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Aim: To evaluate the effect on type 2 diabetes remission of short‐term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed‐ratio insulin degludec/liraglutide. Methods: In a multicentre open‐label randomized controlled trial, insulin‐naïve participants within 5 years of diabetes diagnosis were assigned to a 16‐week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose‐lowering drugs. Results: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16‐week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period. Conclusions: An intensive remission‐induction intervention including fixed‐ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Alleviation of unrecognized glucotoxicity, with resultant recovery of β-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-cell function and glycemia is amplified. RESEARCH DESIGN AND METHODS: IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-cell function between those at/above the indicated glucose level and those below it. RESULTS: The relationship between baseline fasting glucose and the differential change in β-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified. CONCLUSIONS: The respective improvements in β-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity. [ABSTRACT FROM AUTHOR]

Hematologic malignancies are rare causes of sellar masses and hypopituitarism. We report 2 cases of hypopituitarism due to sellar masses from hematologic malignancies. The first patient was found to have hypopituitarism but initial non-gadolinium-enhanced magnetic resonance imaging (MRI) sella did not demonstrate a mass. Subsequent gadolinium-enhanced MRI and transsphenoidal biopsy confirmed a diagnosis of intravascular lymphoma. Treatment with systemic chemotherapy resulted in resolution of abnormalities on MRI. The second patient had a known diagnosis of chronic lymphocytic leukemia, and sellar involvement contributing to hypopituitarism was confirmed on biopsy. Treatment with ibrutinib, acalabrutinib, and stereotactic radiosurgery resulted in resolution of abnormalities on MRI. Both patients were treated with hormone replacement for hypopituitarism. These cases highlight that hematologic malignancies should be suspected as causes of sellar masses/hypopituitarism in patients with concurrent symptoms atypical for a pituitary adenoma (eg, constitutional symptoms), known diagnoses of hematologic malignancies, or rapid tumor growth and invasion on imaging. Gadolinium-enhanced MRI should be pursued if nonenhanced MRI is nondiagnostic. Transsphenoidal biopsy can be considered for diagnosis. Malignancy-directed systemic therapy may improve hypopituitarism and radiographic abnormalities on MRI. [ABSTRACT FROM AUTHOR]

Aim: Non‐surgical options for inducing type 2 diabetes remission are limited. We examined whether remission can be achieved by combining lifestyle approaches and short‐term intensive glucose‐lowering therapy. Methods: In this trial, 160 patients with type 2 diabetes on none to two diabetes medications other than insulin were randomised to (a) an intervention comprising lifestyle approaches, insulin glargine/lixisenatide and metformin, or (b) standard care. Participants with glycated haemoglobin (HbA1c) <7.3% (56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for an additional 52 weeks. The primary outcome was diabetes relapse defined as HbA1c ≥6.5% (48 mmol/mol) at 24 weeks or thereafter, capillary glucose ≥10 mmol/L on ≥50% of readings, or use of diabetes medications, analysed as time‐to‐event. Main secondary outcomes included complete or partial diabetes remission at 24, 36, 48 and 64 weeks defined as HbA1c <6.5% (48 mmol/mol) off diabetes medications since 12 weeks after randomisation. A hierarchical testing strategy was applied. Results: The intervention significantly reduced the hazard of diabetes relapse by 43% (adjusted hazard ratio 0.57, 95% confidence interval 0.40‐0.81; p =.002). Complete or partial diabetes remission was achieved in 30 (38.0%) intervention group participants versus 16 (19.8%) controls at 24 weeks and 25 (31.6%) versus 14 (17.3%) at 36 weeks [relative risk 1.92 (95% confidence interval 1.14‐3.24) and 1.83 (1.03‐3.26), respectively]. The relative risk of diabetes remission in the intervention versus control group was 1.88 (1.00‐3.53) at 48 weeks and 2.05 (0.98‐4.29) at 64 weeks. Conclusions: A 12‐week intensive intervention comprising insulin glargine/lixisenatide, metformin and lifestyle approaches can induce remission of diabetes. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to evaluate remission of type 2 diabetes following a short-term intervention with insulin glargine, sitagliptin/metformin, and lifestyle approaches.Research Design and Methods: In this open multicenter trial, 102 patients with type 2 diabetes were randomized to 1) a 12-week intervention with sitagliptin/metformin, insulin glargine, and lifestyle therapy or 2) control group. Participants with HbA1c <7.3% (<56 mmol/mol) at 12 weeks were asked to stop diabetes medications and were followed for evidence of relapse over 52 weeks. Diabetes relapse criteria included HbA1c ≥6.5% (≥48 mmol/mol), ≥50% of capillary glucose readings >10 mmol/L over 1 week, and reinitiation of diabetes medications with or without abnormal fasting plasma glucose (FPG) or 2-h plasma glucose on an oral glucose tolerance test (OGTT). Time-to-relapse analysis was conducted to compare the treatment groups with (primary analysis) and without (supplementary analysis) FPG/OGTT relapse criteria.Results: With the FPG/OGTT relapse criteria included, the hazard ratio (HR) of relapse was 0.72 (95% CI 0.47-1.10) in the intervention group compared with the control group (primary analysis), and the number of participants remaining in remission was not significantly different between treatment groups at 24, 36, 48, and 64 weeks. In the supplementary analyses without these criteria, HR of relapse was 0.60 (95% CI 0.39-0.95), and the number of participants remaining in remission was significantly higher (26 vs. 10%) in the intervention group at 36 weeks.Conclusions: Although our primary outcome was not statistically significant, the tested approach deserves further study with further optimization of its components. [ABSTRACT FROM AUTHOR]

Aim: To test the hypothesis that the addition of periodic courses of short‐term intensive insulin therapy (IIT) could enhance the effect of metformin (MET) maintenance therapy on preservation of beta‐cell function following induction IIT. Methods: In this multicentre, randomized controlled trial, 108 adults with type 2 diabetes (median 1.3 years' duration; HbA1c 6.6% ± 0.6%) were randomized to 3 weeks of induction IIT (glargine, lispro) followed by MET maintenance, either with or without periodic 2‐week courses of IIT every 3 months for 2 years. Beta‐cell function was assessed by the Insulin Secretion Sensitivity Index‐2 (ISSI‐2) at an oral glucose tolerance test every 3 months. Results: In both arms, induction IIT increased ISSI‐2, improved whole‐body insulin sensitivity and reduced hepatic insulin resistance (all P ≤.0004). The primary outcome of baseline‐adjusted ISSI‐2 at 2 years was not improved by the addition of intermittent IIT (MET + IIT) and was slightly higher in the MET arm (baseline‐adjusted difference −35 [95% CI: −66, –3]), with three additional beta‐cell measures showing no significant differences. Baseline‐adjusted HbA1c at 2 years did not differ between MET and MET + IIT (6.3% ± 0.1% vs. 6.4% ± 0.1%, P =.46), with 32.6% of participants in each arm maintaining HbA1c of 6.0% or less at 2 years. Conclusion: Although initial induction IIT induces metabolic improvement, subsequent repeat courses of IIT every 3 months do not further enhance the effect of MET maintenance therapy on beta‐cell function. [ABSTRACT FROM AUTHOR]

High levels of distress in post-secondary students, alongside the real or perceived barriers to accessing services, highlight the need for evidence-based, accessible, and brief interventions for students such as mindfulness-based interventions (MBIs). This systematic review and meta-analysis seeks to determine the effectiveness of MBIs for mental health outcomes in post-secondary students. We searched OVID MEDLINE In-Process, EMBASE, CENTRAL, CINAHL, PsychInfo, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Google Scholar, Proquest Dissertations, and OpenGrey. When possible, data were pooled using a random-effects model. Effect estimates were reported as standardized mean differences (SMDs) and then back-transformed into common scales of measurement. This review includes 41 randomized controlled trials reported in 49 studies. When comparing to a passive control, MBIs appear to reduce symptoms of depression [SMD − 0.49 (95% CI − 0.68, − 0.30)], anxiety [SMD − 0.53 (95% CI − 0.78, − 0.29)], and perceived stress [SMD -0.39 (95% CI -0.50, -0.27)] post-intervention (low-quality evidence). These findings were similar for shorter compared to longer interventions, although mindfulness-based cognitive therapy appeared to be the most effective for depression and anxiety. This review found no differential effects of MBIs compared to active comparators for depressive symptoms, anxiety symptoms, or perceived stress (low-quality evidence). Overall, MBIs of at least 2 weeks in duration appear to be a better alternative than no intervention for students with symptoms of depression, anxiety, and perceived stress. [ABSTRACT FROM AUTHOR]

Aims Materials and Methods Results Conclusions When administered in early type 2 diabetes (T2DM), the strategy of ‘induction’ with short‐term intensive insulin therapy (IIT) followed by ‘maintenance’ with metformin thereafter can yield outstanding glycaemic control, with some patients achieving A1c in the normal range of its assay. We thus sought to identify determinants of sustained normalisation of A1c in response to this treatment strategy.In this study, adults with T2DM of mean duration 1.7 ± 1.4 years received induction IIT (glargine, lispro) for 3 weeks, followed by metformin maintenance either with or without periodic 2‐week courses of IIT every 3 months for 2 years. Sustained glycaemic normalisation was defined by A1c <6.0% at 2 years.Of 101 participants, 26 achieved A1c <6.0% at 2 years. At baseline, these individuals had lower A1c and fasting glucose than the other participants, along with better beta‐cell function. During maintenance therapy from 3 weeks to 2 years, they had greater reduction of adiposity (body mass index: p = 0.02; waist circumference: p = 0.02), hepatic insulin resistance (HOMA‐IR: p = 0.02) and ALT (p = 0.005), coupled with relative stabilisation of beta‐cell function and glycaemia. On logistic regression analyses, significant independent predictors of normalisation of A1c at 2 years were baseline A1c (adjusted odds ratio [aOR] = 0.01 [95% CI 0.001–0.16], p = 0.001) and the changes in waist circumference (aOR = 0.77 [0.63–0.94], p = 0.012) and ALT (aOR = 0.90 [0.82–0.98], p = 0.019) during maintenance therapy from 3 weeks to 2 years.While lower baseline A1c and greater reduction in central adiposity predicted A1c <6.0% at 2 years as anticipated, the emergence of greater reduction in ALT as a concomitant determinant highlights the role of the liver in the achievement of sustained glycaemic normalisation. [ABSTRACT FROM AUTHOR]

Background: Diabetes remission due to non-surgical approaches has not been well studied. We investigated induction of diabetes remission following a short-term treatment with insulin glargine, lixisenatide and metformin and changes in exercise and dietary behaviours. Methods: We randomized 160 individuals with type 2 diabetes to (i) 12-week intensive treatment with insulin glargine, lixisenatide, metformin and lifestyle approaches or (ii) standard glycemic management. At 12 weeks, diabetes medications were stopped in patients with HbA1C<7.3%, and participants were followed for diabetes relapse over the subsequent 52 weeks. Diabetes relapse was defined as either the use of diabetes medications, ≥50% of capillary glucose levels ≥10 mmol/L over 1 week, or HbA1C≥6.5% at 24, 36, 48 or 64 weeks and analyzed as time to event. Treatment groups were compared using a Cox Proportional Hazards model with adjustment for duration of diabetes and baseline HbA1C (primary analysis). Key secondary outcomes included the proportion of participants in remission at 24, 36, 48 and 64 weeks. Results: The intervention significantly reduced the hazard of diabetes relapse (HR 0.57, 95% CI 0.40-0.81; p=0.002). The proportion of participants with diabetes remission was significantly higher in the intervention group compared to the control group at 24 weeks (38% vs. 20%; relative risk RR 1.92 (1.14-3.24)) and at 36 weeks (32% vs. 17%; RR 1.83 (1.03-3.26)), but not at 48 and 64 weeks (RR 1.88 (1.00-3.53) and 2.05 (0.98-4.29), respectively). Conclusion: Short-term intensive treatment targeting normoglycemia and weight loss with insulin glargine, lixisenatide, metformin and lifestyle changes can induce sustained remission of type 2 diabetes. Disclosure: N. Mcinnes: Other Relationship; Self; Merck & Co., Inc., Novo Nordisk, Sanofi. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker's Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. F. Sultan: Employee; Self; Abbott Diabetes. A. C. Smith: None. R. E. Otto: None. D. Sherifali: None. Y. Liu: None. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Remit-iglarlixi collaborative group: n/a. S. Hall: None. H. A. Lochnan: Research Support; Self; Novo Nordisk Inc., Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Z. Punthakee: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Self; AstraZeneca, Lexicon Pharmaceuticals, Inc., Novo Nordisk. R. J. Sigal: Advisory Panel; Self; Novo Nordisk, Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk. I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. M. Azharuddin: Consultant; Self; Novo Nordisk Canada Inc. J. F. Liutkus: Advisory Panel; Self; Novo Nordisk Canada Inc., Research Support; Self; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., IQVIA, Kowa Research Institute, Inc., Novo Nordisk Canada Inc., Sanofi, Speaker's Bureau; Self; Novo Nordisk Canada Inc., Stock/Shareholder; Self; Bayer Inc., Novo Nordisk, Pfizer Inc., Stock/Shareholder; Spouse/Partner; Bayer Inc., Eisai Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Canada Inc., Pfizer Inc. Funding: Sanofi [ABSTRACT FROM AUTHOR]