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This document discusses the challenges of using glucagon-like peptide (GLP) analogs for people with type 1 diabetes (T1D). It highlights the global issue of overweight and obesity and the associated health problems. While GLP analogs have been shown to be effective in improving glucose control and weight loss in type 2 diabetes (T2D), they are not currently approved for use in T1D by the FDA. The document also addresses the difficulties of obtaining insurance coverage for GLP analogs and the high cost of these medications. It provides tips for the safe use of GLP analogs in T1D patients. Another article discusses the use of GLP analogs in T1D patients, specifically the off-label use of semaglutide and tirzepatide. The authors found that both medications resulted in significant weight loss and improved glucose control without an increased risk of severe hypoglycemia or diabetic ketoacidosis. However, there are challenges in determining the appropriate dosage and potential side effects such as gastrointestinal issues. The authors stress the importance of personalized treatment and regular communication with healthcare providers. They also note the lack of randomized controlled trials in this population. [Extracted from the article]

Introduction and Objective: Most patients with type 1 diabetes (T1D) in the United States are overweight (OW) or obese (OB), contributing to insulin resistance and suboptimal glucose control. The primary Food and Drug Administration-approved treatment for T1D is insulin, which may adversely affect weight. Tirzepatide is approved for managing type 2 diabetes, improves glucose control, facilitates weight loss, and improves cardiovascular disease outcomes. We assessed the use of tirzepatide in OW/OB subjects with T1D. Methods: This was a retrospective single-center real-world study in 62 OW/OB adult patients with T1D who were prescribed tirzepatide (treated group) and followed for 1 year. At least 3 months of use of tirzepatide was one of the inclusion criteria. Based on the inclusion criteria, this study represents 62 patients out of 184 prescribed tirzepatide. The control group included 37 OW/OB patients with T1D (computer frequency matched by age, duration of diabetes, gender, body mass index (BMI), and glucose control) who were not using any other weight-loss medications during the same period. The mean (±standard deviation [SD]) dose of weekly tirzepatide at 3 months was 5.6 ± 1.9 mg that increased to 9.7 ± 3.3 mg at 1 year. Results: The gender, mean baseline age, duration of diabetes, and glycosylated hemoglobin (HbA1c) were similar in the two groups, whereas BMI and weight were higher in the treated group. There were significantly larger declines in BMI and weight in the treated group than in controls across all time points among those in whom data were available. HbA1c decreased in the treated group as early as 3 months and was sustained through a 1-year follow-up (−0.67% at 1 year). As expected, insulin dose decreased at 3 months and throughout the study period. There were no reported hospitalizations from severe hypoglycemia or diabetic ketoacidosis. The mean glucose, time-in-range, time-above-range, SD, and coefficient of variation (continuous glucose monitoring metrics) significantly improved in the treated group. Conclusions: In this pilot (off label) study, we conclude that tirzepatide facilitated an average 18.5% weight loss (>46 pounds) and improved glucose control in OW/OB patients with T1D at 1 year. For safe use of tirzepatide in patients with T1D, we strongly recommend a large prospective randomized control trial in OW/OB patients with T1D. [ABSTRACT FROM AUTHOR]

This article provides an overview of the development and future of automated insulin delivery (AID) systems, which include insulin pumps, continuous glucose monitoring (CGM), and smart algorithms. It discusses the advancements in insulin pump technology, from the first portable pump in 1963 to the smaller, wearable pumps introduced in the 1980s and beyond. The article also explores the integration of CGM with insulin pumps and the introduction of AID systems that automatically deliver insulin based on real-time glucose data. It highlights specific AID systems, such as the MiniMed™ 670G and 780G, and the t:slim X2™ with Control-IQ technology. The document further provides an overview of various artificial pancreas systems for the management of type 1 diabetes (T1D), including the Tandem AHCL Control-IQ, OmniPod 5 HCL, Diabeloop generation 1, CamAPS FX, Tidepool Loop, and Beta Bionics iLet. It discusses the results of clinical trials and real-world data for these systems and addresses barriers to adoption, such as cost and user experience. The article concludes that the use of artificial pancreas systems improves glucose control and reduces the burden of diabetes, with the potential to prevent long-term complications. [Extracted from the article]

Introduction: More than two-thirds of patients with type 1 diabetes (T1D) are overweight (OW) and/or obese (OB) in the USA and Western Europe, resulting in insulin resistance as in type 2 diabetes. None of the currently available glucagon like polypeptide 1 (GLP-1) analogs are approved for patients with T1D. A higher dose of semaglutide has been approved by the Food and Drug Administration (FDA) for subjects with body mass index (BMI) >27 kg/m2. We evaluated the real-world use of semaglutide in patients with T1D. Methods: This was a retrospective chart review study of 50 OW or OB patients with T1D who were initiated on semaglutide and followed for 1 year. The control group comprised of 50 computer-matched patients (for sex, race, weight, BMI, and diabetes duration) during a similar time period and were not on any weight loss medications. Results: Most patients (92%) were non-Hispanic white in both arms. Mean ± standard deviation (SD) age and duration of diabetes were 42 ± 11 and 27 ± 12 years, respectively. The continuous glucose monitors (CGM), insulin pump use, baseline BMI and body weight were also similar in the two groups. Baseline glycosylated hemoglobin (HbA1c) was insignificantly lower in the semaglutide group (7.6% vs. 8.2%, respectively; P = non-significant [NS]). Total daily insulin dose (TDD) and insulin dose per kg body weight were higher in the semaglutide group at baseline with no difference in basal or prandial insulin dose. There were significantly greater declines in mean (±SD), BMI (7.9% ± 2.6%), body weight (15.9 lbs ± 5.4 lbs), HbA1c, CGM glucose SD and coefficient of variation (CV), and increase in CGM time in range (TIR) in the semaglutide group compared to the control group with no difference in insulin dose changes, time above range (TAR), or time below range (TBR). Conclusions: We conclude that use of semaglutide in patients who are OW and/or OB with T1D was effective in lowering body weight and BMI, and improving glycemic metrics in this pilot real-world study. We strongly recommend performing prospective, large-randomized clinical trials with newer GLP-1 analogs like semaglutide and tirzepatide (twin-cretin) for subjects with T1D associated with OW and/or OB. [ABSTRACT FROM AUTHOR]

Aims. We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes. Methods. Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks' gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were "estimated glomerular filtration rate" (eGFR) at each visit and onset of PE. Results. In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all p < 0.05). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE. Conclusions. Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women. [ABSTRACT FROM AUTHOR]

Global prevalence of diabetes, both type 1 (T1D) and type 2 (T2D) diabetes, continues to increase and is expected to reach beyond 700 million people by 2040.[1] Most of this increase in prevalence is in the emerging economies: Middle East,[1] China,[1] and India.[2] Similarly, the cost of caring for diabetes also has significantly increased in the past decade[2],[3] Unfortunately, social-economically disadvantaged individuals and minorities are not offered the same treatment options, and thus, have poor overall long-term health outcomes.[4] Fortunately, there have been significant developments in the technologies and therapeutic options for people with diabetes. Our predictions are that CGM will pretty much replace SMBG for insulin-requiring patients with diabetes, assuming cost is not a barrier. Diabetes Technol Ther. Although current clinical guidelines provide various treatment algorithms for diabetes management, they do not address the individual needs of each patient. [Extracted from the article]

The article discusses the use of closed-loop insulin delivery systems, also known as automated insulin delivery systems, in pregnant women with type 1 diabetes. It highlights the potential benefits of such systems in improving glycemic control during pregnancy, with a focus on the AiDAPT trial. The study found that early closed-loop use during pregnancy can significantly increase the time spent in the target glucose range, reducing the risk of adverse maternal and neonatal health outcomes.

Objective: To evaluate safety and effectiveness of MiniMed™ 670G hybrid closed loop in comparison with continuous subcutaneous insulin infusion (CSII) therapy for six months, in persons with type 1 diabetes (T1D).Methods: Adults (aged 18-80 years), adolescents, and children (aged 2-17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to six months of HCL intervention (N=151, mean age of 39.9±19.8 years) or CSII control (N=151, 35.7±18.4 years) without continuous glucose monitoring. Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR<70 mg/dL) for Group 2 (baseline A1C ≤8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR<70 mg/dL for Group 2 and Group 1, respectively, to show non-inferiority of HCL intervention versus control. Primary safety endpoints were rates of severe hypoglycemia and diabetic ketoacidosis (DKA).Results: Change in A1C and difference in %TBR<70 mg/dL for the overall group were significantly improved, in favor of HCL intervention. In addition, a significant mean (95% CI) change in A1C was observed for both Group 1 (-0.8% [-1.1%,-0.4%], p<0.0001) and Group 2 (-0.3% [-0.5%,-0.1%], p<0.0001), in favor of HCL intervention. The same was observed for difference in %TBR<70 mg/dL for Group 1 (-2.2% [-3.6%,-0.9%]) and Group 2 (-4.9% [-6.3%,-3.6%]) (p<0.0001 for both). There was one DKA event during run-in and six severe hypoglycemic events: two during run-in and four during study (HCL: N=0 and CSII: N=4 [6.08 per 100 patient-years]).Conclusions: This RCT demonstrate that the MiniMed 670G system safely and significantly improved A1C and %TBR<70 mg/dL with HCL intervention compared with CSII control in persons with T1D, irrespective of baseline A1C level. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether an increased bolus: basal insulin ratio (BBR) with liver‐targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv). Patient Population and Methods: We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic‐directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90‐day run‐in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV‐insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose. Results: At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The −10% and −40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% (P =.02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient‐reported HEv in the −10% and −40% BaI cohorts, respectively. Conclusions: Our study shows that liver‐targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver‐targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage. [ABSTRACT FROM AUTHOR]

Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694). [ABSTRACT FROM AUTHOR]

Background: We evaluated the accuracy and safety of a seventh generation (G7) Dexcom continuous glucose monitor (CGM) during 10.5 days of use in adults with diabetes. Methods: Adults with either type 1 or type 2 diabetes (on intensive insulin therapy or not) participated at 12 investigational sites in the United States. In-clinic visits were conducted on days 1 or 2, 4 or 7, and on the second half of day 10 or the first half of day 11 for frequent comparisons with comparator blood glucose measurements obtained with the YSI 2300 Stat Plus glucose analyzer. Participants wore sensors concurrently on the upper arm and abdomen. Accuracy evaluation included the proportion of CGM values within 15% of comparator glucose levels >100 mg/dL or within 15 mg/dL of comparator levels ≤100 mg/dL (%15/15), along with the %20/20 and %30/30 agreement rates. The mean absolute relative difference (MARD) between temporally matched CGM and comparator values was also calculated. Results: Data from 316 participants (619 sensors, 77,774 matched pairs) were analyzed. For arm- and abdomen-placed sensors, overall MARDs were 8.2% and 9.1%, respectively. Overall %15/15, %20/20, and %30/30 agreement rates were 89.6%, 95.3%, and 98.8% for arm-placed sensors and were 85.5%, 93.2%, and 98.1% for abdomen-placed sensors. Across days of wear, glucose concentration ranges, and rates of change, %20/20 agreement rates varied by no more than 9% from the overall %20/20. No serious adverse events were reported. Conclusions: The G7 CGM provides accurate glucose readings with single-digit MARD with arm or abdomen placement in adults with diabetes. Clinicaltrials.gov: NCT04794478. [ABSTRACT FROM AUTHOR]

Background: Use of continuous glucose monitoring (CGM) systems is being rapidly adopted as standard of care for insulin-requiring patients with diabetes. The PROMISE study (NCT03808376) evaluated the accuracy and safety of the next-generation implantable Eversense CGM system for up to 180 days. Methods: This was a prospective multicenter study involving 181 subjects with diabetes at 8 USA sites. All subjects were inserted with a primary sensor. Ninety-six subjects had a second sensor, either an identical sensor or a modified sensor (sacrificial boronic acid [SBA]), inserted in their other arm (53 and 43 subjects, respectively). Accuracy was evaluated by comparing CGM to YSI 2300 glucose analyzer (Yellow Springs Instrument [YSI]) values during 10 clinic visits (day 1-180). Confirmed event detection rates, calibration stability, sensor survival, and serious adverse events (SAEs) were evaluated. Results: For primary sensors, the percent CGM readings within 20%/20% of YSI values was 92.9%; overall mean absolute relative difference (MARD) was 9.1%. The confirmed alert detection rate at 70 mg/dL was 93% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 56%. Sixty-five percent of the primary sensors survived to 180 days. For the SBA sensors, the percent CGM readings within 20%/20% of YSI values was 93.9%; overall MARD was 8.5%. The confirmed alert detection rate at 70 mg/dL was 94% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 63%. Ninety percent of the SBA sensors survived to 180 days. No device- or insertion/removal procedure-related SAEs were reported. Conclusion: These data show the next-generation Eversense CGM system had sustained accuracy and safety up to 180 days, with an improved calibration scheme and survival, using the primary or SBA sensors. [ABSTRACT FROM AUTHOR]

33 Carlson AL, Martens TW, Johnson L, Criego AB: Continuous glucose monitoring integration for remote diabetes management: virtual diabetes care with case studies. Diabetes prevalence continues to increase globally with current estimates at 463 million people with both type 1 diabetes (T1D) and type 2 diabetes (T2D).[1] The overall prevalence of diabetes in the United States is ~9%.[2] The prevalence of both T1D and T2D is increasing at the rate of ~4% annually and about 1/3 of patients remain undiagnosed.[2] However, the highest concentration of diabetes, globally, is in the Middle East.[3] As expected, all patients with T1D and about 20% of patients with T2D require insulin therapy for managing their diabetes effectively during their lifetime.[4] Disparities in Diabetes Diabetes continues to affect communities of color disproportionately higher. 26 American Diabetes Association: FDA Expands Remote Patient Monitoring in Hospitals for People with Diabetes During COVID-19; Manufacturers Donate CGM Supplies. Fortunately, now, most commercial payers, Medicare and Medicaid (in many States of the United States), do cover CGM use in patients requiring insulin for their diabetes management (especially during the pandemic). [Extracted from the article]

The increasing prevalence of diabetes, combined with a growing global shortage of health care professionals (HCP), necessitates the need to develop new approaches to diabetes care delivery to expand access to care, lessen the burden on people with diabetes, improve efficiencies, and reduce the unsustainable financial liability on health systems and payers. Use of digital diabetes technologies and telehealth protocols within a digital/virtual diabetes clinic has the potential to address these challenges. However, several issues must be resolved to move forward. In February 2020, organizers of the Advanced Technologies & Treatments for Diabetes Annual Conference convened an international panel of HCP, researchers, patient advocates, and industry representatives to review the status of digital diabetes technologies, characterize deficits in current technologies, and identify issues for consideration. Since that meeting, the importance of using telehealth and digital diabetes technologies has been demonstrated amid the global coronavirus disease (COVID-19) pandemic. This article summarizes the panel's discussion of the opportunities, obstacles, and requisites for advancing the use of these technologies as a standard of care for the management of diabetes. [ABSTRACT FROM AUTHOR]

Background: Ultra rapid lispro (URLi) is a new insulin lispro formulation that has accelerated absorption and improved postprandial glucose control compared with insulin lispro (Humalog®). The compatibility and safety of URLi versus lispro were evaluated in patients with type 1 diabetes using continuous subcutaneous insulin infusion (insulin pump). Methods: In this phase 3, double-blind, crossover study, 49 patients were randomized to two 6-week treatment periods, after a 2-week lead-in period on lispro. The primary endpoint was the rate of infusion set failures due to a pump occlusion alarm, or unexplained hyperglycemia with blood glucose >13.9 mmol/L (250 mg/dL) that did not decrease within 1 h after a correction bolus. Results: There was no significant difference in the rate of infusion set failures between URLi and lispro (0.03 vs. 0.05 events/30 days, P = 0.375). A higher rate of premature infusion set changes was observed with URLi (1.13 vs. 0.78 events/30 days; P = 0.028), translating to one additional infusion set change approximately every 3 months. A trend toward improved glycemic control was observed with URLi treatment: Time in range 3.9-10.0 mmol/L (71-180 mg/dL) was 65.7% ± 1.3% versus 63.0% ± 1.3%. Treatment-emergent adverse events (TEAEs) were reported by 46.9% of patients on URLi treatment and 18.8% on lispro. This difference was driven by an increase in infusion site reactions-more than 90% were mild. Incidence of all other TEAEs and severe hypoglycemia was similar between treatments. Conclusions: URLi was compatible with insulin pump use with a safety profile similar to lispro. [ABSTRACT FROM AUTHOR]

Background: The Stay at Home order in Colorado and The Stay Safe at Home order in California during COVID-19 pandemic have forced a majority of the endocrinologists/diabetologists to adapt to providing diabetes care remotely through telehealth. This may provide increased access to diabetes health care in certain settings. However, health care disparities continue to challenge availability of diabetes technologies for underprivileged communities. We report our experience with two patients providing diabetes care effectively and preventing hospital admissions by using telehealth. Methods: Two adult patients with type 1 diabetes (T1D): one new onset and the other one with established T1D are presented where telehealth facilitated by Clarity Software and the "Share" feature with the use of Dexcom G6 continuous glucose monitoring (CGM) for management of diabetic ketosis and hyperglycemia. Results: Both patients were managed effectively virtually despite higher risk of diabetic ketoacidosis (DKA). Shared glucose data through CGM facilitated frequent insulin dose adjustments, increased fluid and carbohydrate intake, and prevented hospital admissions in both cases. In the case of new onset patient with T1D, most of the education was done remotely by certified diabetes care and education specialists. Conclusion: Acute diabetes complication like DKA increases morbidity and mortality in addition to adding cost to the health care system. The current pandemic of COVID-19 has allowed newer ways (with the help of newer technologies) to manage high-risk patients with T1D and DKA through telehealth and may result in lasting benefits to people with T1D. [ABSTRACT FROM AUTHOR]

Background: The current COVID-19 pandemic provides an incentive to expand considerably the use of telemedicine for high-risk patients with diabetes, and especially for the management of type 1 diabetes (T1D). Telemedicine and digital medicine also offer critically important approaches to improve access, efficacy, efficiency, and cost-effectiveness of medical care for people with diabetes. Methods: Two case reports are presented where telemedicine was used effectively and safely after day 1 in person patient education. These aspects of the management of new-onset T1D patients (adult and pediatric) included ongoing diabetes education of the patient and family digitally. The patients used continuous glucose monitoring with commercially available analysis software (Dexcom Clarity and Glooko) to generate ambulatory glucose profiles and interpretive summary reports. The adult subject used multiple daily insulin injections; the pediatric patient used an insulin pump. The subjects were managed using a combination of e-mail, Internet via Zoom, and telephone calls. Results: These two cases show the feasibility and effectiveness of use of telemedicine in applications in which we had not used it previously: new-onset diabetes education and insulin dosage management. Conclusions: The present case reports illustrate how telemedicine can be used safely and effectively for new-onset T1D training and education for both pediatric and adult patients and their families. The COVID-19 pandemic has acutely stimulated the expansion of the use of telemedicine and digital medicine. We conclude that telemedicine is an effective approach for the management of patients with new-onset T1D. [ABSTRACT FROM AUTHOR]

Background: This study compared the efficacy, safety, and immunogenicity of insulin aspart biosimilar/follow-on biologic product SAR341402 (SAR-Asp) with originator insulin aspart-NovoLog®/NovoRapid® (NN-Asp) in people with type 1 diabetes (T1D) or type 2 diabetes (T2D) treated with multiple daily injections in combination with insulin glargine (Lantus®; Gla-100). Materials and Methods: This 6-month, randomized, open-label, phase 3 study (NCT03211858) enrolled 597 people with T1D (n = 497) or T2D (n = 100). Participants were randomized 1:1 to mealtime SAR-Asp (n = 301) or NN-Asp (n = 296) in combination with Gla-100. The primary objective was to demonstrate noninferiority (by 0.3% margin in the intent-to-treat population) of SAR-Asp versus NN-Asp in HbA1c change from baseline to week 26. Immunogenicity was also assessed in terms of anti-insulin aspart antibody (AIA) status (positive/negative) and titers during the study. Results: HbA1c was similarly improved in both treatment groups (SAR-Asp -0.38%; NN-Asp -0.30%); the least squares mean difference at week 26 for SAR-Asp minus NN-Asp was -0.08% (95% confidence interval: -0.192 to 0.039), thus meeting the criteria for noninferiority between SAR-Asp and NN-Asp and inverse noninferiority of NN-Asp versus SAR-Asp. Changes in fasting plasma glucose and seven-point self-monitored plasma glucose profile, including postprandial glucose excursions, and insulin dosages were similar in both groups at week 26. Safety and tolerability, including AIA responses (incidence, prevalence), hypoglycemia, and adverse events (including hypersensitivity events and injection site reactions), were similar between groups. Conclusions: SAR-Asp demonstrated effective glycemic control with a similar safety and immunogenicity profile to NN-Asp in people with diabetes treated for 26 weeks. [ABSTRACT FROM AUTHOR]

Objective: To evaluate effects of the dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibitor sotagliflozin in combination with insulin on glucose time in range (TIR) and glucose excursions, postprandial glucose (PPG), and other glycemic metrics in adults with type 1 diabetes using masked continuous glucose monitoring (CGM).Research Design and Methods: Data sets from the inTandem1 (clinical trial reg. no. NCT02384941) and inTandem2 (clinical trial reg. no. NCT02421510) double-blind randomized trials evaluating sotagliflozin versus placebo in adults with type 1 diabetes treated with optimized insulin were pooled for analyses of masked CGM data from a subset of participants in each trial. The pooled cohort included patients randomized to receive placebo (n = 93), sotagliflozin 200 mg (n = 89), or sotagliflozin 400 mg (n = 96). The primary outcome was change from baseline to week 24 in glucose TIR (3.9-10.0 mmol/L [70-180 mg/dL]). Secondary end points included time below and above the target range and 2-h PPG level assessed after a standardized mixed meal.Results: Mean percentage of glucose TIR/percentage time spent at <3.9 mmol/L (<70 mg/dL) during week 24 was 51.6%/5.9%, 57.8%/5.5%, and 64.2%/5.5% with placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively, which corresponded to a placebo-adjusted change from a baseline of +5.4%/-0.3% (P = 0.026; +1.3/-0.1 h/day) for sotagliflozin 200 mg and +11.7%/-0.1% (P < 0.001; +2.8/-0.02 h/day) for sotagliflozin 400 mg. Placebo-adjusted PPG reductions were 1.9 ± 0.7 mmol/L (35 ± 13 mg/dL; P = 0.004) and 2.8 ± 0.7 mmol/L (50 ± 13 mg/dL; P < 0.001) with sotagliflozin 200 and 400 mg, respectively.Conclusions: Combined with optimized insulin in type 1 diabetes, sotagliflozin significantly increased glucose TIR without increasing time spent at <3.9 mmol/L and reduced PPG, thereby improving glycemic control. [ABSTRACT FROM AUTHOR]

An editorial is presented which discusses the mitigation of diabetic ketoacidosis in type 1 diabetes patients on adjunctive treatment with sodium glucose cotransporter inhibitors, and talks about the incorporation of the STICH protocol in the event of ketosis confirmation.

An introduction is presented in which the editor discusses the contents within the issue including articles on topics such as the role of continuous glucose monitoring (CGM) in insulin-requiring patients, the glucagon-like polypetide-1 (GLP-1) analogues, and skin issues with use of insulin.

Aim: The impact of weight gain on insulin dosage and glycemic control in adults with type 1 diabetes (T1D) aged 25 years and older was investigated in the T1D Exchange Registry participants. Methods: Participants were categorized into four groups based on their change in weight from T1D Exchange registry enrollment to year 5: stable weight (−5 to <5 lb), gained 5 to <10 lb, gained 10 to <20 lb, or gained ≥20 lb. Those who lost >5 lb were excluded. The primary outcomes were glucose control, as measured by glycosylated hemoglobin (HbA1c), and total daily insulin dose (TDD) at year 5. Linear regression models were used to evaluate the association between weight gain, HbA1c, and TDD. Results: There were 1969 participants included in the analyses. The mean ± standard deviation age was 45 ± 13 years, 57% were female, and 92% were White non-Hispanic. For those with an enrollment HbA1c <8.0%, the mean HbA1c at year 5 was higher for those who gained ≥20 lb compared to those with a stable weight of −5 to <5 lb (7.4% ± 1.1% vs. 7.2% ± 0.8%, respectively; P = 0.005). For this cohort, the mean TDD at year 5 increased from 49 ± 25 to 61 ± 29 U for those who gained ≥20 lb, while decreased from 45 ± 27 to 44 ± 25 U for those with stable weight of −5 to <5 lb (P < 0.001). Among participants with an enrollment HbA1c ≥9.0%, the mean HbA1c at year 5 was statistically insignificant at 8.4% ± 1.3% for those who gained ≥20 lb compared to 9.2% ± 1.7% for those with a stable weight of −5 to <5 lb (P = 0.09). Conclusion: Significant weight gain in adults with T1D who had good to adequate glycemic control was associated with modest deterioration in glucose control despite an increase in TDD. Worsening glucose control may indicate insulin resistance related to weight gain despite significantly increased insulin dosage which was insufficient to maintain adequate glycemic control. [ABSTRACT FROM AUTHOR]

Background: In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes.Methods: In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end points included the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin.Results: A significantly larger proportion of patients in the sotagliflozin group than in the placebo group achieved the primary end point (200 of 699 patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change from baseline was significantly greater in the sotagliflozin group than in the placebo group for glycated hemoglobin (difference, -0.46 percentage points), weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus dose of insulin (-2.8 units per day) (P≤0.002 for all comparisons). The rate of severe hypoglycemia was similar in the sotagliflozin group and the placebo group (3.0% [21 patients] and 2.4% [17], respectively). The rate of documented hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per liter) or below was significantly lower in the sotagliflozin group than in the placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively).Conclusions: Among patients with type 1 diabetes who were receiving insulin, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% with no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rate of diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035 .). [ABSTRACT FROM AUTHOR]

A 3-month pivotal trial using the MiniMed™ 670G hybrid closed-loop (HCL) system in adolescent and adult patients with type 1 diabetes (T1D), relative to a 2-week baseline run-in period, resulted in increased sensor glucose (SG) values in target range (71-180 mg/dL), reduced HbA1c levels, and no events of diabetic ketoacidosis or severe hypoglycemia ( Clinicaltrials.gov : NCT02463097). This brief report evaluated how prior continuous glucose monitoring (CGM) experience influenced glycemic outcomes, in the same pivotal trial. HbA1c levels and the percentage of SG values in low, high, and in-target ranges were analyzed from participants (n = 124) completing the Hybrid Closed-Loop Pivotal Trial in T1D. There were 78 individuals comprising the prior CGM group and 46 comprising the no prior CGM group. Compared to baseline, HbA1c was reduced from 7.4% ± 0.9% to 6.9% ± 0.7% for the prior CGM group and from 7.5% ± 0.9% to 6.8% ± 0.5% for the no prior CGM group. For those with prior CGM experience, the mean percentage of in-target SG values increased from 66.9% ± 12.5% to 72.6% ± 9.1%, and for those with no prior CGM experience it increased from 66.6% ± 11.7% to 71.5% ± 8.5%. Similar improvement in glucose values in the low and high ranges, relative to baseline, was observed for both groups. Resulting outcomes, from baseline to study end, did not differ between each group. These findings suggest that individuals without prior CGM experience, and those already using CGM, will benefit similarly with use of the FDA-approved MiniMed 670G HCL system therapy. [ABSTRACT FROM AUTHOR]

Background: SAR342434 is a biosimilar follow-on of insulin lispro-Humalog®. This study aimed to show similar efficacy, safety, and immunogenicity of SAR342434 (SAR-Lis) versus insulin lispro-Humalog (Ly-Lis) in adult patients with type 1 diabetes (T1DM) treated with multiple daily injections while using basal insulin glargine (Lantus®; GLA-100).Materials and Methods: SORELLA-1 was a randomized, open-label phase 3 study (NCT02273180). Patients completing the 6-month main study continued on SAR-Lis or Ly-Lis, as randomized, for a 6-month safety extension. Assessments included change in HbA1c, fasting plasma glucose (FPG), seven-point self-monitored plasma glucose (SMPG) profiles, hypoglycemic events, treatment-emergent adverse events (TEAEs), and anti-insulin antibodies (AIAs).Results: Five hundred seven patients were randomized (SAR-Lis n = 253; Ly-Lis n = 254). Least square (LS) mean (SEM) change in glycosylated hemoglobin (HbA1c) (baseline to week 26; primary endpoint) was similar in both treatment groups (SAR-Lis: -0.42% [0.051]; Ly-Lis: -0.47% [0.050]). Noninferiority at prespecified 0.3% noninferiority margin and inverse noninferiority were demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: 0.06% [95% confidence interval: -0.084 to 0.197]). At week 52 (end of extension period) versus week 26, a small HbA1c increase was observed in both groups. FPG and seven-point SMPG profile changes, including postprandial glucose excursions, were similar between groups. At week 52, similar changes in mean daily mealtime and basal insulin doses were observed. Hypoglycemia, TEAEs, and AIAs (incidence, prevalence) did not differ between groups.Conclusions: Results from this controlled study in patients with T1DM also using GLA-100 support similar efficacy and long-term safety (including immunogenicity) of SAR-Lis and Ly-Lis. [ABSTRACT FROM AUTHOR]

Background: The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose monitoring were investigated.Methods: Adolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed® 670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase.Results: Adolescents (mean ± standard deviation [SD] 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range [IQR] 68.0%-88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA1c levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT® blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort.Conclusions: HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA1c, hyperglycemia and hypoglycemia, compared to baseline.Trial Registration: Clinicaltrials.gov identifier: NCT02463097. [ABSTRACT FROM AUTHOR]

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The article discusses type 2 diabetes mellitus and its treatment with the use of empagliflozin either in combination therapy or monotherapy .

The prevalence of diabetes is increasing globally. Technology to improve care among individuals with diabetes is constantly being developed. Women living with Type 1 Diabetes Mellitus (T1DM) have unique challenges affecting their glucose control relating to menstrual cycles, pregnancy, and menopause. The purpose of this review is to examine the literature related to the use of technology to help women with T1DM manage their diabetes during the reproductive years, pregnancy, and beyond. Continuous subcutaneous insulin infusion (CSII) therapy can provider equivalent or better glucose control when compared with multiple daily injections (MDI), with less hypoglycemia, diabetic ketoacidosis, and weight gain. The CSII therapy has features that could help improve glucose control over the menstrual cycle, menopause, and pregnancy, although the most studied of these stages is pregnancy. Continuous glucose monitoring (CGM) can be combined with any insulin delivery system (MDI or CSII) to provide data on glucose values every few minutes and show glucose trends over time. CGM introduction can highlight glucose variability for women with T1DM, may be beneficial during pregnancy, and can reduce hypoglycemia. Sensor-augmented pump therapy and hybrid artificial pancreas (closed-loop) systems are promising tools that improve outcomes among individuals with diabetes. The use of modern technology to improve glucose and metabolic control among menopausal women with diabetes has not been well studied. Internet and phone-based technologies are emerging as important tools that may help with diabetes self-care for women living with diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment. RESULTS In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70-180 mg/dL (3.9-10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range >180mg/dL (10.0mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group. CONCLUSIONS As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes. [ABSTRACT FROM AUTHOR]

The article focuses on the management of Type 1 Diabetes, and discusess improving health outcomes among diabetes patients; challenges associated with the treatment options of the same; and use of sodium glucose cotransporter inhibitors for the same.

The author reflects on the applications of non-insulin therapies for type I diabetes. Topics discussed include treatment of type I diabetes with the help of sulfonylureas (SFUs), metformin and thiazolidinediones (TZDs), introduction of new non-insulin agents for treatment including glucagon-like peptide-1 (GLP-1) analogs, dipeptidyl peptidase-4 (DPP-4) inhibitors and amylin analogs, and inhibition of brush border enzyme a-glucosidase by a-glucosidase inhibitors.

OBJECTIVE--Inflammation and endothelial dysfunction have been associated with the immunobiology of preeclampsia (PE), a significant cause of adverse pregnancy outcomes. The prevalence of PE is elevated several fold in the presence of maternal type 1 diabetes mellitus (T1DM). Although cross-sectional studies of pregnancies among women without diabetes have shown altered inflammatory markers in the presence of PE, longitudinal studies of diabetic women are lacking. In maternal serum samples, we examined the temporal associations of markers of inflammation with the subsequent development of PE in women with T1DM. RESEARCH DESIGN AND METHODS--We conducted longitudinal analyses of serum C-reactive protein (CRP), adhesion molecules, and cytokines during the first (mean ± SD, 12.2 ± 1.9 weeks), second (21.6 ± 1.5 weeks), and third (31.5 ± 1.7 weeks) trimesters of pregnancy (visits 1-3, respectively). All study visits took place before the onset of PE. Covariates were BMI, HbAic, age of onset, duration of diabetes, and mean arterial pressure. RESULTS--In women with T1DM who developed PE versus those who remained normoten-sive, CRP tended to be higher at visits 1 (P = 0.07) and 2 (P = 0.06) and was significantly higher at visit 3 (P < 0.05); soluble E-selectin and interferon-γ-inducible protein-10 (IP-10) were significantly higher at visit 3; interleukin-1 receptor antagonist (IL-lra) and eotaxin were higher and lower, respectively, at visit 2 (all P < 0.05). These conclusions persisted following adjustment for covariates. CONCLUSIONS--In pregnant women with T1DM, elevated CRP, soluble E-selectin, IL-1ra, and IP-10 and lower eotaxin were associated with subsequent PE. The role of inflammatory factors as markers and potential mechanisms of the high prevalence of PE in T1DM merits further investigation. [ABSTRACT FROM AUTHOR]

In this article, the author focuses on the working of real-time continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D) and also mentions the use of technologies for assessments of the patients with diabetes.

Objective: To see if insulin glargine improves glycemic control in a clinical setting. Research design and methods: A questionnaire and electronic database were used to assess glycemic parameters for 292 type 1 diabetic subjects taking ≥4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months. Sixty-three subjects were taking glargine in the morning, 125 were taking glargine in the evening, and 104 were splitting the glargine dose between the morning and evening. Results: The mean (±S.D.) age and duration of diabetes were 32±10 years and 15.9±10.3 years, respectively. The mean (±S.E.M.) durations of treatment with glargine were 13.1±0.6 months, 12.2±0.4 months, and 14.3±0.5 months for the morning, evening, and split treatment groups, respectively (P<0.01). The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined. The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose. The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year. The weight gain was significantly higher in the group that took the split glargine dose (P<0.01). Conclusions: Similar or improved glycemic control was achieved by administering glargine in the morning, evening, or using a split dose without any further increase in severe hypoglycemic episodes. Splitting the glargine dose did not offer any advantages in glycemic control parameters. [Copyright &y& Elsevier]

Objective: Adults with type 1 diabetes (T1D) are increasingly overweight or obese, in part due to intensive insulin therapy. Newer non-insulin medications targeting both hyperglycemia and weight loss are approved for people with type 2 diabetes. These drugs also reduce cardiovascular disease, the major cause of mortality in people with diabetes. We assessed the real-world use of semaglutide and tirzepatide, in adults with T1D followed in a specialty diabetes clinic. Materials and Methods: This retrospective chart review included 100 adults who were prescribed semaglutide or tirzepatide (50 each) and 50 controls frequency matched for age, sex, diabetes duration, body mass index, and glycosylated hemoglobin (HbA1c) and who did not receive any weight loss medications during the study period. Data were collected prior to initiation of weight loss medications (baseline) and then for up to 1 year for each patient. Results: Matching characteristics did not differ between cases and controls. There were declines in weight in both semaglutide (−19.2 ± standard error (SE) 2.9 lbs. [9.1% body weight lost]) and tirzepatide (−49.4 ± SE 3.0 lbs. [21.4% body weight lost]) groups, and HbA1c decreased in both semaglutide (−0.54 ± SE 0.14%, P = 0.0001) and tirzepatide users (−0.68 ± SE 0.16%, P < 0.0001) over 12 months. Weight and HbA1c didn't change in controls. Conclusions: We observed weight loss of 9.1% and 21.4% and improved glucose control in semaglutide and tirzepatide users, respectively, after 1 year of off-label use. As off-label use of these drugs is increasing in patients with T1D, larger, prospective safety and efficacy trials are needed. [ABSTRACT FROM AUTHOR]

Many of us attended the last in-person meeting in Madrid in February of 2020 (13 SP th sp annual ATTD conference) and after which the COVID-19 pandemic impacted many parts of Europe and then the USA. The US has done a better job than most other parts of the world, in vaccinating people with COVID-19 vaccines (majority receiving Moderna or Pfizer mRNA vaccines). For the past eighteen months, the COVID-19 pandemic has affected more than 220 countries and as of May 20 SP th sp , 2021 there were 163 million cases of COVID-19 reported globally. [Extracted from the article]

The risk for preeclampsia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 weeks' gestation ("Visits" (V) 1, 2, and 3, respectively) in 23 T1DM women who developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs. 22%, p < 0.05), but no measure of 25(OH)D predicted PE. By contrast, higher 1,25(OH)2D concentrations at V2 (total, bioavailable, and free: p < 0.01) and V3 (bioavailable: p < 0.05; free: p < 0.01), lower concentrations of VDBP at V3 (p < 0.05), and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p < 0.01) and 1,25(OH)2D/25(OH)D (V3, p < 0.05) were all associated with PE, and significance persisted in multivariate analyses. In summary, in women with T1DM, concentrations of 1,25(OH)2D were higher, and VDBP lower, in the second and third trimesters in women who later developed PE than in those who did not. 1,25(OH)2D may serve as a new marker for PE risk and could be implicated in pathogenesis. [ABSTRACT FROM AUTHOR]

An editorial is presented which discusses about the Diabetes Technology & Therapeutics (DTT), providing healthcare professionals with information on new devices, drugs, drug delivery system; mentions due to the increased risk of diabetic ketoacidosis (DKA) with the drugs, we must find ways to reduce the overall risk of DKA; and also mentions DTT has high visibility throughout the word, with readers in over 170 countries.

The article presents a response on the comment of the study regarding the association of sublicnical first trimester renal abnormalities with preeclampsia (PE) in women in pregnant women with type 1 diabetes. It highlights several important issues in the comment and recognizes the need for a confirmatory study before translating the findings into clinical use. The authors also argue that they provide important clues to the underlying reasons for susceptibility to PE in women with diabetes.

The article presents author's views on availability of self-monitoring of blood glucose (SMBG) and its usefulness in controlling diabetes.

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods: This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test. Results: Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase. Conclusions: These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423. [ABSTRACT FROM AUTHOR]

Background: The aim was to assess the safety and tolerability of the insulin aspart biosimilar/follow-on product SAR341402 (100 U/mL solution; SAR-Asp) and originator insulin aspart (100 U/mL; NN-Asp; NovoLog®) self-administered through an insulin pump. Materials and Methods: This randomized, open-label, 2 × 4-week crossover study enrolled 45 adults with type 1 diabetes (T1D). Participants were randomized 1:1 to the treatment sequence SAR-Asp/NN-Asp or NN-Asp/SAR-Asp. The basal and prandial insulin doses were individually titrated. The primary outcome was the number of participants with at least one infusion set occlusion (infusion set change due to failure-to-correct hyperglycemia [plasma glucose ≥250 mg/dL] by insulin pump bolus) during the 4-week treatment. The main secondary outcome was the number of participants with at least one episode of unexplained hyperglycemia (regardless of correction by an insulin pump bolus without apparent material defect, medical, dietary, insulin dosing reason, or pump problem). Results: The number of participants reporting ≥1 infusion set occlusion were similar between treatments: 14/43 on SAR-Asp (33 events) and 12/43 on NN-Asp (24 events). The estimated difference in infusion set occlusion risk for SAR-Asp versus NN-Asp was 4.1% (95% confidence interval: -9.3% to 17.4%). The number of participants with ≥1 episode of unexplained hyperglycemia was similar between treatments (31/43 on SAR-Asp [154 events]; 32/43 on NN-Asp [175 events]). Hypoglycemia, treatment-emergent adverse events, hypersensitivity, and injection site reactions were similar between treatments. Conclusions: SAR-Asp and NN-Asp were well tolerated and had similar infusion set occlusions over a 4-week period in insulin pump users with T1D. [ABSTRACT FROM AUTHOR]

Multivariable regression analysis for personal and clinical factors associated with NAFLD showed that among the study sample, only body mass index (BMI) was found to be significant factor: the risk of NAFLD was significantly higher among overweight T2DM patients (adjusted odds ratio, aOR=6.112 [95% CI 1.529-4.432]) and obese patients (aOR=10.455 [2.645-41.326]). Hypoglycemia can be one important predictive factor for the progression of hepatic fibrosis in patients with NAFLD, and postprandial hypoglycemia frequently occurs in NAFLD patients; however, the details regarding the causes and background on hypoglycemia are not well understood. The prevalence of DR was lower in patients with NAFLD than in those without NAFLD (37.2% vs 46.6%, I P i =0.065), and significantly lower in patients with moderate and severe NAFLD (30.2% vs 46.6%, I P i =0.012; 14.3% vs 46.6%, I P i =0.024). Differences between the guidelines were noted in these categories: how NAFLD is defined, opportunities for NAFLD screening in high-risk patients, proposed noninvasive test for NAFLD diagnosis, the identification of NAFLD patients with advanced fibrosis in the follow-up protocols, and lastly, treatment strategy (particularly proposed pharmacological management). [Extracted from the article]

Background: Hypoglycemia rates usually increase when insulin treatment is intensified to improve glycemic control. We evaluated (post hoc) hypoglycemic rates in adult patients with type 1 diabetes (T1D) on sotagliflozin (a dual sodium-glucose cotransporter [SGLT] 1 and 2 inhibitor) in two phase 3, 52-week clinical trials (inTandem 1 and 2; NCT02384941 and NCT02421510). Materials and Methods: We analyzed rates of documented hypoglycemia (level 1, blood glucose ≥54 to <70 mg/dL) and clinically important hypoglycemia (level 2, glucose <54 mg/dL) in a patient-level pooled analysis (n = 1362) using a negative binomial model adjusted for hemoglobin A1c (HbA1c) at 52 weeks in patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg. Results: Rates of level 1 hypoglycemia events per patient-year were 58.25 (95% confidence interval: 50.26-67.50) with placebo, 44.86 (38.83-51.82; P = 0.0138 vs. placebo) with sotagliflozin 200 mg, and 45.68 (39.52-52.81; P = 0.0220) with sotagliflozin 400 mg. Sotagliflozin was also associated with lower rates of level 2 hypoglycemia: 15.95 (14.37-17.70), 11.51 (10.39-12.76; P < 0.0001), and 11.13 (10.03-12.35; P < 0.0001) for placebo and sotagliflozin 200 and 400 mg, respectively. The difference in rates of hypoglycemia with sotagliflozin versus placebo became more pronounced as HbA1c decreased. Conclusions: At week 52, level 1 and 2 hypoglycemia events were 22% to 30% less frequent with sotagliflozin added to optimized insulin therapy versus placebo in adults with T1D at any HbA1c level, with greater differences at lower HbA1c values. These findings support the use of sotagliflozin as an insulin adjunct in T1D. [ABSTRACT FROM AUTHOR]

Background: The majority of therapies have generally targeted fasting glucose control, and current mealtime insulin therapies have longer time action profiles than that of endogenously secreted insulin. The primary purpose of this study was to assess both glucose time-in-range (TIR: 70-180 mg/dL) and postprandial glucose excursions (PPGE) in 1-4 h using a real-time continuous glucose monitor (CGM) with Technosphere insulin (TI) versus insulin aspart in patients with type 1 diabetes (T1DM) on multiple daily injections (MDI).Research Design and Methods: This pilot, investigator-led, collaborative, open-label, multicenter, clinical research trial enrolled 60 patients with T1DM with HbA1c levels ≥6.5% and ≤10%. Individuals were randomized to treatment with titrated TI (n = 26) or titrated insulin aspart (n = 34), stratified by baseline HbA1c levels (≤8% or >8%). All were required to wear a real-time CGM throughout the trial. All patients in the TI group were advised to take supplemental inhalations at 1 and 2 h after meals if indicated based on postprandial glucose (PPG) values. The coprimary outcomes were assessed both in the full intent-to-treat population and in those individuals randomized to TI who were compliant with supplemental doses ≥90% of the time (n = 15). The CGM data were analyzed using linear regression models.Results: Overall, those treated with TI versus aspart achieved comparable TIR, but less time spent in hypoglycemia (<60 and <50 mg/dL, both P < 0.05). In the TI-compliant group (n = 15), TIR was significantly greater (62.5% ± 2.6% vs. 53.8% ± 1.7%, P = 0.009) and time in hyperglycemia >180 mg/dL was lower (34.2% ± 2.7% vs. 41.0% ± 1.7%, P = 0.045) as compared with the aspart group. PPG was also significantly lower in the TI cohort at 60 and 90 min postmeal, and PPGE were lower in the TI-compliant group as compared with the aspart group over 1-4-h postmeal (P < 0.05). In addition, there was weight gain in the aspart group compared with weight loss in the TI group (P = 0.006) despite higher prandial TI insulin dose.Conclusions: We conclude that using TI appropriately at mealtimes with supplemental dosing improves prandial glucose (TIR and 1-4 h) control without any increase in time in hypoglycemia or weight gain in patients with T1DM on MDI. The study results support a larger study using a treat-to-target design to confirm these findings. Clinical trial reg. no. NCT03143816, clinicaltrials.gov . [ABSTRACT FROM AUTHOR]

The article offers information on the methods to improve postprandial glucose (PPG) control in patients with type 1 diabetes, discussing the correlation between postprandial hyperglycemia and increased intraocular pressure, and the role of carbohydrates in postprandial hyperglycemia.