Background and aims: Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity. Methods: Teduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with ,50% colon in continuity (dose 0.03 mg/kg/day), and five with >50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with >50% colon in continuity.Results: Pooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p,0.001) and relative (+22 (16)%; p,0.001) wet weight absorption, urine weight (+555 (485) g/day; p,0.001), and urine sodium excretion (+53 (40) mmol/day; p,0.001). Teduglutide decreased faecal wet weight (2711 (734) g/day; p = 0.001) and faecal energy excretion (2808 (1453) kJ/day (2193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice. Conclusion: Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.

The long‐term success of photosynthetic organisms has resulted in their global superabundance, which is sustained by their widespread, continual mass‐production of the integral proteins that photocatalyze the chemical processes of natural photosynthesis. Here, a fast, general method to assemble multilayer films composed of one such photocatalytic protein complex, Photosystem I (PSI), onto a variety of substrates is reported. The resulting films, akin to the stacked thylakoid structures of leaves, consist of a protein matrix that is permeable to electrochemical mediators and contain a high concentration of photoelectrochemically active redox centers. These multilayer assemblies vastly outperform previously reported monolayer films of PSI in terms of photocurrent production when incorporated into an electrochemical system, and it is shown that these photocatalytic properties increase with the film thickness. These results demonstrate how the assembly of micron‐thick coatings of PSI on non‐biological substrates yields a biohybrid ensemble that manifests the photocatalytic activity of the film’s individual protein constituents, and represent significant progress toward affordable, biologically‐inspired renewable energy conversion platforms.

To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)related hospitalization and illness severity in type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study to identify case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity. RESULTS We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA 1c), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity. CONCLUSIONS Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA 1c) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community. The medical community currently lacks sufficient data to adequately mitigate the impact of the novel coronavirus disease 2019 (COVID-19) in the type 1 diabetes community. At present, our knowledge is largely extrapolated from recent retrospective analyses of hospitalized patients (1-5), which have strongly suggested "diabetes" increases risk for COVID-19 morbidity and mortality. These studies did not, however, distinguish between type 1 diabetes and type 2 diabetesdtwo pathophysiologically distinct conditions. Although reports of COVID-19 in type 1 diabetes are emerging, the scope of these investigations to date has been limited by including only hospitalized

<i>Objective: To quantify and contextualize the risk for COVID-19 related hospitalization and illness severity in type 1 diabetes.</i> <p> </p> <p><i>Research Design and Methods: We conducted a prospective cohort study to identify COVID-19 cases across a regional healthcare network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity. </i></p> <p> </p> <p><i>Results: We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios (ORs) of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among type 1 diabetes patients, glycosylated hemoglobin (HbA1c), hypertension, race, recent diabetic ketoacidosis (DKA), health insurance status, and less diabetes technology use were significantly associated with illness severity.</i></p> <p> </p> <h2>Conclusions: Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA1c) had significant but modest impact compared to comparatively static factors (e.g. race, insurance) in type 1 diabetes indicating an urgent and continued need to mitigate SARS-CoV-2 infection risk in this community.</h2>

Hypoglycemia limits optimal glycemic control in type 1 diabetes mellitus (T1DM), making novel strategies to mitigate it desirable. We hypothesized that portal (Po) vein insulin delivery would lessen hypoglycemia. In the conscious dog, insulin was infused into the hepatic Po vein or a peripheral (Pe) vein at a rate four times of basal. In protocol 1, a full counterregulatory response was allowed, whereas in protocol 2, glucagon was fixed at basal, mimicking the diminished α-cell response to hypoglycemia seen in T1DM. In protocol 1, glucose fell faster with Pe insulin than with Po insulin, reaching 56 ± 3 vs. 70 ± 6 mg/dL (P = 0.04) at 60 min. The change in area under the curve (ΔAUC) for glucagon was similar between Pe and Po, but the peak occurred earlier in Pe. The ΔAUC for epinephrine was greater with Pe than with Po (67 ± 17 vs. 36 ± 14 ng/mL/180 min). In protocol 2, glucose also fell more rapidly than in protocol 1 and fell faster in Pe than in Po, reaching 41 ± 3 vs. 67 ± 2 mg/dL (P < 0.01) by 60 min. Without a rise in glucagon, the epinephrine responses were much larger (ΔAUC of 204 ± 22 for Pe vs. 96 ± 29 ng/mL/180 min for Po). In summary, Pe insulin delivery exacerbates hypoglycemia, particularly in the presence of a diminished glucagon response. Po vein insulin delivery, or strategies that mimic it (i.e., liver-preferential insulin analogs), should therefore lessen hypoglycemia.

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Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups (n = 10/group) with differing insulinemia and glycemia: healthy control subjects (euinsulinemia and euglycemia), glucokinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 diabetes (hyperinsulinemia and hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. Hemoglobin A 1c was normal in control subjects and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin levels in control subjects and GCK-MODY were nearly equal but were 2.5-fold higher in type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose production similarly in all groups and suppressed nonesterified fatty acids similarly between control subjects and GCK-MODY, but to a lesser extent for type 1 diabetes. High-dose insulin infusion stimulated glucose disposal similarly in control subjects and GCK-MODY but was 29% and 22% less effective in type 1 diabetes, respectively. Multivariable linear regression showed that insulinemia-but not glycemia-was significantly associated with muscle insulin sensitivity. These data suggest that iatrogenic hyperinsulinemia predominates in driving insulin resistance in type 1 diabetes.

The Medtronic MiniMed 670G system delivers insulin to patients with type 1 diabetes mellitus (T1DM) using either its hybrid closed‐loop (HCL) “Auto Mode” feature or an open‐loop mode. In this retrospective, cross‐sectional analysis, we quantified the association between time in Auto Mode and both haemoglobin A1c (HbA1c) and time in range (TIR, sensor glucose 70–180 mg/dL) among 96 paediatric and young adult patients with T1DM. The median percentage time in Auto Mode was 38.5% (interquartile range 0%–64%). The percentage time in Auto Mode significantly correlated with HbA1c after adjustment for covariables (β = −0.008, P = 0.014). Each daily 3.4‐h increase in Auto Mode time was associated with a 0.1% decrease in HbA1c. Auto Mode time was also correlated with TIR after adjustment for covariables (β = 0.14, P = 0.02): for each daily 8.6‐h increase in Auto Mode time, TIR increased by 5%. While Auto Mode use was low, increased time in Auto Mode was associated with a significantly lower HbA1c and increased TIR. These findings emphasize the importance of identifying strategies to improve the ease of use of HCL systems.