Cardiovascular phenotypes in type 2 diabetes: Latent class analysis of the CANVAS Program and CREDENCE trial.

AIM: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis. METHODS: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes. RESULTS: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05). CONCLUSION: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability.

Personalized insulin dosing using reinforcement learning for high-fat meals and aerobic exercises in type 1 diabetes: a proof-of-concept trial.

In type 1 diabetes, high-fat meals require more insulin to prevent hyperglycemia while meals followed by aerobic exercises require less insulin to prevent hypoglycemia, but the adjustments needed vary between individuals. We propose a decision support system with reinforcement learning to personalize insulin doses for high-fat meals and postprandial aerobic exercises. We test this system in a single-arm 16-week study in 15 adults on multiple daily injections therapy (NCT05041621). The primary objective of this study is to assess the feasibility of the novel learning algorithm. This study looks at glucose outcomes and patient reported outcomes. The postprandial incremental area under the glucose curve is improved from the baseline to the evaluation period for high-fat meals (378 ± 222 vs 38 ± 223 mmol/L/min, p = 0.03) and meals followed by exercises (-395 ± 192 vs 132 ± 181 mmol/L/min, p = 0.007). The postprandial time spent below 3.9 mmol/L is reduced after high-fat meals (5.3 ± 1.6 vs 1.8 ± 1.5%, p = 0.003) and meals followed by exercises (5.3 ± 1.2 vs 1.4 ± 1.1%, p = 0.003). Our study shows the feasibility of automatically personalizing insulin doses for high-fat meals and postprandial exercises. Randomized controlled trials are warranted.

Age of obesity onset affects subcutaneous adipose tissue cellularity differently in the abdominal and femoral region.

OBJECTIVE: We aimed to examine the effect of age of obesity onset, sex, and their interaction on abdominal and femoral subcutaneous adipose tissue (SAT) morphology (degree of adipocyte hyperplasia or hypertrophy). METHODS: In this cross-sectional study, we isolated adipocytes via collagenase digestion from abdominal and femoral SAT biopsies taken from male and female adults with childhood-onset obesity (CO; n = 8 males, n = 16 females) or adult-onset obesity (AO; n = 8 males, n = 13 females). Regional body composition was measured with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan. Mean adipocyte size was measured in abdominal and femoral SAT and was used to quantify morphology in android and gynoid subcutaneous fat, respectively. RESULTS: Abdominal SAT morphology was more hyperplastic in females with CO than females with AO (p = 0.004) but did not differ between males with CO and males with AO (p = 0.996). Conversely, femoral SAT morphology was more hypertrophic in males and females with CO than those with AO. CONCLUSIONS: Age of obesity onset appears to affect SAT morphology differently in the abdominal and femoral regions of male and female adults. Our findings challenge the notion that SAT is uniformly hyperplastic in CO and hypertrophic in AO.

Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada.

BACKGROUND: In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements. METHODS: We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874. FINDINGS: 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred. INTERPRETATION: The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted. FUNDING: Juvenile Diabetes Research Foundation.

Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof-of-concept results from the DECIDE-CV clinical programme.

AIM: The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline-directed medical therapy (GDMT). METHODS: We retrospectively analysed consecutive patients assessed in the 'synchronized' DECIDE-CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, renin-angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline-to-last-visit change in surrogate laboratory biomarkers. RESULTS: The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin-to-creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium-glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon-like peptide 1 receptor agonists (from 8% to 45%), renin-angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin-to-creatinine ratio and N-terminal proB-type natriuretic peptide levels significantly dropped from baseline (p < .05 for all). CONCLUSIONS: Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis.

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

Participant Experiences of Low-Dose Empagliflozin Use as Adjunct Therapy to Hybrid Closed Loop: Findings From a Randomized Controlled Trial.

BACKGROUND: Very few patient-reported outcomes have been published in regard to opinions of individuals with type 1 diabetes concerning adjunctive therapy. The aim of this subanalysis was to qualitatively and quantitatively assess the thoughts and experiences of participants with type 1 diabetes who have used low doses of empagliflozin as an adjunct to hybrid closed-loop therapy. METHODS: Semi-structured interviews were performed with adult participants who completed a double-blinded, crossover, randomized controlled trial using low-dose empagliflozin as an adjunct to hybrid closed-loop therapy. Participant experiences were captured through qualitative and quantitative methods. A descriptive analysis was performed using a qualitative approach; attitudes toward relevant topics were extracted from interview transcripts. RESULTS: Twenty-four participants were interviewed; 15 (63%) perceived differences between interventions despite blinding, due to glycemic control or side effects. Advantages that arose were better glycemic control, in particular postprandially, requiring less insulin, and ease of use. Disadvantages were thought to be adverse effects, increased incidence of hypoglycemia, and increased pill burden. Thirteen (54%) participants were interested in using low-dose empagliflozin beyond the study. CONCLUSIONS: Many participants had positive experiences with low-dose empagliflozin as an adjunct to the hybrid closed-loop therapy. A dedicated study with unblinding would be beneficial to better characterize patient-reported outcomes.

Senescence markers in subcutaneous preadipocytes differ in childhood- versus adult-onset obesity before and after weight loss.

OBJECTIVE: The aim of this study was to determine the effect of age of obesity onset on senescence-related markers in abdominal (AB) and femoral (FEM) subcutaneous adipose tissue (SAT) before and after moderate (~10%) weight loss. METHODS: AB and FEM SAT were collected from human females with childhood-onset obesity (CO) or adult-onset obesity (AO) before and after diet- and exercise-induced weight loss. Immunofluorescence analysis of γH2AX/RAD51 (DNA damage/repair markers) and p53/p21 (senescence markers) was conducted in cultured preadipocytes, and senescence-associated ß-galactosidase (SA-ß-gal) activity was measured in SAT. RESULTS: CO had proportionately more AB and FEM preadipocytes with DNA damage (γH2AX+ ) and senescence markers (p53+ and/or p21+ ) than AO at baseline. The proportion of γH2AX+ FEM preadipocytes declined with weight loss in CO and was similar between groups after weight loss. The number of γH2AX foci in γH2AX+ preadipocytes decreased similarly between groups and regions with weight loss in parallel with an increase in RAD51. The proportion of p53+ and p21+ preadipocytes and SA-ß-gal+ cells in SAT did not change with weight loss, but the total p21 intensity in p53+ /p21+ FEM preadipocytes declined in AO. CONCLUSIONS: These results provide preliminary evidence that females with CO have an accelerated preadipocyte aging state that improves with weight loss in terms of DNA damage but not senescence.

Low-Dose Empagliflozin as Adjunct to Hybrid Closed-Loop Insulin Therapy in Adults With Suboptimally Controlled Type 1 Diabetes: A Randomized Crossover Controlled Trial.

OBJECTIVE: To assess whether low doses of empagliflozin as adjunct to hybrid closed-loop therapy improve glycemia compared with placebo in adults with type 1 diabetes (T1D) who are not able to achieve targets with the system alone. RESEARCH DESIGN AND METHODS: A double-blind crossover randomized controlled trial was performed in adults with suboptimally controlled T1D (HbA1c 7.0-10.5%) who were not able to achieve a target time in range (3.9-10.0 mmol/L) ≥70% after 14 days of hybrid closed-loop therapy. Three 14-day interventions were performed with placebo, 2.5 mg empagliflozin, or 5 mg empagliflozin as adjunct to the McGill artificial pancreas. Participants were assigned at a 1:1:1:1:1:1 ratio with blocked randomization. The primary outcome was time in range (3.9-10.0 mmol/L). Analysis was by intention to treat, and a P value <0.05 was regarded as significant. RESULTS: A total of 24 participants completed the study (50% male; age 33 ± 14 years; HbA1c 8.1 ± 0.5%). The time in range was 59.0 ± 9.0% for placebo, 71.6 ± 9.7% for 2.5 mg empagliflozin, and 70.2 ± 8.0% for 5 mg empagliflozin (P < 0.0001 between 2.5 mg empagliflozin and placebo and between 5 mg empagliflozin and placebo). Mean daily capillary ketone levels were not different between arms. There were no serious adverse events or cases of diabetic ketoacidosis or severe hypoglycemia in any intervention. CONCLUSIONS: Empagliflozin at 2.5 and 5 mg increased time in range during hybrid closed-loop therapy by 11-13 percentage points compared with placebo in those who otherwise were unable to attain glycemic targets. Future studies are required to assess long-term efficacy and safety.

Care Endpoints in Adults With Type 2 Diabetes: Screening and Therapeutic Targets at a Canadian Tertiary Diabetes Care Centre.

OBJECTIVES: Although national diabetes guidelines recommend targets for various health parameters, studies have demonstrated a gap between recommendations and real-life practice. The objectives of the present study were to 1) assess measurements in type 2 diabetes (T2DM) care performed by diabetologists in tertiary care, 2) determine whether these measurements were within recommended targets by Canadian guidelines, and 3) identify how these measurements compare with previously published Canadian studies. METHODS: A retrospective chart review analyzed electronic medical records of patients seen by diabetes specialists at the McGill University Health Centre (MUHC). Patients 18 to 75 years of age and diagnosed with T2DM were assessed for blood pressure <130/80 mmHg, low-density lipoprotein cholesterol (LDL-C) ≤2 mmol/L and glycated hemoglobin (A1C) ≤7%. Urinary albumin:creatinine ratio (uACR) was also assessed. Comparisons were made with existing literature data. RESULTS: The percentages of patients with recent screening of A1C, LDL-C, blood pressure and uACR were higher compared with the earlier studies. The calculated means for A1C, LDL-C and blood pressure were comparable with those studies. The percentage of measurements achieving target was comparable with subspecialty care data but differed from primary care data. CONCLUSIONS: Patients with T2DM at the MUHC receive guideline-based measurements of health parameters more frequently than at other institutions. Achievement of target values was closer to that seen by Canadian specialists than by primary care. Although further analyses are necessary to help implement effective strategies for improvement, quality assurance is nonetheless an essential part of ensuring the standards of tertiary care.

Empagliflozin add-on therapy to closed-loop insulin delivery in type 1 diabetes: a 2 × 2 factorial randomized crossover trial.

There is a need to optimize closed-loop automated insulin delivery in type 1 diabetes. We assessed the glycemic efficacy and safety of empagliflozin 25 mg d-1 as add-on therapy to insulin delivery with a closed-loop system. We performed a 2 × 2 factorial randomized, placebo-controlled, crossover two-center trial in adults, assessing 4 weeks of closed-loop delivery versus sensor-augmented pump (SAP) therapy and empagliflozin versus placebo. The primary outcome was time spent in the glucose target range (3.9-10.0 mmol l-1). Primary comparisons were empagliflozin versus placebo in each of closed-loop or SAP therapy; the remaining comparisons were conditional on its significance. Twenty-four of 27 randomized participants were included in the final analysis. Compared to placebo, empagliflozin improved time in target range with closed-loop therapy by 7.2% and in SAP therapy by 11.4%. Closed-loop therapy plus empagliflozin improved time in target range compared to SAP therapy plus empagliflozin by 6.1% but by 17.5% for the combination of closed-loop therapy and empagliflozin compared to SAP therapy plus placebo. While no diabetic ketoacidosis or severe hypoglycemia occurred during any intervention, uncomplicated ketosis events were more common on empagliflozin. Empagliflozin 25 mg d-1 added to automated insulin delivery improves glycemic control but increases ketone concentration and ketosis compared to placebo.

Glucagon-like peptide-1 receptor agonists as adjunctive treatment for type 1 diabetes: Renewed opportunities through tailored approaches?

Exogenous insulin has been the mainstay treatment for individuals living with type 1 diabetes (T1D). Although there has been tremendous growth in both pharmacological and technological advancements, insulin monotherapy has proven to be insufficient for maintaining optimal glycaemic targets for most adults with T1D. At present, there is still no breakthrough for the treatment of T1D. Adjunctive pharmacotherapies might therefore complement insulin management to achieve better glycaemic control, while possibly offering additional benefits. Recent interest in re-purposing glucagon-like peptide-1 receptor agonists (GLP-1RAs), a leading antihyperglycaemic medication class approved for type 2 diabetes, has prompted the field to seek extended potential for the T1D population. The adjunctive use of GLP-1RAs has been at the forefront of T1D research, albeit with some conflicting trial findings to date. However, the potential of GLP-1 agonism for T1D may have been underestimated, possibly from missed opportunities or categorized effects. Moreover, some GLP-1RAs have demonstrated extra-pancreatic potential with emerging multi-organ protection involving the heart, kidneys, liver and brain in varied cohorts, which may bode well for the growing T1D profile of comorbid complications. This narrative review aims to summarize and critically appraise the current evidence-based literature from large-scale randomized controlled trials and closed-loop system pilot studies that examined GLP-1RAs as adjunctive therapy for T1D. Furthermore, we outline uncharted opportunities with GLP-1 agonism using versatile approaches in selected T1D populations that may inspire and re-direct future research in this field.

Strategically Playing with Fire: SGLT Inhibitors as Possible Adjunct to Closed-Loop Insulin Therapy.

As closed-loop insulin therapies emerge into clinical practice and evolve in medical research for type 1 diabetes (T1D) treatment, the limitations in these therapies become more evident. These gaps include unachieved target levels of glycated hemoglobin in some patients, postprandial hyperglycemia, the ongoing need for carbohydrate counting, and the lack of non-glycemic benefits (such as prevention of metabolic syndrome and complications). Multiple adjunct therapies have been examined to improve closed-loop systems, yet none have become a staple. Sodium-glucose-linked cotransporter inhibitors (SGLTi's) have been extensively researched in T1D, with average reductions in placebo-adjusted HbA1c by 0.39%, and total daily dose by approximately 10%. Unfortunately, many trials revealed an increased risk of diabetic ketoacidosis, as high as 5 times the relative risk compared to placebo. This narrative review discusses the proven benefits and risks of SGLTi in patients with T1D with routine therapy, what has been studied thus far in closed-loop therapy in combination with SGLTi, the potential benefits of SGLTi use to closed-loop systems, and what is required going forward to improve the benefit to risk ratio in these insulin systems.

A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial.

BACKGROUND: For people with type 1 diabetes, there is currently no automated insulin delivery system that does not require meal input. We aimed to assess the efficacy of a novel faster-acting insulin aspart (Fiasp) plus pramlintide fully closed-loop system that does not require meal input. METHODS: In this open-label, randomised controlled, crossover, non-inferiority trial we compared the Fiasp (Novo Nordisk, Bagsværd, Denmark) plus pramlintide closed-loop system with no meal input (fully artificial pancreas) and the Fiasp-alone closed-loop system with precise carbohydrate counting (hybrid artificial pancreas). Adults (≥18 years) who had a clinical diagnosis of type 1 diabetes for at least 12 months, had glycated haemoglobin 12% or lower, and had been on insulin pump therapy for at least 6 months were enrolled at McGill University Health Centre, Montreal, QC, Canada. The Fiasp plus pramlintide fully closed-loop system delivered pramlintide in a basal-bolus manner with a fixed ratio of 10 µg:U relative to insulin. A research staff member counted the carbohydrate content of meals to input in the hybrid closed-loop system. Participants completed the two full-day crossover interventions in a random order allocated by a computer-generated code implementing a blocked randomisation (block size of four). The primary outcome was the percentage of time spent within the glucose target range (3·9-10·0 mmol/L), with a 6% non-inferiority margin, assessed in all participants who completed both interventions. This trial is registered with ClinicalTrials.gov, NCT03800875. FINDINGS: Between Feb 8, 2019, and Sept 19, 2020, we enrolled 28 adults, of whom 24 completed both interventions and were included in analyses. The percentage of time spent in the target range was 74·3% (IQR 61·5-82·8) with the fully closed-loop system versus 78·1% (66·3-87·5) with the hybrid Fiasp-alone closed-loop system (paired difference 2·6%, 95% CI -2·4 to 12·2; non-inferiority p=0·28). Eight (33%) participants had at least one hypoglycaemia event (<3·3 mmol/L) with the fully closed-loop system compared with 14 (58%) participants with the hybrid closed-loop system (2200-2200 h). Non-mild nausea was reported by three (13%) participants and non-mild bloating by one (4%) participant with the fully closed-loop system compared with zero participants with the hybrid closed-loop system. INTERPRETATION: The Fiasp plus pramlintide fully closed-loop system was not non-inferior to the Fiasp-alone hybrid closed-loop system for the overall percentage of time in the glucose target range. However, participants still spent a high percentage of time within the target range with the fully-closed loop system. Outpatient studies comparing the fully closed-loop hybrid systems with patient-estimated, rather than precise, carbohydrate counting are warranted. FUNDING: Diabetes Canada.

The impact of flash glucose monitoring on glycated hemoglobin in type 2 diabetes managed with basal insulin in Canada: A retrospective real-world chart review study.

BACKGROUND: The real-world effect of intermittently scanned continuous glucose monitoring on glucose control in type 2 diabetes treated with basal insulin is uncertain. This retrospective real-world study aimed to evaluate change in glycated hemoglobin (HbA1c) amongst adults with type 2 diabetes managed with basal insulin starting flash glucose monitoring. METHODS: Medical records were reviewed for adults with type 2 diabetes treated with basal insulin for ⩾1 year and using FreeStyle LibreTM Flash Glucose Monitoring for ⩾3 months. Prior to device use an HbA1c 8.0%-12.0% was recorded and a further HbA1c result was recorded 3-6 months (90-194 days) after starting device use. RESULTS: Medical records (n = 91) analyzed from six Canadian diabetes centers showed HbA1c significantly decreased by 0.8% ± 1.1 (mean ± SD, [p < 0.0001]) from mean baseline HbA1c 8.9% ± 0.9 to 8.1% ± 1.0 at 3-6 months after initiating flash glucose monitoring. HbA1c improvement was not independently associated with age, BMI, insulin use duration, or sex. CONCLUSION: This Canadian real-world retrospective study showed significantly reduced HbA1c following initiation of flash glucose monitoring technology to further support management of type 2 diabetes treated with basal insulin.

Alleviating carbohydrate counting with a FiASP-plus-pramlintide closed-loop delivery system (artificial pancreas): Feasibility and pilot studies.

AIM: To assess whether a FiASP-and-pramlintide closed-loop system has the potential to replace carbohydrate counting with a simple meal announcement (SMA) strategy (meal priming bolus without carbohydrate counting) without degrading glycaemic control compared with a FiASP closed-loop system. MATERIALS AND METHODS: We conducted a 24-hour feasibility study comparing a FiASP system with full carbohydrate counting (FCC) with a FiASP-and-pramlintide system with SMA. We conducted a subsequent 12-day outpatient pilot study comparing a FiASP-and-placebo system with FCC, a FiASP-and-pramlintide system with SMA, and a FiASP-and-placebo system with SMA. Basal-bolus FiASP-and-pramlintide were delivered at a fixed ratio (1 U:10 µg). Glycaemic outcomes were measured, surveys evaluated gastrointestinal symptoms and diabetes distress, and participant interviews helped establish a preliminary coding framework to assess user experience. RESULTS: Seven participants were included in the feasibility analysis. Time spent in 3.9-10 mmol/L was similar between both interventions (81%-84%). Four participants were included in the pilot analysis. Time spent in 3.9-10 mmol/L was similar between the FiASP-and-placebo with FCC and FiASP-and-pramlintide with SMA interventions (70%), but was lower in the FiASP-and-placebo with SMA intervention (60%). Time less than 3.9 mmol/L and gastrointestinal symptoms were similar across all interventions. Emotional distress was moderate at baseline, after the FiASP-and-placebo with FCC and SMA interventions, and fell after the FiASP-and-pramlintide with SMA intervention. SMA reportedly afforded participants flexibility and reduced mealtime concerns. CONCLUSIONS: The FiASP-and-pramlintide system has the potential to substitute carbohydrate counting with SMA without degrading glucose control.

Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments.

OBJECTIVES: A fully automated insulin-pramlintide-glucagon artificial pancreas that alleviates the burden of carbohydrate counting without degrading glycemic control was iteratively enhanced until convergence through pilot experiments on adults with type 1 diabetes. METHODS: Nine participants (age, 37±13 years; glycated hemoglobin, 7.7±0.7%) completed two 27-hour interventions: a fully automated multihormone artificial pancreas and a comparator insulin-alone artificial pancreas with carbohydrate counting. The baseline algorithm was a model-predictive controller that administered insulin and pramlintide in a fixed ratio, with boluses triggered by a glucose threshold, and administered glucagon in response to low glucose levels. RESULTS: The baseline multihormone dosing algorithm resulted in noninferior time in target range (3.9 to 10.0 mmol/L) (71%) compared with the insulin-alone arm (70%) in 2 participants, with minimal glucagon delivery. The algorithm was modified to deliver insulin and pramlintide more aggressively to increase time in range and maximize the benefits of glucagon. The modified algorithm displayed a similar time in range for the multihormone arm (79%) compared with the insulin-alone arm (83%) in 2 participants, but with undesired glycemic fluctuations. Subsequently, we reduced the glucose threshold that triggers glucagon boluses. This resulted in inferior glycemic control for the multihormone arm (81% vs 91%) in 2 participants. Thereafter, a model-based meal-detection algorithm to deliver insulin and pramlintide boluses closer to mealtimes was added and glucagon was removed. The final dual-hormone system had comparable time in range (81% vs 83%) in the last 3 participants. CONCLUSION: The final version of the fully automated system that delivered insulin and pramlintide warrants a randomized controlled trial.

Association between rs174537 FADS1 polymorphism and immune cell profiles in abdominal and femoral subcutaneous adipose tissue: an exploratory study in adults with obesity.

Fatty acid desaturase 1 (FADS1) polymorphisms alter fatty acid content in subcutaneous adipose tissue (SAT); however, existing evidence is limited and conflicting regarding the association between FADS1 variants and SAT inflammatory status. To advance this area, we conducted an exploratory study to investigate whether the common rs174537 polymorphism in FADS1 was associated with immune cell profiles in abdominal and femoral SAT in individuals with obesity. FADS1 gene expression and immune cell profiles in SAT depots were assessed by qPCR and flow cytometry, respectively. Although FADS1 gene expression was associated with genotype, no associations were observed with immune cell profiles in either depot. Our study provides additional evidence that rs174537 in FADS1 has minimal impact on inflammatory status in obese SAT.