1. |
- Tobias, Deirdre K, et al.
(author)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Research review (peer-reviewed)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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2. |
- Ahren, Bo, et al.
(author)
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Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes : The adjunct two randomized trial
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:10, s. 1693-1701
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Journal article (peer-reviewed)abstract
- OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c ) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6mmol/mol]; 1.2mg: -0.22% [2.4mmol/mol]; 0.6 mg: -0.23% [2.5mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2mg vs. placebo and of hyperglycemia with ketosis >1.5mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
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3. |
- Frid, Anders H., et al.
(author)
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New Insulin Delivery Recommendations
- 2016
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In: Mayo Clinic Proceedings. - : Elsevier BV. - 0025-6196. ; 91:9, s. 1231-1255
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Research review (peer-reviewed)abstract
- Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.
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4. |
- Isaksson, Sofia Sterner, et al.
(author)
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Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials
- 2024
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In: DIABETOLOGIA. - : SPRINGER. - 0012-186X .- 1432-0428. ; 67, s. 1517-1526
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA(1c) values. The aim of this study was to further elucidate how MG and TIR are associated with HbA(1c). Methods Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA(1c)/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data. Results In the GOLD trial, the mean age of the participants (+/- SD) was 44 +/- 13 years, 63 (44%) were female, and the mean HbA(1c) (+/- SD) was 72 +/- 9.8 mmol/mol (8.7 +/- 0.9%). When correlating MG with HbA(1c), MG explained 63% of the variation in HbA(1c) (r=0.79, p<0.001). The variation in HbA(1c) explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG-HbA(1c) relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA(1c) of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA(1c) based on the overall association between MG and TIR with HbA(1c). TBR and TAR level 2 significantly influenced the association between TIR and HbA(1c). At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA(1c) (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA(1c) (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA(1c) when accounting for MG. Conclusions/interpretation Inter-individual variations exist between MG and HbA(1c), as well as between TIR and HbA(1c), with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.
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5. |
- Lind, Marcus, 1976, et al.
(author)
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Design and Methods of a Randomized Trial of Continuous Glucose Monitoring in Persons With Type 1 Diabetes With Impaired Glycemic Control Treated With Multiple Daily Insulin Injections (GOLD Study).
- 2016
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 10:3, s. 754-61
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Journal article (peer-reviewed)abstract
- The majority of individuals with type 1 diabetes today have glucose levels exceeding guidelines. The primary aim of this study was to evaluate whether continuous glucose monitoring (CGM), using the Dexcom G4 stand-alone system, improves glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections (MDI).Individuals with type 1 diabetes and inadequate glycemic control (HbA1c ≥ 7.5% = 58 mmol/mol) treated with MDI were randomized in a cross-over design to the Dexcom G4 versus conventional care for 6 months followed by a 4-month wash-out period. Masked CGM was performed before randomization, during conventional treatment, and during the wash-out period to evaluate effects on hypoglycemia, hyperglycemia, and glycemic variability. Questionnaires were used to evaluate diabetes treatment satisfaction, fear of hypoglycemia, hypoglycemia confidence, diabetes-related distress, overall well-being, and physical activity during the different phases of the trial. The primary endpoint was the difference in HbA1c at the end of each treatment phase.A total of 205 patients were screened, of whom 161 were randomized between February and December 2014. Study completion is anticipated in April 2016.It is expected that the results of this study will establish whether using the Dexcom G4 stand-alone system in individuals with type 1 diabetes treated with MDI improves glycemic control, reduces hypoglycemia, and influences quality-of-life indicators and glycemic variability.
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7. |
- Lind, Marcus, 1976, et al.
(author)
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Sustained Intensive Treatment and Long-term Effects on HbA(1c) Reduction (SILVER Study) by CGM in People With Type 1 Diabetes Treated With MDI
- 2021
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In: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:1, s. 141-149
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Journal article (peer-reviewed)abstract
- OBJECTIVE Continuous glucose monitoring (CGM) reduces HbA(1c) and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time. RESEARCH DESIGN AND METHODS The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. RESULTS The primary end point of the change in HbA(1c) over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA(1c) of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% (P < 0.001) and from 5.4% to 2.9% (P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence (P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA(1c) was lowered by 0.45% (P < 0.001) and 0.68% (P < 0.001) after 2.3 and 2.5 years, respectively. CONCLUSIONS The SILVER study supports beneficial long-term effects from CGM on HbA(1c), hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.
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8. |
- Nyström, Thomas, et al.
(author)
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Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With MDI: An Analysis Based on the GOLD Randomized Trial (GOLD 8)
- 2024
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 18:1, s. 89-98
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Journal article (peer-reviewed)abstract
- Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P =.16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P <.001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
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9. |
- Sofizadeh, Sheyda, et al.
(author)
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Effect of Liraglutide on Times in Glycaemic Ranges as Assessed by CGM for Type 2 Diabetes Patients Treated With Multiple Daily Insulin Injections
- 2019
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In: Diabetes Therapy. - : Springer Science and Business Media LLC. - 1869-6953 .- 1869-6961. ; 10:6, s. 2115-2130
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Journal article (peer-reviewed)abstract
- Introduction: The effects of the GLP-1 analogue liraglutide on time in hypoglycaemia, time in hyperglycaemia, and time in range for type 2 diabetes patients initially treated with multiple daily insulin injections (MDI) were investigated. Variables associated with hypoglycaemia in the current population were also identified. Methods: Analyses were based on data from a previously performed double-blind, placebo-controlled trial in which 124 MDI-treated patients with type 2 diabetes were randomized to liraglutide or placebo. Masked continuous glucose monitoring (CGM) was performed at baseline and week 24 in 99 participants. Results: The mean time in hypoglycaemia was similar for participants receiving liraglutide and those receiving placebo after 24 weeks of treatment. Mean time in target was greater in the liraglutide group than in the placebo group: 430 versus 244 min/24 h (p < 0.001) and 960 versus 695 min/24 h (p < 0.001) for the two glycaemic ranges considered, 4–7 mmol/l and 4–10 mmol/l, respectively. Mean time in hyperglycaemia was lower in the liraglutide group: 457 versus 723 min/24 h (p = 0.001) and 134 versus 264 min/24 h (p = 0.023) for the two cutoffs considered, > 10 mmol/l and > 14 mmol/l, respectively. Lower mean glucose level, lower C-peptide, and higher glucose variability were associated with an increased risk of hypoglycaemia in both treatment groups. Higher proinsulin level was associated with a lower risk of hypoglycaemia in the liraglutide group. Conclusion: For type 2 diabetes patients initially treated with MDI, introducing liraglutide had a beneficial effect on glucose profiles estimated by masked CGM. Mean glucose level, glycaemic variability, C-peptide, and proinsulin level influenced the risk of hypoglycaemia in this population. Trial Registration: ClinicalTrials.gov, number (EudraCT nr: 2012-001941-42). Funding: Novo Nordisk funded this study. The Diabetes Research Unit, NU-Hospital Group funded the journal’s Rapid Service Fee.
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11. |
- Westman, Klara, et al.
(author)
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Variables associated with insulin production in persons with type 2 diabetes treated with multiple daily insulin injections
- 2021
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In: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 15:3, s. 607-613
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Journal article (peer-reviewed)abstract
- From the MDI-liraglutide study, we evaluated variables associated with endogenous insulin production in persons with multiple daily insulin injections-treated type 2 diabetes by relating C-peptide, proinsulin and proinsulin/C-peptide ratio at baseline to baseline variables. Lower insulin production was related to longer diabetes duration, shorter abdominal sagittal diameter and more glycaemic variability.
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12. |
- Wijkman, Magnus, et al.
(author)
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Predictors and correlates of systolic blood pressure reduction with liraglutide treatment in patients with type 2 diabetes
- 2019
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In: Journal of Clinical Hypertension. - : Wiley. - 1751-7176 .- 1524-6175. ; 21:1, s. 105-115
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Journal article (peer-reviewed)abstract
- Liraglutide is associated with blood pressure reduction in patients with type 2 diabetes. However, it is not known whether this blood pressure reduction can be predicted prior to treatment initiation, and to what extent it correlates with weight loss and with improved glycemic control during follow-up. We analyzed data from a double-blind, placebo-controlled trial, in which 124 insulin-treated patients with type 2 diabetes were randomized to liraglutide or placebo. We evaluated various baseline variables as potential predictors of systolic blood pressure (SBP) reduction, and evaluated whether changes in SBP correlated with weight loss and with improved glycemic control. A greater reduction in SBP among liraglutide-treated patients was predicted by higher baseline values of SBP (P < 0.0001) and diastolic blood pressure (P = 0.012), and by lower baseline values of mean glucose measured by continuous glucose monitoring (CGM; P = 0.044), and serum fasting C-peptide (P = 0.015). The regression coefficients differed significantly between the liraglutide group and the placebo group only for diastolic blood pressure (P = 0.037) and mean CGM (P = 0.021). During the trial period, SBP reduction correlated directly with change in body weight and BMI, but not with change in HbA1c. We conclude that patients with lower mean CGM values at baseline responded to liraglutide with a larger reduction in SBP, and that improved HbA1c during follow-up was not associated with reductions of SBP. Our data suggest that some patients with type 2 diabetes may benefit from liraglutide in terms of weight and SBP reduction.
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