A sub-analysis of the SAGE study in Italy indicates good glycemic control in type 1 diabetes.

BACKGROUND AND AIMS: Intensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26-44, 45-64, and ≥65 years) of the global SAGE study. METHODS AND RESULTS: The primary endpoint was proportion of participants who achieved an HbA1c <7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m2. Mean HbA1c was 7.5% and 29.4% had HbA1c <7.0%, with the highest percentage in those 26-45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were experienced by 16.3% and 12% of patients, of which 7.1 and 9.5%, respectively, required hospitalization/emergency visits. More patients achieved HbA1c <7% with CSII (30%) than with multiple daily insulin injections (27.9%). In multivariate analysis, BMI (OR 0.94, 95% CI 0.89-0.99, p = 0.032) and adherence to diet (OR 0.36, 95% CI 0.18-0.70, p = 0.0028) were significantly associated with HbA1c <7.0%. CONCLUSIONS: Glycemic control can be considered good in the Italian SAGE cohort, especially in younger patients, who more frequently use pumps/continuous glucose monitoring. Greater patient education and use of technology may further support this achievement. Patients should be encouraged to maintain a low BMI and adhere to their diet.

Glycemic control after switching to faster aspart in adults with type 1 diabetes.

AIMS: Post-prandial hyperglycemia remains an unmet need in the management of type 1 diabetes (T1D). In randomized trials, faster insulin aspart (FIA) showed modest but significant reductions of glycemic spikes after meals. Whether such benefit is evident in routine clinical practice is unclear. METHODS: We analyzed data of patients with T1D at the time they switched from a prior bolus insulin to FIA and at the first available follow-up. The primary endpoint was the change in the time spent in hyperglycemia > 250 mg/dl during daytime from flash glucose monitoring (FGM). Secondary outcomes included the change in HbA1c, body weight, insulin dose and other FGM metrics. RESULTS: We included 117 patients with T1D on multiple daily injections who switched to FIA, 57 of whom had data from FGM. Patients were 41-year-old, 51.3% men, with 19.3 years diabetes duration and a baseline HbA1c of 7.7% (60 mmol/mol). Mean observation time was 4.3 months. After switching to FIA, HbA1c declined by 0.1% (1 mmol/mol) only in patients with baseline HbA1c > 7.0% (53 mmol/mol). Time spent in hyperglycemia > 250 mg/dl during daytime was significantly reduced from 14.8 to 11.9% (p = 0.006). Time in range improved from 48.3 to 51.0% (p = 0.028). Results were consistent across various patient characteristics. CONCLUSIONS: Under routine care, patients with T1D who switched to FIA experienced a reduction in the time spent in hyperglycemia > 250 mg/dl during daytime and an increase in time in range. These improvements may be due to better control of post-prandial hyperglycemia, as observed in trials.

Implantable and transcutaneous continuous glucose monitoring system: a randomized cross over trial comparing accuracy, efficacy and acceptance.

AIM: To compare accuracy, efficacy and acceptance of implantable and transcutaneous continuous glucose monitoring (CGM) systems. METHODS: In a randomized crossover trial we compared 12 weeks with Eversense implantable sensor (EVS) and 12 weeks with Dexcom G5 transcutaneous sensor (DG5) in terms of accuracy, evaluated as Mean Absolute Relative Difference (MARD) vs capillary glucose (SMBG), time of CGM use, adverse events, efficacy (as HbA1c, time in range, time above and below range) and psychological outcomes evaluated with Diabetes Treatment Satisfaction Questionnaire (DTSQ), Glucose Monitoring Satisfaction Survey (GMSS), Hypoglycemia Fear Survey (HFS2), Diabetes Distress Scale (DDS). RESULTS: 16 subjects (13 males, 48.8 ± 10.1 years, HbA1c 55.8 ± 7.9 mmol/mol, mean ± SD) completed the study. DG5 was used more than EVS [percentage of use 95.7 ± 3.6% vs 93.5 ± 4.3% (p = 0.02)]. MARD was better with EVS (12.2 ± 11.5% vs. 13.1 ± 14.7%, p< 0.001). No differences were found in HbA1c. While using EVS time spent in range increased and time spent in hyperglycemia decreased, but these data were not confirmed by analysis of retrofitted data based on SMBG values. EVS reduced perceived distress, without significant changes in other psychological outcomes. CONCLUSIONS: CGM features may affect glycemic control and device acceptance.

Effects of glucose variability on hematopoietic stem/progenitor cells in patients with type 1 diabetes.

BACKGROUND AND PURPOSE: Diabetes reduces the levels of hematopoietic stem/progenitor cells (HSPCs), which can contribute to organ and tissue homeostasis. Among patients with diabetes, lower HSPC levels predict the development or worsening of micro- and macro-angiopathy. High glucose variability is also associated with diabetic complications and we have previously shown that acute hypoglycaemia can stimulate stem/progenitor cells. Thus, we evaluated the relationship between glucose variability or time in hypoglycaemia and HSPCs in patients with type 1 diabetes (T1D). METHODS: Patients with T1D were compared to healthy subjects. HSPCs (CD34+, CD133+, CD34+CD133+, CD34 + CD45dim) were quantified by flow cytometry. Using flash glucose monitoring system for 90 days, we calculated several measures of glucose variability and time in hypoglycaemia. RESULTS: Forty-four patients with T1D and 44 healthy subjects were enrolled. Compared to healthy controls, T1D patients had significantly lower levels of HSPCs and duration of diabetes was inversely correlated with HSPC levels. Significant direct correlations were found between HSPC levels and the coefficient of variation of glucose levels or time in hypoglycaemia, which were stronger in patients with short-term than in those with long-standing diabetes. CONCLUSION: This study confirms the pauperization of HSPCs in T1D patients and demonstrates a potential HSPC-stimulatory effect of hypoglycaemia, which mitigates with long-lasting diabetes. These data are consistent with a model whereby disease chronicity progressively blunts the release of HSPCs in response to adrenergic triggers, like hypoglycaemic events.

The use of real time continuous glucose monitoring or flash glucose monitoring in the management of diabetes: A consensus view of Italian diabetes experts using the Delphi method.

Until recently, in Italy, the use of continuous glucose monitoring (CGM) systems has been limited, but is now rapidly increasing, including the so-called real-time CGM (rtCGM) and the intermittently viewed CGM (iCGM), also called Flash Glucose Monitoring (FGM). These technologies overcome many of the limitations of self-monitoring of blood glucose (SMBG) by fingerprick and allow to go beyond HbA1c to check glucose control in diabetes. However, standardized protocols for applying and interpreting rtCGM and FGM data are lacking. In this paper, we delineate a consensus amongst Italian diabetes physicians on the attributes of rtCGM and FGM technologies, and introduce a consistent approach for their use by Italian healthcare professionals. Most experts consider rtCGM and FGM as two separate categories of interstitial subcutaneous fluid (ISF) sensing technologies, and see them as superior to SMBG. Furthermore, there is strong consensus that rtCGM and FGM reduce hypoglycemia risk, increase the amount of time in the target glucose range and augment treatment satisfaction. However, there is still no agreement on the indication of the FGM for subjects who suffer asymptomatic hypoglycemia. Consensus on the role of education in initiating and optimizing use of rtCGM/FGM and about the interpretation of glucose trends was near unanimous, whereas no consensus was reached on the statement that there are no disadvantages/risks of rtCGM/FGM. Some issues remain in rtCGM/FGM management: a) risk of excessive correction of high or low glucose; b) risk of alert fatigue leading to alert silencing or rtCGM termination; c) allergic reaction to the adhesive keeping rtCGM or FGM sensors in place. The panel almost unanimously agreed that sensor accuracy depends on multiple variables, that alarm setting should be individualized, and that global glycemic profile represent an useful tool in interpreting glucose data. More clinical studies and a wider use of these devices will increase the efficacy and effectiveness of continuous glucose monitoring in Italy.

Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes.

PURPOSE: In patients with type 1 diabetes (T1D), the prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 10 to 53% and contrasting evidence suggests that vitamin D deficiency may favor liver fat accumulation. Here, we investigated the association between vitamin D status and NAFLD in adults with T1D. METHODS: 220 consecutive adult T1D patients on multiple daily injections or continuous subcutaneous insulin infusion and not taking calcium or vitamin D supplements were included. Patient characteristics, 25(OH)D serum levels, and metabolic parameters were analyzed. Vitamin D status was defined as sufficiency ( ≥ 75 nmol/L; 30 ng/ml), insufficiency (50-75 nmol/L; 20-30 ng/ml), or deficiency ( < 50 nmol/L; 20 ng/ml). NAFLD was diagnosed at ultrasound examination and graded 0-3. RESULTS: NAFLD was present in 57 patients (29.5%): 51 grade 1, 5 grade 2, and 1 grade 3. Median 25(OH)D levels were 53 nmol/L (IQR 38-70) in patients with NAFLD and 50 nmol/L (34-69) in patients without (p = 0.46). At multivariable analysis, NAFLD was not associated with 25(OH)D levels (p = 0.42) or vitamin D deficiency (p = 0.55), while BMI (OR 1.16, 95% CI 1.07-1.27) and serum triglycerides (OR 1.02, 95% CI 1.01-1.03) were independently associated with NAFLD. CONCLUSIONS: Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.

Parental evaluation of a telemonitoring service for children with Type 1 Diabetes.

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. The service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents' perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents' perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children's diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents' suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0-100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value = 0.0001). The analysis of free text comments highlighted an improvement in mood, and parents' commitment was also proved by their willingness to pay for the service (median = 200 euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family's own peace of mind.

FreeStyle Libre and Dexcom G4 Platinum sensors: Accuracy comparisons during two weeks of home use and use during experimentally induced glucose excursions.

BACKGROUND AND AIMS: This study compared the accuracy of the FreeStyle Libre (Abbott, Alameda, CA) and Dexcom G4 Platinum (DG4P, Dexcom, San Diego, CA) CGM sensors. METHODS AND RESULTS: Twenty-two adults with type 1 diabetes wore the two sensors simultaneously for 2 weeks. Libre was used according to manufacturer-specified lifetime (MSL); DG4P was used 7 days beyond MSL. At a clinical research center (CRC), subjects were randomized to receive the same breakfast with standard insulin bolus (standard) or a delayed and increased (delayed & increased) bolus to induce large glucose swings during weeks 1 and 2; venous glucose was checked every 5-15 min for 6 h. Subjects performed ≥4 reference fingersticks/day at home. Accuracy was assessed by differences in mean absolute relative difference (%MARD) in glucose levels compared with fingerstick test (home use) and YSI reference (CRC). During home-stay the Libre MARD was 13.7 ± 3.6% and the DG4P MARD 12.9 ± 2.5% (difference not significant [NS]). With both systems MARD increased during hypoglycaemia and decreased during hyperglycaemia, without significant difference between sensors. In the euglycaemic range MARD was smaller with DG4P [12.0 ± 2.4% vs 14.0 ± 3.6%, p = 0.026]. MARD increased in both sensors following delayed & increased vs. standard bolus (Libre: 14.9 ± 5.5% vs. 10.9 ± 4.1%, p = 0.008; DG4P: 18.1 ± 8.1% vs. 13.1 ± 4.6%, p = 0.026); between-sensor differences were not significant (p = 0.062). Libre was more accurate during moderate and rapid glucose changes. CONCLUSIONS: DG4P and Libre performed similarly up to 7 days beyond DG4P MSL. Both sensors performed less well during hypoglycaemia but Libre was more accurate during glucose swings. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov (NCT02734745) April 12, 2016.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

AIM: To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. METHODS: People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. RESULTS: We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). CONCLUSIONS: In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control.

Psychological outcomes of evening and night closed-loop insulin delivery under free living conditions in people with Type 1 diabetes: a 2-month randomized crossover trial.

AIM: To assess the impact on fear of hypoglycaemia and treatment satisfaction with an artificial pancreas system used for 2 consecutive months, as well as participant acceptance of the artificial pancreas system. METHODS: In a randomized crossover trial patient-related outcomes associated with an evening-and-night artificial pancreas and sensor-augmented pump therapy were compared. Both intervention periods lasted 8 weeks. The artificial pancreas acceptance questionnaire (range 0-90, higher scores better), Hypoglycaemia Fear Survey II (range 0-72, higher scores worse) and Diabetes Treatment Satisfaction Questionnaire (range 0-36, higher scores better) were completed by 32 participants. Semi-structured interviews were conducted after study completion in a subset of six participants. Outcomes were compared using a repeated-measures anova model or paired t-test when appropriate. RESULTS: The total artificial pancreas acceptance questionnaire score at the end of the artificial pancreas period was 69.1 (sd 14.7; 95% CI 63.5, 74.7), indicating a positive attitude towards the artificial pancreas. No significant differences were found among the scores at baseline, end of sensor-augmented pump therapy period or end of the artificial pancreas period with regard to fear of hypoglycaemia [28.2 (sd 17.5), 23.5 (sd 16.6) and 23.5 (sd 16.7), respectively; P = 0.099] or diabetes treatment satisfaction [29.0 (sd 3.9), 28.2 (sd 5.2) and 28.0 (sd 7.1), respectively; P = 0.43]. Themes frequently mentioned in the interviews were 'positive effects at work', 'improved blood glucose', 'fewer worries about blood glucose', but also 'frequent alarms', 'technological issues' and 'demand for an all-in-one device'. CONCLUSIONS: The psychological outcomes of artificial pancreas and sensor-augmented pump therapy were similar. Current artificial pancreas technology is promising but user concerns should be taken into account to ensure utility of these systems.

Switching from twice-daily glargine or detemir to once-daily degludec improves glucose control in type 1 diabetes. An observational study.

BACKGROUND AND AIMS: Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec. METHODS AND RESULTS: In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved. CONCLUSION: Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.

Survey on the use of insulin pumps in Italy: comparison between pediatric and adult age groups (IMITA study).

AIMS: The aim of the study was to evaluate and compare continuous subcutaneous insulin infusion (CSII) use in pediatric and adult age groups. METHODS: Data were collected with a questionnaire sent by e-mail to CSII-experienced Diabetes Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2) patient demographic data and characteristics; (3) structure and organization of Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional pump, sensor-augmented pump); and (5) CSII dropouts. RESULTS: A total of 217 out of 1093 Italian centers participated: 51 pediatric (23.5 %) and 166 (76.5 %) adult centers (AP). Compared to a survey performed in 2005, there was a significant increase in the number of pediatric units when compared to adult units (112 vs 37 %, respectively, p < 0.05). Pediatric age is characterized by a greater concern for quality of life and injections, and a higher dropout rate (10.6 vs 8.9 %) mainly related to pump wearability and site reactions. A complete diabetes-care team is associated with a superior use of technology (fewer dropouts, increased CGM and advanced bolus use) which is, however, still used in a small percentage of patients. CONCLUSIONS: In Italy, the number of CSII-treated pediatric patients (PP) is growing more significantly when compared to adults. Only 60 % of all patients are using advanced functions and 20 % are using CGMs continuously. This confirms the great interest in diabetes technology that is growing in pediatric diabetologists. However, much improvement is warranted in the organization and specialized training of pediatric, adult and transitional facilities.

Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes.

AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.

Accuracy of two continuous glucose monitoring systems: a head-to-head comparison under clinical research centre and daily life conditions.

AIMS: To assess the accuracy and reliability of the two most widely used continuous glucose monitoring (CGM) systems. METHODS: We studied the Dexcom®G4 Platinum (DG4P; Dexcom, San Diego, CA, USA) and Medtronic Paradigm Veo Enlite system (ENL; Medtronic, Northridge, CA, USA) CGM systems, in 24 patients with type 1 diabetes. The CGM systems were tested during 6-day home use and a nested 6-h clinical research centre (CRC) visit. During the CRC visit, frequent venous blood glucose samples were used as reference while patients received a meal with an increased insulin bolus to induce an aggravated postprandial glucose nadir. At home, patients performed at least six reference capillary blood measurements per day. A Wilcoxon signed-rank test was performed using all data points ≥15 min apart. RESULTS: The overall mean absolute relative difference (MARD) value [standard deviation (s.d.)] measured at the CRC was 13.6 (11.0)% for the DG4P and 16.6 (13.5)% for the ENL [p < 0.0002, confidence interval of difference (CI Δ) 1.7-4.3%, n = 530]. The overall MARD assessed at home was 12.2 (12.0)% for the DG4P and 19.9 (20.5)% for the ENL (p < 0.0001, CI Δ = 5.8-8.7%, n = 839). During the CRC visit, the MARD in the hypoglycaemic range [≤3.9 mmol/l (70 mg/dl)], was 17.6 (12.2)% for the DG4P and 24.6 (18.8)% for the ENL (p = 0.005, CI Δ 3.1-10.7%, n = 117). Both sensors showed higher MARD values during hypoglycaemia than during euglycaemia [3.9-10 mmol/l (70-180 mg/dl)]: for the DG4P 17.6 versus 13.0% and for the ENL 24.6 versus 14.2%. CONCLUSIONS: During circumstances of intended use, including both a CRC and home phase, the ENL was noticeably less accurate than the DG4P sensor. Both sensors showed lower accuracy in the hypoglycaemic range. The DG4P was less affected by this negative effect of hypoglycaemia on sensor accuracy than was the ENL.

Costs of treatment and complications of adult type 1 diabetes.

BACKGROUND AND AIMS: Costs associated with diabetes represent a large burden for patients and the health-care system. However, few studies examined the costs for diabetes treatment in adults with type 1 diabetes (T1DM). This analysis was aimed to assess the costs of treatment associated with T1DM among adults in Italy from the national health-care system perspective. METHODS AND RESULTS: Data were collected using a questionnaire assessing resource consumption retrospectively (drugs, visits, diagnostics, hospitalisations and self-monitoring of blood glucose (SMBG)). One-year costs were calculated for the 12 months preceding the survey. Cost estimation, referred to 2006, was carried out using univariate and multivariate Poisson regression models. Fifty-eight centres enrolled 1193 patients (49.5% women; aged between 18 and 55 years, average diabetes duration was 16.1 ± 9.8 years). The average annual cost for an adult patient with TDM1 was € 2450 (95% confidence interval (CI): 2358-2544). Insulin therapy and SMBG accounted together for 71.2% of total costs (35.6% and 35.6%, respectively); the remainder was shared by hospitalisations (18%), visits (4.0%), diagnostics (3.9%) and other drugs (2.9%). Univariate analyses showed that the presence of complications was associated with excess of costs, mainly related to the hospitalisation and drugs. Multivariate analyses confirmed these results showing that the presence of micro-vascular plus macrovascular complications doubles the cost of treatment. CONCLUSION: Strategies of care for T1DM that can improve disease management and prevent or delay the onset of complications could represent the most important tool to reduce costs in the long term while improving clinical outcomes and quality of life.

Type 1 diabetes control and pregnancy outcomes in women treated with continuous subcutaneous insulin infusion (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI).

AIM: The best way to treat pregnant patients who have type 1 diabetes is still unclear. For this reason, the present study compared metabolic control and maternal-fetal outcomes in patients treated with continuous subcutaneous infusions of rapid-acting insulin analogues (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI). METHODS: This retrospective multicentre study involved 144 women with type 1 diabetes, 100 of whom were using CSII and 44 glargine-MDI. Outcomes analyzed were metabolic control, diabetes complications, pregnancy outcome, perinatal morbidity and mortality, and fetal malformations. RESULTS: The two groups were comparable for age, prepregnancy BMI, primiparous rate and diabetes complications, although patients using CSII had longer duration of diabetes (P=0.03) and higher White classifications (P=0.04). In both groups, metabolic control improved during pregnancy, but good control was reached earlier among patients using CSII. At parturition, patients using CSII had lower HbA(1c) (6.2±0.7% vs 6.5±0.8%; P=0.02) and required less insulin (P<0.01). Weight gain was similar in both groups, and maternal-fetal outcomes did not differ. CONCLUSION: In pregnant patients with type 1 diabetes, MDI and CSII are equivalent in terms of metabolic control and fetal-maternal outcomes, although patients using CSII achieved good control earlier and with less insulin.

Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial.

AIMS: To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. METHODS: In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with Type 1 diabetes (40 women) currently treated with multiple daily injections, age 18-65 years and HbA(1c) ≥ 8.2% (≥ 66 mmol/mol) to 26 weeks of treatment with either a sensor-augmented insulin pump (n = 44) (Paradigm(®) REAL-Time) or continued with multiple daily injections (n = 39). Change in HbA(1c) between baseline and 26 weeks, sensor-derived endpoints and patient-reported outcomes were assessed. RESULTS: The trial was completed by 43/44 (98%) patients in the sensor-augmented insulin pump group and 35/39 (90%) patients in the multiple daily injections group. Mean HbA(1c) at baseline and at 26 weeks changed from 8.46% (SD 0.95) (69 mmol/mol) to 7.23% (SD 0.65) (56 mmol/mol) in the sensor-augmented insulin pump group and from 8.59% (SD 0.82) (70 mmol/mol) to 8.46% (SD 1.04) (69 mmol/mol) in the multiple daily injections group. Mean difference in change in HbA(1c) after 26 weeks was -1.21% (95% confidence interval -1.52 to -0.90, P < 0.001) in favour of the sensor-augmented insulin pump group. This was achieved without an increase in percentage of time spent in hypoglycaemia: between-group difference 0.0% (95% confidence interval -1.6 to 1.7, P = 0.96). There were four episodes of severe hypoglycaemia in the sensor-augmented insulin pump group and one episode in the multiple daily injections group (P = 0.21). Problem Areas in Diabetes and Diabetes Treatment Satisfaction Questionnaire scores improved in the sensor-augmented insulin pump group. CONCLUSIONS: Sensor augmented pump therapy effectively lowers HbA(1c) in patients with Type 1 diabetes suboptimally controlled with multiple daily injections.

Lipoatrophy induced by subcutaneous insulin infusion: ultrastructural analysis and gene expression profiling.

CONTEXT AND OBJECTIVE: Subcutaneous adipose tissue (SAT) lipoatrophy (LA) is a rare complication of insulin therapy. We aimed to analyze the ultrastructural and molecular aspects of LA lesions. SETTING AND PATIENTS: Macroscopic and microscopic morphology of SAT beneath the LA areas from patients with type 1 diabetes treated with Lispro insulin by continuous sc insulin infusion was studied using magnetic resonance imaging, immunohistochemistry, electron microscopy, and quantitative PCR for adipose tissue-specific genes. RESULTS: SAT was present in LA lesions characterized by: 1) smaller, unilocular perilipin-positive adipocytes, with lipofuscin granules; 2) some "slimmed cells" losing lipid droplets as those we observed during starvation; and 3) numerous perivascular preadipocytes. We did not identify inflammatory cells. SAT in LA areas displayed a strong leptin down-regulation and an increase of AEBP1, a preadipocyte marker. CONCLUSIONS: Our results clearly indicate that the remarkable reduction in fat cell lipid droplets and adipocyte size justifies the decrease of SAT without a reduction in adipocyte number because of necrosis or apoptosis. Thus, immune cells and any other toxic damaging fat cells were not involved in the generation of LA. We speculate that adipocytes chronically exposed to high local insulin concentrations could become severely insulin resistant, dramatically increasing lipolysis and giving rise to "slimmed cells." Clinical LA regression could be explained by the active recruitment of preadipocytes, even if they were unable to differentiate and regenerate adipose tissue unless the insulin injection was removed.

Correlates of quality of life in adults with type 1 diabetes treated with continuous subcutaneous insulin injection.

BACKGROUND AND AIMS: Aim of this study was to identify subgroups of adults with Type 1 Diabetes Mellitus (T1DM) treated with Continuous Subcutaneous Insulin Infusion (CSII) at higher risk of poor quality of life (QoL). A sample of consecutive patients completed the Diabetes Specific Quality of Life Scale (DSQOLS), investigating the daily burden and restrictions related to diabetes. Lower DSQOLS scores indicate worse QoL perception. METHODS AND RESULTS: The main results were obtained by using a regression-tree technique (RECursive Partitioning and AMalgamation - RECPAM) and multivariate logistic regression. Overall, 472 patients aged between 18 and 55 years were recruited by 43 Italian centers. RECPAM analysis led to the identification of 5 classes characterized by a marked difference in QoL. Male patients not reporting episodes of ketoacidosis and using CSII for >2 years had the lowest likelihood of scoring in the lower tertile of the DSQOLS summary score, and thus represented the reference category. Patients who reported > or =1 ketoacidosis episodes (OR = 5.4; 95% CI 2.4-12.1) and female patients with a duration of diabetes of <10 years (OR = 5.9; 95% CI 2.6-13.5) had the highest likelihood of reporting poor QoL, while females with longer diabetes duration (OR = 2.4; 95% CI 1.3-4.7) and males treated with CSII for < or =2 years (OR = 2.2; 95% CI 1.1-4.6) showed a two-fold risk of poor QoL. Patient age, diabetic complications and civil status were globally predictive variables associated with poor QoL. CONCLUSION: We identified subgroups of T1DM individuals treated with CSII showing a major impairment in QoL. Specific strategies are needed to help the patient cope with this therapeutic modality, especially during the initial phase of treatment.