Abstracts / Can J Diabetes 36 (2012) S2eS22 S17

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Current Diabetes Management Does Not Prevent NocturnalHypoglycemia among Patients with Type 1 Diabetes in Real LifeConditions - Preliminary ResultsKATHERINE DESJARDINS*, ANNE-SOPHIE BRAZEAU,CATHERINE LEROUX, IRENE STRYCHAR, RÉMI RABASA-LHORETMontreal, QC

Hypoglycemia is an important barrier to achieve good glycemiccontrol among patients with type 1 diabetes (T1D). The aim of thisstudy was to describe in real life conditions: nocturnal hypogly-cemia (NH), glucose profiles and bedtime snack.

Sixty-five patients with T1D (54% men, mean�SD: age 45.5�12.6years, A1c 7.9�1.0%, total daily insulin 0.66�0,29U/kg/day), usingmultiple daily injections (n¼44) or continuous subcutaneousinsulin infusion (n¼21) with insulin analogs wore a blindedcontinuous glucose monitoring device and completed a food diaryfor 3 days.

NH occurred on 32% of the 190 nights studied. Of those NH, 85%were unrecognized. In nights with (NH+) vs. without (NH-) hypo-glycemia mean glucose value (GV) were 5.1�2.1 vs. 8.8�3.0 mmol/L(p<0.001), but with similar time between 4 and 8 mmol/L(49.0�16.2% vs. 46.3�22.9%, p¼0.75). GV 3 hours after the dinner inNH+ and NH- were respectively 6.1�3.1 vs. 8.3�4.0 mmol/L(p<0.001). For each 1.0 mmol/L decrease in bedtime GV, the risk ofNH increased by 21% (p<0.001).

Patients ate a bedtime snack 68.9% of the time (mean carbohy-drates content: 35.3�27.1g) of which 23.7% was taken with aninsulin bolus. Themain reason reported for snackingwas to preventNH according to self monitoring of blood glucose. However, NH riskwas not different with or without snack (p¼0.14).

In conclusion, NH remains extremely frequent and unrecognizedwhile NH- nights are characterized by a hyperglycemic state.Bedtime snacking was driven by bedtime GV but was not associatedwith less NH. Strategies to achieve overnight glycemic control areneeded.

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Significant Reduction in Hypoglycemia with the Low GlucoseSuspend (LGS) Feature of the Veo Insulin Pump During Exercise-Induced Hypoglycemia and During Routine In-Home UsePRATIK AGRAWAL, JOHN J. SHIN*, SCOTT W. LEE, JOHN B. WELSH,TOM TROUB, FRANCINE R. KAUFMANNorthridge, CA

The LGS feature of the Veo pump stops insulin delivery whena low sensor glucose (SG) threshold is met. Its effects were evalu-ated in the ASPIRE trial and through retrospective analysis ofroutine usage data. The ASPIRE trial evaluated the glycemic impactof LGS during exercise-induced hypoglycemia. Fifty type 1 diabetessubjects exercised to achieve hypoglycemia during two phases:LGS-ON experiments had cessation of insulin for 2 hours after SGreached 70 mg/dL; LGS-OFF experiments continued insulindelivery. The mean duration of hypoglycemia was significantly lesswith LGS-ON compared to LGS-OFF (138.5�76.68 vs. 170.7�75.91min, p¼0.006). Mean end-observation YSI glucose values(91.4�41.84 vs 66.2�13.48 mg/dL, p<0.001) were higher with LGS-ON than with LGS-OFF. The LGS feature was evaluated throughreview of data from the CareLink Personal database representingroutine use from 7810 subjects from 1/10 to 11/11. Comparison ofLGS-ON versus LGS-OFF patient-days showed that hypoglycemiawas reduced during LGS-ON periods. There was a lower AUC<70mg/dL (0.62 vs 1.00 mg/dL, p<0.001), less time spent <70 mg/dL(5.3% vs 7.4%, p<0.001), and shorter mean duration of excursions to<70 mg/dL (37.9 vs 46.5 min, p<0.001) when LGS was used. Therewere statistically (but not clinically) significant decreases in thepercentage of time >240 mg/dL (11.23% vs 11.30%, p¼0.001) and>300 mg/dL (3.43% vs 3.59%, p<0.001) when LGS was used. LGSholds promise for reducing hypoglycemia in type 1 diabetes

without deteriorating glycemic control. Automating insulin shut-off at a hypoglycemic threshold is the next step to improve type 1diabetes outcomes.

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Localized Delivery of IL-10 to Colonic Epithelium of Non-ObeseMice (NOD) to Prevent DiabetesMAJID MOJIBIAN*, YVONNE LUU, ANTHONY T. CHEUNG,TIMOTHY J. KIEFFERVancouver, BC

Interleukin-10 (IL-10) is a cytokine with a critical role in sup-pressing inflammation and inducing tolerance in autoimmunediseases. We hypothesized that ectopic production of IL-10 incolonic epithelium using a non-viral gene delivery system opti-mized for the intestinalmucosa could alter diabetes development innon-obese diabetic (NOD)mice. Chitosan nanoparticles carrying thehuman IL-10 gene were delivered intracolonically to NOD micestarting at 10weeks of age,with 5 bi-weekly treatments followed by3monthly treatments. By thismethod, IL-10 expression is restrictedto the intestine. Delivery of IL-10 DNA resulted in higher percentsurvival in NOD mice (75% at age 30 weeks) compared to controlnanoparticles and non-treated animals in which 30-40% remainednon-diabetic by this age. By 56 weeks of age, IL-10 treated animalsremained normoglycemic while almost all of the control animalsbecame diabetic. At 12weeks of age therewas a significant decreaseof predictory CD8+ specific NRP-V7+ Tcells in the periphery of IL-10treated animals compared to controls. In a second cohort of 10weekoldNODmice that underwent 4weekly treatments of nanoparticles,we detected a significant increase of regulatory type T cells inmesenteric lymph nodes (MLN) of IL-10 treated mice. Conversely,we observed a significant decrease in T cell proliferation responsesto insulin antigen in immune cells isolated from the MLN of NODmice treated with IL-10 compared to controls. Collectively, ourobservations indicate a beneficial role of gut-localized delivery of IL-10 in preventing diabetes development in NOD mice.

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Imaging Maturation in Single Adult b-Cells using FluorescentReporters for Ins1, Pdx1, MafA and MafB Promoter ActivitiesMARTA SZABAT*, TOBIAS ALBRECHT, FORSON CHAN, JAMES M. PIRET,JAMES D. JOHNSONVancouver, BC

The functional maturation and dedifferentiation of b-cells iscentral to diabetes pathogenesis and to b-cell replacement therapy.‘Snapshots’ of adult b-cells show variable levels of insulin promoteractivity, insulin protein and insulin secreting function. We haveshown, using a dual fluorescent Pdx1/Ins1 reporter, that thisapparent heterogeneity in part reflects a dynamic process ofmaturation (i.e. gaining insulin promoter activity over time). Geneexpression profiling revealed that immature b-cells had increasedexpression of multiple islet hormones and genes involved indevelopment, proliferation and apoptosis, including MafB. Matureb-cells were enriched in genes that maintain the differentiated b-cell phenotype, including MafA. A follow-up study demonstratednovel roles for Musashi in the control of insulin expression and b-cell proliferation. A factorial screen uncovered that activin A and itsantagonist follistatin reciprocally control maturity of adult b-cells.Here, we report the development of new tools that allow forsimultaneous analysis of MafA and MafB promoter activities, usingfluorescent proteins targeted to the plasma membrane. We foundthat MafA/MafB promoter-reporters showed differential activitybetween single b-cells and quantified the dynamics of these geneexpression transitions. Using these tools, we have developed ultra-high-content screening platforms to further decode the level ofmaturity of single adult b-cells in various culture conditions andhealth/diabetic states. Collectively, these experiments contribute tothe understanding of heterogeneity, maturation and putative