Hybrid closed Loop improved glucose control compared to sensor-augmented pumps in outpatients with type 1 diabetes in real-life conditions with telehealth monitoring.

OBJECTIVES: The study aims at evaluating glucose metrics and HbA1C values after pump initiation in outpatient settings. RESEARCH DESIGN AND METHODS: This single center observational study enrolled 121 subjects with type 1 diabetes between September 2020 and May 2021 initiating sensor-augmented pump therapy with stand-alone CGM (n = 26) or pump users who only changed their device (n = 51), with predictive low glucose management (n = 8) or with Hybrid Closed Loop using Medtronic 780G (n = 36) systems. Changes in HbA1C levels and glucose metrics were analyzed after 3 months. All subjects received diabetes and carbohydrate-counting education if needed at time of initiation and were proposed a telehealth monitoring by a diabetic nurse educator. RESULTS: There was no episodes of severe hypoglycemia or diabetic ketoacidosis nor serious pump-related adverse events despite outpatient model of care. While only 18/121 (14.8%) participants reached initially the recommended HbA1C levels, 23/85 (27%) in the conventional group and 33/36 (91%) subjects in the Hybrid Closed Loop group reached target levels after 3 months of follow-up. Time in target range 3.9-10 mmol/L (70-180 mg/dl) also improved and was optimal with closed loop with 30/36 (83%) subjects with time in range above 70%. CONCLUSIONS: Initiation of insulin pump therapy for outpatients is safe with a dedicated facility. Telehealth monitoring after outpatient initiation provides tools for improvement in glucose control with an insulin pump. Outpatient pump initiation is compatible with Hybrid Closed Loop systems which provide the largest improvements in glucose control.

Design of a prospective, longitudinal cohort of people living with type 1 diabetes exploring factors associated with the residual cardiovascular risk and other diabetes-related complications: The SFDT1 study.

Type 1 diabetes mellitus (T1DM) is associated with a high risk of cardiovascular (CV) complications, even after controlling for traditional CV risk factors. Therefore, determinants of the residual increased CV morbidity and mortality remain to be discovered. This prospective cohort of people living with T1DM in France (SFDT1) will include adults and children aged over six years living with T1DM, recruited throughout metropolitan France and overseas French departments and territories. The primary objective is to better understand the parameters associated with CV complications in T1DM. Clinical data and biobank samples will be collected during routine visits every three years. Data from connected tools, including continuous glucose monitoring, will be available during the 10-year active follow-up. Patient-reported outcomes, psychological and socioeconomic information will also be collected either at visits or through web questionnaires accessible via the internet. Additionally, access to the national health data system (Health Data Hub) will provide information on healthcare and a passive 20-year medico-administrative follow-up. Using Health Data Hub, SFDT1 participants will be compared to non-diabetic individuals matched on age, gender, and residency area. The cohort is sponsored by the French-speaking Foundation for Diabetes Research (FFRD) and aims to include 15,000 participants.

Effects of remote care of patients with poorly controlled type 1 diabetes included in an experimental telemonitoring programme.

AIM: To assess, in a real-life setting, the effectiveness of telemonitoring adults with type 1 diabetes (T1D) using continuous glucose monitoring in a telemedicine experiment. METHODS: Experimentation in Telemedicine for the Improvement of Healthcare Pathways (ETAPES), an experimental telehealth programme for five chronic diseases, is supported by the French national healthcare system to promote telemedical care. Using data from a single university hospital centre, 72 adults were studied, including 42 subjects (58%) receiving insulin pump therapy and 30 (42%) receiving multiple daily injections, with a median age of 35.5 years [28.0; 45.0] and poorly controlled type 1 diabetes (T1D) with a mean ± standard error of mean (SEM) HbA1c value of 8.69 ± 0.13%. The primary study outcome was the difference in HbA1c values between baseline and the end of a 6-month follow-up. Other end points of interest were mean blood glucose, glucose management indicator (GMI) level and % time in range (3.9-10 mmol/L) or below or above range. RESULTS: At month 6, mean HbA1c levels were significantly reduced by -0.5% (P < 0.001) as were also mean blood glucose levels (P = 0.015), with a significant increase of 6.75 ± 1.36% of time in range at month 3 and of 4.98 ± 1.4% at month 6. Such improvements did not depend on age, gender or type of insulin therapy, but were inversely correlated to initial HbA1c values on multivariate analysis (P < 0.001). CONCLUSION: Although the use of telehealth monitoring offers efficacy and safety in the metabolic control of patients with T1D, it does not fulfil all of these patients' clinical needs. As such, this new healthcare pathway cannot replace, but is a useful complement to, face-to-face in-person clinical visits.

Pumps that predict and manage low blood glucose are superior to pumps with stand-alone CGM for reducing hypoglycaemia in type 1 diabetes patients in a real-world setting.

BACKGROUND: This study aimed to assess the efficacy of insulin pumps with automated predictive low-glucose insulin suspension in a real-world setting compared with stand-alone flash glucose monitoring (FGM). METHODS: The data analyzed were uploaded by patients with type 1 diabetes (n=195) treated with external insulin pumps [either a MiniMed 640G system (Medtronic) including SmartGuard technology that predicts and manages low glucose (n=61) or an Omnipod patch pump accompanied by a FreeStyle Libre sensor (Abbott) for FGM (n=134)]. RESULT: The median (25th-75th percentile) time spent with sensor glucose values≤3.9mmol/L was 0.9% (0.4-1.55) vs. 5.6% (3.05-9.55) in the predictive low-glucose suspend group vs. FGM users, respectively (P<0.0001), with similar results obtained for median time spent with sensor glucose values≤3mmol/L (P<0.0001). The group using sensor-integrated pumps had lower % coefficient of variation (CV) values and lower mean amplitude glycaemic excursions (P<0.0001). Mean glucose values as well as measured HbA1c levels were also lower. CONCLUSION: These real-world data show that predictive low-glucose insulin suspension is more effective than pumps with stand-alone FGM for reducing hypoglycaemic events, and could be of benefit to patients at risk of hypoglycaemia as well as those lacking in hypoglycaemic awareness.

Practical implementation of automated closed-loop insulin delivery: A French position statement.

Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice.

Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports.

Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.

Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon.

Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes.

Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?

AIM: This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk. METHODS: A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated. RESULTS: Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) µg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant. CONCLUSION: Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).

Increased TSH in obesity: Evidence for a BMI-independent association with leptin.

AIM: This study aimed to determine whether the association between thyroid-stimulating hormone (TSH) and body mass index (BMI) is related to leptin concentration in obese individuals. METHODS: Plasma TSH and leptin assays were performed in 800 consecutive patients, hospitalized for a nutritional checkup, with a BMI ≥ 30 kg/m(2). Various anthropometric, hormonal and metabolic parameters, including age, weight, BMI, insulin, leptin and TSH, were measured or calculated. Univariate and multivariate regression analyses were performed to identify any significant relationships between these parameters. Also, characteristics of the patients in the lowest and highest quartiles of TSH distribution were compared. RESULTS: TSH was positively correlated with both BMI and leptin. When multiple regression analysis was performed, TSH and leptin maintained a significant association independent of BMI. Patients in the fourth quartile of TSH distribution displayed higher BMI and higher leptin levels in comparison to the first quartile. CONCLUSION: Our study has confirmed an increase in TSH in conjunction with BMI in obese subjects. This increase was correlated with leptin independently of BMI. It is hypothesized that the increase in TSH observed in obese subjects was the consequence of both fat mass accumulation and a positive energy-balance.

Oesophageal function assessed by high-resolution manometry in patients with diabetes and inadequate glycaemic control.

AIMS: To describe oesophageal function in people with diabetes and poor glycaemic control using oesophageal high-resolution manometry and to compare the result between control subjects and patients with gastro-oesophageal reflux disease. METHODS: The results of oesophageal high-resolution manometry and a gastric emptying test were reviewed in 20 patients with diabetes. The high-resolution manometry protocol consisted of 5-ml swallows of water and multiple swallows of water. Oesophageal motility disorders were classified according to the Chicago classification system. The occurence of multiphasic contractions and intragastric and intrabolus pressures were measured. High-resolution manometry results were compared between 10 control subjects and 20 patients with gastro-oesophageal reflux disease. Data were expressed as medians and compared using Mann-Whitney and chi-squared tests. RESULTS: Oesophageal motility disorders were similarly distributed between the groups. Multiphasic contractions occurred more frequently in patients with diabetes than in those with gastro-oesophageal reflux disease (60 vs 20% per patient; P<0.01) and were not observed in control subjects. Gastric emptying was delayed in six patients with diabetes and did not correlate with symptoms or oesophageal motility disorders. Intrabolus pressure was higher in patients with diabetes and gastroparesis than in those without (17 vs 10 mmHg; P=0.02) and correlated with intragastric pressure (r=0.46, P<0.01). During multiple swallows of water, oesophageal contractile activity was incompletely inhibited in 83% of patients with diabetes and gastroparesis vs 9% without (P<0.01). Oesophageal function and gastric emptying were not influenced by fasting glycaemia. CONCLUSIONS: Patients with gastroparesis might present with impaired inhibition of contractile activity during multiple swallows of water. Increased intrabolus pressure is suggestive of delayed oesophageal clearance as a consequence of gastroparesis.

Assessing diabetic foot osteomyelitis remission with white blood cell SPECT/CT imaging.

AIMS: Diabetic foot osteomyelitis is an important risk factor of lower limb amputation. Antibiotic therapy is often effective in preventing surgery. However, the duration of antibiotic therapy is difficult to define in the absence of a marker to diagnose osteomyelitis remission at the end of the treatment. In this study, we assessed the diagnostic performance of white blood cell SPECT/CT imaging for evaluating osteomyelitis remission. PATIENTS AND METHODS: Twenty-nine out of 42 episodes of diabetic foot osteomyelitis seen between December 2009 and April 2012 had radiographs, a three-phase bone scintigraphy and a white blood cell SPECT/CT at the end of antibiotic therapy. They were treated with antibiotics alone and considered in clinical remission. White blood cell SPECT/CT results were considered positive when abnormal uptake in the osteomyelitis location was identified. Osteomyelitis remission was defined by the absence of an osteomyelitis relapse after 12 months' follow-up. RESULTS: A negative white blood cell SPECT/CT was seen for 22 episodes of osteomyelitis. All of them were in remission. A positive white blood cell SPECT/CT was observed for seven episodes. A relapse occurred in five episodes (71.5%) after a median duration of 4 months (2-7 months). Sensitivity, specificity, positive predictive value and predictive negative value in predicting osteomyelitis relapse after the discontinuation of antibiotic treatment were, respectively, for radiographs 80%, 33%, 20% and 89%; for three-phase bone scintigraphy 100%, 12.5%, 15.5% and 100%; and for the white blood cell SPECT/CT 100%, 91.5%, 71.5% and 100%. CONCLUSION: Negative uptake on white blood cell SPECT/CT is a good marker for diagnosis of diabetic foot osteomyelitis remission and might be very useful in guiding antibiotic therapy.

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.

The first simultaneous kidney-adrenal gland-pancreas transplantation: outcome at 1 year.

Adrenal insufficiency is a rare but life-threatening disease. Replacement therapy sometimes fails to prevent an acute adrenal crisis and most often does not lead to restoration of well-being. We report here the 1-year outcome of the first simultaneous kidney-adrenal gland-pancreas transplantation in a 33-year-old patient with type 1 diabetes and concomitant autoimmune adrenal insufficiency. En bloc left adrenal gland and kidney grafts were anastomosed on the left iliac vessels in normal vascular conditions and the pancreas graft was anastomosed on the right iliac vessels. The immunosuppressive regimen was not modified by the addition of the adrenal gland. We observed no additional morbidity due to the adrenal gland transplantation, as there were no surgical complications. One-year kidney and pancreas graft functions were satisfactory (estimated glomerular filtration rate: 55 mL/min/1.73 m(2) and HbA1c: 4.8%). The adrenal graft functioned well at 12 months with a normalization of cortisol and aldosterone baseline levels. Functional imaging at 3 months showed good uptake of [(123) I]-metaiodobenzylguanidine by the adrenal graft. Transplantation of the adrenal gland en bloc with the left kidney appears to be a good therapeutic option in patients with adrenal insufficiency awaiting kidney or kidney-pancreas transplantation.

Predictive factors of type 2 diabetes remission 1 year after bariatric surgery: impact of surgical techniques.

Type 2 diabetes (T2D) remission after bariatric procedures has been highlighted in many retrospective and some recent prospective studies. However, in the most recent prospective study, more than 50 % of patients did not reach T2D remission at 1 year. Our aim was to identify baseline positive predictors for T2D remission at 1 year after bariatric surgery and to build a preoperative predictive score. We analysed the data concerning 161 obese operated on between June 2007 and December 2010. Among them, 46 were diabetic and were included in the study-11 laparoscopic adjustable gastric banding (LAGB), 26 Roux-en-Y gastric bypass (RYGB) and 9 sleeve gastrectomy (SG). We compared anthropometric and metabolic features during 1 year of follow-up. A receiver operating characteristic analysis was performed to predict T2D remission. RYGB and SG were similarly efficient for body weight loss and more efficient than LAGB; 62.8 % of patients presented with T2DM remission at 1 year, with no significant difference according to the surgical procedure. A 1-year body mass index (BMI) <35 kg m(-2) was predictive of T2DM remission whatever the procedure. The preoperative predictive factors of diabetes remission were baseline BMI ≤50 kg m(-2), duration of type 2 diabetes ≤4 years, glycated haemoglobin ≤7.1 %, fasting glucose <1.14 g/l and absence of insulin therapy. A short duration of diabetes and good preoperative glycaemic control increase the rate of T2DM remission 1 year after surgery. Preoperative metabolic data could be of greater importance than the choice of bariatric procedure.

Heterogeneity of pregnancy outcomes and risk of LGA neonates in Caucasian females according to IADPSG criteria for gestational diabetes mellitus.

OBJECTIVE: The International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes. MATERIAL AND METHODS: Of the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24-32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group. RESULTS: GDM women with IFG, including isolated IFG and combined IFG+IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The>5.1mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants. CONCLUSION: IFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.