Rizvi, Shafaq R.

Abstract Background Customized and standard automated insulin delivery (AID) systems for use in pregnancies of women with preexisting type 1 diabetes (T1D) are being developed and tested to achieve pregnancy appropriate continuous glucose monitoring (CGM) targets. Guidance on the use of CGM for treatment decisions during pregnancy in the United States is limited. Methods Ten pregnant women with preexisting T1D participated in a trial evaluating at-home use of a pregnancy-specific AID system. Seven-point self-monitoring of blood glucose (SMBG) was compared to the closest sensor glucose (Dexcom G6 CGM) value biweekly to assess safety and reliability based on the 20%/20 mg/dL criteria. Results All participants completed the study with 7 participants satisfying the safety and reliability criteria with a mean absolute relative difference of 10.3%. Three participants did not fulfill the criteria, mainly because the frequency of SMBG did not meet the requirements. Conclusion Dexcom G6 CGM is safe and accurate in the real-world setting for use in pregnant women with preexisting T1D with reduced SMBG testing as part of a pregnancy-specific AID system.

AbstractPancreas transplantation alone (PTA) is a β cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2, and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10‐year eGFR (mL/min/1.73 m2) were 76.3 (58.1–100.8) and 51.3 (35.3–65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post‐transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post‐PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death‐censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

Abstract Introduction: Pancreas Transplantation (PT) improves quality of life in Type 1 Diabetes (T1D) patients but limited longitudinal data are available regarding comprehensive metabolic assessment and lifestyle. Our objective was to comprehensively assess T1D patients who underwent PT (PTA and SPK) ≥ 1 year prior on two separate visits 1 year apart. Methodology: We studied 12 PT recipients ≥1 year post PT. Two assessments 1 year apart included comprehensive assessment of graft function using standard mixed meal tolerance test (MMTT), Continuous Glucose Monitoring (CGM) for 1 week, body composition using DEXA scan, physical activity using ActiGraph for 1 week and dietary assessment by VIOCARE®. Results: PT recipients (9F) were 55.5± 9.7 years old, 91.7 % Caucasian with 34.9 ± 12.3 years of diabetes, 6.7 ± 5.2 years (range-1.3–17.6 years) after PT. Ten participants underwent Pancreas Transplantation alone and two received Simultaneous Pancreas Kidney transplantation. Visit 1(V1) showed HbA1c 5.5 ± 0.7%, Fructosamine 238.4 ± 25.6 mcmol/L, BMI 31.2 ± 6.7 kg/m2, fasting plasma glucose (FPG) 95.2 ± 19.4mg/dL and C-peptide 2.6 ± 1.0 ng/ml and visit 2 (V2) HbA1c 5.5 ± 0.6%, Fructosamine 244.4 ± 41.3 mcmol/L, BMI 29.9 ± 5.1kg/m2, FPG 95.4 ± 27.7mg/dL, and C-peptide 2.5 ± 0.8 ng/ml (p-value not significant). One week CGM (n=9) showed excellent glucose control at both visits with mean glucose 117.8 ± 7.0 vs.112 ± 6.2 mg/dl and 96.3 ± 3.6 vs. 96.9±2.8 % time in target range (70-180mg/dl). Time &gt;180mg/dl and &gt;250mg/dl were 2.7 ± 3.0 vs. 1.3±1.7 % (p=0.0413) and 0.2 ± 0.6 vs. 0.1 ± 0.1 % respectively. Mild CGM hypoglycemia (&lt;70 mg/dl) was observed during both visits (1.0 ± 1.0 vs. 1.7± 2 %). CV was 21.1 ± 5.5 and 20.1 ± 4.8 %. Eight recipients underwent MMTT and showed excellent response to Boost® with no significant difference between visits with exception of insulin concentrations at 60 mins (increased from V1) and 90 mins (decreased from V1) (p=0.0424 and 0.0235). DEXA (n=10) revealed similar total % mean fat, and fat distribution in arms, legs and trunk. ActiGraph (n=10) showed similar physical activity during both visits with 16761 ± 5176 and 14499 ± 4192 average steps/day respectively. Mean MET score was 1.6 ± 0.4 and 1.6 ± 0.2 indicating light intensity activity during both periods. Total mean sedentary bouts increased over 1 year (49.6 ± 39.1 vs. 60.8 ± 43.7, p=0.0038). Dietary assessment in 11 recipients showed no significant difference in dietary intake with calories intake 1.3± 0.4 vs. 1.2±0.5 daily Harris-Benedict and macronutrient intake with fat of 36.7 ± 4.3 % and 36.5 ± 5.7 %, CHO of 45.7 ± 5.5 % and 45.7 ± 5.5 % and Omega-3 of 0.1 ± 0.1 g and 0.05 ± 0.1 g respectively. Conclusion: PT recipients have excellent glucose control and pancreas graft function 1 or more years after PT when assessed over successive 2 years with suboptimal body composition and dietary intake and above average physical activity.

Abstract INTRODUCTION: Type 1 Diabetes (T1D) patients have an increased risk for major adverse cardiovascular events (MACE). Pancreas Transplantation Alone (PTA) in patients with T1D achieves near normal glucose control for a prolonged period but limited data are available to date regarding MACE during a 10 year follow up period after the procedure. OBJECTIVE: We studied incidence of MACE after PTA in T1D patients over a 10 year follow-up period. METHODS: Retrospectively, we studied 113 T1D recipients of PTA at Mayo Clinic, Rochester with the procedure performed between January 1998 and August 2018 and follow up of at least 1 year. Data were collected before transplantation and up to 10 year follow up after the first PTA. MACE data were gathered until primary non function, re-transplantation, or complete loss of c-peptide (&lt;0.01ng/ml). We report vascular risk factors including hypertension, hyperlipidemia, smoking and BMI along with MACE (defined as cardiac events as unstable angina, Myocardial Infarction (MI), need for re-vascularization, cardiac death, cerebral events as Transient ischemic attack (TIA), stroke, need for re-vascularization and peripheral arterial disease as need for re-vascularization, gangrene and amputation). RESULTS: Eighteen subjects had pre-transplant MACE. A total of 14 subjects had graft failure within 24 to 36 hours due to thrombosis, with 3 in pre-transplant MACE cohort and 11 in no MACE cohort. Thus, we followed 99 subjects for the development of post-transplant MACE for a period of 6.3 ± 3.6 years. T1D subjects with MACE (n=15) had baseline characteristics: Age 48± 7.8 years, gender F/M 9/6,, duration of diabetes 33 ± 12 years, BMI 26± 3.1(Kg/m2), HbA1c 9.3 ± 1.5% and C-peptide 0.09 ng/ml. 84 T1D patients without MACE were age 42 ± 10.6 years, gender F/M 55/29, duration of diabetes 26.5 ± 10.7 years, BMI 26 ± 5.2(Kg/m2), HbA1c 6.7 ± 2.5 and C-peptide 0.09 ng/ml. There are a total of 584 person-years of follow up to first MACE event and 632 person-years of graft failure, death or last follow-up. Nine patients developed 11 MACE events post-PTA. Therefore, the event rate is 1.5 MACE events per 100 person-years for first MACE event and the total event rate is 1.7 MACE events per 100 person-years of follow-up. Age, smoking (yes), gender, duration of diabetes, HTN and Hyperlipidemia presence did not show any significant impact on post-transplant MACE outcome based on univariate Cox regression but the pre-transplant BMI (HR = 1.14; CI = (1.04, 1.26); p = 0.008) and pre-transplant HbA1c (HR = 1.26; CI = (1.06, 1.51); p = 0.01) showed statistically significant impact. CONCLUSIONS: At our center, MACE is low in PTA recipients. There is no impact of presence of pre-transplant MACE on development of post-transplant MACE but pre-transplant BMI and HbA1c account for risk of MACE.