Optimizing the Replacement of Basal Insulin in Type 1 Diabetes Mellitus: No Longer an Elusive Goal in the Post-NPH Era

Background: The safe method of instructing insulin dose reduction in combination with SGLT2 inhibitors, dapagliflozin for patients with type 1 diabetes mellitus has not been clarified. In this study, we conducted a stratified, 2-arm, parallel comparative study with the primary endpoint of decreasing the frequency of hypoglycemia by instructing basal insulin dose reduction. Methods: The study has a multicenter, open-label, 2-arm design; 60 type 1 diabetes mellitus patients are being recruited from 7 hospitals. Study subjects have been stratified into 2 groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects whose Basal/TDD ratio is <0.4 are instructed not to reduce Basal but to reduce bolus insulin dose by 10% (group A), and subjects with a Basal/TDD ratio >0.4 will be instructed to reduce Basal by 10% (group B). The primary outcome is the daily frequency of hypoglycemia during the intervention period (SGLT2 inhibitor administration), as determined by self-monitoring of blood glucose. We aimed to confirm a greater reduction in frequency of hypoglycemia in group B (reduced Basal), than in group A (non-reduction of Basal and reduced insulin effect levels by 10%). Baseline hypoglycemia was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of .05 for a 1-sided t-test with a statistical power at 80% is determined. When the sample size is 26 patients in 1 group, the percentage increase in hypoglycemia exceeds 60%, and the sample size is considered sufficient. Discussion: In this pilot study, we assumed that, given a sufficient Basal, hypoglycemia would be more frequent in patients with type 1 diabetes when combined with SGLT2 inhibitors, provided the Basal was not reduced.

Download Full-text

Multicenter, open-label, two-arm pilot trial for safety reduction of basal insulin dose combined with SGLT2 inhibitor in type 1 diabetes mellitus: A study protocol for RISING-STAR

10.21203/rs.3.rs-52292/v2 ◽

2020 ◽

Author(s):

Masahide Hamaguchi ◽

Yoshitaka Hashimoto ◽

Toru Tanaka ◽

Goji Hasegawa ◽

Michiyo Ishii ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Sample Size ◽

Basal Insulin ◽

Insulin Dose ◽

Sglt2 Inhibitor ◽

Open Label ◽

Group B

Abstract Background SGLT2 inhibitor combined with insulin is a novel therapy for patients with type 1 diabetes mellitus. Without the reduction of basal insulin, hypoglycemia could occur frequently in this therapy. However, ketoacidosis is an undesirable adverse effect in cases with basal insulin reduction. Methods This was a multicenter, open-label, two-arm study. Sixty subjects with type 1 diabetes mellitus were recruited from 7 hospitals. Subjects whose basal insulin daily dose to total daily insulin dose (TDD) ratio was < 0.4 were instructed not to reduce the basal insulin dose but to reduce the bolus insulin dose by 10% (Group A), and subjects with a basal-to-TDD ratio > 0.4 were instructed to reduce the basal insulin dose by 10% (Group B). We hypothesized that the frequency of hypoglycemia would be reduced in Group B. The primary outcome was the frequency of hypoglycemia per day during the intervention period (administration of SGLT2 inhibitor) as determined by self-monitoring of blood glucose (SMBG). The baseline number of hypoglycemic attacks was set at 7 ± 6 times/month. The minimum sample size required to achieve a significance of 0.05 for a one-sided t-test with a statistical power of 80% was determined. When the sample size was 26 patients in one group, the percent increase in hypoglycemia was more than 60%; thus, the sample size was estimated to be sufficient. The secondary outcome was the frequency of ketosis before and after the intervention. We aimed to confirm that the frequency of ketosis does not increase in Group B compared with Group A. The frequency of adverse events, including the frequency of hypoglycemia detected using flash glucose monitoring (FGM), was set as the safety endpoint. Discussion The RISING-STAR study will contribute results from a two-arm randomized trial in which a reduction in basal insulin dose is indicated or no reduction in basal insulin dose is instructed for concomitant use of SGLT2 inhibitors in patients with type 1 diabetes to prevent the development of hypoglycemia.Trial registration Registered with the Japan Registry of Clinical Trials (jRCTs051190114) on March 2, 2020.

Download Full-text

Basal insulin peglispro increases lipid oxidation, metabolic flexibility, thermogenesis and ketone bodies compared to insulin glargine in subjects with type 1 diabetes mellitus

Diabetes Obesity and Metabolism ◽

10.1111/dom.13215 ◽

2018 ◽

Vol 20 (5) ◽

pp. 1193-1201 ◽

Cited By ~ 1

Author(s):

Niels K. Porksen ◽

Helle Linnebjerg ◽

Eric Chen Quin Lam ◽

Parag Garhyan ◽

Alok Pachori ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Insulin Glargine ◽

Lipid Oxidation ◽

Type 1 Diabetes Mellitus ◽

Basal Insulin ◽

Ketone Bodies ◽

Metabolic Flexibility

Download Full-text

Variation in 24-h basal insulin requirements with age in children and young people with type 1 diabetes mellitus

Endocrine Abstracts ◽

10.1530/endoabs.39.ep41 ◽

2015 ◽

Author(s):

Catherine Peters ◽

Peter Hindmarsh

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Young People ◽

Type 1 Diabetes Mellitus ◽

Basal Insulin ◽

Children And Young People ◽

Insulin Requirements

Download Full-text

Multicenter, Open-Label, Two-Arm, Pilot Trial for Safety Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for RISING-STAR.

10.21203/rs.3.rs-52292/v1 ◽

2020 ◽

Author(s):

Masahide Hamaguchi ◽

Yoshitaka Hashimoto ◽

Toru Tanaka ◽

Goji Hasegawa ◽

Michiyo Ishii ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Basal Insulin ◽

Insulin Dose ◽

Sglt2 Inhibitor ◽

Daily Insulin ◽

Daily Insulin Dose ◽

Daily Dose

Abstract Background: SGLT2 inhibitor combined with insulin therapy is a novel therapy for patients with type 1 diabetes mellitus. Without the reduction of basal insulin, hypoglycemia could occur frequently in this therapy. But diabetic ketoacidosis is an undesirable adverse effect in case with basal insulin reduction. The aim of this study is to explore whether the reduction of the basal insulin dose combined with SGLT2 inhibitor in patients with type 1 diabetes mellitus can reduce the frequency of hypoglycemia and be used safely. We hypothesized that with an adequate basal insulin dose, the frequency of hypoglycemia is higher if the basal insulin dose is not reduced when combined with SGLT2 inhibitor.Methods and Analysis: The study has a two-arm design; 60 subjects with type 1 diabetes mellitus are being recruited from 7 hospitals. The basal insulin dose before the start of the SGLT2 inhibitor combination therapy is the reference. Study subjects are stratified into two groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects are instructed to reduce the basal insulin dose by 10% or 0% for Basal to TDD ratio of <0.4 and > 0.4, respectively.The primary outcome is the frequency of hypoglycemia per day during the intervention period (administration of SGLT2 inhibitor) as determined by self-monitoring of blood glucose (SMBG). The secondary outcome is the frequency of ketosis before and after the intervention. Discussion: 10% basal insulin reduction could reduce hypoglycemia as well as could not increase ketosis in case that the ratio of basal insulin daily dose to total daily insulin dose is 0.4 or higher, which improve the efficacy and safety of SGLT2 inhibitor treatment patients with type 1 diabetes mellitus.Ethics and Dissemination: The study was approved by Kyoto Prefectural University of Medicine, Clinical Research Review Board (CRB5180001). The results will be disseminated through presentations at appropriate conferences and meetings, and published in peer-reviewed journals.Trial registration: Registered with Japan Registry of Clinical Trials (jRCTs051190114) on 2 March, 2020. https://rctportal.niph.go.jp/detail/jr?trial_id=jRCTs051190114)

Download Full-text

The altered circadian pattern of basal insulin requirements – an early marker of autoimmune polyendocrine syndromes in type 1 diabetes mellitus

Endocrine Regulations ◽

10.2478/enr-2020-0015 ◽

2020 ◽

Vol 54 (2) ◽

pp. 126-132

Author(s):

Maria Pallayova ◽

Dagmar Breznoscakova

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Basal Insulin ◽

Late Afternoon ◽

Early Marker ◽

Insulin Requirements ◽

Autoimmune Polyendocrine Syndrome ◽

Immune Mediated

AbstractObjectives. The purpose of the present paper is to propose and introduce novel biomarkers of autoimmune polyendocrine syndromes that are relevant to the early diagnosis and optimal medical management of the patients who already suffer from type 1 diabetes mellitus.Methods. We hypothesize and demonstrate on a case study that various organ-specific autoimmune endocrinopathies can result in lowered basal insulin requirements, leading to unexplained hypoglycemia.Results. It can be hypothesized that hypothyroidism in patients with type 1 diabetes mellitus may deteriorate glycemic control and can lead to an increased rate of hypoglycemia, particularly the overnight and morning hypoglycemia. Thus, the decreased requirements for particularly overnight basal insulin can be an early marker of the autoimmune polyendocrine syndrome-3 with subclinical autoimmune thyroiditis in immune-mediated type 1 diabetes mellitus. Further, it could be proposed that unexplained hypoglycemia during the late afternoon or evening could be an early marker of the autoimmune polyendocrine syndrome-2 with subclinical autoimmune Addison disease in immune-mediated type 1 diabetes mellitus. As a result, an altered circadian pattern of basal insulin requirements can occur, characterized by a decreased late afternoon basal insulin rate.Conclusions. After exclusion of other causes, the unexplained reoccurring hypoglycemia can be a remarkable feature of autoimmune polyendocrine syndromes in immune-mediated type 1 diabetes mellitus on intensive insulin replacement therapy.

Download Full-text