Pratik Choudhary

Insulin Pump Therapy With Automated Insulin Suspension in Response to Hypoglycemia: Reduction in nocturnal hypoglycemia in those at greatest risk

OBJECTIVE To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. CONCLUSIONS Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients.

Normal Reference Range for Mean Tissue Glucose and Glycemic Variability Derived from Continuous Glucose Monitoring for Subjects Without Diabetes in Different Ethnic Groups

BACKGROUND Glycemic variability has been proposed as a contributing factor in the development of diabetes complications. Multiple measures exist to calculate the magnitude of glycemic variability, but normative ranges for subjects without diabetes have not been described. For treatment targets and clinical research we present normative ranges for published measures of glycemic variability. METHODS Seventy-eight subjects without diabetes having a fasting plasma glucose of <120 mg/dL (6.7 mmol/L) underwent up to 72 h of continuous glucose monitoring (CGM) with a Medtronic Minimed (Northridge, CA) CGMS(®) Gold device. Glycemic variability was calculated using EasyGV(©) software (available free for non-commercial use at www.easygv.co.uk ), a custom program that calculates the SD, M-value, mean amplitude of glycemic excursions (MAGE), average daily risk ratio (ADRR), Lability Index (LI), J-Index, Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), continuous overlapping net glycemic action (CONGA), mean of daily differences (MODD), Glycemic Risk Assessment in Diabetes Equation (GRADE), and mean absolute glucose (MAG). RESULTS Eight CGM traces were excluded because there were inadequate data. From the remaining 70 traces, normative reference ranges (mean±2 SD) for glycemic variability were calculated: SD, 0-3.0; CONGA, 3.6-5.5; LI, 0.0-4.7; J-Index, 4.7-23.6; LBGI, 0.0-6.9; HBGI, 0.0-7.7; GRADE, 0.0-4.7; MODD, 0.0-3.5; MAGE-CGM, 0.0-2.8; ADDR, 0.0-8.7; M-value, 0.0-12.5; and MAG, 0.5-2.2. CONCLUSIONS We present normative ranges for measures of glycemic variability in adult subjects without diabetes for use in clinical care and academic research.

Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study.

BACKGROUND Closed-loop insulin delivery is a promising option to improve glycaemic control and reduce the risk of hypoglycaemia. We aimed to assess whether overnight home use of automated closed-loop insulin delivery would improve glucose control. METHODS We did this open-label, multicentre, randomised controlled, crossover study between Dec 1, 2012, and Dec 23, 2014, recruiting patients from three centres in the UK. Patients aged 18 years or older with type 1 diabetes were randomly assigned to receive 4 weeks of overnight closed-loop insulin delivery (using a model-predictive control algorithm to direct insulin delivery), then 4 weeks of insulin pump therapy (in which participants used real-time display of continuous glucose monitoring independent of their pumps as control), or vice versa. Allocation to initial treatment group was by computer-generated permuted block randomisation. Each treatment period was separated by a 3-4 week washout period. The primary outcome was time spent in the target glucose range of 3·9-8·0 mmol/L between 0000 h and 0700 h. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01440140. FINDINGS We randomly assigned 25 participants to initial treatment in either the closed-loop group or the control group, patients were later crossed over into the other group; one patient from the closed-loop group withdrew consent after randomisation, and data for 24 patients were analysed. Closed loop was used over a median of 8·3 h (IQR 6·0-9·6) on 555 (86%) of 644 nights. The proportion of time when overnight glucose was in target range was significantly higher during the closed-loop period compared to during the control period (mean difference between groups 13·5%, 95% CI 7·3-19·7; p=0·0002). We noted no severe hypoglycaemic episodes during the control period compared with two episodes during the closed-loop period; these episodes were not related to closed-loop algorithm instructions. INTERPRETATION Unsupervised overnight closed-loop insulin delivery at home is feasible and could improve glucose control in adults with type 1 diabetes. FUNDING Diabetes UK.

Real-Time Continuous Glucose Monitoring Significantly Reduces Severe Hypoglycemia in Hypoglycemia-Unaware Patients With Type 1 Diabetes

OBJECTIVE To evaluate the effect of continuous glucose monitoring (CGM) on the frequency of severe hypoglycemia (SH) in patients with established hypoglycemia unawareness. RESEARCH DESIGN AND METHODS We conducted a retrospective audit of 35 patients with type 1 diabetes and problematic hypoglycemia unawareness, despite optimized medical therapy (continuous subcutaneous insulin infusion/multiple daily insulin injections), who used CGM for >1 year. RESULTS Over a 1-year follow-up period, the median rates of SH were reduced from 4.0 (interquartile range [IQR] 0.75–7.25) episodes/patient-year to 0.0 (0.0–1.25) episodes/patient-year (P < 0.001), and the mean (±SD) rates were reduced from 8.1 ± 13 to 0.6 ± 1.2 episodes/year (P = 0.005). HbA1c was reduced from 8.1 ± 1.2% to 7.6 ± 1.0% over the year (P = 0.005). The mean Gold score, measured in 19 patients, did not change: 5.1 ± 1.5 vs. 5.2 ± 1.9 (P = 0.67). CONCLUSIONS In a specialist experienced insulin pump center, in carefully selected patients, CGM reduced SH while improving HbA1c but failed to restore hypoglycemia awareness.

Hypoglycemia unawareness is associated with reduced adherence to therapeutic decisions in patients with type 1 diabetes: evidence from a clinical audit.

OBJECTIVE Hypoglycemia unawareness increases severe hypoglycemia risk. Hypoglycemia avoidance restores awareness, but it is difficult to sustain. We compared adherence to treatment changes by awareness status. RESEARCH DESIGN AND METHODS Case notes of 90 type 1 diabetic patients were analyzed retrospectively, identifying awareness status and insulin regimens over four visits. The proportion of patients adhering to advice and percent advice taken were calculated. RESULTS A total of 31 patients with hypoglycemia awareness and 19 patients with hypoglycemia unawareness were identified, with insulin regimens available in 23 and 13, respectively. Patients with hypoglycemia unawareness were older (P = 0.001) and had longer diabetes duration (P = 0.002) and lower A1C (P = 0.007). More patients with hypoglycemia unawareness reported severe hypoglycemia (P = 0.002) and fewer were adherent (53.8 vs. 87.0%, P = 0.046), with lower adherence scores (42.5 ± 24.7 vs. 75.3 ± 27.5%, P = 0.001). CONCLUSIONS Reduced adherence to changes in insulin regimen in hypoglycemia unawareness is compatible with habituation to hypoglycemic stress. Therapies aimed at reversing repetitive harmful behaviors may be useful to restore hypoglycemia awareness and protection from severe hypoglycemia.

Evidence-informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia

Problematic hypoglycemia, defined as two or more episodes per year of severe hypoglycemia or as one episode associated with impaired awareness of hypoglycemia, extreme glycemic lability, or major fear and maladaptive behavior, is a challenge, especially for patients with long-standing type 1 diabetes. Individualized therapy for such patients should include a composite target: optimal glucose control without problematic hypoglycemia. Therefore, we propose a tiered, four-stage algorithm based on evidence of efficacy given the limitations of educational, technological, and transplant interventions. All patients with problematic hypoglycemia should undergo structured or hypoglycemia-specific education programs (stage 1). Glycemic and hypoglycemia treatment targets should be individualized and reassessed every 3–6 months. If targets are not met, one diabetes technology—continuous subcutaneous insulin infusion or continuous glucose monitoring—should be added (stage 2). For patients with continued problematic hypoglycemia despite education (stage 1) and one diabetes technology (stage 2), sensor-augmented insulin pumps preferably with an automated low-glucose suspend feature and/or very frequent contact with a specialized hypoglycemia service can reduce hypoglycemia (stage 3). For patients whose problematic hypoglycemia persists, islet or pancreas transplant should be considered (stage 4). This algorithm provides an evidence-informed approach to resolving problematic hypoglycemia; it should be used as a guide, with individual patient circumstances directing suitability and acceptability to ensure the prudent use of technology and scarce transplant resources. Standardized reporting of hypoglycemia outcomes and inclusion of patients with problematic hypoglycemia in studies of new interventions may help to guide future therapeutic strategies.

Hypoglycemia Prevention and User Acceptance of an Insulin Pump System with Predictive Low Glucose Management

Abstract Background: The MiniMed 640G sensor-augmented insulin pump system (Medtronic, Inc., Northridge, CA) can automatically suspend insulin delivery in advance of predicted hypoglycemia and restart it upon recovery. The aims of this analysis were to determine the rate at which predicted hypoglycemia was avoided with this strategy, as well as to assess user acceptance of the system and its insulin management features. Subjects and Methods: Forty subjects with type 1 diabetes used the system for 4 weeks. We retrospectively evaluated performance of the system, using downloaded pump and sensor data, and evaluated user acceptance via questionnaires. Results: There were 2,322 suspend before low events (2.1 per subject-day). The mean (± SD) duration of pump suspension events was 56.4 ± 9.6 min, and the mean subsequent sensor glucose (SG) nadir was 71.8 ± 5.2 mg/dL. SG values following 1,930 (83.1%) of the predictive suspensions did not reach the preset low limit. Nadir SG values of ≤50 and ≤60 mg/dL were seen in 207 (8.9%) and 356 (15.3%) of the predictive suspensions, respectively. Blood glucose (BG) and SG values before and during the study were comparable (P > 0.05). The mean absolute relative difference between paired SG and BG values was 10.9 ± 13.8%. Subjects felt confident using the system, agreed that it helped protect them from hypoglycemia, and wished to continue using it. Conclusions: Automatic insulin pump suspension as implemented in the MiniMed 640G system can help patients avoid hypoglycemia, without significantly increasing hyperglycemia.

Frequency of biochemical hypoglycaemia in adults with Type 1 diabetes with and without impaired awareness of hypoglycaemia: no identifiable differences using continuous glucose monitoring.

Diabet. Med. 27, 666–672 (2010)

A Psychoeducational Program to Restore Hypoglycemia Awareness: The DAFNE-HART Pilot Study

OBJECTIVE To develop and pilot a novel intervention addressing motivational and cognitive barriers to avoiding hypoglycemia in people with type 1 diabetes and persistent impaired awareness of hypoglycemia (IAH) despite training in flexible insulin therapy. RESEARCH DESIGN AND METHODS A 6-week intervention using motivational interviewing and cognitive behavioral techniques was designed. Diabetes educators were trained and supported in its delivery to 23 people with IAH (Gold score ≥4). RESULTS Twelve months postcourse, hypoglycemia awareness had improved (P < 0.001). Median (range) rates of severe hypoglycemia (SH) fell from 3 (0–104) to 0 (0–3) per person per year (P < 0.0001) and moderate from 14 (0–100) to 0 (0–18) per person per 6 weeks (P < 0.001). Worry and behavior around hyperglycemia improved. HbA1c was unchanged. CONCLUSIONS A pilot intervention targeting motivation and cognitions around hypoglycemia engaged patients with resistant IAH and recurrent SH and was associated with significant improvement, supporting the hypothesis that these factors underpin problematic hypoglycemia.

Hypoglycaemia: current management and controversies

Hypoglycaemia is a major burden on patients and society and is often a barrier to the achievement of tight glycaemic control. Intact awareness of hypoglycaemia is crucial to recognising and treating hypoglycaemia before it becomes severe enough to impair consciousness. Repeated hypoglycaemia can lead to impaired awareness increasing the risk of severe hypoglycaemia up to sixfold. Hypoglycaemia is much less common in those with type 2 diabetes, the incidence increasing with longer duration of treatment with insulin, associated comorbidities, and in the elderly. Alcohol, advancing age and exercise may predispose to hypoglycaemia. Newer agents acting via the incretin axis are associated with low rates of hypoglycaemia. Intensification of therapy to achieve tight glucose control can increase the risk of hypoglycaemia in the outpatient as well as critical care setting. In some studies this has also been associated with increased mortality, although causality has not been proven. Insulin treated patients are currently restricted from driving heavy goods vehicles or public service vehicles, although it is unclear if those with diabetes have any higher rates of accidents than those without diabetes. Surveys show that professionals are poor at emphasising the Driver and Vehicle Licensing Agency recommendations for drivers with diabetes in the UK. At every visit, patients with diabetes on hypoglycaemic agents should be assessed for frequency, severity, and awareness of hypoglycaemia. The main therapeutic strategies for reducing hypoglycaemia are structured patient education, use of modern insulin analogues, insulin pumps, and continuous glucose monitoring. Transplantation of islets or whole pancreas is indicated in those with recurrent disabling hypoglycaemia.