total of 1636 KT changes were analyzed in 134 patients: 72 women (54%), age: 35.6 ± 15.7 years, BMI: 25.2 ± 4.7 kg/m2, and HbA1c: 7.5 ± 0.8%. %TAR180 in the 2 h before the KT change was 51.3 ± 37.0% in OL and 33.2 ± 30.0% in AID mode. In OL, significant absolute increases of %TAR180 at D0 versus D1 (+6.9%; P < 0.0001) or versus D2 (+6.8%; P < 0.0001) were observed. In AID, significant absolute increases of %TA180R at D0 versus D1 (+4.8%; P < 0.0001) or versus D2 (+4.2%; P < 0.0001) were also observed. Conclusion: This study shows an increase in time spent in hyperglycemia on the day of the KT change both in OL and AID modes. This additional information should be taken into account to improve current AID algorithms. ClinicalTrials.gov: NCT04939766.

Efficacy and Safety of a Tubeless AID System Compared With Pump Therapy With CGM in the Treatment of Type 1 Diabetes in Adults With Suboptimal Glycemia: A Randomized, Parallel-Group Clinical Trial.

OBJECTIVE: To examine the efficacy and safety of the tubeless Omnipod® 5 Automated Insulin Delivery (AID) System compared with pump therapy with a continuous glucose monitor (CGM) in adults with type 1 diabetes with suboptimal glycemic outcomes. RESEARCH DESIGN AND METHODS: In this 13-week multicenter, parallel-group, randomized controlled trial performed in the U.S. and France, adults aged 18-70 years with type 1 diabetes and HbA1c 7-11% (53-97 mmol/mol) were randomly assigned (2:1) to intervention (tubeless AID) or control (pump therapy with CGM) following a 2-week standard therapy period. The primary outcome was a treatment group comparison of time in range (TIR) (70-180 mg/dL) during the trial period. RESULTS: A total of 194 participants were randomized, with 132 assigned to the intervention and 62 to the control. TIR during the trial was 4.2h/day higher in the intervention compared with the control group (mean difference 17.5% [95% CI 14.0%, 21.1%]; P < 0.0001). The intervention group had a greater reduction in HbA1c from baseline compared with the control group (mean ± SD -1.24 ± 0.75% [-13.6 ± 8.2 mmol/mol] vs. -0.68 ± 0.93% [-7.4 ± 10.2 mmol/mol], respectively; P < 0.0001), accompanied by a significantly lower time <70 mg/dL (1.18 ± 0.86% vs. 1.75 ± 1.68%; P = 0.005) and >180 mg/dL (37.6 ± 11.4% vs. 54.5 ± 15.4%; P < 0.0001). All primary and secondary outcomes were met. No instances of diabetes-related ketoacidosis or severe hypoglycemia occurred in the intervention group. CONCLUSIONS: Use of the tubeless AID system led to improved glycemic outcomes compared with pump therapy with CGM among adults with type 1 diabetes, underscoring the clinical benefit of AID and bolstering recommendations to establish AID systems as preferred therapy for this population.

Epidemiology and health impact of diabetes in France.

OBJECTIVES: Diabetes is a growing health concern. An update on epidemiology and health outcomes is mandatory to devise strategies to alleviate the burden of diabetes. The objective of this study was to assess the prevalence of diabetes and associated complications in France in 2017. METHODS: Demographics and healthcare data from a representative permanent secondary database were analyzed. Patients with at least 2 national health insurance payments for anti-diabetic drugs in 2017 were selected, with the index date set to the last payment date. Patients were grouped as diabetes treated with insulin only (DTi), diabetes treated with anti-diabetic drugs other than only insulin (DT2) or gestational diabetes. Comorbidities, diabetes-related complications and hospital admissions, healthcare consumption and medical follow-up were extracted for a 5- or 2-year period prior to the index date and summarized using descriptive statistics. RESULTS: Overal, 29,288 patients were included in the study population: 1964 (6.7%) were categorized as DTi and 27,243 (93.0%) as DT2. Patients with gestational diabetes (81 [0.3%]) are not further described here. Prevalence was estimated at 4.9%. For DT2, marked geographic disparities were observed, with prevalence being highest in the northeast France. Diabetes-related complications were more frequent in DTi than in DT2 over a 5-year period (52.2% vs 34.7%). Diabetes-related admissions were also more common in DTi than in DT2 over a 2-year period (29.8% vs 16.9%). In the DT2 category, another antidiabetic drug was added during the 3 months prior to the index date in 16.5% of cases overall and in 25% of patients with recent hospital admission or diabetes-related complications. Although more than 80% of patients in the DTi and DT2 categories had at least 1 healthcare consultation during 2 years prior to the index date, only 10% to 20% of patients complied with guidelines for all 5 recommended examinations. CONCLUSIONS: Prevalence of diabetes is high in the French population, while compliance with recommended healthcare consultations falls short of the 80% goal set by regulations. New strategies are mandatory in order to reduce the burden of diabetes-related complications and admissions, focusing on patient and physician information and education in order to increase proactive treatment adjustment and reduce therapeutic inertia.

Reduced Acute Diabetes Events After FreeStyle Libre System Initiation in People 65 Years or Older with Type 2 Diabetes on Intensive Insulin Therapy in France.

Background and Aims: Older people with type 2 diabetes (T2DM) on insulin are at increased risk of hypoglycemia and associated morbidity. Management of T2DM in older people must optimize glycemic control, while minimizing risks for hypoglycemia and diabetic ketoacidosis (DKA). In France, the FreeStyle Libre® (FSL) system has been reimbursed since June 2017 for T2DM on intensive insulin therapy. We assessed the impact of starting FSL on hospitalizations for acute diabetes events (ADEs) in people ≥65 years old, with T2DM on intensive insulin therapy. Materials and Methods: A retrospective study on the French Système National des Données de Santé (SNDS) claims database was conducted on people ≥65 years old with T2DM, treated with multiple daily injections (MDI) or insulin pump and starting FSL between August 1, 2017, to December 31, 2018. The analysis covered claims data for 12 months before, and up to 24 months after FSL initiation. Hospitalizations for severe hypoglycemia (SH), DKA, comas, and hyperglycemia were identified using ICD-10 codes. Results: We identified 38,312 people with T2DM ≥65 years old on intensive insulin therapy initiating FSL during the selection period. Hospitalizations for ADEs were observed in 1.6% of subjects in the 12 months before FSL initiation, compared to 1.05% after 12 months and 0.96% after 24 months, a -34% and -40% reduction, driven by fewer DKA admissions after 12 months and by fewer SH admissions at 24 months. Conclusions: These results indicate that FSL can reduce hospitalization for ADEs in this vulnerable older population of adults 65 years of age and older with T2DM on intensive insulin therapy, in whom optimal glycemic control must be achieved, while minimizing risk of hypoglycemia and other ADEs.