Initiation of iGlarLixi Versus Basal-Bolus Insulin in Adults With Type 2 Diabetes Advancing From Basal Insulin Therapy: The SoliComplex Real-World Study.

Background: When type 2 diabetes is suboptimally controlled with basal insulin, prandial insulin injections are commonly added (i.e., a basal-bolus insulin regimen), which can increase treatment burden and hypoglycemia risk. The once-daily injectable iGlarLixi is an alternative treatment. Methods: This retrospective analysis of the U.S. Optum Clinformatics database compared outcomes in adults (≥18 years of age) with type 2 diabetes who previously received basal insulin and were newly initiated on iGlarLixi or basal-bolus insulin therapy. Cohorts were propensity score-matched in a 1:1 ratio on baseline characteristics, and imbalances were adjusted in multivariate analyses. Subgroup analyses were performed for people ≥65 years of age and those with a baseline A1C ≥9%. The primary end point was persistence with therapy at 12 months in the overall population. Secondary end points were treatment adherence, health care resource utilization (HCRU), costs, any hypoglycemia, and A1C change at 12 months. Results: Cohorts each comprised 1,070 participants. Treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus basal-bolus insulin therapy (43.7 vs. 22.3%, hazard ratio 0.51, 95% CI 0.46-0.57, adjusted P <0.001). Adherence was numerically higher for iGlarLixi, and hypoglycemia events, HCRU, and costs were numerically lower for iGlarLixi. A1C reduction from baseline was slightly greater for basal-bolus insulin. Results for both subgroups (≥65 years of age and baseline A1C ≥9%) were similar to those of the overall population. Conclusion: In this observational study, initiation of once-daily iGlarLixi versus basal-bolus insulin was associated with higher persistence, lower hypoglycemia, and similar A1C reduction without increasing HCRU or costs regardless of age or A1C. iGlarLixi could be an alternative to basal-bolus insulin, particularly for older adults with type 2 diabetes who require treatment simplification with lower hypoglycemia risk.

Late-Onset T1DM and Older Age Predict Risk of Additional Autoimmune Disease.

OBJECTIVE: Type 1 diabetes (T1DM) is associated with other autoimmune diseases (AIDs), which may have serious health consequences. The epidemiology of AIDs in T1DM is not well defined in adults with T1DM. In this cross-sectional cohort study, we sought to characterize the incident ages and prevalence of AIDs in adults with T1DM across a wide age spectrum. RESEARCH DESIGN AND METHODS: A total of 1,212 adults seen at the Washington University Diabetes Center from 2011 to 2018 provided informed consent for the collection of their age, sex, race, and disease onset data. We performed paired association analyses based on age at onset of T1DM. Multivariate logistic regression was used to evaluate the independent effects of sex, race, T1DM age of onset, and T1DM duration on the prevalence of an additional AID. RESULTS: Mean ± SD age of T1DM onset was 21.2 ± 14.4 years. AID incidence and prevalence increased with age. Female sex strongly predicted AID risk. The most prevalent T1DM-associated AIDs were thyroid disease, collagen vascular diseases, and pernicious anemia. T1DM age of onset and T1DM duration predicted AID risk. Patients with late-onset T1DM after 30 years of age had higher risks of developing additional AIDs compared with patients with younger T1DM onset. CONCLUSIONS: The prevalence of AIDs in patients with T1DM increases with age and female sex. Later onset of T1DM is an independent and significant risk factor for developing additional AIDs. Individuals who are diagnosed with T1DM at older ages, particularly women, should be monitored for other autoimmune conditions.

Cholinergic signaling mediates the effects of xenin-25 on secretion of pancreatic polypeptide but not insulin or glucagon in humans with impaired glucose tolerance.

We previously demonstrated that infusion of an intestinal peptide called xenin-25 (Xen) amplifies the effects of glucose-dependent insulinotropic polypeptide (GIP) on insulin secretion rates (ISRs) and plasma glucagon levels in humans. However, these effects of Xen, but not GIP, were blunted in humans with type 2 diabetes. Thus, Xen rather than GIP signaling to islets fails early during development of type 2 diabetes. The current crossover study determines if cholinergic signaling relays the effects of Xen on insulin and glucagon release in humans as in mice. Fasted subjects with impaired glucose tolerance were studied. On eight separate occasions, each person underwent a single graded glucose infusion- two each with infusion of albumin, Xen, GIP, and GIP plus Xen. Each infusate was administered ± atropine. Heart rate and plasma glucose, insulin, C-peptide, glucagon, and pancreatic polypeptide (PP) levels were measured. ISRs were calculated from C-peptide levels. All peptides profoundly increased PP responses. From 0 to 40 min, peptide(s) infusions had little effect on plasma glucose concentrations. However, GIP, but not Xen, rapidly and transiently increased ISRs and glucagon levels. Both responses were further amplified when Xen was co-administered with GIP. From 40 to 240 min, glucose levels and ISRs continually increased while glucagon concentrations declined, regardless of infusate. Atropine increased resting heart rate and blocked all PP responses but did not affect ISRs or plasma glucagon levels during any of the peptide infusions. Thus, cholinergic signaling mediates the effects of Xen on insulin and glucagon release in mice but not humans.

Making Insulin Accessible: Does Inhaled Insulin Fill an Unmet Need?

UNLABELLED: Glycemic control is fundamental to the management of diabetes. However, studies suggest that a significant proportion of people with diabetes, particularly those using insulin, are not achieving glycemic targets. The reasons for this are likely to be multifactorial. The real and perceived risk of hypoglycemia and the need for multiple daily injections are widely recognized as key barriers to effective insulin therapy. Therefore, there is a clear unmet need for a treatment option which can help mitigate these barriers. Alternative methods of insulin administration have been under investigation for several years, and pulmonary delivery has shown the most promise to date. Inhaled Technosphere(®) Insulin (TI; Afrezza(®); MannKind Corporation) was approved in 2014 for use as prandial insulin in people with diabetes. TI shows a more rapid onset of action and a significantly faster decline in activity than current subcutaneous rapid-acting insulin analogs (RAAs), and TI is more synchronized to the physiologic timing of the postprandial glucose excursion. This results in lower postprandial hypoglycemia with similar glycemic control compared with RAAs, and less weight gain. Together with the ease of use of the TI inhaler and the reduction in the number of daily injections, these findings imply that TI may be useful in helping to overcome patient resistance to insulin, improve adherence and mitigate clinical inertia in health-care providers, with potential beneficial effects on glycemic control. FUNDING: Writing and editorial support in the preparation of this publication was funded by Sanofi US, Inc., Bridgewater, New Jersey, USA. Funding for the article processing charges for this publication was provided by MannKind Corporation.

Prevention of inpatient hypoglycemia with a real-time informatics alert.

BACKGROUND: Severe hypoglycemia (SH), defined as a blood glucose (BG) <40 mg/dL, is associated with an increased risk of adverse clinical outcomes in inpatients. OBJECTIVE: To determine whether a predictive informatics hypoglycemia risk-alert supported by trained nurse responders would reduce the incidence of SH in our hospital. DESIGN: A 5-month prospective cohort intervention study. SETTING: Acute care medical floors in a tertiary care academic hospital in St. Louis, Missouri. PATIENTS: From 655 inpatients on designated medical floors with a BG of <90 mg/dL, 390 were identified as high risk for hypoglycemia by the alert system. MEASUREMENTS: The primary outcome was the incidence of SH occurring in high-risk intervention versus high-risk control patients. Secondary outcomes included: number of episodes of SH in all study patients, incidence of BG < 60 mg/dL and severe hyperglycemia with a BG >299 mg/dL, length of stay, transfer to a higher level of care, the frequency that high-risk patient's orders were changed in response to the alert-intervention process, and mortality. RESULTS: The alert process, when augmented by nurse-physician collaboration, resulted in a significant decrease by 68% in the rate of SH in alerted high-risk patients versus nonalerted high-risk patients (3.1% vs 9.7%, P = 0.012). Rates of hyperglycemia were similar on intervention and control floors at 28% each. There was no difference in mortality, length of stay, or patients requiring transfer to a higher level of care. CONCLUSION: A real-time predictive informatics-generated alert, when supported by trained nurse responders, significantly reduced inpatient SH.

Severe ovarian hyperstimulation syndrome in patients with autoimmune disorders: a report of two cases.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) following ovulation induction is common and varies in severity from mild to severe. Severe OHSS can be life threatening and requires hospitalization and procedures to reduce the extracellular fluid accumulation. Ovulation induction regimen and patient characteristics such as young age and low body weight have been identified as risk factors for OHSS, and follicle count >20 may be predictive of increased risk for moderate to severe OHSS. Whether any other patient factors are important in this risk equation is unknown. CASES: We report on 2 patients with type 1 diabetes mellitus (T1DM) and other autoimmune diseases who experienced a total of 4 episodes of OHSS, 2 of which were severe. CONCLUSION: T1DM, with or without other concomitant autoimmune diseases, may increase the risk for severe OHSS. Awareness of the interaction of preexisting conditions and risk for vascular leak disorders is needed for comprehensive counseling prior to embarking on ovarian stimulation. Preventive measures may be important considerations in this population.