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.

Genetic predisposition to pheochromocytoma and paraganglioma: 21 years' experience in the field.

CONTEXT: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date. PURPOSE: To describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001-2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS). METHOD: The activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared. RESULTS: In total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX. CONCLUSION: Our experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.

Association Between Treatment Adherence and Continuous Glucose Monitoring Outcomes in People With Diabetes Using Smart Insulin Pens in a Real-World Setting.

OBJECTIVE: To evaluate the association of insulin injection adherence, smart insulin pen engagement, and glycemic control using real-world data from 16 countries from adults self-administering basal insulin degludec and bolus insulin with a smart insulin pen (NovoPen 6 or NovoPen Echo Plus) alongside continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS: Data were aggregated over 14-day periods. Treatment adherence was defined according to the number of missed basal and missed bolus insulin doses and smart pen engagement according to the number of days with data uploads. RESULTS: Data from 3,945 adults, including 25,157 14-day periods with ≥70% CGM coverage, were analyzed. On average, 0.2 basal and 6.0 bolus insulin doses were missed over 14 days. The estimated probability of missing at least one basal insulin dose over a 14-day period was 17.6% (95% CI 16.5, 18.7). Missing one basal or bolus insulin dose per 14 days was associated with a significant decrease in percentage of time with glucose levels in range (TIR) (3.9-10.0 mmol/L), of -2.8% (95% CI -3.7, -1.8) and -1.7% (-1.8, -1.6), respectively; therefore, missing two basal or four bolus doses would decrease TIR by >5%. Smart pen engagement was associated positively with glycemic outcomes. CONCLUSIONS: This combined analysis of real-world smart pen and CGM data showed that missing two basal or four bolus insulin doses over a 14-day period would be associated with a clinically relevant decrease in TIR. Smart insulin pens provide valuable insights into treatment injection behaviors.

Carbohydrate counting knowledge and ambulatory glucose profile in persons living with type 1 diabetes.

CONTEXT: The amount of consumed carbohydrates is the strongest factor influencing glucose levels during the four hours following a meal. Our aim was to evaluate the association between carbohydrate counting knowledge and continuous glucose monitoring (CGM) parameters in patients with type 1 diabetes (T1D) using different insulin regimens. METHOD: In this multicenter prospective study, the GluciQuizz questionnaire was used to evaluate carbohydrate knowledge. CGM data for the 14 days preceding completion of the questionnaire were analyzed. The primary endpoint was evaluation of the correlation between the GluciQuizz total score and time in range (TIR) in the study population. RESULTS: The mean age of the 170 participants was 40.7 ± 14.8 years and duration of T1D 18.8 ± 12.1 years. The mean GluciQuizz total score for all participants was 66 ± 13 %. Mean TIR was 58.6 ± 18.7 %. GluciQuizz total score positively correlated with TIR (r = 0.3001; p < 0.0001). This correlation was observed in CSII users (r = 0.2526; p < 0.05) but not in MDI (r = 0.2510; p = 0.1134) and HCL users (r = -0.1065; p = 0.4914). TIR was also negatively correlated with the mean carb count error in all study participants (r = -0.2317; p < 0.01). CONCLUSION: In conclusion, as the Gluciquizz score was associated with metabolic control, this easy-to-use self-administered questionnaire could be used widely on a routine basis to assess the carbohydrate knowledge of T1D patients and to offer them targeted education tailored to their needs.

[Tomorrow, what evolutions in diabetes?] / Demain, quelles évolutions en diabétologie ?

TOMORROW, WHAT EVOLUTIONS IN DIABETES ? Diabetes care has undergone a major digital nutation over the past decade. The devices used to treat and monitor patients with diabetes are increasingly "connected", generating large amounts of data. These data, hosted in clouds, facilitate the development of remote monitoring and teleconsultations in diabetology. The advent of continuous glucose monitoring (CGM) and insulin pumps has also enabled the development of control algorithms (known as "hybrid closed loops" (HCL) thhat automatically modulate insulin pump delivery rate according to real-time CGM data, in order to maintain glucose level in the normal range. HCL have proved high efficacy for patients with type 1 diabetes and are currently being assessed for other insulin-requiring diabetes type. Artificial intelligence (AI), which is currently being developed for all human actiiviities, also concerns diabetology, with a wide range of future applications in screening, diagnosis, therapy, support and research.

DEMAIN, QUELLES ÉVOLUTIONS EN DIATÉTOLOGIE? La diabétologie connaît une importante mutation mumériique depuis une décennie. Les dispositifs utilisés pour le traitement et la surveillance des patients atteints de diabète sont de plus en plus "connetés", générant de grandes quantités de données. Ces données sont hébergées sur des portails de surveillance qui facilitent le développement de la télésuurveillance et des téléconsultations en diabétologie. L'avènement des capteurs de glucose interstitiel et des pompes à insuline a également permis le développement d'algorithmes de contrôle (dits" boucles fermées"[BF]) qui modulent de façon automatisée le débit de la pompe à insuline en fonction des données du capteur en temps réel, afin de maintenir le glucose le plus proche possible de la zone normale. Ces systèmes de BF ont démontré leur grande efficacité pour les patients atteints de diabète de type 1 et sont en cours d'évaluation dans d'autres situations de diabète insulinorequérant. L'intelligence artificielle (IA), en cours de développement dans toutes les activités humaines, concerne également la diabétologie, avec des applications très diverses qui concerneront demain le dépistage, le diagnstic, la thérapeutique, l'accompagnement ou encore la recherche.

12-Month Real-Life Efficacy of the MiniMed 780G Advanced Closed-Loop System in Patients Living with Type 1 Diabetes: A French Observational, Retrospective, Multicentric Study.

Aim: To evaluate the evolution of glycemic outcomes in patients living with type 1 diabetes (T1D) after 1 year of use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. Methods: We conducted an observational, retrospective, multicentric study in 20 centers in France. The primary objective was to evaluate the improvement in glycemic control after 1-year use of AHCL. The primary endpoint was the variation of time in range (TIR) between pre-AHCL and after 1-year use of AHCL. Secondary objectives were to analyze the glycemic outcomes after 3, 6, and 12 months of AHCL use, the safety, and the long-term observance of AHCL. Results: Two hundred twenty patients were included, and 200 were analyzed for the primary endpoint. 92.7% of patients continued to use AHCL. After 1 year of use of AHCL, TIR was 72.5% ± 10.6% (+9.1%; 95% confidence interval [CI] [7.6-10.5] compared to pre-AHCL initiation, P < 0.001), HbA1c 7.1% ± 0.7% (-0.5%; 95% CI [-0.6 to -0.4]; P < 0.001), time below range 2.0% [1.0; 3.0] (0.0% [-2.0; 0.0], P < 0.001), and time above range 24.8% ± 10.9% (-7.3%; 95% CI [-8.8 to -5.7]; P < 0.001). More patients achieved the glycemic treatment goals of HbA1c <7.0% (45.1% vs. 18.1%, P < 0.001) and TIR >70% (59.0% vs. 29.5% P < 0.001) when compared with pre-AHCL. Five patients experienced severe hypoglycemia events and two patients experienced ketoacidosis. Conclusion: After 1 year of use of AHCL, people living with T1D safely improved their glucose control and a higher proportion of them achieved optimal glycemic control.

Cardiovascular and renal diseases in type 2 diabetes patients: 5-year cumulative incidence of the first occurred manifestation and hospitalization cost: a cohort within the French SNDS nationwide claims database.

BACKGROUND: Myocardial infarction (MI), stroke, peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD) are common cardiovascular renal diseases (CVRD) manifestations for type 2 diabetes. The objective was to estimate the incidence of the first occurring CVRD manifestation and cumulative hospitalization costs of each CVRD manifestation for type 2 diabetes without CVRD history. METHODS: A cohort study of all type 2 diabetes free of CVRD as of January 1st 2014, was identified and followed-up for 5 years within the French SNDS nationwide claims database. The cumulative incidence of the first occurring CVRD manifestation was estimated using the cumulative incidence function, with death as a competing risk. Cumulative hospitalization costs of each CVRD manifestations were estimated from the perspective of all payers. RESULTS: From 2,079,089 type 2 diabetes without cancer or transplantation, 76.5% were free of CVRD at baseline with a mean age of 65 years, 52% of women and 7% with microvascular complications history. The cumulative incidence of a first CVRD manifestation was 15.3% after 5 years of follow-up with a constant linear increase over time for all CVRD manifestations: The most frequent was CKD representing 40.6% of first occurred CVRD manifestation, followed by HF (23.0%), then PAD (13.5%), stroke (13.2%) and MI (9.7%). HF and CKD together reached about one patient out of ten after 5 years and represented 63.6% of first CVRD manifestations. The 5-year global cost of all CVRD hospitalizations was 3.9 billion euros (B€), i.e. 2,450€ per patient of the whole cohort, with an exponential increase over time for each specific CVRD manifestation. The costliest was CKD (2.0 B€), followed by HF (1.2 B€), then PAD (0.7 B€), stroke (0.6 B€) and MI (0.3 B€). CONCLUSIONS/INTERPRETATION: While MI, stroke and PAD remain classic major risks of complications for CVRD-free type 2 diabetes, HF and CKD nowadays represent individually a higher risk and cost than each of these classic manifestations, and jointly represents a risk and a cost twice as high as these three classic manifestations all together. This should encourage the development of specific HF and CKD preventive strategies.

Cost-utility of real-time continuous glucose monitoring versus self-monitoring of blood glucose in people with insulin-treated Type II diabetes in France.

Aim: Clinical trials and real-world data for Type II diabetes both show that glycated hemoglobin (HbA1c) levels and hypoglycemia occurrence can be reduced by real-time continuous glucose monitoring (rt-CGM) versus self-monitoring of blood glucose (SMBG). The present cost-utility study investigated the long-term health economic outcomes associated with using rt-CGM versus SMBG in people with insulin-treated Type II diabetes in France. Materials & methods: Effectiveness data were obtained from a real-world study, which showed rt-CGM reduced HbA1c by 0.56% (6.1 mmol/mol) versus sustained SMBG. Analyses were conducted using the IQVIA Core Diabetes Model. A French payer perspective was adopted over a lifetime horizon for a cohort aged 64.5 years with baseline HbA1c of 8.3% (67 mmol/mol). A willingness-to-pay threshold of €147,093 was used, and future costs and outcomes were discounted at 4% annually. Results: The analysis projected quality-adjusted life expectancy was 8.50 quality-adjusted life years (QALYs) for rt-CGM versus 8.03 QALYs for SMBG (difference: 0.47 QALYs), while total mean lifetime costs were €93,978 for rt-CGM versus €82,834 for SMBG (difference: €11,144). This yielded an incremental cost-utility ratio (ICUR) of €23,772 per QALY gained for rt-CGM versus SMBG. Results were particularly sensitive to changes in the treatment effect (i.e., change in HbA1c), annual price and quality of life benefit associated with rt-CGM, SMBG frequency, baseline patient age and complication costs. Conclusion: The use of rt-CGM is likely to be cost-effective versus SMBG for people with insulin-treated Type II diabetes in France.

Functional sequelae after pancreatic resection for cancer.

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients.

Glucose fluctuation promotes mitochondrial dysfunctions in the cardiomyocyte cell line HL-1.

AIMS: Glycemic variability has been suggested as a risk factor for diabetes complications but the precise deleterious mechanisms remain poorly understood. Since mitochondria are the main source of energy in heart and cardiovascular diseases remain the first cause of death in patients with diabetes, the aim of the study was to evaluate the impact of glucose swings on mitochondrial functions in the cardiomyocyte cell line HL-1. METHODS: HL-1 cells were exposed to low (LG, 2.8 mmol/l), normal (NG, 5.5 mmol/l), high (HG, 25 mmol/l) or intermittent high glucose (IHG, swing between low and high) every 2h during 12h (short-time treatment) or every 12h during 72h (long-time treatment). Anaerobic catabolism of glucose was evaluated by measuring glucose consumption and lactate production, oxidative phosphorylation was evaluated by polarography and ATP measurement, mitochondrial superoxide anions and the mitochondrial membrane potential (MMP) were analysed using fluorescent probes, and the protein oxidation was measured by oxyblot. RESULTS: IHG and HG increased glucose consumption and lactate production compared to LG and NG but without any difference between short- and long-time treatments. After 72h and unlike to LG, NG and HG, we didn't observe any increase of the mitochondrial respiration in the presence of succinate upon IHG treatment. IHG, and to a lesser extent HG, promoted a time-dependent decrease of the mitochondrial membrane potential compared to LG and NG treatments. HG and IHG also increased superoxide anion production compared to LG and NG both at 12 and 72h but with a higher increase for IHG at 72h. At last, both HG and IHG stimulated protein oxidation at 72h compared to LG and NG treatments. CONCLUSIONS: Our results demonstrated that exposure of HL-1 cells to glucose swings promoted time-dependent mitochondrial dysfunctions suggesting a deleterious effect of such condition in patients with diabetes that could contribute to diabetic cardiomyopathy.

Safety and Efficacy of Sustained Automated Insulin Delivery Compared With Sensor and Pump Therapy in Adults With Type 1 Diabetes at High Risk for Hypoglycemia: A Randomized Controlled Trial.

OBJECTIVE: Assess the safety and efficacy of automated insulin delivery (AID) in adults with type 1 diabetes (T1D) at high risk for hypoglycemia. RESEARCH DESIGN AND METHODS: Participants were 72 adults with T1D who used an insulin pump with Clarke Hypoglycemia Perception Awareness scale score >3 and/or had severe hypoglycemia during the previous 6 months confirmed by time below range (TBR; defined as sensor glucose [SG] reading <70 mg/dL) of at least 5% during 2 weeks of blinded continuous glucose monitoring (CGM). Parallel-arm, randomized trial (2:1) of AID (Tandem t:slim ×2 with Control-IQ technology) versus CGM and pump therapy for 12 weeks. The primary outcome was TBR change from baseline. Secondary outcomes included time in target range (TIR; 70-180 mg/dL), time above range (TAR), mean SG reading, and time with glucose level <54 mg/dL. An optional 12-week extension with AID was offered to all participants. RESULTS: Compared with the sensor and pump (S&P), AID resulted in significant reduction of TBR by -3.7% (95% CI -4.8, -2.6), P < 0.001; an 8.6% increase in TIR (95% CI 5.2, 12.1), P < 0.001; and a -5.3% decrease in TAR (95% CI -87.7, -1.8), P = 0.004. Mean SG reading remained similar in the AID and S&P groups. During the 12-week extension, the effects of AID were sustained in the AID group and reproduced in the S&P group. Two severe hypoglycemic episodes occurred using AID. CONCLUSIONS: In adults with T1D at high risk for hypoglycemia, AID reduced the risk for hypoglycemia more than twofold, as quantified by TBR, while improving TIR and reducing hyperglycemia. Hence, AID is strongly recommended for this specific population.

STYLCONNECT Study: An Assessment of Automatic Data Collection Devices by People Living with Diabetes and Using an Insulin Pen.

INTRODUCTION: The use of devices to connect insulin pens could facilitate management and improve glycaemic control in people with type 1 (PwT1D) and type 2 diabetes (PwT2D). However, their acceptance seems little studied. We conducted an online survey with the main objective of assessing the level of interest among insulin-treated people with diabetes (PwD) in a device connected to a disposable pen and secondary objectives of assessing the perceived benefits and important features expected of a connected device and identifying factors associated with interest scores. METHODS: An ad-hoc questionnaire, validated by PwD, was used. Responses from 1798 PwD (975 PwT1D and 823 PwT2D) were analysed. RESULTS: The mean interest rating was 7.4/10 (PwT1D: 7.2 vs PwT2D: 7.7; p < 0.001). PwD perceived that the device would make it easier to record their diabetes-related information (7.7/10) and keep all insulin and diabetes data in a single location (7.7/10). It was particularly important for PwD that this type of device could integrate data from glucose-measuring devices (7.8/10) and could set an alarm when all insulin in the body had been metabolised (7.7/10). CONCLUSION: Our study highlighted PwD's strong interest in automating the collection of their insulin therapy data, with significantly more interest among PwT2D than PwT1D, and the importance of interoperability between glucose measurement devices and interchangeability between the different brands of insulin. More generally, for the first time and on a large scale, our study provided a greater understanding of the expectations of PwD regarding these devices.

[Renewed interest for the control of post-prandial hyperglycaemia]. / Regain d'intérêt pour le contrôle de l'hyperglycémie postprandiale.

Postprandial hyperglycaemia (PPH) may sometimes be relegated to the background in the treatment of diabetic patients, while its control seems important if not essential to reach an adequate overall glycaemic control. PPH is correlated with glycated haemoglobin and diabetic complications. It is also identified as a cardiovascular risk factor. PPH's monitoring and adequate control are not only a therapeutic goal for diabetes itself but also for reducing associated adverse outcomes other than diabetic complications. PPH is related to the quality of life of patients. Continuous glucose monitoring allows a better appraisal of PPH. The use of new insulin formulations as ultra-fast insulins seems to be the better way to manage post-prandial blood glucose peaks.

L'hyperglycémie postprandiale (HGPP) peut parfois passer au second plan lors de la prise en charge globale du patient diabétique. Néanmoins, sa maîtrise est indispensable pour obtenir un équilibre glycémique global optimal. L'HGPP est corrélée à l'hémoglobine glyquée ainsi qu'aux complications du diabète. Elle semble également jouer un rôle par rapport au risque cardiovasculaire. Outre son intérêt dans la prise en charge thérapeutique du diabète proprement dit, l'HGPP doit être maîtrisée en raison de son lien avec d'autres conséquences médicales et de son impact négatif sur la qualité de vie des patients. Le monitoring continu du glucose permet une meilleure appréciation de l'HGPP. Les nouvelles insulines ultra-rapides paraissent être les molécules les plus adéquates pour réduire, au mieux et au plus vite, l'HGPP.

Sensor-Augmented Insulin Pump with Predictive Low-Glucose Suspend (PLGS): Determining Optimal Settings of Pump and Sensor in a Multicenter Cohort of Patients with Type 1 Diabetes.

INTRODUCTION: The use of predictive low-glucose suspend (PLGS) sensor-augmented pumps has been shown to lead to a significant reduction in hypoglycemic episodes in patients with type 1 diabetes (T1D), but their effects on hyperglycemia exposure are heterogeneous. The aim of this study was to determine the settings of the Medtronic 640G system to obtain the optimal balance between occurrence of both hypoglycemia and hyperglycemia. METHODS: The hypo- and hyperglycemia area under the curve (AUC), as well as system settings [hypoglycemic threshold, mean insulin total daily dose (TDD), mean basal insulin percentage, and mean daily duration of PLGS] were collected between 2 and 12 times during 1 year in patients from four university hospital centers. Univariate/multivariate analyses and receiver operating characteristics (ROC) curves were performed to determine factors associated with hyper- and hypoglycemia AUC. RESULTS: A total of 864 observations were analyzed from 110 patients with T1D. Two preselected settings predictive of low hyperglycemia AUC were a basal insulin percentage < 52.0% [sensitivity (Se) = 0.66 and specificity (Sp) = 0.53] and a PLGS duration > 157.5 min/day (Se = 0.47 and Sp = 0.73). The preselected setting predictive of a low hypoglycemia AUC was a PLGS duration ≤ 174.4 min (Se = 0.83 and Sp = 0.51). Between-visit variation of PLGS and TDD was positively correlated (r = 0.61; p < 0.0001). CONCLUSION: The most important Medtronic 640G setting was the mean daily PLGS duration, where a value between 157.5 and 174.4 min/day was associated with the best reduction in both hypo- and hyperglycemia AUC. In this study, we showed that PLGS duration could be indirectly modified through total daily insulin dose adaptation. TRIAL REGISTRATION: This study is registered in clinicaltrials.gov (NCT03047486).

The switch from rapid-acting to concentrated regular insulin improves glucose control in type 2 diabetes patients on pump therapy: A cohort survey.

BACKGROUND: To evaluate the impact of switching from U-100 to U-500 insulin in patients with type 2 diabetes mellitus (T2DM) uncontrolled with continuous subcutaneous insulin infusion (CSII) by pump. METHODS: We retrospectively collected data from patients with T2DM, treated by U-100 CSII, who were switched to U-500 regular insulin where haemoglobin A1c (HbA1c) was >8% and/or insulin total daily dose (TDD) was >100 UI/d. Data collection from patient medical records included HbA1c, lipid levels, liver biomarkers, weight, TDD, declared hypoglycaemic episodes and measured by continuous glucose monitoring (CGM). RESULTS: Sixty-five patients were included, aged 63.9 ± 8.6 years, insulin pump since 3.7 ± 3 years, TDD 186 ± 52 U/day, body mass index 39.4 ± 5.3 kg/m², HbA1c 9.03 ± 1.6%. After switching to U-500 insulin, HbA1c dropped by -0.96% (P < 0.0001) at one year with the effect maintained at three years (- 0.95%, P < 0.01). A subgroup analysis (n=42/65) using a severity score which covered the three previous years on U-100 and the next three years on U-500 insulin confirmed the latter's efficacy. Body weight increased by + 4.8 kg and TDD by 16% at three years. Declared non-severe hypoglycaemia increased significantly three- to four-fold during follow up, but % time-below-range at six months did not differ between the two treatments. Baseline HbA1c correlated with improved glucose control with U-500. CONCLUSIONS: U-100 to U-500 insulin switch improves glucose control in CSII T2DM patients, especially with high baseline HbA1c. Use of concentrated insulin in pumps may represent an advance in the strategy for treating T2DM insulin resistant states with uncontrolled hyperglycaemia after a switch from multiple daily injections to pump therapy.

Prospective Independent Evaluation of the Carbohydrate Counting Accuracy of Two Smartphone Applications.

INTRODUCTION: Smartphone applications (apps) have been designed that help patients to accurately count their carbohydrate intake in order to optimize prandial insulin dose matching. Our aim was to evaluate the accuracy of two carbohydrate (carb) counting apps. METHODS: Medical students, in the role of mock patients, evaluated meals using two smartphone apps: Foodvisor® (which uses automatic food photo recognition technology) and Glucicheck® (which requires the manual entry of carbohydrates with the help of a photo gallery). The macronutrient quantifications obtained with these two apps were compared to a reference quantification. RESULTS: The carbohydrate content of the entire meal was underestimated with Foodvisor® (Foodvisor® quantification minus gold standard quantification = - 7.2 ± 17.3 g; p < 0.05) but reasonably accurately estimated with Glucicheck® (Glucicheck® quantification minus gold standard quantification = 1.4 ± 13.4 g; ns). The percentage of meals with an absolute error in carbohydrate quantification above 20 g was greater for Foodvisor® compared to Glucicheck® (30% vs 14%; p < 0.01). CONCLUSION: The carb counting accuracy was slightly better when using Glucicheck® compared to Foodvisor®. However, both apps provided a lower mean absolute carb counting error than that usually made by T1D patients in everyday life, suggesting that such apps may be a useful adjunct for estimating carbohydrate content.

Efficacy and safety of exenatide as add-on therapy for patients with type 2 diabetes with an intensive insulin regimen: A randomized double-blind trial.

AIM: To assess the safety and efficacy of the short-acting glucagon-like peptide-1 receptor agonist exenatide on a population of patients with type 2 diabetes (T2D) mostly treated with continuous subcutaneous insulin injection (CSII). MATERIALS AND METHODS: A phase 2/3, multicentre, randomized, parallel-group, double-blind, placebo-controlled, 6-month trial was conducted. Patients were randomized to receive subcutaneous (SC) injections of exenatide (10 µg BID) or matched placebo. RESULTS: A total of 46 patients with T2D and elevated HbA1c were randomized (42% of the planned sample size): exenatide (n = 28) and placebo (n = 18). CSII treatment was used by 75% and 89% of patients of the exenatide and placebo groups, respectively. At 6 months, the change in HbA1c was -0.62% ± 0.94% and 0.08% ± 0.81% in the exenatide and placebo groups, respectively (difference, -0.70%; 95% CI [-1.24%; -0.15%], P = .014); body weight and body mass index decreased in the exenatide group (-2.55 ± 3.25 kg and -1.00 ± 1.31 kg/m2 ) and increased in the placebo group (1.29 ± 2.82 kg and 0.46 ± 1.16 kg/m2 ) (observed difference, -3.85 and -1.45, respectively, both P < .001); the postdinner capillary blood glucose value was lower in the exenatide group compared with the placebo group (162.4 ± 80.5 vs. 259.1 ± 94.4 mg/dL, respectively; observed difference, -96.7, P < .01). Hypoglycaemic risk, quality of life and overall safety were not different between the groups, apart from the expected occurrence of digestive effects in the exenatide group. CONCLUSIONS: Although we failed to reach our planned sample size, the addition of exenatide treatment 10 µg BID SC in T2D patients with uncontrolled HbA1c despite an intensified insulin regimen, resulted in a significant reduction of HbA1c and body weight with a good overall safety profile and acceptance.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.