A simplified longitudinal model for the development of Type 2 Diabetes Mellitus.

Obesity and diabetes are a progressively more and more deleterious hallmark of modern, well fed societies. In order to study the potential impact of strategies designed to obviate the pathological consequences of detrimental lifestyles, a model for the development of Type 2 diabetes geared towards large population simulations would be useful. The present work introduces such a model, representing in simplified fashion the interplay between average glycemia, average insulinemia and functional beta-cell mass, and incorporating the effects of excess food intake or, conversely, of physical activity levels. Qualitative properties of the model are formally established and simulations are shown as examples of its use.

Magnetic Resonance Imaging of Idiopathic Orbital Myositis.

PURPOSE: To characterize the qualitative and quantitative features of idiopathic orbital myositis (IOM) on MRI. METHODS: This was a multicenter retrospective study of patients with active IOM with MRI. Patients with incomplete clinical records, poor-quality or interval scans without active myositis, and specific orbital myositis (i.e., orbital myositis secondary to an identified condition) were excluded. An enlargement ratio was calculated by dividing the diameters of the affected extraocular muscle (EOM) by the contralateral unaffected EOM. RESULTS: Twenty-four patients (mean age: 44.4 ± 17.8 years-old, male: 11) between 2011 and 2022 were included. One case (4.2%) was pediatric (17 years old), and 6 cases presented with recurrence. Active IOM was characterized by fusiform EOM enlargement, high T2 signal, and contrast enhancement. Average maximal EOM diameters ranged from 4.6 to 7.7 mm (enlargement ratio: 1.4-2.2). Eighteen (75%) patients had single EOM involvement, most commonly the medial rectus. Other ipsilateral structures affected included focal orbital fat (16/24, 66.7%) and lacrimal gland (8/24, 33.3%). Contralateral changes in the EOM and/or lacrimal gland were observed in 7 patients (29.2%). Patients presenting with recurrence were likely to develop ongoing recurrent episodes (p = 0.003). CONCLUSIONS: Various radiological patterns of involvement described including EOM enlargement, contrast enhancement, abnormal signal, and involvement of other orbital structures are indicative of active IOM. IOM remains a heterogeneous spectrum of acute and chronic clinico-radiological presentations. Inflammation may involve other ipsilateral or contralateral orbital structures or may be bilateral despite presenting clinically as unilateral disease. Quantitative measurements may have utility in differentiating IOM from other causes of orbital myositis.

Interrater reliability of photographic assessment of thyroid eye disease using the VISA classification.

PURPOSE: To determine the interrater reliability (IRR) of thyroid eye disease (TED) photographic assessment using the VISA classification. To assess whether a VISA grading atlas improves ophthalmology trainees' performance in photographic assessment of TED. METHODS: A prospective, partially randomized, international study conducted from September 2021 to May 2022. Online study invitation was emailed to a volunteer sample group of 68 ophthalmology college accredited consultants and trainees, and 6 were excluded from the study. Participants were asked to score 10 patient photographs of TED using only the inflammation and motility restriction components of the VISA classification. IRR was compared between groups of practitioners by their level of experience. A clinical activity grading atlas was randomized to 50% of the ophthalmology trainees. RESULTS: Overall rater ICC was 0.96 for inflammation and 0.99 for motility restriction. No statistically significant difference in IRR between rater groups was identified. Trainees with a grading atlas had the highest IRR for inflammation (ICC = 0.95). Each subcomponent of the inflammation and motility restriction components of VISA classification had an ICC considered good to excellent. The mean overall rater score was 4.6/9 for inflammation and 3.5/12 for motility restriction. For motility restriction there was a reduced mean score variance among all raters when scoring photographs with more severe motility restriction. CONCLUSION: IRR using the inflammation and motility restriction components of the VISA classification was excellent. A VISA grading atlas improved trainee performance in grading inflammation.

Radiologic Features of Well-circumscribed Orbital Tumors With Histopathologic Correlation: A Multi-center Study.

PURPOSE: To delineate specific imaging characteristics of solitary fibrous tumors, schwannomas, cavernous venous malformations, and well-circumscribed orbital lymphoma. METHODS: Patients undergoing excisional biopsy of solitary fibrous tumor, schwannomas, cavernous venous malformations, or well-circumscribed orbital lymphoma with preoperative MRIs available for review were identified at 3 academic centers in the United States and Australia. An exploratory statistical analysis was performed to identify important radiologic features, which were subsequently included in a random forest model. Histopathologic correlates were evaluated in representative cases. RESULTS: A total of 91 cases were included with a mean age of 52.9 ± 17.2 years. Nearly all solitary fibrous tumors were located in the anterior or mid orbit (87.5%) and they more commonly demonstrated intralesional heterogeneity on T2-weighted imaging (45.5%) (p < 0.01). Compared with the other tumors, schwannomas tended to be intraconal (66.7%) and were often in the mid or posterior orbit (83.4%) (p < 0.01). Cavernous venous malformations characteristically demonstrated progressive contrast enhancement (93.9%; p < 0.01). Most lesions in all 4 groups were hypointense on T1-weighted imaging (80%-100%; p = 0.14) and only well-circumscribed orbital lymphoma tended to also be hypointense on T2 (81.8%) (p < 0.01). Finally, cases of lymphoma had significantly lower apparent diffusion coefficient ratios (0.9 ± 0.2) (p < 0.001), while the other 3 groups were not significantly different from one another (cavernous venous malformations: 1.8 ± 0.4; schwannomas: 1.8 ± 0.5; and solitary fibrous tumor: 1.6 ± 0.6) (p = 0.739). CONCLUSIONS: Key features that aid in the differentiation of these 4 tumors from one another include T2 intensity and homogeneity, early contrast-enhancement pattern, and ADC ratio.

Ultra rapid lispro (Lyumjev®) shortens time to recovery from hyperglycaemia compared to Humalog® in individuals with type 1 diabetes on continuous subcutaneous insulin infusion.

AIMS: To compare the time to hyperglycaemia recovery after ultra rapid lispro (URLi; Lyumjev®) versus Humalog in a randomized, double-blind crossover study. MATERIALS AND METHODS: Thirty-two adults with type 1 diabetes on continuous subcutaneous insulin infusion participated in two periods: each period included hyperglycaemia induced by a missed mealtime bolus (day 1) and by suspension of basal insulin delivery (day 2). When hyperglycaemia [plasma glucose (PG) >240 mg/dl] occurred, a correction bolus of URLi or Humalog was given and time to hyperglycaemia recovery (PG = 140 mg/dl), pharmacokinetics and glucodynamics were compared. RESULTS: Following a missed mealtime bolus, URLi significantly reduced maximum PG (-13 mg/dl; p = .02), and produced numerically more rapid decline in PG (23 mg/dl/h; p = .07), and faster recovery from hyperglycaemia (-23 min; p = .1) versus Humalog, although differences were not significant. Following basal suspension, URLi significantly reduced maximum PG (-6 mg/dl; p = .02), and produced faster PG decline (24 mg/dl/h; p < .001) and faster recovery from hyperglycaemia (-16 min; p < .01) vs. Humalog. Following a correction bolus of URLi, accelerated insulin lispro absorption was observed versus Humalog: early 50% tmax was reduced by 6 or 12 min, and AUC0-15min was increased 2.5- or 4.3-fold after correction boluses by subcutaneous infusion (day 1) or injection (day 2), respectively (all p < .001). CONCLUSIONS: During episodes of hyperglycaemia commonly experienced in people with type 1 diabetes, URLi provided a faster recovery versus Humalog from a missed mealtime bolus or during basal insulin suspension. URLi shows significant acceleration of insulin absorption versus Humalog when boluses are administered by subcutaneous infusion or injection.

Dysthyroid optic neuropathy: a case series at a tertiary ophthalmic referral centre.

BACKGROUND/OBJECTIVES: To determine risk factors and treatment outcomes in dysthyroid optic neuropathy (DON) at a single tertiary ophthalmic centre. METHODS: Retrospective audit of DON patients who have received intravenous methylprednisolone (IVMP) therapy at Royal Victorian Eye and Ear Hospital, Melbourne, Australia from July 2015 to October 2021. RESULTS: Study included 24 patients (58% female) with an average age of 59.8 ± 14.7 years at DON diagnosis. Majority (92%) had Graves' hyperthyroidism and 77% had a smoking history. At diagnosis, average visual acuity (VA) of worse eye was LogMAR 0.46, and 48% had relative afferent pupillary defect. Proptosis (89%) and diplopia (73%) were most commonly present at diagnosis. 78% showed predominantly extra-ocular muscle enlargement, and apical crowding (52%) on radiology. 38% (n = 9/24) responded to IVMP alone, 58% (n = 14/24) progressed to surgical orbital decompression. The average total cumulative dose of IVMP during DON treatment was 6.8 ± 1.9 g. 29% required further treatment after IVMP and surgical decompression, 4 (17%) had additional radiotherapy, and three (13%) required immuno-modulatory therapy. Average final VA was LogMAR 0.207, with all patients having inactive TED at final follow-up (mean 1.7 years). In refractory DON cases, 71% retained VA ≥ 6/9 and 48% had DON reversal. CONCLUSIONS: DON patients typically present in late 50s, with a smoking history and predominant extra-ocular muscle enlargement. High-dose IVMP fully resolved DON in only 38%. A considerable proportion required urgent orbital decompression. Most patients retained good vision at final follow-up.

A 20-year multicentre retrospective review of optic nerve sheath fenestration outcomes.

Background: Optic nerve sheath fenestration (ONSF) longitudinal outcomes remain unclear and are vital in the assessment of vision failure in patients with raised intracranial pressure (ICP). Furthermore, limited observational data exists regarding its use in other causes of raised ICP. Objective: To determine the efficacy and safety of ONSF for idiopathic intracranial hypertension (IIH), cerebral venous sinus thrombosis (CVST), and other indications. Method: Multicentre study from a tertiary hospital and specialty eye referral hospital in Melbourne, Australia, from July 2000 to December 2020. A total of 116 eyes from 70 patients undergoing ONSF were retrospectively reviewed with patient demographics, surgery indications, visual acuity (VA), visual fields, fundus photos of optic discs, retinal nerve fibre layer (RNFL) thickness, average thickness of optic discs on optical coherence tomography (OCT), and complications recorded. Parametric tests were used to compare the treatment groups pre- and post-operatively. Results: A total of 116 eyes from 70 patients underwent ONSF, which involved 92 eyes with IIH, 9 eyes with CVST, and 15 eyes with other aetiologies ('Other'). Post ONSF, there was a best corrected visual acuity (BCVA) improvement or stabilisation in 84% of patients in all groups, with 50% achieving a BCVA of 6/6 or better at the final follow-up. RNFL, visual fields, and fundus grades all trended towards improvement, with most improvement noted by day 360. Common complications included transient diplopia (n = 29, 25%) and worsening of visual function requiring further cerebrospinal fluid (CSF) diversion procedures (n = 20, 17%). Complications were most significant in the 'Other' group with 1/3 of eyes requiring further CSF diversion procedures. Conclusion: Our data demonstrates effectiveness in the use of ONSF in papilloedema with visual failure due to IIH or CVST and when other CSF diversion procedures or medical therapies have failed.

Peripheral Ophthalmic Artery Aneurysm Associated with Multifocal Intracranial and Extracranial Aneurysms: Case Report and Literature Review.

Peripheral ophthalmic artery aneurysm is a rare disease entity. We review the relevant literature and report a case of fusiform aneurysm involving the entire intraorbital ophthalmic artery in association with multiple intracranial and extracranial aneurysms, diagnosed on digital subtraction angiography. The patient suffered irreversible blindness secondary to compressive optic neuropathy which did not improve after a 3-day trial of intravenous methylprednisolone. Autoimmune screen was normal. The underlying cause is unknown.

Acute periocular haemorrhage associated with severe proptosis as a presenting sign of orbital tumours.

Periocular haemorrhage without a preceding history of trauma, and in the absence of vascular malformations is rare. While acute proptosis is well described in the setting of orbital pathology, accompanying periocular haemorrhage has been rarely reported. We describe three cases with these concomitant presenting signs in orbital malignancies - metastatic small cell bladder carcinoma, haemangiopericytoma (solitary fibrous tumour) and myeloma. Clinical photographs and radiology are presented with review of the current literature. All cases had an associated rapid onset of severe proptosis and co-existing periocular bruising on the same side. The presence of ecchymosis of the eyelids in addition to proptosis without a history of trauma warrants thorough investigation to rule out underlying potential sight and life threatening illness.

Mirror Therapy for the Management of Phantom Limb Pain: A Single- Center Experience.

BACKGROUND: Phantom limb pain (PLP) can have devastating consequences, affecting up to 90% of amputees. PLP is associated with analgesia dependence and impaired quality of life. Mirror therapy (MT) is a novel treatment that has been applied in other pain syndromes. We prospectively evaluated MT in the management of PLP. METHODS: A prospective study of patients recruited between 2008 and 2020 who underwent unilateral major limb amputation, with a healthy contralateral limb. Participants were invited to attend weekly MT sessions. Pain in the 7 days prior to each MT session was scored on a Visual Analog Scale (VAS: 0-10 mm) and the short form McGill pain questionnaire. RESULTS: Ninety eight patients (68 males and 30 females) aged 17-89 years were recruited over 12 years. Forty four percent of patients had amputations due to peripheral vascular disease. Over an average of 2.5 sessions, the final treatment score on the VAS scale was 2.6 (standard deviation ± 3.0) with a reduction of 4.5 points on VAS score. As a comparison using the short form McGill pain questionnaire scoring system, the average final treatment score was 3.2 (± 5.0) with 91% overall improvement. CONCLUSIONS: MT is a very powerful and effective intervention for PLP. It is an exciting addition to the armory of vascular surgeons in the management of this condition.

The use of the paramedian forehead flap alone or in combination with other techniques in the reconstruction of periocular defects and orbital exenterations.

PURPOSE: The paramedian forehead flap (PMFF) is a reconstructive option for large eyelid defects and orbital exenterations. We report a series of cases where PMFF reconstruction was carried out at various institutions in Australia. METHODS: This study was a multi-centre, retrospective, non-comparative case series investigating the clinical outcomes of the PMFF for reconstructing periocular defects and orbital exenterations. RESULTS: This case series describes twenty-seven patients (Female = 15, Male = 12), operated between 1991 to 2019, with a median age of 81 years (range: 45-93 years). Defect locations involved combinations of the medial canthus (16/27, 59.3%), upper eyelids (7/27, 25.9%), lower eyelid (4/27, 14.8%), both upper and lower eyelids (5/27, 18.5%), and orbital (7/27, 25.9%). There were no cases of flap necrosis. Minor post-operative complications were observed in ten patients with the most common being lagophthalmos. Median duration of follow-up was 17months (Range: 2months- 23years). CONCLUSIONS: The PMFF is a versatile reconstructive tool for a range of periocular defects and orbital exenterations with minor post-operative complications.

Orbito-cranial schwannoma-a multicentre experience.

OBJECTIVES: To describe the features, management approaches, and outcomes of orbito-cranial schwannomas. METHODS: Retrospective review of ten patients with orbito-cranial schwannomas managed in six orbital services over 22 years. Data collected included demographics, presenting features, neuroimaging characteristics, histology, management approach, complications, and outcomes. RESULTS: Mean age of the patients was 41.4 ± 19.9 years, and 6 (60%) were females. The majority presented with proptosis (90%), limited extraocular motility (80%), eyelid swelling (60%), and optic neuropathy (60%). Most lesions (80%) involved the entire anterior-posterior span of the orbit, with both intra- and extraconal involvement. All tumours involved the orbital apex, the superior orbital fissure, and extended at least to the cavernous sinus. Surgical resection was performed for all. Seven (70%) of the tumours were completely or subtotally resected combining an intracapsular approach by an orbital-neurosurgical collaboration, with no recurrence on postoperative follow-up (6-186 months). Three underwent tumour debulking. Of these, two remained stable on follow-up (6-34 months) and one showed progression of the residual tumour over 9 years (cellular schwannoma on histology) necessitating stereotactic radiotherapy (SRT) for local control. Adjuncts to the orbito-cranial resection included perioperative frozen section (n = 5), endoscopic transorbital approach (n = 2), and image-guided navigation (n = 1). Post-surgical adjuvant SRT was used in three subjects. CONCLUSIONS: These results highlight the possibility of successful surgical control in complex orbito-cranial schwannomas. A combined neurosurgical/orbital approach with consideration of an intracapsular resection is recommended. Recurrence may not occur with subtotal excision and observation may be reasonable. Adjunctive SRT for progression or residual tumour can be considered.

Odontogenic Lemierre's syndrome with septic superior ophthalmic vein and cavernous sinus thrombophlebitis complicated by blindness and ophthalmoplegia.

Lemierre's syndrome is a triad consisting of oropharyngeal infection, internal jugular vein thrombophlebitis, and systemic embolisation typically involving lung and brain. Orbital involvement in this life-threatening condition is rare but potentially blinding and may be an indicator of intracranial involvement. We describe a case of odontogenic Lemierre's syndrome complicated by extensive orbital and intracranial septic venous thrombosis, with optic and cranial neuropathy resulting in monocular blindness and ophthalmoplegia. A multidisciplinary approach with abscess drainage, antibiotic and antithrombotic therapy, and close radiological monitoring was critical for preserving contralateral vision and neurological function.

Primary Extradural Ectopic Orbital Meningioma in a Child.

The authors describe a rare case of primary extradural ectopic meningioma of the orbit in a 13-year-old female managed with surgical excision, adding to the very limited literature of this diagnosis in children. This is the second case to show a radiological abnormality in the gyrus rectus and olfactory bulb; however, in our case, there was no radiological evidence of connection seen.

An online breathing and wellbeing programme (ENO Breathe) for people with persistent symptoms following COVID-19: a parallel-group, single-blind, randomised controlled trial.

BACKGROUND: There are few evidence-based interventions for long COVID; however, holistic approaches supporting recovery are advocated. We assessed whether an online breathing and wellbeing programme improves health related quality-of-life (HRQoL) in people with persisting breathlessness following COVID-19. METHODS: We conducted a parallel-group, single-blind, randomised controlled trial in patients who had been referred from one of 51 UK-based collaborating long COVID clinics. Eligible participants were aged 18 years or older; were recovering from COVID-19 with ongoing breathlessness, with or without anxiety, at least 4 weeks after symptom onset; had internet access with an appropriate device; and were deemed clinically suitable for participation by one of the collaborating COVID-19 clinics. Following clinical assessment, potential participants were given a unique online portal code. Participants were randomly assigned (1:1) to either immediate participation in the English National Opera (ENO) Breathe programme or to usual care. Randomisation was done by the research team using computer-generated block randomisation lists, with block size 10. The researcher responsible for randomisation was masked to responses. Participants in the ENO Breathe group participated in a 6-week online breathing and wellbeing programme, developed for people with long COVID experiencing breathlessness, focusing on breathing retraining using singing techniques. Those in the deferred group received usual care until they exited the trial. The primary outcome, assessed in the intention-to-treat population, was change in HRQoL, assessed using the RAND 36-item short form survey instrument mental health composite (MHC) and physical health composite (PHC) scores. Secondary outcome measures were the chronic obstructive pulmonary disease assessment test score, visual analogue scales (VAS) for breathlessness, and scores on the dyspnoea-12, the generalised anxiety disorder 7-item scale, and the short form-6D. A thematic analysis exploring participant experience was also conducted using qualitative data from focus groups, survey responses, and email correspondence. This trial is registered with ClinicalTrials.gov, NCT04830033. FINDINGS: Between April 22 and May 25, 2021, 158 participants were recruited and randomly assigned. Of these, eight (5%) individuals were excluded and 150 participants were allocated to a treatment group (74 in the ENO Breathe group and 76 in the usual care group). Compared with usual care, ENO Breathe was associated with an improvement in MHC score (regression coefficient 2·42 [95% CI 0·03 to 4·80]; p=0·047), but not PHC score (0·60 [-1·33 to 2·52]; p=0·54). VAS for breathlessness (running) favoured ENO Breathe participation (-10·48 [-17·23 to -3·73]; p=0·0026). No other statistically significant between-group differences in secondary outcomes were observed. One minor self-limiting adverse event was reported by a participant in the ENO Breathe group who felt dizzy using a computer for extended periods. Thematic analysis of ENO Breathe participant experience identified three key themes: (1) improvements in symptoms; (2) feeling that the programme was complementary to standard care; and (3) the particular suitability of singing and music to address their needs. INTERPRETATION: Our findings suggest that an online breathing and wellbeing programme can improve the mental component of HRQoL and elements of breathlessness in people with persisting symptoms after COVID-19. Mind-body and music-based approaches, including practical, enjoyable, symptom-management techniques might have a role supporting recovery. FUNDING: Imperial College London.

Bilateral Enophthalmos as an Unusual Presenting Feature of Non-Hodgkin's Orbital Lymphoma.

Lymphoma is the commonest orbital malignancy. The typical presentation is proptosis or swelling, which warrants imaging and confirmation by tissue biopsy. Enophthalmos is a much rarer clinical sign and if bilateral and symmetrical can often present late. We describe a patient who presented with bilateral enophthalmos and symptomatic, secondary entropion due to bilateral non-Hodgkin's lymphoma in which orbital fat was replaced by a monoclonal proliferation of small B cells. Low-dose orbital radiotherapy and entropion surgery relieved the patient's symptoms.

PARACENTRAL ACUTE MIDDLE MACULOPATHY IN A CASE OF HIGH-FLOW DIRECT CAROTID CAVERNOUS FISTULA.

PURPOSE: To report a case of paracentral acute middle maculopathy in a patient with high-flow carotid cavernous fistula. METHODS: A case report of a 53-year-old male patient who sustained an iatrogenic high-flow carotid cavernous fistula and secondary paracentral acute middle maculopathy. RESULTS: At review 1-week postembolization of the carotid cavernous fistula, there was no significant improvement in visual acuity, tests of optic nerve function, external ophthalmoplegia, and ptosis. Spectral domain optical coherence tomography was performed, which revealed hyperreflectivity of the parafoveal plexiform layers of the right eye with ill-defined margins straddling the inner nuclear layer. CONCLUSION: We suggest that spectral domain optical coherence tomography be performed in cases of high-flow direct carotid cavernous fistula where the best-corrected visual acuity is reduced out of keeping with other ophthalmic manifestations.

Orbital giant cell myositis is an unusual and potentially lethal cause of bilateral ophthalmoplegia - A case report and literature review.

We present a case of orbital giant cell myositis (OGCM), presenting with bilateral subacute progressive ophthalmoplegia and optic nerve dysfunction. An early extraocular muscle biopsy confirmed the diagnosis and guided appropriate management. Comprehensive investigation excluded any underlying systemic disease, including myocarditis. Twenty two months after presentation, the patient remains well on azathioprine with complete resolution of orbital signs.

Clinical and Radiological Features of Intramuscular Orbital Amyloidosis: A Case Series and Literature Review.

PURPOSE: Orbital amyloidosis of the extraocular muscles (EOMs) is a rare condition, and its clinicoradiological features are not well elucidated. This study describes the characteristic clinical signs, MRI features, and potential treatment options. METHODS: Retrospective multicenter case series and literature review of EOM amyloidosis. RESULTS: Five cases were identified for inclusion. Common clinical findings were diplopia, ophthalmoplegia, and proptosis. Systemic amyloidosis was more likely to present with multiple muscle involvement, but no particular pattern was observed with localized disease. On MRI, amyloid deposition was characterized as a heterogeneous intramuscular mass with T2 hypointensity and post contrast enhancement. Management is dependent on the extent of disease and functional impairment; options include surgical debulking and radiation therapy. CONCLUSION: EOM amyloidosis is uncommon. The combination of clinical and radiologic findings described in this study should lead to its clinical suspicion.

Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study.

AIMS: To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: This was a two-part, randomized, double-blind Phase 1b study. Part A used a six-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, or 15 minutes after the start of the meal. Part B evaluated URLi or Humalog during 2 weeks of multiple daily dosing with a parallel design. The PK and GD were assessed following MMTTs at the beginning and end of the 2 weeks when insulins were administered immediately before the start of the meal. RESULTS: URLi increased the insulin exposure within the first 30 minutes postdose by 2.2-fold and reduced the time to the early half-maximal drug concentration by 22.6% compared with Humalog. Overall, URLi resulted in better postprandial glucose lowering when dosed before, immediately before, or after a meal. In comparing the same meal-to-dose timing between the insulins, the postprandial glucose excursion over 5 hours was significantly reduced by 29%-105% for all three dose timings (-15, 0 and +15 minutes) with URLi. The PK and GD were sustained after daily subcutaneous dosing for 2 weeks in patients with T2D. URLi had more hypoglycaemic events during the MMTTs; few events occurred for both treatments during the 2 weeks of outpatient dosing. CONCLUSIONS: URLi demonstrated accelerated insulin lispro absorption and greater postprandial glucose reduction at different meal-to-dose timings compared with Humalog and was well tolerated in patients with T2D.