Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis

Dutta, Deep; Mohindra, Ritin; Mahajan, Kunal; Sharma, Meha

doi:10.4093/dmj.2022.0035

Cited by 4 publications

(2 citation statements)

References 24 publications

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Section: Introductionmentioning

confidence: 99%

“…Subcutaneous administration of FIAsp has demonstrated superior early glucose-lowering efficiency and efficacy compared to IAsp (Hsu et al, 2021). Regarding mechanism, FIAsp exhibits enhanced compatibility for insulin pump use compared to IAsp and other analogs of rapid-acting insulins (Dutta et al, 2023; Hsu et al, 2021). The latest ultra-rapid-acting insulins introduce additional bolus insulin alternatives for individuals with type 1 or type 2 diabetes (T1D, T2D) (Avgerinos et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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X-ray Crystallographic and Hydrogen Deuterium Exchange Studies Confirm Alternate Kinetic Models for Homolog Insulin Monomers

Ayan,

Türk,

Tatlı

et al. 2024

Preprint

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Despite the crucial role of various insulin analogs in achieving satisfactory glycemic control, a comprehensive understanding of their dynamic mechanisms still holds the potential to further optimize ultra-fast-acting insulin analogs, thus significantly improving the well-being of individuals with Type 1 Diabetes. Here, we present new insights derived from our 2.5 Å resolution X-ray crystal structure of modified insulin analog at ambient temperature. Furthermore, we obtained a distinctive side-chain conformation of the Asn3 residue on the B chain (AsnB3) by operating a comparative analysis with a previously available cryogenic rapid-acting insulin structure (PDB_ID: 4GBN). Additionally, we employed hydrogen-deuterium exchange mass spectrometry to decipher the molecular dynamics of these insulin analogs. A comparative analysis of H/D dynamics demonstrated that the modified insulin exchanges deuterium atoms faster and more extensively than the intact insulin aspart. The hybrid structural approach combined with computational analysis employed in this study provides novel insight into the structural dynamics of newly modified insulin and insulin aspart monomeric entities. It allows further molecular understanding of intermolecular interrelations driving dissociation kinetics and, thus, a fast action mechanism.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

X-ray Crystallographic and Hydrogen Deuterium Exchange Studies Confirm Alternate Kinetic Models for Homolog Insulin Monomers

Ayan,

Türk,

Tatlı

et al. 2024

Preprint

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Unveiling the Spectrum of Glucose Variability: A Novel Perspective on FreeStyle Libre Monitoring Data

Heald,

Stedman,

Warner-Levy

et al. 2024

Diabetes Ther

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Introduction Since the introduction of insulin therapy, it has become apparent that type 1 diabetes (T1D) is accompanied by long-term microvascular and macrovascular complications. In the context of the many benefits of continuous glucose monitoring (CGM), there remain opportunities to study the large amount of data now available in order to maximise its potential in the endeavour to reduce the occurrence of diabetes tissue complications in the longer term . Methods Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82 − (Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) − 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT). Results The mean age of the participants was 42.6 years, and the mean duration of T1D was 18.4 years. A total of 3.22 million readings were analysed, yielding an average blood glucose level of 10.3 mmol/l and a GMI of 57.2 mmol/mol. There was a strong correlation between GMI and measured HbA1c ( r 2 = 0.82). However, there were patients who had an above-critical threshold (ACT) of 4–10% at a GMI of 60 mmol/mol or less. The percentage average value at the time of day (%AVTD) was applied to all blood glucose readings at each 15-min interval throughout the day, averaged over 18 months. The %AVTD of GMI (overall average 57.2 mmol/mol) increased after midday, dipped at 18:00, and peaked at 22:00. The %AVTD of AGF (overall average 0.60 mmol/l) showed higher change rates after 09:00 declining at the end of the day. The %AVTD of ACT peaked at 22:00, with those having the highest %ACT showing an additional peak at 15:00. Conclusions We have shown here that the percentage glucose results above 18 mmol/l (top 5% of distribution) increased exponentially above 54 mmol/mol HbA1c. The %AVTD is introduced as a useful measure. Our data indicate that over the 24-h period, improvement in metabolic control could be focussed on the afternoon and evening, when there are higher-than-average levels...

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Burden and Coping Strategies of Hypoglycemia in People with Diabetes

Liakos,

Karagiannis,

Avgerinos

et al. 2024

CDR

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Hypoglycemia is a limiting adverse effect of glucose-lowering medications and particularly insulin replacement therapy. This review provides insights into the burden of hypoglycemia in the management of diabetes and outlines strategies available to reduce the risk of hypoglycemia and improve patients’ well-being. People with type 1 diabetes are primarily affected by hypoglycemic episodes which are associated with direct physical harms like injuries and cardiac events as well as indirect psychosocial consequences including constant anxiety, absenteeism, increased healthcare costs and overall poorer quality of life. These complications are more prominent amongst individuals with hypoglycemia unawareness or overnight hypoglycemia and could even extend to caregivers such as parents of children with diabetes. Patients experiencing frequent or severe hypoglycemic events might also develop a pathological fear of hypoglycemia and adopt aberrant behaviors intending to maintain higher blood glucose levels. Modern pharmaceutical options with a safer profile in terms of hypoglycemia are available including novel basal insulins with lower rates of nocturnal hypoglycemia along with ultra-rapid-acting insulin analogs with a shorter duration of action that might avert late post-meal hypoglycemia. Continuous glucose monitoring and sensor-augmented insulin pump therapy with low glucose suspend technology can also prevent hypoglycemia, although concerns about cost and patient satisfaction remain. Advancements in insulin therapy and technological modalities should be coupled with ongoing education and support for patients to become co-managers of their disease and reduce the risk of hypoglycemia.

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Performance of Fast-Acting Aspart Insulin as Compared to Aspart Insulin in Insulin Pump for Managing Type 1 Diabetes Mellitus: A Meta-Analysis

Cited by 4 publications

References 24 publications

X-ray Crystallographic and Hydrogen Deuterium Exchange Studies Confirm Alternate Kinetic Models for Homolog Insulin Monomers

X-ray Crystallographic and Hydrogen Deuterium Exchange Studies Confirm Alternate Kinetic Models for Homolog Insulin Monomers

Unveiling the Spectrum of Glucose Variability: A Novel Perspective on FreeStyle Libre Monitoring Data

Burden and Coping Strategies of Hypoglycemia in People with Diabetes

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