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AIM: To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections. MATERIALS AND METHODS: We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements. RESULTS: Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire. CONCLUSION: The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines.
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Diabetes Mellitus Tipo 1 , Hipoglicemia , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemiantes , Insulina , MasculinoRESUMO
This study aimed to confirm the efficacy and safety of mealtime and post-meal fast-acting insulin aspart versus insulin aspart, both with basal insulin degludec, in Japanese patients with type 1 diabetes. This was a subgroup analysis of onset 8, a randomized multicenter, treat-to-target trial of mealtime fast-acting insulin aspart (subgroup n = 73), mealtime insulin aspart (n = 83), or open-label post-meal fast-acting insulin aspart (n = 89), all for 26 weeks. Change from baseline in HbA1c was considered the primary endpoint. After 26 weeks, the estimated treatment difference (ETD, 95% CI) for change from baseline in HbA1c between mealtime fast-acting insulin aspart or post-meal fast-acting insulin aspart vs. insulin aspart was 0.01% (-0.16;0.19) and 0.10% (-0.07;0.27), respectively. Following a standardized meal test, ETD for change from baseline in postprandial glucose (PPG) increment at 1 hour was -16.91 mg/dL (-32.15;-1.68) for mealtime fast-acting insulin aspart and 40.16 mg/dL (25.46;54.87) for post-meal fast-acting insulin aspart, both versus insulin aspart. Mean self-measured blood glucose 1-hour PPG increments also showed a trend towards improved PPG control with mealtime fast-acting insulin aspart versus insulin aspart. Rates of overall hypoglycemia (35.56, 37.72 and 38.75 per patient-year of exposure with mealtime fast-acting insulin aspart, post-meal fast-acting insulin aspart and insulin aspart, respectively) and meal-related hypoglycemia were similar between treatment arms. Consistent with findings of onset 8, this analysis confirmed mealtime and post-meal fast-acting insulin aspart provided effective HbA1c and PPG control versus insulin aspart, with similar safety profiles, in Japanese adults with type 1 diabetes.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Hipoglicemiantes/efeitos adversos , Insulina Aspart/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Japão , Pessoa de Meia-Idade , Período Pós-Prandial , Resultado do TratamentoRESUMO
The aim of this post-hoc subgroup analysis, which was based on data from the treat-to-target, 26-week, onset 7 trial, was to confirm the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both in combination with basal insulin degludec, in children and adolescents from Japan with type 1 diabetes (T1D). Of the onset 7 trial population (1 to <18 years; N = 777), 66 participants from Japan (65 Asian and one non-Asian) were randomized to mealtime faster aspart (n = 24), post-meal faster aspart (n = 19), or IAsp (n = 23). Data for the subgroup from Japan were analysed descriptively. Change from baseline in hemoglobin A1c 26 weeks after randomization was 0.23%, 0.74%, and 0.39%, for mealtime faster aspart, post-meal faster aspart, and IAsp respectively. Change from baseline in 1-h post-prandial glucose increment (based on 8-point self-measured blood glucose profiles) showed numerical differences in favor of mealtime faster aspart versus IAsp at breakfast (-30.70 vs. -2.88 mg/dL) and over all meals (-18.21 vs. -5.55 mg/dL). There were no clinically relevant numerical differences between treatment arms in the overall rate of severe or blood glucose-confirmed hypoglycemia. At week 26, mean total insulin dose was 1.119 U/kg/day for mealtime faster aspart, 1.049 U/kg/day for post-meal faster aspart, and 1.037 U/kg/day for IAsp. In conclusion, in children and adolescents with T1D from Japan, mealtime and post-meal faster aspart with insulin degludec was efficacious in controlling glycemia without additional safety concerns versus IAsp.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Adolescente , Glicemia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemiantes/efeitos adversos , Lactente , Insulina Aspart/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Japão , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS: Children and adolescents (aged 1 to <18 years) with T1D. METHODS: A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6 years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp + IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet + IAsp). The primary end-point was HbA1c change from baseline at week 16. RESULTS: A total of 362 participants were randomized to IDegAsp + IAsp (n = 182) or IDet + IAsp (n = 180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15]95%CI (-0.45 mmol/mol [-2.51; 1.60]95%CI ), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp + IAsp vs IDet + IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp + IAsp and IDet + IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp + IAsp vs IDet + IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. CONCLUSIONS: IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Adolescente , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Lactente , Insulina de Ação Prolongada/efeitos adversos , Cetose , MasculinoRESUMO
The International Association of Diabetes and Pregnancy Study Groups (IADPSG) has suggested new diagnostic criteria for gestational diabetes mellitus. Many centers in Europe still use the World Health Organization (WHO) criteria. In southern Sweden we use the 2-h threshold of the European Association for the Study of Diabetes criteria based on universal screening with a 75-g oral glucose tolerance test. We have retrospectively scrutinized oral glucose tolerance tests in a subset of 174 women included in a previous study, diagnosed with gestational diabetes mellitus 1996-1999. A complete repeat oral glucose tolerance test was performed directly after diagnosis in 120 women. When applying the current Swedish criteria, and the IADPSG and the WHO criteria to the material, gestational diabetes mellitus was confirmed in 67% (80/120), 84% (101/120), and 80% (96/120), respectively. Hence, 26% (101/80) more women were identified by the IADPSG criteria and 20% (96/80) more women by the WHO criteria, compared with the criteria presently in use.
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Glicemia/metabolismo , Diabetes Gestacional/diagnóstico , Adulto , Biomarcadores/sangue , Diabetes Gestacional/sangue , Feminino , Seguimentos , Teste de Tolerância a Glucose , Humanos , Projetos Piloto , Guias de Prática Clínica como Assunto , Gravidez , Padrões de Referência , Estudos Retrospectivos , SuéciaRESUMO
Background: In the onset 5 trial, fast-acting insulin aspart (faster aspart) was noninferior to insulin aspart (IAsp) for change from baseline glycated hemoglobin at 16 weeks, when used in continuous subcutaneous insulin infusion by participants with type 1 diabetes. The aim of this post hoc analysis was to investigate whether infusion set wear-time was associated with changes in sensor glucose, measured using continuous glucose monitoring (CGM). Materials and Methods: This was a post hoc analysis of onset 5 data. Mean infusion set wear-time and duration of CGM-wearing period were assessed. Mean CGM sensor glucose 24 h before and 24 h after were used to calculate the before-after difference (CGM sensor glucose drift). Results: Mean infusion set wear-time was 2.9 and 3.0 days in the faster aspart and IAsp arms, respectively. At 16 weeks, the average duration of the CGM wearing period was 13.7 and 13.8 days, respectively. Mean CGM sensor glucose before versus after an infusion set change, at week 16, was 10.14 versus 9.39 mmol/L with faster aspart and 9.48 versus 9.47 mmol/L with IAsp. The estimated treatment difference in CGM sensor glucose drift at 16 weeks for faster aspart versus IAsp was +0.72 mmol/L (95% confidence interval: 0.48-0.96, P < 0.001). Conclusions: Mean infusion set wear-time and duration of CGM-wearing period were similar for faster aspart and IAsp. A significantly greater upward drift in CGM sensor glucose values measured during an infusion set wearing period was observed with faster aspart versus IAsp. Clinical trial registration: NCT02825251.
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Diabetes Mellitus Tipo 1 , Insulina Aspart , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Método Duplo-Cego , Hemoglobinas Glicadas/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Aspart/uso terapêuticoRESUMO
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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AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Gravidez em Diabéticas , Feminino , Humanos , Gravidez , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Hipoglicemiantes/uso terapêutico , Gravidez em Diabéticas/tratamento farmacológico , Gravidez em Diabéticas/epidemiologia , Glucose , Gestantes , Estudos Transversais , Insulina/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Ácido Fólico/uso terapêutico , GlicemiaRESUMO
INTRODUCTION: Medtronic has developed a virtual patient simulator for modeling and predicting insulin therapy outcomes for people with type 1 diabetes (T1D). An enhanced simulator was created to estimate outcomes when using the MiniMedTM 670G system with standard NovoLog® (EU: NovoRapid, US: NovoLog) versus Fiasp ® by using clinical data. METHODS: Sixty-seven participants' PK profiles were generated per type of insulin (Total of 134 PK profiles). 7,485 virtual patients' PK measurements was matched with one of the 67 NovoLog® PK Tmax values. These 7,485 virtual patients were then simulated using the Medtronic MiniMed™ 670G algorithm following an in-silico protocol of 90 days: 14 days in open loop (Manual Mode) followed by 76 days in closed loop (Auto Mode). Simulation study was repeated with each NovoLog® PK profile being replaced by its corresponding Fiasp® PK profile in the same virtual patient. To validate our in-silico analysis, we compared the results of "actual" 19 "real life" patients from a clinical study RESULTS: Simulated overall and postprandial glycemic outcomes improved in all age groups with Fiasp®. The percentage of time in the euglycemic range increased by about ~2.2% with Fiasp®, in all age groups (p < 0.01). The percentage of time spent at <70 mg/dL was reduced by about ~0.6% with insulin Fiasp® (p < 0.01) and the mean glucose was reduced by about 1.3 mg/dL (p < 0.01), excluding those age <7 years. The simulated mean postprandial SG was reduced by ~5 mg/dL, a significant difference for all age groups. A clinical study results showed similar improvements with MiniMedTM 670G system when switching from NovoLog® to Fiasp®. CONCLUSIONS: The simulation studies indicate that using Fiasp® in place of NovoLog® with the MiniMedTM 670G system will significantly improve the time spent in the healthy, euglycemic range and reduce exposure to hyperglycemia and hypoglycemia in most patients.
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Diabetes Mellitus Tipo 1 , Insulina Aspart , Glicemia , Automonitorização da Glicemia , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Insulina Aspart/uso terapêutico , Sistemas de Infusão de InsulinaRESUMO
Background: Although guidelines advocate similar continuous glucose monitoring (CGM) targets for insulin-treated persons with type 1 diabetes (T1D) and type 2 diabetes (T2D), it is unclear how these persons differ with respect to hypoglycemia, glucose variability, and other CGM metrics in clinical practice. Methods: We used data from 2 multicenter randomized-controlled trials (GOLD and MDI-Liraglutide) where 161 persons with T1D and 124 persons with T2D treated with multiple daily injections were included and monitored with masked CGM. Results: Persons from both cohorts had similar mean glucose levels, 10.9 mmol/L (196 mg/dL) in persons with T1D and 10.8 mmol/L (194 mg/dL) in persons with T2D. Time in hypoglycemia (<3.9 mmol/L [70 mg/dL]) was 5.1% and 1.0% for persons with T1D and T2D, respectively (P < 0.001). Corresponding estimates for the standard deviations of mean glucose levels were 4.4 mmol/L (79 mg/dL) versus 3.0 (54 mg/dL) (P < 0.001), for coefficient of variation 41% versus 28% (P < 0.001), and for time in range 38.2% versus 45.3%, respectively (P = 0.004). Mean C-peptide levels were 0.05 nmol/L and 0.67 nmol/L (P < 0.001) for persons with T1D and T2D, respectively. Conclusions: Persons with T1D compared with persons with T2D treated with multiple daily insulin injections spend considerably more time in hypoglycemia, have higher glucose variability, and less "time in range." This needs to be taken into account in daily clinical care and in recommended targets for CGM metrics.
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Diabetes Mellitus Tipo 2 , Insulina , Benchmarking , Glicemia , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Hemoglobinas Glicadas/análise , Humanos , Insulina/uso terapêuticoRESUMO
INTRODUCTION: We investigated the safety of, and glucose control by, the insulin-only configuration of the iLet® bionic pancreas delivering fast-acting insulin aspart (faster aspart), using the same insulin-dosing algorithm but different time to maximal serum drug concentration (tmax) settings, in adults with type 1 diabetes. METHODS: We performed a single-center, single-blinded, crossover (two 7-day treatment periods) escalation trial over three sequential cohorts. Participants from each cohort were randomized to a default tmax setting (t65 [tmax = 65 min]) followed by a non-default tmax setting (t50 [tmax = 50 min; cohort 1], t40 [tmax = 40 min; cohort 2], t30 [tmax = 30 min; cohort 3]), or vice versa, all with faster aspart. Each cohort randomized eight new participants if escalation-stopping criteria were not met in the previous cohort. RESULTS: Overall, 24 participants were randomized into three cohorts. Two participants discontinued treatment, one due to reported 'low blood glucose' during the first treatment period of cohort 3 (t30). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all tmax settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default tmax settings, with comparable insulin dosing. The mean time sensor glucose was in range (70-180 mg/dl) was > 70% for all cohorts, except the default tmax setting in cohort 1. No severe hypoglycemic episodes were reported. Furthermore, there were no clinically significant differences in adverse events between the groups. CONCLUSION: There were no safety concerns with faster aspart in the iLet at non-default tmax settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default tmax settings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03816761.
One way to give insulin is to use an insulin delivery system. The iLet® is a new type of insulin delivery system that works together with a continuous sugar monitoring tool (CGM). The CGM shows the blood sugar level in the body throughout the day. Based on this, the iLet automatically gives the insulin that is needed to control the blood sugar. Fast-acting insulin aspart (faster aspart) is a type of insulin that doctors can prescribe for use with insulin pens and insulin pumps. The researchers wanted to test the safety of faster aspart when given to people at different delivery settings in the iLet. Twenty-four men and women with type 1 diabetes from the USA took part. The different insulin delivery settings were the standard setting (tmax65 = 65 min) and new settings (tmax50 = 50 min; tmax40 = 40 min; tmax30 = 30 min). The shorter the tmax setting, the faster the insulin was assumed to be absorbed into the body by the iLet. People had good blood sugar control with faster aspart delivered using the iLet. The time with low blood sugar (i.e., < 54 mg/dl) was low for both the standard setting and the new settings. The average blood sugar was lower with the shorter, non-standard tmax settings. No people had serious side effects. No severe hypoglycemic episodes were reported. In this study, researchers found that it was safe to use faster aspart with the different settings in the iLet.
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AIMS: This survey aimed to explore real-world physician experiences and treatment satisfaction with fast-acting insulin aspart (faster aspart) in clinical practice across Europe and Canada. MATERIALS AND METHODS: An online web-based survey was used for physicians treating people with type 1 or type 2 diabetes. General practitioners and specialists, with experience using faster aspart, were interviewed. RESULTS: A total of 191 physicians participated in the survey. Most of their patients (68% of those with T1D and 63% of those with T2D) were previously treated with another mealtime insulin before switching to faster aspart. At the time of initiating faster aspart, nearly half of patients had an HbA1c level between 7.5% (59 mmol/mol) and 8.5% (69 mmol/mol). The main prescription drivers for faster aspart, versus other mealtime insulins, were faster onset of action, improved postprandial glucose (PPG) control, and dosing flexibility. Most physicians were more satisfied with faster aspart than other mealtime insulins regarding at-meal (66%) and post-meal (71%) dosing flexibility, improved PPG levels (66%), and onset of action (61%). Main reasons for not prescribing faster aspart included a good response to current treatment (76%) or patient reluctance to switch (57%). Overall, 12% of patients discontinued faster aspart, for reasons including concerns of hypoglycemia (17%), poor adherence (17%), and level of patient co-pay (17%). More than half of physicians had fewer concerns regarding postprandial hyperglycemia, and were more confident in their patients reaching their HbA1c target with faster aspart than with other mealtime insulins. LIMITATIONS: The findings of this survey are based heavily on physicians' experiences, and could therefore be subject to recall bias. CONCLUSIONS: Reported physician and patient experiences of using faster aspart have been positive, and better PPG control and increased dosing flexibility are expected to improve glycemic management.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Médicos/psicologia , Glicemia , Relação Dose-Resposta a Droga , Feminino , Financiamento Pessoal , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/economia , Insulina Aspart/administração & dosagem , Insulina Aspart/economia , Masculino , Adesão à Medicação , Período Pós-Prandial , Fatores de TempoRESUMO
OBJECTIVE: According to recent guidelines, individuals with type 1 diabetes should spend <4.0% of time per day with glucose levels <3.9 mmol/L (<70 mg/dL) and <1.0% per day with glucose levels <3.0 mmol/L (<54 mg/dL). RESEARCH DESIGN AND METHODS: In the GOLD randomized crossover trial, 161 individuals with type 1 diabetes treated with multiple daily insulin injections (MDI) were randomized to continuous glucose monitoring (CGM) or conventional therapy with self-monitoring of blood glucose (SMBG) and evaluated over 16 months. We estimated the association between time spent in hypoglycemia and various mean glucose and HbA1c levels. RESULTS: Time spent in hypoglycemia (<3.9 mmol/L and <3.0 mmol/L) increased significantly with lower mean HbA1c and mean glucose levels during both CGM and conventional therapy. During CGM, 24 (57.1%) individuals with HbA1c <7.5% (<58 mmol/mol) had <1.0% time spent in hypoglycemia <3.0 mmol/L and 23 (54.8%) had <4.0% time spent in hypoglycemia <3.9 mmol/L. During CGM, mean time spent in hypoglycemia for individuals with mean HbA1c 7.0% (52 mmol/mol) was estimated to be 5.4% for <3.9 mmol/L and 1.5% for <3.0 mmol/L. The corresponding values during SMBG were 9.2% and 3.5%, respectively. Individuals with mean glucose levels of 8 mmol/L spent 4.9% units more time with glucose levels <3.9 mmol/L and 2.8% units more time <3.0 mmol/L during SMBG compared with CGM. CONCLUSIONS: Reaching current targets for time in hypoglycemia while at the same time reaching HbA1c targets is challenging for patients with type 1 diabetes treated with MDI both with CGM and SMBG monitoring. However, CGM is associated with considerably less time in hypoglycemia than SMBG at a broad range of HbA1c levels and is crucial for patients with MDI treatment if they are to have a chance to approach hypoglycemia targets.
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Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Hipoglicemia/sangue , Insulina/administração & dosagem , Adulto , Glicemia/análise , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia , Estudos Cross-Over , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/patologia , Injeções Subcutâneas , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Suécia , Fatores de TempoRESUMO
INTRODUCTION: The majority of elderly patients (≥ 65 years of age) with type 2 diabetes mellitus (T2DM) will eventually require insulin therapy, but they are particularly vulnerable to hypoglycemia and challenging to treat. Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart administered in a single injection, either once or twice daily with main meals. METHODS: A combined analysis of the phase 3 BOOST INTENSIFY PREMIX I (NCT01009580) and BOOST INTENSIFY ALL (NCT01059812) trials has previously reported lower rates of hypoglycemia during the maintenance period in patients with T2DM treated with IDegAsp twice daily (BID) versus biphasic insulin aspart 30 (BIAsp 30) BID. This post hoc analysis examined the safety and efficacy of IDegAsp versus BIAsp 30 in elderly patients from the global population of these two trials, and also from the Japanese cohort of BOOST INTENSIFY ALL. RESULTS: Change in HbA1c was similar for IDegAsp versus BIAsp 30 (p > 0.5). Compared with BIAsp 30, IDegAsp resulted in significant reductions in fasting plasma glucose (p < 0.0001), numerically lower rates of overall and nocturnal hypoglycemia (global estimated rate ratios: 0.92 [0.67; 1.26]95% confidence interval [CI], p = 0.5980 and 0.67 [0.39; 1.18]95% CI, p = 0.1676, respectively), and a significantly lower total daily insulin dose at end of trial (global estimated treatment difference 0.79 [0.73; 0.87]95% CI, p < 0.0001) in elderly patients. CONCLUSION: The results described here are consistent with those of the overall trial populations, demonstrating that IDegAsp BID is efficacious in elderly patients and suggesting that there is no need for special safety precautions. FUNDING: Novo Nordisk. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01009580 and NCT01059812. Plain language summary available for this article.
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INTRODUCTION: Insulin dosing based on carbohydrate counting is the gold standard for improving glycaemic control in type 1 diabetes (T1D). This post hoc analysis aimed to explore the efficacy and safety of fast-acting insulin aspart (faster aspart) according to bolus dose adjustment method in people with T1D. METHODS: Post hoc analysis of two 26-week, treat-to-target, randomised trials investigating treatment with double-blind mealtime faster aspart, insulin aspart (IAsp), or open-label post-meal faster aspart (onset 1, n = 1143; onset 8, n = 1025). Participants with previous experience continued carbohydrate counting (onset 1, n = 669 [58.5%]; onset 8, n = 428 [41.8%]), while remaining participants used a bolus algorithm. RESULTS: In onset 1, HbA1c reduction was statistically significantly in favour of mealtime faster aspart versus IAsp with carbohydrate counting (estimated treatment difference [ETD 95% CI] - 0.19% [- 0.30; - 0.09]; - 2.08 mmol/mol [- 3.23; - 0.93]). In onset 8, there was no statistically significant difference in HbA1c reduction with either dose adjustment method, although a trend towards improved HbA1c was observed for mealtime faster aspart with carbohydrate counting (ETD - 0.14% [- 0.28; 0.003]; - 1.53 mmol/mol [- 3.10; 0.04]). In both trials, bolus insulin doses and overall rates of severe or blood glucose-confirmed hypoglycaemia were similar between treatments across dose adjustment methods. CONCLUSION: For people with T1D using carbohydrate counting, mealtime faster aspart may offer improved glycaemic control versus IAsp, with similar insulin dose and weight gain and no increased risk of hypoglycaemia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01831765 (onset 1) and NCT02500706 (onset 8). FUNDING: Novo Nordisk.
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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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OBJECTIVE: To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes. RESEARCH DESIGN AND METHODS: After a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years) to double-blind mealtime faster aspart (n = 260), mealtime IAsp (n = 258), or open-label postmeal faster aspart (n = 259). The primary end point was change from baseline in glycated hemoglobin (HbA1c) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect. RESULTS: At week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference -0.17% [95% CI -0.30; -0.03], -1.82 mmol/mol [-3.28; -0.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose-confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp. CONCLUSIONS: In children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA1c control compared with IAsp.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina Aspart/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Adolescente , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Método Duplo-Cego , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Lactente , Insulina Aspart/efeitos adversos , Insulina de Ação Prolongada/efeitos adversos , Masculino , Refeições , Período Pós-Prandial/efeitos dos fármacos , Resultado do TratamentoRESUMO
AIMS: To compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. METHODS: In this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin⯱â¯oral antidiabetic drugs for ≥90â¯days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8-20â¯weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30-50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose <3.1â¯mmol/L [56â¯mg/dL]), nocturnal (00:01-05:59) or severe (requiring assistance of another person). RESULTS: During the treatment period, IDegAsp (nâ¯=â¯131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (nâ¯=â¯132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: -0.54â¯mmol/L [-1.02; -0.07]95% CI, pâ¯=â¯.0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. CONCLUSIONS: IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum/sangue , Hemoglobinas Glicadas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Adulto , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Combinação de Medicamentos , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Insulina Aspart/farmacologia , Insulina de Ação Prolongada/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To identify predictors of diabetes development up to 5 years after gestational diabetes mellitus (GDM) and to develop a prediction model for individual use. METHODS: Five years after GDM, a 75-g oral glucose tolerance test (OGTT) was performed in 362 women, excluding women already diagnosed with diabetes at 1- to 2-year follow-up or later (n = 45). All but 21 women had results from follow-up at 1-2 years, while 84 women were lost from that point. Predictive variables were identified by logistic regression analysis. RESULTS: Five years after GDM, 28/362 women (8 %) were diagnosed with diabetes whereas 187/362 (52 %) had normal glucose tolerance (NGT). Of the latter, 139/187 (74 %) also had NGT at 1- to 2-year follow-up. In simple regression analysis, using NGT at 1-2 years and at 5 years as the reference, diabetes at 1- to 2-year follow-up or later was clearly associated with easily assessable clinical variables, such as BMI at 1- to 2-year follow-up, 2-h OGTT glucose concentration during pregnancy, and non-European origin (P < 0.0001). A prediction model based on these variables resulting in 86 % correct classifications, with an area under the receiver-operating characteristic curve of 0.91 (95 % CI 0.86-0.95), was applied in a function-sheet line diagram illustrating the individual effect of weight on diabetes risk. CONCLUSIONS: The results highlight the importance of BMI as a potentially modifiable risk factor for diabetes after GDM. Our proposed prediction model performed well, and should encourage validation in other populations in future studies.
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OBJECTIVE: To investigate whether genetic susceptibility to type 1 diabetes or maturity-onset diabetes of the young (MODY) increases susceptibility to gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We studied mutations in MODY1-4 genes, the presence of GAD antibodies, and HLA DQB1 risk genotypes in 66 Swedish women with GDM and a family history of diabetes. An oral glucose tolerance test was repeated in 46 women at 1 year postpartum. RESULTS: There was no increase in type 1 diabetes-associated HLA-DQB1 alleles or GAD antibodies when compared with a group of type 2 diabetic patients (n = 82) or healthy control subjects (n = 86). Mutations in known MODY genes were identified in 3 of the 66 subjects (1 MODY2, 1 MODY3, and 1 MODY4). Of the 46 GDM subjects, 2 had diabetes (4%) and 17 had impaired glucose tolerance (IGT) (37%) at 1 year postpartum. Of the two subjects who developed manifest diabetes, one carried a MODY3 mutation (A203H in the hepatocyte nuclear factor-1alpha gene). There was no increase in high-risk HLA alleles or GAD antibodies in the women who had manifest diabetes or IGT at 1 year postpartum. CONCLUSIONS: MODY mutations but not autoimmunity contribute to GDM in Swedish women with a family history of diabetes and increase the risk of subsequent diabetes.