Sulfonylurea monotherapy is the standard treatment for patients with the most common form of permanent neonatal diabetes,
neonatal diabetes, but it is not always sufficient. For the first time, we ...present a case of successful use of a GLP-1 receptor agonist as add-on therapy in the treatment of a patient with
neonatal diabetes and insufficient effect of sulfonylurea monotherapy. Good glycaemic control was maintained with a HbA1c level of 48 mmol/mol (6.5%) at the end of 26 months' follow-up.
Genetic testing is important in patients with neonatal diabetes.Sulfonylurea is the standard treatment for patients with the most common mutation (
).We present the novel use of a GLP-1 receptor agonist as effective add-on therapy in a patient with
neonatal diabetes and insufficient effect of sulfonylurea monotherapy.
Aims/hypothesis
We aimed to compare the effects of intermittently scanned continuous glucose monitoring (isCGM) and carbohydrate counting with automated bolus calculation (ABC) with usual care.
...Methods
In a randomised, controlled, open-label trial carried out at five diabetes clinics in the Capital Region of Denmark, 170 adults with type 1 diabetes for ≥1 year, multiple daily insulin injections and HbA
1c
> 53 mmol/mol (7.0%) were randomly assigned 1:1:1:1 with centrally prepared envelopes to usual care (
n
= 42), ABC (
n
= 41), isCGM (
n
= 48) or ABC+isCGM (
n
= 39). Blinded continuous glucose monitoring data, HbA
1c
and patient-reported outcomes were recorded at baseline and after 26 weeks. The primary outcome was change in time in range using isCGM vs usual care.
Results
Baseline characteristics were comparable across arms: mean age 47 (SD 13.7) years, median (IQR) diabetes duration 18 (10–28) years and HbA
1c
65 (61–72) mmol/mol (8.1% 7.7–8.7%). Change in time in range using isCGM was comparable to usual care (% difference of 3.9 −12–23,
p
= 0.660). The same was true for the ABC and ABC+isCGM arms and for hypo- and hyperglycaemia. Also compared with usual care, using ABC+isCGM reduced HbA
1c
(4 95% CI 1, 8 mmol/mol) (0.4 0.1, 0.7 %-point) and glucose CV (11% 4%, 17%) and improved treatment satisfaction, psychosocial self-efficacy and present life quality. Treatment satisfaction also improved by using isCGM alone vs usual care. Statistical significance was maintained after multiple testing adjustment concerning glucose CV and treatment satisfaction with ABC+isCGM, and treatment satisfaction with isCGM. Discontinuation was most common among ABC only users, and among completers the ABC was used 4 (2–5) times/day and the number of daily isCGM scans was 5 (1–7) at study end.
Conclusions/interpretation
isCGM alone did not improve time in range, but treatment satisfaction increased in technology-naive people with type 1 diabetes and suboptimal HbA
1c
. The combination of ABC+isCGM appears advantageous regarding glycaemic variables and patient-reported outcomes, but many showed resistance towards ABC.
Trial registration
ClinicalTrials.gov
NCT03682237.
Funding
The study is investigator initiated and financed by the Capital Region of Denmark.
Graphical abstract
OBJECTIVE: To investigate the effect of flexible intensive insulin therapy (FIIT) and an automated bolus calculator (ABC) in a Danish type 1 diabetes population treated with multiple daily ...injections. Furthermore, to test the feasibility of teaching FIIT in a 3-h structured course. RESEARCH DESIGN AND METHODS: The BolusCal Study was a 16-week randomized, controlled, open-label, three-arm parallel, clinical study of 51 adults with type 1 diabetes. Patients aged 18–65 years in poor metabolic control (HbA1c 8.0–10.5%) were randomized to the Control (n = 8), CarbCount (n = 21), or CarbCountABC (n = 22) arm. During a 3-h group teaching, the Control arm received FIIT education excluding carbohydrate counting. CarbCount patients were taught FIIT and how to count carbohydrates. CarbCountABC group teaching included FIIT and carbohydrate counting and patients were provided with an ABC. RESULTS: At 16 weeks, the within-group change in HbA1c was –0.1% (95% CI –1.0 to 0.7%; P = 0.730) in the Control arm, –0.8% (–1.3 to –0.3%; P = 0.002) in the CarbCount arm, and –0.7% (–1.0 to –0.4%; P < 0.0001) in the CarbCountABC arm. The difference in change in HbA1c between CarbCount and CarbCountABC was insignificant. Adjusting for baseline HbA1c in a regression model, the relative change in HbA1c was –0.6% (–1.2 to 0.1%; P = 0.082) in CarbCount and –0.8% (–1.4 to –0.1%; P = 0.017) in CarbCountABC. Treatment satisfaction measured by the Diabetes Treatment Satisfaction Questionnaire (status version) improved in all study arms, but the improvement was significantly greater in CarbCountABC. CONCLUSIONS: FIIT and carbohydrate counting were successfully taught in 3 h and improved metabolic control and treatment satisfaction. Concurrent use of an ABC improved treatment satisfaction further.
In a randomized controlled multicenter trial, 170 adults with type 1 diabetes ≥1 year, multiple daily insulin injections, HbA1c >7.0% (53 mmol/mol), were randomized to usual care (n=42), carbohydrate ...counting with automated bolus calculation (ABC) (n=41), intermittently scanned continuous glucose monitoring (isCGM) (n=48), or ABC+isCGM (n=39). HbA1c, blinded CGM and patient-reported outcomes were recorded at baseline and after 26 weeks. Primary outcome was change in time in range (TIR) with isCGM vs. usual care. Baseline characteristics were comparable across intervention arms; median (Q1;Q3) diabetes duration 18 (10;28) years, HbA1c 8.1 (7.7;8.7) % (65 (61;72) mmol/mol) and mean (SD) BMI 26.7 (3.9) kg/m2. Changes in TIR, hypo- and hyperglycemia were similar in the intervention arms compared to usual care. Daytime TIR increased 22 (95% CI: 1;47) % with ABC and nighttime hyperglycemia increased 258 (40;814) % with isCGM compared to usual care. With ABC+isCGM, HbA1c was reduced 0.4 (0.1;0.7) % (4 (1;8) mmol/mol) and glucose coefficient of variation (CV) was reduced 11 (4;17) % compared to usual care. Treatment satisfaction improved with isCGM and ABC+isCGM. With ABC+isCGM, empowerment and present life quality also improved. Within the ABC and isCGM arms, we observed HbA1c reductions of 0.3 and 0.3% (4 and 3 mmol/mol), respectively, however not significantly different from usual care. Statistical significance was maintained after adjustment for multiple testing with regards to CV and treatment satisfaction with ABC+isCGM, and treatment satisfaction with isCGM only.
In conclusion, although no significant improvement in TIR was achieved, simultaneous intervention with ABC+isCGM improved the coefficient of variation and treatment satisfaction compared to usual care, and HbA1c was clinically relevant reduced, in adult technology-naïve persons with type 1 diabetes and suboptimal HbA1c.
Disclosure
A. L. Secher: None. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. O. L. Svendsen: None. B. Gade-rasmussen: None. T. P. Almdal: None. L. H. Raimond: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K. Nørgaard: Advisory Panel; Self; Medtronic, Other Relationship; Self; Novo Nordisk Inc., Zealand Pharma A/S, Speaker’s Bureau; Self; Medtronic.
IntroductionThere are beneficial effects of advanced carbohydrate counting with an automatic bolus calculator (ABC) and intermittently scanned continuous glucose monitoring (isCGM) in persons with ...type 1 diabetes. We aim to compare the effects of isCGM, training in carbohydrate counting with ABC and the combination of the two concepts with standard care.Methods and analysisA multi-centre randomised controlled trial with inclusion criteria: ≥18 years, type 1 diabetes ≥1 year, injection therapy, HbA1c >53 mmol/mol, whereas daily use of carbohydrate counting and/or CGM/isCGM wear are exclusion criteria. Inclusion was initiated in October 2018 and is ongoing. Eligible persons are randomised into four groups: standard care, ABC, isCGM or ABC+isCGM. Devices used are FreeStyle Libre Flash and smart phone diabetes application mySugr. Participants attend group courses according to treatment allocation with different educational contents. Participants are followed for 26 weeks with clinical visits and telephone consultations. At baseline and at study end, participants wear blinded CGM, have blood samples performed and fill in questionnaires on person-related outcomes, and at baseline also on personality traits and hypoglycaemia awareness. The primary outcome is the difference in time spent in normoglycaemia (4–10 mmol/L) at study end versus baseline between the isCGM group and the standard care group. Secondary outcomes will also be analysed. Results are expected in 2020.Ethics and disseminationRegional Scientific Ethics Committee approval (H-17040573). Results will be sought disseminated at conferences and in high impact journals.Trial registration numberClinicalTrial.gov registry (NCT03682237).
Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month ...multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (
p
= 0.001) (between group difference change), while the increases in CTX levels (
p
= 0.11) were not different. CRP was inversely associated (
p
= 0.012) and insulin dosage (
p
= 0.011) was positively related with change in P1NP levels. BMI (
p
= 0.002) and HbA1C (
p
= 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.
Abstract Objective Recent literature on acute diabetic Charcot osteoarthropathy (CA) reports unusually long periods of off-loading. Data suggest that this might increase the re-currence rate. ...Subsequently we evaluated the influence of duration of off-loading on the risk of required re-casting. Research Design and Methods In this retrospective consecutive series from 2000 to 2005, 56 people with diabetes and an acute Charcot foot were included. The inclusion criteria were an initial persistent temperature difference more than 2 °C between the two feet, oedema, and typical hot spots on a bone scintigram, radiology, and a typical clinical course. Treatment was off-loading in a removable cast and 2 crutches. In-door walking was allowed. Gradually augmented weight bearing was prescribed when the skin temperature difference had decreased to a level less than 2 °C and edema had subsided. Re-casting was required for immediate exacerbation during re-load as well as for recurrence — defined as new swelling and skin temperature difference of more than 2 °C in the same foot occurring after a stable interval of at least one month after full weight bearing. Results The duration of off-loading for all patients was 141 ± 21 days (mean ± SD). Three patients (5%) were re-casted immediately for exacerbation after re-load and 7 patients (12 %) after recurrence of the CA. Duration of re-casting was 79 ± 44 days. The primary period of off-loading was not statistically significantly different for those not requiring versus those requiring re-casting: 142 ± 24 days compared to 134 ± 41 days. Neither were the differences in demographic data, metabolic regulation, BMI or localization of CA. Conclusions Patients with risk of exacerbation or recurrence of CA could not be identified in the present study and there was no relation to the duration of off-loading. Nevertheless off-loading periods with immobilisation should be kept as short as possible, due to other side effects. This can be obtained by early gradual augmented re-loading.
In this case report a 40-year-old insulin-treated male patient presented with a KCNJ11 R201H mutation, which can cause neonatal diabetes. After initiation of treatment with high doses of the ...sulfonylurea glibencamide in combination with the glucagon-like peptide 1 receptor agonist liraglutide, insulin treatment of the patient could be terminated. The first nine months after termination of insulin treatment the glycated haemoglobin concentration was 48-54 mmol/mol (i.e. 6.5-7.1%).
ObjectiveTo assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 ...diabetes.Design and settingInvestigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design conducted at eight hospitals in Denmark.Participants and interventions412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤7.0% (≤53 mmol/mol).OutcomesThe primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes.ResultsChange in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI −0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference −0.42% (95% CI −0.62% to −0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference −2.6 kg (95% CI −3.3 to −1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001).ConclusionsMetformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results.Trial registration numberNCT00657943; Results.
PDF
