The Effect of Insulin Degludec Versus Insulin Glargine U100 on Glucose Metrics Recorded During Continuous Glucose Monitoring in People With Type 1 Diabetes and Recurrent Nocturnal Severe Hypoglycemia.

AIM: Comparing continuous glucose monitoring (CGM)-recorded metrics during treatment with insulin degludec (IDeg) versus insulin glargine U100 (IGlar-100) in people with type 1 diabetes (T1D) and recurrent nocturnal severe hypoglycemia. MATERIALS AND METHODS: This is a multicenter, two-year, randomized, crossover trial, including 149 adults with T1D and minimum one episode of nocturnal severe hypoglycemia within the last two years. Participants were randomized 1:1 to treatment with IDeg or IGlar-100 and given the option of six days of blinded CGM twice during each treatment. CGM traces were reviewed for the percentage of time-within-target glucose range (TIR), time-below-range (TBR), time-above-range (TAR), and coefficient of variation (CV). RESULTS: Seventy-four participants were included in the analysis. Differences between treatments were greatest during the night (23:00-06:59). Treatment with IGlar-100 resulted in 54.0% vs 49.0% with IDeg TIR (70-180 mg/dL) (estimated treatment difference [ETD]: -4.6%, 95% confidence interval [CI]: -9.1, -0.0, P = .049). TBR was lower with IDeg at level 1 (54-69 mg/dL) (ETD: -1.7% [95% CI: -2.9, -0.5], P < .05) and level 2 (<54 mg/dL) (ETD: -1.3% [95% CI: -2.1, -0.5], P = .001). TAR was higher with IDeg compared with IGlar-100 at level 1 (181-250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.3], P < .05) and level 2 (> 250 mg/dL) (ETD: 4.0% [95% CI: 0.8, 7.2], P < .05). The mean CV was lower with IDeg than that with IGlar-100 (ETD: -3.4% [95% CI: -5.6, -1.2], P < .05). CONCLUSION: For people with T1D suffering from recurrent nocturnal severe hypoglycemia, treatment with IDeg, compared with IGlar-100, results in a lower TBR and CV during the night at the expense of more TAR.

Effect of insulin degludec versus insulin glargine U100 on nocturnal glycaemia assessed by plasma glucose profiles in people with type 1 diabetes prone to nocturnal severe hypoglycaemia.

AIM: To compare nocturnal glucose profiles according to hourly plasma glucose measurements during treatment with insulin degludec and insulin glargine U100 in a cohort of people with type 1 diabetes prone to nocturnal severe hypoglycaemia. MATERIALS AND METHODS: The HypoDeg trial is a 2-year investigator-initiated, randomized, controlled crossover trial in 149 participants randomized to treatment with insulin degludec and insulin glargine U100 for 12 months each. The 51 participants in this predefined substudy stayed at least one night in hospital during each treatment arm for plasma glucose samples to be taken. Endpoints were glucose profiles, including mean plasma glucose, glycaemic variability and risk of hypoglycaemia. RESULTS: There were no differences between treatments regarding mean plasma glucose. We saw a flatter glucose profile during insulin degludec compared with insulin glargine U100 treatment, which had a nadir at 4:00 AM, with a subsequent rise. During treatment with insulin degludec, the participants had lower glycaemic variability, with an estimated treatment difference of -4.3% (95% confidence interval [CI] -8.1 to -0.5; P < 0.05). Participants treated with insulin degludec were less likely to experience nocturnal hypoglycaemia below 3.0 mmol/L (hazard ratio 0.36 [95% CI 0.17-0.73; P < 0.05]). CONCLUSION: Based on nocturnal plasma glucose measurements, treatment with insulin degludec compared with insulin glargine U100 administered in the evening results in lower glycaemic variability and lower risk of nocturnal hypoglycaemia without differences in mean plasma glucose.

Long-term glucose-lowering effect of intermittently scanned continuous glucose monitoring for type 1 diabetes patients in poor glycaemic control from Region North Denmark: An observational real-world cohort study.

BACKGROUND: Lowering glucose levels is a complex task for patients with type 1 diabetes, and they often lack contact with health care professionals. Intermittently scanned continuous glucose monitoring (isCGM) has the potential to aid them with blood glucose management at home. The aim of this study was to investigate the long-term effect of isCGM on HbA1c in type 1 diabetes patients with poor glycaemic control in a region-wide real-world setting. METHODS: All patients with type 1 diabetes receiving an isCGM due to poor glycaemic control (≥70 mmol/mol [≥8.6%]) in the period of 2020-21 in Region North Denmark ("T1D-CGM") were compared with all type 1 diabetes patients without isCGM ("T1D-NOCGM") in the same period. A multiple linear regression model adjusted for age, sex, diabetes duration and use of continuous subcutaneous insulin infusion was constructed to estimate the difference in change from baseline HbA1c between the two groups and within subgroups of T1D-CGM. RESULTS: A total of 2,527 patients (T1D-CGM: 897; T1D-NOCGM: 1,630) were included in the study. The estimated adjusted difference in change from baseline HbA1c between T1D-CGM vs T1D-NOCGM was -5.68 mmol/mol (95% CI: (-6.69 to -4.67 mmol/mol; p<0.0001)). Older patients using isCGM dropped less in HbA1c. CONCLUSIONS: Our results indicate that patients with type 1 diabetes in poor glycaemic control from Region North Denmark in general benefit from using isCGM with a sustained 24-month improvement in HbA1c, but the effect on HbA1c may be less pronounced for older patients.

Continuous Glucose Monitoring-Recorded Hypoglycemia with Insulin Degludec or Insulin Glargine U100 in People with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia.

Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).

Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia: The HypoDeg randomized, controlled, open-label, crossover trial.

AIM: To investigate whether the long-acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D). METHODS: Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2-year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal-bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run-in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention-to-treat. RESULTS: Treatment with insulin degludec resulted in a 28% (95% CI: 9%-43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%-53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%-58%; P = .04) RRR in all-day severe hypoglycaemia compared with insulin glargine U100. CONCLUSIONS: Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all-day severe hypoglycaemia with insulin degludec compared with insulin glargine U100.

The effect of insulin degludec on risk of symptomatic nocturnal hypoglycaemia in adults with type 1 diabetes and high risk of nocturnal severe hypoglycaemia (the HypoDeg trial): study rationale and design.

BACKGROUND: Hypoglycaemia, especially nocturnal, remains the main limiting factor of achieving good glycaemic control in type 1 diabetes. The effect of first generation long-acting insulin analogues in reducing nocturnal hypoglycaemia is well documented in patient with type 1 diabetes. The effect of the newer long-acting insulin degludec on risk of nocturnal hypoglycaemia remains undocumented in patients with type 1 diabetes and recurrent severe nocturnal hypoglycaemia. The HypoDeg trial is designed to investigate whether insulin degludec in comparison with insulin glargine U100 is superior in limiting the occurrence of nocturnal hypoglycaemia in patients with recurrent nocturnal severe hypoglycaemia. This paper reports the study design of the HypoDeg trial. METHODS/DESIGN: A Danish investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, two-year cross-over study investigating the effect of insulin degludec versus insulin glargine U100 on frequency of nocturnal hypoglycaemia in patients with type 1 diabetes and one or more episodes of nocturnal severe hypoglycaemia during the preceding two years as the major inclusion criteria. Patients are randomised (1:1) to basal therapy with insulin degludec or insulin glargine. Insulin aspart is used as bolus therapy in both treatment arms. DISCUSSION: In contrast to most other insulin studies the HypoDeg trial includes only patients at high risk of hypoglycaemia. The HypoDeg trial will compare treatment with insulin degludec to insulin glargine U100 in terms of risk of nocturnal hypoglycaemic episodes in patients with type 1 diabetes with the greatest potential to benefit from near-physiological insulin replacement therapy. www.clinicaltrials.gov : NCT02192450.

Iodine deficiency influences thyroid autoimmunity in old age--a comparative population-based study.

OBJECTIVE: To assess thyroid autoimmunity among elderly people living in an area with low iodine intake compared to the sustained recommended iodine intake from a natural source, and to estimate the importance of migration. DESIGN AND SETTING: Iodine content of drinking water is highly different in the Danish towns Randers and Skagen. We collected blood and spot urine samples from 430 long-term Randers and Skagen dwellers aged 75-80 years, who filled in a questionnaire. We measured thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in serum and iodine and creatinine in urine. RESULTS: Participation rate was 47% (n=212 (men/women 82/130) in Randers; 218 (84/134) in Skagen). Iodine deficiency prevailed in Randers while Skagen dwellers were iodine replete (median urinary iodine 74 µg/24h vs. 184 µg/24h, p<0.001). Thyroid antibodies were more frequent in Randers than in Skagen residents (42% vs. 32%; p=0.006) and more likely with iodine excretion <50 µg/24h (OR, 95%CI: 1.9, 1.1-3.4). Differences between towns increased with longer duration of residence as trends in the occurrence of TGAb and TPOAb were opposite (p<0.001; p=0.007). CONCLUSIONS: Thyroid autoantibodies were common in old age, influenced by the iodine intake level, and the lowest frequency was found at the recommended iodine intake level.

More hypothyroidism and less hyperthyroidism with sufficient iodine nutrition compared to mild iodine deficiency--a comparative population-based study of older people.

OBJECTIVE: To assess the occurrence of thyroid disorders and autoimmunity in a geriatric population with long-standing recommended iodine intake of natural origin compared to mild iodine deficiency. DESIGN AND SETTING: Cross-sectional, comparative, population-based study in two areas with different iodine intakes due to different tap water iodine contents. PARTICIPANTS: Residents of Randers (n=212) or Skagen (n=218), Denmark, aged 75-80 years. MEASURES: Blood samples were collected for measuring thyrotropin (TSH), triiodothyronine, thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), thyroglobulin (TG); iodine excretion estimated from iodine and creatinine measured in spot urine samples; questionnaire on history of thyroid disease, medication and vitamin use; clinical examination of the neck. RESULTS: Median urinary iodine excretion was 50 microg/24h in Randers and 177 microg/24h in Skagen (p<0.001). A history of thyroid disease was reported by 40 (9.3%) dominated by goitre (n=22) in Randers and hypothyroidism and Graves Disease (n=15) in Skagen (p<0.001). We found visible goitre in 26% of Randers dwellers and none in Skagen (p<0.001). Hyperthyroidism with TSH below the reference range was present in 26% of Randers and 6% of Skagen dwellers while 6% and 13%, respectively, were hypothyroid with TSH above the reference range (p<0.001). More Randers than Skagen participants harboured a thyroid antibody (42% vs. 32%, p=0.006). CONCLUSIONS: Recommended iodine intake associated with more hypothyroidism, less hyperthyroidism and goiters, low TGAb prevalence and lower TG level in serum than did iodine deficiency. TPOAb was similar in the iodine replete and deficient geriatric populations.

Naturally occurring iodine in humic substances in drinking water in Denmark is bioavailable and determines population iodine intake.

Iodine intake is important for thyroid function. Iodine content of natural waters is high in some areas and occurs bound in humic substances. Tap water is a major dietary source but bioavailability of organically bound iodine may be impaired. The objective was to assess if naturally occurring iodine bound in humic substances is bioavailable. Tap water was collected at Randers and Skagen waterworks and spot urine samples were collected from 430 long-term Randers and Skagen dwellers, who filled in a questionnaire. Tap water contained 2 microg/l elemental iodine in Randers and 140 microg/l iodine bound in humic substances in Skagen. Median (25; 75 percentile) urinary iodine excretion among Randers and Skagen dwellers not using iodine-containing supplements was 50 (37; 83) microg/24 h and 177 (137; 219) microg/24 h respectively (P < 0.001). The fraction of samples with iodine below 100 microg/24 h was 85.0 % in Randers and 6.5 % in Skagen (P < 0.001). Use of iodine-containing supplements increased urinary iodine by 60 microg/24 h (P < 0.001). This decreased the number of samples with iodine below 100 microg/24 h to 67.3 % and 5.0 % respectively, but increased the number of samples with iodine above 300 microg/24 h to 2.4 % and 16.1 %. Bioavailability of iodine in humic substances in Skagen tap water was about 85 %. Iodine in natural waters may be elemental or found in humic substances. The fraction available suggests an importance of drinking water supply for population iodine intake, although this may not be adequate to estimate population iodine intake.