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.

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.

Disagreement between capillary blood glucose and flash glucose monitoring sensor can lead to inadequate treatment adjustments during pregnancy.

OBJECTIVE: Continuous glucose monitoring tends to replace capillary blood glucose (CBG) self-monitoring. Our aim was to determine the agreement between CBG and a flash glucose monitoring system (Flash-GMS) in treatment decision-making during pregnancy. RESEARCH DESIGN AND METHODS: Insulin-treated women with either type 1 (n=25), type 2 (n=4) or gestational diabetes (n=4) were included. A Flash-GMS sensor was applied for 14 days. Women scanned the sensor whenever they monitored their CBG. The primary endpoint was the proportion of discordant therapeutic decisions they would have made based on Flash-GMS rather than CBG results. Glucose averages, mean absolute difference (MAD), mean absolute relative difference (MARD) and Flash-GMS accuracy were also estimated. RESULTS: Data for forty 14-day periods were available. Preprandial Flash-GMS and CBG values were 93±42mg/dL and 105±45mg/dL, respectively (P<10-4), and 2-h postprandial (PP) values were 106±45mg/dL and 119±47mg/dL, respectively (P<10-4). MAD was 14±22mg/dL preprandial and 15±24mg/dL 2-h PP; MARD was 19%; and 99% of glucose value pairs were within the clinically acceptable A and B zones of the Parkes error grid. Concordance rate for therapeutic decision-making was 80-85% according to ADA targets and 65-75% according to a pragmatic threshold. At different time points of the day, 83-92% of discordant results were due to Flash-GMS values being lower than their corresponding CBG values. CONCLUSION: Flash-GMS tends to give lower estimates than CBG. Thus, in cases requiring therapeutic changes to treat or prevent hypo- or hyperglycaemia, 25-35% of choices would have been divergent if based on Flash-GMS rather than CBG.

Impact of a sports project centered on scuba diving for adolescents with type 1 diabetes mellitus: New guidelines for adolescent recreational diving, a modification of the French regulations.

BACKGROUND: Recreational scuba diving has been authorized for type 1 diabetics over 18 years old - the age of majority in France - since 2004, but it remained forbidden for younger diabetics by the French underwater federation (FFESSM). Here, we present a study to evaluate: - the conditions under which diving could be authorized for 14- to 18 year olds with type 1 diabetes; - the value of continuous glucose monitoring (CGM) while diving. A secondary objective was to monitor the impact of diving on the teenagers' quality of life. SUBJECT AND METHODS: Sixteen adolescents (14-17.5 years old) were included. Diabetes was known for 6 years (range, 1-14) and Hb1Ac was 9.0% (range, 7.7-11.9). The study was conducted in Mayotte with both capillary glycemia (CG) and CGM measurements taken during five dives. RESULTS: The average CG prior to diving was 283mg/dL and decreased by 75±76mg/dL during the dive. No hypoglycemia occurred during the dives and four episodes occurred after. Glycemia variations during dives and for the overall duration of the study were greater than for adults, most likely due to the general adolescent behavior, notably regarding diet and diabetes management. CGM was greatly appreciated by the adolescents. They had an overall satisfactory quality of life. No significant variations were observed during the entire course of the study. CONCLUSIONS: Although in need of further studies, these preliminary results show that CGM can be used while diving. CGM records show a continuous decrease of glycemia during dives. Based on these results, the French underwater federation has now authorized diving for adolescent type 1 diabetics following a specific diving protocol that includes HbA1c<8.5%, autonomous management of diabetes by the adolescent, reduction of insulin doses, and target glycemia prior to the dive>250mg/dL.

Practical implementation, education and interpretation guidelines for continuous glucose monitoring: A French position statement.

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.

Indication, organization, practical implementation and interpretation guidelines for retrospective CGM recording: A French position statement.

AIM: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described. METHOD: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement. RESULTS: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings. CONCLUSION: This consensus document should help clinicians in the proper use of retroCGM.

Effect of dietary protein on post-prandial glucose in patients with type 1 diabetes.

BACKGROUND: In flexible insulin therapy, determination of the prandial insulin dose only takes into account the carbohydrate content of the evening meal, and not the protein content. Protein can, however, contribute to gluconeogenesis. We compared the glycaemic effect of a standard evening meal with that of a test evening meal enriched in protein. METHODS: The present study was conducted in 28 C-peptide negative patients with type 1 diabetes. Two evening meals that were similar in content, except that one was enriched by the addition of 300 g of 0%-fat fromage frais, were taken on two consecutive days. Insulin doses were maintained exactly the same before both evening meals. Patients were monitored with a continuous glucose-monitoring device. RESULTS: Patients ate similar quantities at both evening meals, except for protein (21.5 g more at the test evening meal). The preprandial insulin dose was 0.96 (0.4) U per 10 g carbohydrates. After correction for differences of interstitial glucose at the start of the evening meals, both interstitial and capillary glucose levels were similar after both evening meals, except for the late-post-prandial interstitial glucose level. CONCLUSIONS: We found no effect of dietary protein on post-prandial-, overnight- or late-night glucose levels in patients with type 1 diabetes. This confirms that dietary proteins need not be included in the calculation of prandial insulin dose.

Continuous subcutaneous insulin infusion allows tolerance induction and diabetes treatment in a type 1 diabetic child with insulin allergy.

AIM: Insulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin. CASE REPORT: Three months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA1c 7.6%). CONCLUSION: In T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the "honeymoon" period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements.

Ambulatory 24-hour fast using flexible insulin therapy in patients with type 1 diabetes.

AIM: Prolonged fasting may be necessary in life for religious, medical and other reasons. For this reason, our study investigated the feasibility and safety of a 24-h fast conducted at home for patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Thirty-four patients with type 1 diabetes performed a 24-h complete fast at home. Thirteen patients were treated with multiple insulin injections using either glargine (n=12) or NPH (n=1) as basal insulin. The remaining patients were treated with an insulin pump. All patients received their basal insulin only, which was adjusted to 40% of their total daily dose, and were monitored by either a Gold(®) or Guardian(®) continuous glucose monitoring (CGMS) device. Capillary glucose (SMBG) was targeted at 3.9-7.8 mmol/L, with a standardized protocol for correction of hyper- and hypoglycaemia. Interstitial glucose (IG) profiles were compared with the SMBG values; the IG profiles of patients using glargine or a pump and either of the two CGMS devices were also compared. RESULTS: All of the patients completed the 24-h fast with no major incident. At the end of the fast, 80% of the IG values were on target. The route by which insulin was delivered made no difference, but there were more IG values on target in patients monitored by the Guardian(®) device. IG was below target in 104 occurrences and above-target in 34. After a mean intake of 10 g of sucrose, below-target IG was corrected within 30 min [range: 15-40]. The mean insulin dose to correct above-target episodes was 1 U. CONCLUSION: Prolonged fasting is possible at home in patients with type 1 diabetes, provided the basal dose is adjusted. The use of CGMS is not necessary, but offers useful information on the patient's IG profile during the fast.

Emergent technologies applied to diabetes: what do we need to integrate continuous glucose monitoring into daily practice? Where the long-term use of continuous glucose monitoring stands in 2011.

The earliest continuous glucose monitoring (CGM) devices did not permit real-time readouts of glucose measurements. Instead, they were used to determine the glucose profile of patients in "real life" and as educational tools. In contrast, the latest real-time devices, whether linked or not to an insulin pump, give the patient access to glucose measurements and incorporate alarms that can be set. Thus, they are the newest self-management tools for patients with type 1 diabetes requiring an intensive insulin regimen. Some long-term studies in a selected population of patients with type 1 diabetes have shown improvement of glycaemic control as measured by HbA(1c). Although the characteristics of "responsive" patients have yet to be identified, the ability of the patient to use the system on a near-daily basis (about 80% of the time) is a key point. Initial training of the patient by a professional team with expertise in CGM is also of the utmost importance. To date, CGM is not reimbursed by Social Security in France.

Therapeutic alliance and glycaemic control in type 1 diabetes: a pilot study.

AIM: Effective diabetes care requires integrating physicians' clinical expertise with patients' concerns and resources. This prospective study examined whether or not two measures of therapeutic alliance could predict glycaemic control after 1 year of follow-up in patients with type 1 diabetes. METHODS: Consecutive type 1 diabetic outpatients were recruited, and their age, gender, level of education, marital status and age at the time of diabetes diagnosis were self-reported. The presence of diabetes complications was ascertained by the patients' physicians. Both patients and physicians completed the revised Helping Alliance Questionnaire (HAQ-R) and the 12-item Working Alliance Inventory (WAI-12) to assess therapeutic alliance. Patients also completed the Center for Epidemiological Studies Depression scale to assess depressive mood. HbA(1c) was measured at baseline and 1 year later. RESULTS: Sixty-four type 1 diabetic outpatients (32 men, 32 women; mean age±standard deviation [S.D.]: 38.2±8.0 years) were included. HbA(1c) level at follow-up (mean±S.D.: 7.56±1.18%) was positively correlated with the HbA(1c) level at baseline (r=0.698, P<0.001), and associated with presence of retinopathy at baseline (8.18±1.24% versus 7.41±1.13%, P=0.036). In addition, the HbA(1c) level at follow-up was negatively correlated with therapeutic alliance, as assessed at baseline by the physicians using either the HAQ-R (r=-0.431, P<0.001) or the WAI-12 (r=-0.365, P=0.003), even after controlling for the HbA(1c) at baseline. CONCLUSION: Although the observational nature of the present study prevents causal conclusions to be drawn, these preliminary results suggest that promoting therapeutic alliance can improve glycaemic control in type 1 diabetes.

Peak-time determination of post-meal glucose excursions in insulin-treated diabetic patients.

OBJECTIVE: This study aimed to determine the optimal time to measure peak blood glucose values to find the best approach for self-monitoring blood glucose after a meal. DESIGN AND METHODS: For this retrospective analysis, 69 ambulatory continuous glucose-monitoring system (CGMS) profiles were obtained from 75 consecutive insulin-treated patients with diabetes. The parameters measured were the peak post-meal blood glucose values, peak time, and rates of increase and decrease to and from the zenith of the resulting curves. RESULTS: The mean peak time after breakfast was 72+/-23 min, which was reached in less than 90 min in 80% of the patients. The apparent glucose rate of increase from pre-meal to the maximum postprandial value was 1.23+/-0.76 mg/dL/min, while the glucose rate of decrease was 0.82+/-0.70 mg/dL/min. Peak time correlated with the amplitude of postprandial excursions, but not with the peak glucose value. Also, peak times were similar after breakfast, lunch and dinner, and in type 1 and type 2 diabetic patients. CONCLUSION: To best assess peak postprandial glucose levels, the optimal time for blood glucose monitoring is about 1h and 15 min after the start of the meal, albeit with wide interpatient variability. Nevertheless, 80% of post-meal blood glucose peaks were observed at less than 90 min after the start of the meal.

The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes.

CONTEXT: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. OBJECTIVE: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. PARTICIPANTS: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. RESULTS: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA(1c) was also found and remained significant after adjustment for age at molecular sampling and gender. CONCLUSIONS: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.