|
1
|
Holder M, Kamrath C, Lange K, Kummer S, Ziegler R. Diagnosis, Therapy and Follow-Up of Type 1 Diabetes Mellitus in Children and Adolescents. Exp Clin Endocrinol Diabetes 2025; 133:205-223. [PMID: 40328265 DOI: 10.1055/a-2490-5096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/08/2025]
Affiliation(s)
- Martin Holder
- Olgahospital, Stuttgart Hospital, Stuttgart, Germany
| | | | - Karin Lange
- Hannover Medical School (MHH), Hannover, Germany
| | | | - Ralph Ziegler
- Diabetological Practice for Children and Adolescents, Münster, Germany
| |
Collapse
|
|
2
|
Emad-Eldin M, Balata GF, Elshorbagy EA, Hamed MS, Attia MS. Insulin therapy in type 2 diabetes: Insights into clinical efficacy, patient-reported outcomes, and adherence challenges. World J Diabetes 2024; 15:828-852. [PMID: 38766443 PMCID: PMC11099362 DOI: 10.4239/wjd.v15.i5.828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2023] [Revised: 02/01/2024] [Accepted: 03/20/2024] [Indexed: 05/10/2024] Open
Abstract
Insulin therapy plays a crucial role in the management of type 2 diabetes as the disease progresses. Over the past century, insulin formulations have undergone significant modifications and bioengineering, resulting in a diverse range of available insulin products. These products show distinct pharmacokinetic and pharmacodynamic profiles. Consequently, various insulin regimens have em-erged for the management of type 2 diabetes, including premixed formulations and combinations of basal and bolus insulins. The utilization of different insulin regimens yields disparate clinical outcomes, adverse events, and, notably, patient-reported outcomes (PROs). PROs provide valuable insights from the patient's perspective, serving as a valuable mine of information for enhancing healthcare and informing clinical decisions. Adherence to insulin therapy, a critical patient-reported outcome, significantly affects clinical outcomes and is influenced by multiple factors. This review provides insights into the clinical effectiveness of various insulin preparations, PROs, and factors impacting insulin therapy adherence, with the aim of enhancing healthcare practices and informing clinical decisions for individuals with type 2 diabetes.
Collapse
Affiliation(s)
- Mahmoud Emad-Eldin
- Department of Pharmacy Practice, Faculty of Pharmacy, Zagazig University, Zagazig HFQM+872, Al-Sharqia Governorate, Egypt
| | - Gehan F Balata
- Department of Pharmacy Practice, Faculty of Pharmacy, Heliopolis University, Cairo 44519, Egypt
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Al-Sharqia Governorate, Egypt
| | - Eman A Elshorbagy
- Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig 44519, Al-Sharqia Governorate, Egypt
| | - Mona S Hamed
- Department of Community at Faculty of Medicine, Zagazig University, Zagazig 44519, Al-Sharqia Governorate, Egypt
| | - Mohamed S Attia
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Al-Sharqia Governorate, Egypt
| |
Collapse
|
|
3
|
Hemmingsen B, Metzendorf MI, Richter B. (Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus. Cochrane Database Syst Rev 2021; 3:CD013498. [PMID: 33662147 PMCID: PMC8094220 DOI: 10.1002/14651858.cd013498.pub2] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown. OBJECTIVES To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020. SELECTION CRITERIA We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM. DATA COLLECTION AND ANALYSIS Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument. MAIN RESULTS We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-certainty evidence). Four studies with 1013 participants reported QoL showing no true beneficial effect or harmful effect for either intervention (low-certainty evidence). Severe hypoglycaemia was observed in 122/1191 participants (10.2%) in the insulin glargine group compared with 145/1159 participants (12.5%) in the NPH insulin group (RR 0.84, 95% CI 0.67 to 1.04; 9 studies, 2350 participants; moderate-certainty evidence). No participant experienced a NFMI and one participant in the NPH insulin group experienced a NFS in the single study reporting this outcome (585 participants; low-certainty evidence). A total of 109/1131 participants (9.6%) in the insulin glargine group compared with 110/1098 participants (10.0%) in the NPH insulin group experienced SAEs (RR 1.08, 95% CI 0.63 to 1.84; 8 studies, 2229 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 69/938 participants (7.4%) in the insulin glargine group compared with 83/955 participants (8.7%) in the NPH insulin group (RR 0.83, 95% CI 0.62 to 1.12; 6 studies, 1893 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin glargine with NPH insulin was 0.02%, 95% CI -0.1 to 0.1; 9 studies, 2285 participants; moderate-certainty evidence. Insulin detemir versus insulin glargine (2 RCTs),insulin degludec versus insulin detemir (2 RCTs), insulin degludec versus insulin glargine (4 RCTs): there was no evidence of a clinically relevant difference for all main outcomes comparing (ultra-)long-acting insulin analogues with each other. For all outcomes none of the comparisons indicated differences in tests of interaction for children versus adults. AUTHORS' CONCLUSIONS Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.
Collapse
Affiliation(s)
- Bianca Hemmingsen
- Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Maria-Inti Metzendorf
- Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Bernd Richter
- Cochrane Metabolic and Endocrine Disorders Group, Institute of General Practice, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| |
Collapse
|
|
4
|
Alsaheel AY, Alayed SI, Alotaibi YM, Alfahhad AA, Alothman OM, Alnefaie HF. Mean glycosylated hemoglobin in children with type 1 diabetes at King Fahad Medical City, Riyadh, Saudi Arabia. J Family Community Med 2020; 27:163-167. [PMID: 33354146 PMCID: PMC7745789 DOI: 10.4103/jfcm.jfcm_173_20] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Revised: 07/22/2020] [Accepted: 08/24/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND: Type 1 diabetes is the third most common chronic disease among teenagers. In Saudi Arabia, there is a gap of knowledge regarding hemoglobin A1C (HbA1c) concentration levels, and adherence to regular follow-up visits by patients. The aim of this study was to determine the mean glycosylated hemoglobin (HbA1c) levels in diabetic children who have been diagnosed with type 1 diabetes and were being followed up at a tertiary care center in Saudi Arabia. MATERIALS AND METHODS: This cross-sectional study was conducted among all diabetic children treated at King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. Data were retrieved and analysed during the period from September to December 2018. Diabetic patients of <18 years and who were being followed up at KFMC were included in the study. Data on age, sex, duration of illness, associated comorbidities, antidiabetic regimen, and HbA1c levels were obtained. Student t-test was used to compare quantitative parameters between two groups, and Chi-square employed to test for associations between categorical variables at 5% significance level. RESULTS: A total of 510 patients of were included in the study; about 53% were females. The mean HbA1c level was 10.6% and females showed higher HbA1c levels. Data showed a strong correlation between age and HbA1c levels (P < 0.001), with older patients showing higher HbA1c levels. The HbA1c levels also increased as the duration of disease increased. The median number of patient visits to KFMC was two per year. No statistically significant differences were observeed for type of treatment for diabetes. Celiac disease, the most frequent comorbidity, was seen in 50% of patients. CONCLUSION: Diabetic children who were followed up at KFMC had high HbA1C level (10.6%), and lower than recommended follow-up visits per year. The treating physicians should educate patients and their legal guardians on the importance of follow-up visits and their role in controlling HbA1C levels, and following healthier lifestyle.
Collapse
Affiliation(s)
| | - Sulaiman I Alayed
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Yazzan M Alotaibi
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Aseel A Alfahhad
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Othman M Alothman
- College of Medicine, Imam Mohammed Ibn Saud Islamic University, Riyadh, Saudi Arabia
| | - Hissah F Alnefaie
- Saudi Center for Disease Control and Prevention, Riyadh, Saudi Arabia
| |
Collapse
|
|
5
|
Frier BM, Ratzki‐Leewing A, Harris SB. Reporting of hypoglycaemia in clinical trials of basal insulins: A need for consensus. Diabetes Obes Metab 2019; 21:1529-1542. [PMID: 30924567 PMCID: PMC6767397 DOI: 10.1111/dom.13732] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 03/13/2019] [Accepted: 03/26/2019] [Indexed: 12/31/2022]
Abstract
Hypoglycaemia is a common side-effect of diabetes therapies, particularly insulin, and imposes a substantial burden on individuals and healthcare systems. Consequently, regulatory approval of newer basal insulin (BI) therapies has relied on demonstration of a balance between achievement of good glycaemic control and less hypoglycaemia. Randomized controlled trials (RCTs) are the gold standard for assessing efficacy and safety, including hypoglycaemia risk, of BIs and are invaluable for obtaining regulatory approval. However, their highly selected patient populations and their conditions lead to results that may not be representative of real-life situations. Real-world evidence (RWE) studies are more representative of clinical practice, but they also have limitations. As such, data both from RCTs and RWE studies provide a fuller picture of the hypoglycaemia risk with BI therapies. However, substantial differences exist in the way hypoglycaemia is reported across these studies, which confounds comparisons of hypoglycaemia frequency among different BIs. This problem is ongoing and persists in recent trials of second-generation BI analogues. Although they provide a lower risk of hypoglycaemia when compared with earlier BIs, they do not eliminate it. This review describes differences in the way hypoglycaemia is reported across RCTs and RWE studies of second-generation BI analogues and examines potential reasons for these differences. For studies of BIs, there is a need to standardize aspects of design, analysis and methods of reporting to better enable interpretation of the efficacy and safety of such insulins among studies; such aspects include length of follow-up, glycaemic targets, hypoglycaemia definitions and time intervals for determining nocturnal events.
Collapse
Affiliation(s)
- Brian M. Frier
- British Heart Foundation Centre for Cardiovascular ScienceThe Queen's Medical Research Institute, University of EdinburghEdinburghUK
| | - Alexandria Ratzki‐Leewing
- Department of Epidemiology and BiostatisticsSchulich School of Medicine and Dentistry, Western UniversityLondonOntario, Canada
| | - Stewart B. Harris
- Department of Family MedicineSchulich School of Medicine and Dentistry, Western UniversityLondonOntario, Canada
| |
Collapse
|
|
6
|
Danne T, Phillip M, Buckingham BA, Jarosz-Chobot P, Saboo B, Urakami T, Battelino T, Hanas R, Codner E. ISPAD Clinical Practice Consensus Guidelines 2018: Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2018; 19 Suppl 27:115-135. [PMID: 29999222 DOI: 10.1111/pedi.12718] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 07/01/2018] [Indexed: 12/15/2022] Open
Affiliation(s)
- Thomas Danne
- Kinder- und Jugendkrankenhaus AUF DER BULT, Diabetes-Zentrum für Kinder und Judendliche, Hannover, Germany
| | - Moshe Phillip
- The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Bruce A Buckingham
- Department of Pediatric Endocrinology, Stanford University, Stanford, California
| | | | - Banshi Saboo
- Department of Endocrinology, DiaCare - Advance Diabetes Care Center, Ahmedabad, India
| | - Tatsuhiko Urakami
- Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan
| | - Tadej Battelino
- Department Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital Ljubljana, and Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Ragnar Hanas
- Department of Pediatrics, NU Hospital Group, Uddevalla, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
| | - Ethel Codner
- Institute of Maternal and Child Research (IDMI), School of Medicine, University de Chile, Santiago, Chile
| |
Collapse
|
|
7
|
Bhurayanontachai R, Rattanaprapat T, Kongkamol C. Comparison of Glycemic Control between Continuous Regular Insulin Infusion and Single-dose Subcutaneous Insulin Glargine Injection in Medical Critically Ill Patients. Indian J Crit Care Med 2018; 22:174-179. [PMID: 29657375 PMCID: PMC5879860 DOI: 10.4103/ijccm.ijccm_273_17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Background and Aims: This study aimed to compare glycemic control between continuous intravenous regular insulin infusion and single-dose subcutaneous insulin glargine injection in medical critically ill patients. Subjects and Methods: A prospective noninferiority study was conducted in medical critically ill patients who developed hyperglycemia and required regular insulin infusion by the Intensive Care Unit glycemic control protocol. The eligible patients were switched from the daily regular insulin requirement to single-dose subcutaneous insulin glargine injection by a 100% conversion dose. Arterial blood glucose was checked every 2 h for 24 h. Success cases were blood glucose levels of 80–200 mg/dL during the study period. The mean time-averaged area under the curves (AUCs) of blood glucose levels between the two types of insulin were compared by t-test. Results: Of 20 cases, 14 cases (70%) were successful. The mean time-averaged AUCs of blood glucose levels between the two types of insulin were not significantly different (155.91 ± 27.54 mg/dL vs. 151.70 ± 17.07 mg/dL, P = 0.56) and less than the predefined noninferior margin. No severe hypoglycemic cases were detected during the study period. Conclusions: Single-dose subcutaneous insulin glargine injection was feasibly applied for glycemic control in medical critically ill patients. The glycemic control in the critically ill patients by a single dose of subcutaneous insulin glargine was comparable to standard intravenous regular insulin infusion. A conversion dose of 100% of the daily requirement of regular insulin is suggested.
Collapse
Affiliation(s)
- Rungsun Bhurayanontachai
- Division of Critical Care Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand.,Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Tharittamon Rattanaprapat
- Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Chanon Kongkamol
- Research Unit of Holistic Health and Safety Management in Community, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| |
Collapse
|
|
8
|
Selvakumar D, Al-Sallami HS, de Bock M, Ambler GR, Benitez-Aguirre P, Wiltshire E, Tham E, Simm P, Conwell LS, Carter PJ, Albert BB, Willis J, Wheeler BJ. Insulin regimens for newly diagnosed children with type 1 diabetes mellitus in Australia and New Zealand: A survey of current practice. J Paediatr Child Health 2017; 53:1208-1214. [PMID: 28727196 DOI: 10.1111/jpc.13631] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 03/27/2017] [Accepted: 05/15/2017] [Indexed: 12/16/2022]
Abstract
AIM There is no consensus on the optimal insulin treatment for children newly diagnosed with type 1 diabetes mellitus (T1DM). The aims of this study were (i) to describe the insulin regimens used at diagnosis by patient age and geographical region and (ii) to explore differences between and within Australia (AU) and New Zealand (NZ) with regards to other aspects of patient management and education. METHODS An online survey of medical professionals caring for children with T1DM in AU and NZ was undertaken. Questions included clinic demographics, insulin regimen/dosing choices and patient education. RESULTS Of 110 clinicians identified, 100 responded (91%). The majority of those in AU (69%, P < 0.0001) favour multiple daily injections (MDI) for all ages. In NZ, for patients < 10 years old, (twice daily (BD)) BD therapy was favoured (75%, P < 0.0001), with MDI dominant for ages ≥ 10 years (82%, P < 0.0001). Insulin pump therapy was never considered at diagnosis in NZ, but 38% of clinicians in AU considered using pumps at diagnosis in patients <2 years, but rarely in patients aged 2 and over (16%). Differences in clinician choices were also seen in relation to starting insulin dose. CONCLUSION This is the first study to examine current clinical practice with regards to children newly diagnosed with T1DM. Practice varies across Australasia by clinician and region. This lack of consensus is likely driven by ongoing debates in the current paediatric diabetes evidence base as well as by differences in clinician/centre preference, variations in resourcing and their interpretations of the influence of various patient factors.
Collapse
Affiliation(s)
| | | | - Martin de Bock
- Department of Paediatric and Child Health, Princess Margaret Hospital, Perth, Western Australia, Australia
| | - Geoffrey R Ambler
- Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney, New South Wales, Australia
| | - Paul Benitez-Aguirre
- Institute of Endocrinology and Diabetes, Children's Hospital at Westmead and University of Sydney, Sydney, New South Wales, Australia
| | - Esko Wiltshire
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
| | - Elaine Tham
- Department of Endocrinology and Diabetes, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - Peter Simm
- Department of Endocrinology and Diabetes, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
| | - Louise S Conwell
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia.,Department of Endocrinology and Diabetes, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia
| | - Phillipa J Carter
- Starship Paediatric Diabetes and Endocrinology, Starship Children's Health, Auckland, New Zealand
| | - Benjamin B Albert
- Starship Paediatric Diabetes and Endocrinology, Starship Children's Health, Auckland, New Zealand
| | - Jinny Willis
- Don Beaven Medical Research Centre, Christchurch, New Zealand
| | - Benjamin J Wheeler
- Department of Women's and Children's Health, University of Otago, Dunedin, New Zealand
| | | |
Collapse
|
|
9
|
Laranjeira FO, da Silva EN, Pereira MG. Budget Impact of Long-Acting Insulin Analogues: The Case in Brazil. PLoS One 2016; 11:e0167039. [PMID: 27907034 PMCID: PMC5132224 DOI: 10.1371/journal.pone.0167039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 11/08/2016] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system. OBJECTIVE To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin. METHODS We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0-14 and 20-79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses. RESULTS The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact. CONCLUSIONS The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is established as an economically sustainable strategy. Clinical guidelines restricting the use of insulin analogues would make the decision towards insulin analogue coverage more affordable.
Collapse
|
|
10
|
Onda Y, Nishimura R, Ando K, Takahashi H, Tsujino D, Utsunomiya K. Comparison of glycemic variability in Japanese patients with type 1 diabetes receiving insulin degludec versus insulin glargine using continuous glucose monitoring: A randomized, cross-over, pilot study. Diabetes Res Clin Pract 2016; 120:149-55. [PMID: 27562434 DOI: 10.1016/j.diabres.2016.07.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Revised: 06/10/2016] [Accepted: 07/31/2016] [Indexed: 10/21/2022]
Abstract
AIMS To compare glucose variability in patients with type 1 diabetes (T1D) treated with insulin glargine (IGla) versus insulin degludec (IDeg) using continuous glucose monitoring (CGM). METHODS Thirteen patients with T1D were randomly assigned to receive IDeg once-daily followed by IGla twice-daily or vice versa. They were evaluated for glucose variability by CGM after >4weeks of treatment with either insulin, and then were crossed over to the other, and evaluated by CGM after >4weeks. RESULTS The total daily insulin dose (TDD) (U/kg/day) and the total daily basal insulin dose (U/kg/day) in the patients were significantly lower while taking IDeg than while taking IGla (mean [95% confidence interval] 0.72 [0.61-0.83] vs. 0.76 [0.64-0.88]; P=0.001, 0.29 [0.22-0.36] vs. 0.33 [0.26-0.40]; P=0.001), although no significant difference was noted in the patients while on IDeg versus while on IGla in 24-h mean glucose and SDs of 24-h glucose. Again, the range of postprandial glucose increase was not significantly different between the meals in the patients while taking IDeg (P=0.288) but significantly different in the patients while taking IGla (P=0.033). CONCLUSIONS The use of once-daily IDeg leads not only to similar glycemic control to that seen with twice-daily IGla even in those who received IGla prior to the study, but also to significant decreases in TDD and long-acting basal insulin dose.
Collapse
Affiliation(s)
- Yoshiko Onda
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Rimei Nishimura
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan; Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261, USA.
| | - Kiyotaka Ando
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Hiroshi Takahashi
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Daisuke Tsujino
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Kazunori Utsunomiya
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan
| |
Collapse
|
|
11
|
Abstract
Technological innovations have revolutionized the treatment of type 1 diabetes. Although technological advances can potentially improve diabetes outcomes, maintenance of target glycemic control, at the present time, remains largely dependent on patient and family motivation, competence, and adherence to daily diabetes care requirements. Trials of closed loop or "artificial pancreas" technology show great promise to automate insulin delivery and achieve near normal glucose control and reduced hypoglycemia with minimal patient intervention.
Collapse
Affiliation(s)
- Katharine Garvey
- Division of Endocrinology, Department of Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA.
| | - Joseph I Wolfsdorf
- Division of Endocrinology, Department of Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA
| |
Collapse
|
|
12
|
Danne T, Bangstad HJ, Deeb L, Jarosz-Chobot P, Mungaie L, Saboo B, Urakami T, Battelino T, Hanas R. ISPAD Clinical Practice Consensus Guidelines 2014. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2014; 15 Suppl 20:115-34. [PMID: 25182312 DOI: 10.1111/pedi.12184] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Accepted: 06/16/2014] [Indexed: 02/03/2023] Open
Affiliation(s)
- Thomas Danne
- Kinder- und Jugendkrankenhaus auf der Bult, Diabetes-Zentrum für Kinder und Judendliche, Hannover, Germany
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
13
|
Danne T, Philotheou A, Goldman D, Guo X, Ping L, Cali A, Johnston P. A randomized trial comparing the rate of hypoglycemia--assessed using continuous glucose monitoring--in 125 preschool children with type 1 diabetes treated with insulin glargine or NPH insulin (the PRESCHOOL study). Pediatr Diabetes 2013; 14:593-601. [PMID: 23730996 DOI: 10.1111/pedi.12051] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2013] [Revised: 03/21/2013] [Accepted: 04/18/2013] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Avoidance of hypoglycemia is a key consideration in treating young children with type 1 diabetes (T1DM). KEY OBJECTIVE To evaluate hypoglycemia with insulin glargine vs. neutral protamine Hagedorn (NPH) insulin in young children, using continuous glucose monitoring (CGM). SUBJECTS Children of 1 to <6 yr treated with once-daily glargine vs. once- or twice-daily NPH, with bolus insulin lispro/regular human insulin provided to all. METHODS Twenty-four week, multicenter, randomized, open-label study. Primary endpoint was event rate of composite hypoglycemia [symptomatic hypoglycemia, low CGM excursions (<3.9 mmol/L) or low fingerstick blood glucose (FSBG; <3.9 mmol/L)]. Noninferiority of glargine vs. NPH was assessed for the primary endpoint. RESULTS One hundred and twenty-five patients (mean age, 4.2 yr) were randomized to treatment (glargine, n = 61; NPH, n = 64). At baseline, mean HbA1c was 8.0 and 8.2% with glargine and NPH, respectively. Composite hypoglycemia episodes/100 patient-yr was 1.93 for glargine and 1.69 for NPH; glargine noninferiority was not met. Events/100 patient-yr of symptomatic hypoglycemia were 0.26 for glargine vs. 0.33 for NPH; low CGM excursions 0.75 vs. 0.72; and low FSBG 1.93 vs.1.68. There was a slight difference in between-group severe/nocturnal/severe nocturnal hypoglycemia and glycemic control. All glargine-treated patients received once-daily injections; on most study days NPH-treated patients received twice-daily injections. CONCLUSIONS While glargine noninferiority was not achieved, in young children with T1DM, there was a slight difference in hypoglycemia outcomes and glycemic control between glargine and NPH. Once-daily glargine may therefore be a feasible alternative basal insulin in young populations, in whom administering injections can be problematic.
Collapse
Affiliation(s)
- Thomas Danne
- Kinder- und Jugendkrankenhaus "AUF DER BULT", Hannover, Germany
| | | | | | | | | | | | | |
Collapse
|
|
14
|
Kim J, Kim SM, Nguyen HCT, Redondo MJ. Therapeutics in pediatric diabetes: insulin and non-insulin approaches. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni. Pharmacol Res 2011; 65:1-4. [PMID: 21930210 DOI: 10.1016/j.phrs.2011.08.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2011] [Accepted: 08/29/2011] [Indexed: 12/29/2022]
Abstract
Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analogues and delivery devices such as continuous subcutaneous insulin infusion (CSII, insulin pump) may reduce hypoglycemia and improve glycemic control. CSII combined with continuous glucose monitoring can achieve even better glycemic control. The closed-loop system is rapidly evolving and an artificial pancreas will be available in the near future. It is now recognized that several hormones other than insulin such as glucagon, amylin, and incretins contribute to glucose homeostasis. The role of co-adjuncts such as metformin, amylin analogues, and incretin based therapy is now emerging. Immunotherapy in a high risk population or patients in the early phase of type 1 diabetes may prevent further destruction of pancreatic β cells.
Collapse
Affiliation(s)
- Jongoh Kim
- Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX, United States.
| | | | | | | |
Collapse
|
|
15
|
Abstract
The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal-bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults.
Collapse
Affiliation(s)
- Satish Garg
- Barbara Davis Campus for Childhood Diabetes, University of Colorado-Denver, 1775 Aurora Court, Aurora, CO 80045, USA.
| | | | | | | |
Collapse
|
|
16
|
Abstract
In paediatric diabetes, the concept of intensive therapy in the post-Diabetes Control and Complications Trial period has become subverted by a pharmaco-technological paradigm at the expense of other aspects of care such as goal-setting and psychosocial support. This review examines which patients benefit most from intensive therapy in terms of glycaemic control (HbA1c). It also reviews published controlled trial and observational data relating to the impact of various insulin types and delivery systems on glycaemic control and canvasses the literature dealing with the impact of patient support, philosophy of care, goal setting and treating team dynamic on HbA1c. Taking into account the characteristics of those patients who benefit most from intensive therapy, the quantum of HbA1c change and the persistence of changes that have been reported in selected and non-selected patient groups, it appears that there is a clear hierarchy in aspects of therapy that improve glycaemic control for children and adolescents with Type 1 diabetes. Prime issues appear to be patient support, team cohesion and goal setting. The reported glycaemic benefits achieved by an isolated emphasis upon a pharmaco-technological paradigm are limited in children and adolescents. It appears that only after the prime issues have been first considered will the potential benefits of the insulin types and regimens then be realized.
Collapse
Affiliation(s)
- T C Skinner
- Combined Universities Centre for Rural Health, Geraldton, Western Australia, Australia
| | | |
Collapse
|
|
17
|
Bangstad HJ, Danne T, Deeb L, Jarosz-Chobot P, Urakami T, Hanas R. Insulin treatment in children and adolescents with diabetes. Pediatr Diabetes 2009; 10 Suppl 12:82-99. [PMID: 19754621 DOI: 10.1111/j.1399-5448.2009.00578.x] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
|
|
18
|
Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract 2008; 81:184-9. [PMID: 18495286 DOI: 10.1016/j.diabres.2008.04.007] [Citation(s) in RCA: 147] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2008] [Accepted: 04/07/2008] [Indexed: 12/11/2022]
Abstract
BACKGROUND Long-acting insulin analogues, in comparison with NPH insulin, should warrant a greater reproducibility of absorption after subcutaneous injection, providing better metabolic control with reduced hypoglycaemic risk. Aim of the present meta-analysis is the assessment of differences with respect to HbA1c, incidence of hypoglycaemia, weight gain, between NPH human insulin and each long-acting analogue. METHODS All randomized controlled trials (RCTs) with a duration >12 weeks comparing long-acting insulin analogues (detemir or glargine) with NPH insulin in type 2 diabetic patients were retrieved; data on HbA1c and BMI at endpoint, and incidence of any, symptomatic, nocturnal, and severe hypoglycaemia, were extracted and meta-analysed. RESULTS A total of 14 RCTs was retrieved and included in the analysis. Long-acting analogues did not produce any significant improvement of HbA1c, in comparison with NPH human insulin. When trials with different analogues were analysed separately, NPH showed a significant superiority (by 0.1%) over detemir, but not over glargine. When analysing the effect of long-acting analogues on body weight, detemir, but not glargine, was associated with a significantly smaller weight gain than human insulin Both analogues were associated with a reduced risk for nocturnal and symptomatic hypoglycaemia (OR: 0.46[0.38-0.55] and 0.69[0.60-0.80]; all p<0.01). CONCLUSIONS Long-acting insulin analogues in type 2 diabetic patients does not seem to provide a better glycemic control in comparison with NPH insulin, whereas it reduces the risk of nocturnal and symptomatic hypoglycemia. Detemir, but not glargine, could be associated with smaller weight gain than NPH insulin.
Collapse
Affiliation(s)
- Matteo Monami
- Section of Geriatric Cardiology, Department of Cardiovascular Medicine, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141 Florence, Italy
| | | | | |
Collapse
|
|
19
|
Vardi M, Jacobson E, Nini A, Bitterman H. Intermediate acting versus long acting insulin for type 1 diabetes mellitus. Cochrane Database Syst Rev 2008; 2008:CD006297. [PMID: 18646147 PMCID: PMC6486116 DOI: 10.1002/14651858.cd006297.pub2] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Diabetes mellitus type 1 is a chronic disease with short and long term complications. Its goals of therapy are to eliminate the symptoms of hyperglycaemia, reduce the long term microvascular and macrovascular complications and allow the patients to achieve a normal life-style. Basal insulin replacement for insulin dependent patients can be achieved with either intermediate or long acting insulin preparations. OBJECTIVES To assess the effects of intermediate acting versus long acting insulin preparations for basal insulin replacement in type 1 diabetic patients. SEARCH STRATEGY We searched MEDLINE, EMBASE and The Cochrane Library, as well as reference lists, databases of ongoing trials, and requests from authors of included trials. SELECTION CRITERIA Randomised controlled trials, assessing long acting insulin preparations compared to intermediate acting insulin preparations, in type 1 diabetic patients. DATA COLLECTION AND ANALYSIS Two reviewers independently scanned the titles. Data were extracted and analysed accordingly. MAIN RESULTS Twenty-three randomised controlled trials were identified. A total of 3872 and 2915 participants in the intervention and in the control group, respectively, were analysed. The weighted mean difference (WMD) for the level of glycosylated haemoglobin was -0.08 (95% confidence interval (CI) -0.12 to -0.04) in favour of the long acting insulin arm. The WMD between the groups in fasting plasma and blood glucose levels was -0.63 (95% CI -0.86 to -0.40) and -0.86 (95% CI -1.00 to -0.72) in favour of the long acting insulins. The odds ratio for a patient on long acting insulin to develop any type of hypoglycaemia was 0.93 (95% CI 0.8 to 1.08) compared to that of a patient on intermediate acting insulins. The OR for severe hypoglycaemic episodes was 0.73 (95% CI 0.61 to 0.87), and 0.70 (95% CI of 0.63 to 0.79) for nocturnal episodes. The WMD between the long and intermediate insulin groups for hypoglycaemic events per 100 patient follow up days was -0.77 (95% CI -0.89 to -0.65), -0.0 (95% CI -0.02 to 0.02) and -0.40 (95% CI -0.45 to -0.34) for overall, severe, and nocturnal hypoglycaemic episodes. Weight gain was more prominent in the control group. No difference was noted in the quantity or quality of severe adverse events or deaths. AUTHORS' CONCLUSIONS Long acting insulin preparations seem to exert a beneficial effect on nocturnal glucose levels. Their effect on the overall diabetes control is clinically unremarkable. Their use as a basal insulin regimen for type 1 diabetes mellitus warrants further substantiation.
Collapse
Affiliation(s)
- Moshe Vardi
- Internal Medicine, Carmel Medical Center, 7 Michal St, Haifa, Haifa, Israel, 34362.
| | | | | | | |
Collapse
|
|
20
|
|
|
21
|
Abstract
Since the findings of the Diabetes Control and Complications Trial became public in 1993, intensive insulin therapy has been recommended for all children. However, successful implementation remains a challenge because of developmental, physiological and cultural, as well as practical issues specific to the pediatric population. This article reviews the different insulin regimens that are currently available, from the short- and intermediate-acting insulins to the newer insulin analogs, focusing on insulin therapies that attempt to provide a more physiologic basal-bolus approach to treatment. More and more children are on multiple daily injection regimens or using continuous subcutaneous insulin infusion to achieve better metabolic control. The achievement of optimal glycemic control in children is complicated by their variability in eating habits and activity levels and perhaps more importantly by the risk of hypoglycemia. The hope is that new technologies including continuous subcutaneous glucose monitoring and perhaps a closed-loop system in the near future will help us achieve more optimal glycemic targets in children without increased side effects. In addition, continuous glucose monitoring may teach us better ways to use insulin in children who do not have the technology available to them.
Collapse
Affiliation(s)
- Andrea K Steck
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Denver, CO, USA
| | | | | |
Collapse
|
|
22
|
Abstract
A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.
Collapse
Affiliation(s)
- Stephen C L Gough
- Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK.
| |
Collapse
|
|
23
|
Deiss D, Kordonouri O, Hartmann R, Hopfenmüller W, Lüpke K, Danne T. Treatment with insulin glargine reduces asymptomatic hypoglycemia detected by continuous subcutaneous glucose monitoring in children and adolescents with type 1 diabetes. Pediatr Diabetes 2007; 8:157-62. [PMID: 17550426 DOI: 10.1111/j.1399-5448.2007.00252.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE Unsatisfactory basal insulin substitution may lead to asymptomatic hypoglycemia in children and adolescents with type 1 diabetes (T1D). To investigate the effects of multiple daily injections before and after changing to insulin glargine (IG), continuous glucose monitoring system (CGMS) data were used to analyze glycemic control and hypoglycemic episodes during the two different therapy regimens. METHODS Basal insulin therapy was changed to one daily injection of IG in 30 pediatric patients with T1D (14 boys and 16 girls; age 4.5-18.3 yr, median 14.2 yr; diabetes duration 0.5-15.6 yr, median 4.6 yr) having elevated fasting glucose or recurrent hypoglycemia despite treatment with multiple injection therapy (basal insulin: two to four injections of neutral protamine Hagedorn (NPH) and/or zinc lente insulin). Ambulatory CGMS was applied before and 6-8 wk after treatment change. Frequency of hypoglycemic and hyperglycemic episodes, glucose area under the curve (AUC), and time below 60 mg/dL and above 180 mg/dL, respectively, were calculated from CGMS data during the day (8:00-22:00 hours) and at night (22:00-8:00 hours). RESULTS Nocturnal hypoglycemia was detected by CGMS in 20 patients before and in 12 patients after the change to IG (p = .039), whereas both, the number of nocturnal and diurnal hypoglycemic episodes, decreased not significantly from 41 to 36 (p = .758) and 48 to 28 (p = .055), respectively. AUC and time below 60 mg/dL as well as hemoglobin A1c (HbA1c) were not significantly different before and after the change to IG. CONCLUSION Under treatment with IG, asymptomatic hypoglycemia was reduced without increase of HbA1c.
Collapse
Affiliation(s)
- Dorothee Deiss
- Clinic of General Pediatrics, Otto-Heubner-Centrum, Charité, Campus Virchow-Klinikum, Humboldt University, Berlin, Germany.
| | | | | | | | | | | |
Collapse
|
|
24
|
Bangstad HJ, Danne T, Deeb LC, Jarosz-Chobot P, Urakami T, Hanas R. ISPAD Clinical Practice Consensus Guidelines 2006-2007. Insulin treatment. Pediatr Diabetes 2007; 8:88-102. [PMID: 17448131 DOI: 10.1111/j.1399-5448.2007.00233.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
|
|
25
|
Abstract
Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time–action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients.
Collapse
Affiliation(s)
- Anthony H Barnett
- Birmingham Heartlands Hospital, Undergraduate Centre, Birmingham, West Midlands, England, UK.
| |
Collapse
|
|
26
|
Karges B, Muche R, Riegger I, Moritz M, Heinze E, Debatin KM, Wabitsch M, Karges W. Injection of acidic or neutral insulin and pain: A single-center, prospective, controlled, noninterventional study in pediatric patients with type 1 diabetes mellitus. Clin Ther 2006; 28:2094-101. [PMID: 17296465 DOI: 10.1016/j.clinthera.2006.12.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/31/2006] [Indexed: 11/24/2022]
Abstract
BACKGROUND Pain resulting from injections has a potential influence on the acceptance and thus on the success of insulin treatment. Systematic investigation in humans has suggested that individuals perceive more pain during SC injection of acidic solutions than neutral solutions. Insulin glargine is a long-acting (up to 24-hour duration of effect), parenteral blood glucose-lowering agent. Unlike other insulins, it is injected as an acidic solution (pH 4). OBJECTIVE The aim of this study was to assess whether the SC injection of insulin glargine is more painful than neutral insulin in a clinical setting. METHODS This single-center, prospective, controlled, noninterventional study was performed in consecutively enrolled male and female pediatric patients (7-21 years) with type 1 diabetes mellitus who self-injected insulin >or=3 times per day and who had diabetes duration of >or=6 months. The study was conducted from September 1, 2005, to December 30, 2005, at the Diabetes Clinic, University Children's Hospital, Ulm, Germany. No changes to the patients' current insulin regimen were made. Based on their existing insulin treatment, patients were assigned to 1 of 2 treatment groups: (1) the acidic insulin group, which injected insulin glargine, and (2) the neutral insulin group, which injected neutral protamine Hagedorn or Semilente insulin. All patients also injected shortacting regular insulin or insulin analogs. Pain during SC insulin injection and during self-monitoring of blood glucose (SMBG) (the internal control) was assessed using a standardized, noninterventional protocol and optimized combined 10-cm visual analog scale and 5-point verbal rating scale (minimum = I cannot feel it at all; maximum = it hurts me). Patients were instructed to document pain immediately after insulin injection and SMBG at home 3 times a day on 3 different days. RESULTS A total of 112 patients (mean [SD] age, 14.6 [3.0] years; sex, 60 [53.6%] male; mean [SD] glycosylated hemoglobin [HbA(1c)], 8.0% [1.4%]; mean [SD] diabetes duration, 6.1 [3.9] years) completed the study. Pain scores reported by the acidic group (n = 76) were not significantly different when compared with those of the neutral group (n = 36) (4.0 [2.0] vs 4.2 [1.9]). Pain scores were also similar for the injection of short-acting insulin in those from the acidic group when compared with those from the neutral group (3.7 [1.7] vs 4.1 [2.1]). Insulin injections were generally perceived as more painful than SMBG (3.9 [1.7] vs 2.9 [1.8]; P < 0.001). Using the Spearman rank correlation coefficient, pain perception was determined to be independent of age, gender, HbA(1c) level, and duration of diabetes. CONCLUSION Despite its acidic formulation (pH 4), insulin glargine was not perceived as more painful during SC injection than neutral long-acting or shortacting insulin in these pediatric patients with type 1 diabetes mellitus.
Collapse
Affiliation(s)
- Beate Karges
- Division of Pediatric Endocrinology and Diabetes, University Children's Hospital, University o f Ulm, Ulm, Germany.
| | | | | | | | | | | | | | | |
Collapse
|
|
27
|
Karagüzel G, Satilmiş A, Akçurin S, Bircan I. Comparison of breakfast and bedtime administration of insulin glargine in children and adolescents with Type 1 diabetes. Diabetes Res Clin Pract 2006; 74:15-20. [PMID: 16621116 DOI: 10.1016/j.diabres.2006.03.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2005] [Accepted: 03/09/2006] [Indexed: 10/24/2022]
Abstract
OBJECTIVE The purpose of this study was to evaluate the effect of administration time of insulin glargine (IG) on glycemic control in children and adolescents with Type 1 diabetes. MATERIALS AND METHODS A total of 31 children and adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime NPH and premeal insulin aspart) were randomized to receive once-daily IG either at breakfast (breakfast group, n=15) or bedtime (bedtime group, n=16) while continuing insulin aspart premeals for 6 months. Blood glucose levels were measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body mass index (BMI), glycosylated hemoglobin (HbA(1c)), and frequency of hypoglycemia in the preceding 3 months were assessed at recruitment, third month and sixth month. RESULTS The dose of IG, TDD, and fasting blood glucose levels were similar in both groups during the study period. The only significant difference in blood glucose levels between breakfast and bedtime groups was found for dinnertime at 6 months (135+/-26mg/dl versus 161+/-33mg/dl, respectively, p=0.035). In the breakfast group, the mean HbA(1c) level was significantly lower than that of baseline at month 6 (9.4+/-2.5% versus 8.0+/-0.9%, respectively, p=0.022), whereas there was no significant change in the bedtime group (9.2+/-2.1% versus 8.9+/-2.2%, respectively). The frequency of hypoglycemia was lower with IG than NPH (2.7+/-2.8/6 months versus 6.4+/-6.7/6 months, respectively, p=0.008). CONCLUSIONS Once-daily IG at breakfast in children and adolescents with Type 1 diabetes on intensive therapy is more efficacious than bedtime administration to improve metabolic control. Also, the number of hypoglycaemic events decreased with both breakfast and bedtime administrations of IG.
Collapse
Affiliation(s)
- Gülay Karagüzel
- Pediatric Endocrinolog, Akdeniz University, School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Antalya, Turkey.
| | | | | | | |
Collapse
|
|
28
|
Abstract
Insulin detemir (Levemir, Novo Nordisk) is a novel, biologically engineered analogue of human insulin that has been successfully developed for clinical use in diabetes as a basal insulin. Its unique mechanism of prolongation of action, achieved through acylation to give reversible albumin binding and additional self-association, goes some way to addressing one of the fundamental limitations of previously available, subcutaneously administered basal insulins, a high level of within-person variability in time-action profile from one injection to another. The pharmacological profile of insulin detemir, characterised in a series of studies, suggested it had the potential to offer efficacy and tolerability advantages in the clinical setting. Such advantages, in comparison to NPH (neutral protamine Hagedorn) insulin, have subsequently been illustrated in trials. Despite glucose control targets that are identical to comparators, insulin detemir achieved levels of glycaemic control that, overall, were at least as good as NPH insulin in the Phase III development programme, with lower variability being a consistent finding. This was associated with consistent risk reductions in nocturnal hypoglycaemic events, which are closely linked with the basal component of insulin therapy. Another consistent finding has been a significantly reduced propensity for weight gain. An all-analogue regimen combining insulin detemir with the rapid-acting insulin aspart illustrated the potential benefits achievable when insulins that are designed to achieve defined pharmacokinetic profiles are employed clinically; blood glucose control, including hypoglycaemia, was significantly superior to a human insulin-based mealtime plus basal regimen. Insulin detemir is, therefore, a valuable addition to the range of exogenous insulins, as it should enable treatment regimens to be constructed that offer good outcomes of efficacy and tolerability.
Collapse
Affiliation(s)
- Philip Home
- School of Clinical Medical Sciences--Diabetes, University of Newcastle upon Tyne, Framlington Place, NE2 4HH, UK.
| | | |
Collapse
|
|
29
|
Colino E, López-Capapé M, Golmayo L, Alvarez MA, Alonso M, Barrio R. Therapy with insulin glargine (Lantus) in toddlers, children and adolescents with type 1 diabetes. Diabetes Res Clin Pract 2005; 70:1-7. [PMID: 16126116 DOI: 10.1016/j.diabres.2005.02.004] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2004] [Revised: 01/05/2005] [Accepted: 02/10/2005] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To determine the efficacy and safety of insulin glargine (IG) in children and adolescents with type 1 diabetes. In a prospective, 6-month study, 80 patients, aged 2-19 years, received IG once daily plus insulin regular or rapid analogue before meals. The data of body mass index, frequency of severe hypoglycaemia, daily mean blood glucose, fasting blood glucose, haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected. RESULTS After 6 months, the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70% (p<0.001). Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl (p<0.05) in the total group. Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy. The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day (p<0.05). Body mass index (BMI) remained unchanged. In the 14 preschooler children, the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57% (p<0.05). CONCLUSIONS Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes. It also improved the metabolic control in preschool-age children, without increasing the number of hypoglycaemic events.
Collapse
Affiliation(s)
- E Colino
- Paediatric Diabetes Unit, Department of Paediatrics, Hospital Ramón y Cajal, Crta de Colmenar Km. 9.1, 28034 Madrid, Spain
| | | | | | | | | | | |
Collapse
|
|
30
|
Weinzimer SA, Doyle EA, Tamborlane WV. Disease management in the young diabetic patient: glucose monitoring, coping skills, and treatment strategies. Clin Pediatr (Phila) 2005; 44:393-403. [PMID: 15965545 DOI: 10.1177/000992280504400503] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Type 1 diabetes mellitus was thought to be the prevalent type of diabetes in children and adolescents; however, increasing numbers of juvenile patients appear to have type 2 diabetes. Management of all diabetes in young patients should include regular assessment, careful monitoring for glycemic control and the presence of hypoglycemia, and educational training on disease management. Hypoglycemic episodes, especially nocturnal events, are frequent in the young diabetic patient. Improvements in glycemic control and nocturnal hypoglycemia have been observed with continuous subcutaneous insulin infusion and insulin glargine. A continuous glucose-monitoring system can provide important insight into 24-hour glycemic control. Overall, careful management, monitoring, and education can improve glycemic control and yield positive treatment outcomes in the child or adolescent with diabetes.
Collapse
MESH Headings
- Adaptation, Psychological
- Adolescent
- Adolescent Behavior
- Adult
- Age Factors
- Aged
- Attitude to Health
- Blood Glucose/analysis
- Blood Glucose Self-Monitoring/standards
- Blood Glucose Self-Monitoring/trends
- Child
- Diabetes Mellitus, Type 1/diagnosis
- Diabetes Mellitus, Type 1/drug therapy
- Diabetes Mellitus, Type 1/epidemiology
- Diabetes Mellitus, Type 1/psychology
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/epidemiology
- Diabetes Mellitus, Type 2/psychology
- Female
- Humans
- Hypoglycemic Agents/administration & dosage
- Injections, Subcutaneous
- Insulin/therapeutic use
- Insulin Resistance
- Male
- Middle Aged
- Patient Compliance
- Patient Education as Topic/methods
- Prognosis
- Risk Assessment
- Severity of Illness Index
- Treatment Outcome
Collapse
Affiliation(s)
- Stuart A Weinzimer
- Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA
| | | | | |
Collapse
|
|
31
|
Rungby J, Brock B, Schmitz O. New strategies in insulin treatment: analogues and noninvasive routes of administration. Fundam Clin Pharmacol 2005; 19:127-32. [PMID: 15810892 DOI: 10.1111/j.1472-8206.2004.00306.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes.
Collapse
Affiliation(s)
- Jørgen Rungby
- Department of Clinical Pharmacology and Departments of Endocrinology C & M, Aarhus University Hospital, Bartholin Bldn., University of Aarhus, DK-8000 Aarhus C, Denmark.
| | | | | |
Collapse
|
|
32
|
Abstract
The medical community faces an emerging epidemic of type 2 diabetes mellitus (DM2) in children and adolescents with a disproportionate increase among certain ethnic groups. DM2 represents one arm of the metabolic syndrome and parallels an increasing prevalence of obesity. The metabolic syndrome includes insulin resistance, hyperlipidemia, and hypertension with a consequent risk of early cardiovascular disease. Thus, treatment of DM2 and the metabolic syndrome poses a challenge for pediatric endocrinologists and represents a huge public health issue. This review presents information about treatment of childhood DM2 with emphasis on indications for the use of insulin in management and normalization of blood glucose.
Collapse
Affiliation(s)
- Jennifer L Miller
- Division of Pediatric Endocrinology, University of Florida, Gainesville, FL 32610-0296, USA
| | | |
Collapse
|
|
33
|
Abstract
UNLABELLED The management of diabetes in children presents a number of challenges. The ideal is to achieve optimal glycaemic control using an insulin regimen that is acceptable to the child and family, which improves glycaemic control, whilst avoiding hypoglycaemia. The paediatric population differ from their adult counterparts in several ways, such as variability of exercise and eating patterns, and the hormonal influences of puberty, which means that the insulin regimen must be tailored to suit an individual child and their family. CONCLUSION This review will focus on the particular difficulties of managing diabetes in children and, in particular, the problem of avoiding hypoglycaemia while maintaining adequate glycaemic control.
Collapse
Affiliation(s)
- R M Williams
- Department of Paediatrics, University of Cambridge, Cambridge, UK
| | | |
Collapse
|
|
34
|
Allen KV, Frier BM. Nocturnal hypoglycemia: clinical manifestations and therapeutic strategies toward prevention. Endocr Pract 2004; 9:530-43. [PMID: 14715482 DOI: 10.4158/ep.9.6.530] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To review the features of nocturnal hypoglycemia and various preventive strategies. METHODS We discuss the physiologic changes, the potential precipitating factors, the immediate and long-term effects, and the currently available options for treatment of nocturnal hypoglycemia in patients with diabetes. RESULTS Nocturnal hypoglycemia is common in patients with type 1 diabetes and is usually asymptomatic. Nocturnal hyperinsulinemia frequently occurs with insulin therapy, and although blood glucose levels are often low during sleep, they are seldom measured routinely. Almost 50% of all episodes of severe hypoglycemia occur at night during sleep. Such episodes can cause convulsions and coma and have been implicated as a precipitating factor in cardiac arrhythmias resulting in sudden death--the "dead-in-bed syndrome." Nocturnal hypoglycemia seems to have no immediate detrimental effect on cognitive function; however, on the following day, mood and well-being may be adversely affected. Recurrent exposure to nocturnal hypoglycemia may impair cognitive function; other substantial long-term morbidity includes the development of acquired hypoglycemia syndromes, such as impaired awareness of hypoglycemia, through the putative effect of unsuspected recurrent episodes of nocturnal hypoglycemia. CONCLUSION In efforts to decrease the risk of nocturnal hypoglycemic episodes, various strategies can be used to minimize the nocturnal hyperinsulinemia that is associated with many insulin replacement regimens. Regular blood glucose monitoring (particularly at bedtime), the ingestion of appropriate bedtime snacks, and the utilization of short- and long-acting insulin analogues may all help to prevent or minimize the frequency of nocturnal hypoglycemia.
Collapse
Affiliation(s)
- Kate V Allen
- Department of Diabetes, Royal Infirmary, Edinburgh, Scotland, United Kingdom
| | | |
Collapse
|
|
35
|
Abstract
Type 1 diabetes mellitus in adolescents presents diagnostic and management challenges. Diagnostically, the challenge is to distinguish type 1 from type 2 diabetes. A thin adolescent in diabetic ketoacidosis is easily recognized as having type 1 diabetes. However, since obesity does not negate the presence of type 1 diabetes, it is appropriate to measure diabetes-related antibody, C-peptide, and insulin levels in individuals who are thought to have type 2 diabetes to ensure that they do not have type 1 or a mixed type of diabetes. The goals for the management of type 1 diabetes in adolescents are to (i) prevent diabetic ketoacidosis; (ii) prevent severe hypoglycemia; (iii) maintain normal growth and development; and (iv) prevent long-term diabetic complications. To prevent diabetic ketoacidosis, patients must take their insulin appropriately. To ensure that this happens, increased parental supervision, psychological counseling, or placement in a different home environment may be necessary. All patients must be taught to appropriately manage sick days and test their urine for ketones when hyperglycemia is present. Prevention of severe hypoglycemia involves ensuring that the patient understands the symptoms of hypoglycemia and knows to test and treat it when the signs are present. Patients and families also need to know how to adjust insulin doses to prevent hypoglycemia and how to manage exercise appropriately. Patients with hypoglycemic unawareness need to meticulously avoid hypoglycemia. To maintain normal growth and development, adolescents with type 1 diabetes must have the appropriate tools to effectively match their meals to their lifestyle and to avoid the increased weight gain associated with improved glycemic control without intentionally manipulating their insulin dose to lose weight. The Diabetes Control and Complications Trial demonstrated that improved glycemic control decreased the risk of long-term diabetic complications. The goals of treatment in this study should be the goals for all adolescents with type 1 diabetes. To reach these goals, home glucose monitoring is critical. Patients need to know how to adjust insulin to maintain glucose levels in the range of 70-120 mg/dL (3.9-6.7 mmol/L) before meals. Insulin regimens need to be individually tailored to meet each patient's needs. Patients should be followed in a clinic using a multidisciplinary team approach at least every 3 months. Glycosylated hemoglobin should be measured at each visit. Regular eye exams, blood pressure monitoring, and urinary microalbumin measurements are critical. In this manner, the goals of management of type 1 diabetes in adolescents can be met.
Collapse
Affiliation(s)
- Robert P Hoffman
- Department of Pediatrics, The Ohio State University College of Medicine and Public Health, Columbus, Ohio, USA.
| |
Collapse
|
|
36
|
Abstract
Tight glycaemic control (ideally, HbA1c<7%) is central to reducing the risk of long-term complications of diabetes. This approach, for both Type 1 and Type 2 diabetes, commonly involves the use of basal insulin, and must be achieved with minimal risk of hypoglycaemia (particularly nocturnal episodes). Indeed, concern around hypoglycaemia is a major barrier to achieving tight glycaemic control, and is a common problem with those protracted-acting insulins most frequently used in clinical practice for basal insulin supply. Other drawbacks include inter- and intra-patient variability that compromises dosing reproducibility and unsuitability for single daily dosing. New long-acting human insulin analogues with action profiles designed to overcome these problems are now available in clinical practice or are under evaluation in clinical trials. Clinical evidence suggests efficacy and safety advantages for these analogues over NPH insulin (the most commonly used basal insulin), and may bring closer the goal of tight glycaemic control in patients with diabetes.
Collapse
Affiliation(s)
- Anthony H Barnett
- University of Birmingham and Birmingham Heartlands Hospital, Department of Medicine-Undergraduate Centre, Birmingham, UK.
| |
Collapse
|
|
37
|
Jackson A, Ternand C, Brunzell C, Kleinschmidt T, Dew D, Milla C, Moran A. Insulin glargine improves hemoglobin A1c in children and adolescents with poorly controlled type 1 diabetes. Pediatr Diabetes 2003; 4:64-9. [PMID: 14655261 DOI: 10.1034/j.1399-5448.2003.00014.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
UNLABELLED The pediatric diabetes team at the University of Minnesota made a clinical decision to switch patients with type 1 diabetes with a hemoglobin A1c level greater than 8.0% to insulin glargine in an effort to improve glycemic control. Retrospective chart analysis was performed on 37 patients 6 months after the switch to insulin glargine therapy. RESULTS After 6 months, the average hemoglobin A1c level in the entire cohort dropped from 10.1 +/- 2.0 to 8.9 +/- 1.6% (p = 0.001). Thirty patients responded with an average hemoglobin A1c drop of 1.7 +/- 1.5%, from 10.3 +/- 2.2 to 8.6 +/- 1.5% (p < 0.001). Seven patients did not respond to insulin glargine therapy, with an average hemoglobin A1c rise of 1.0 +/- 0.8% from a baseline of 9.5 +/- 1.0% to 10.4 +/- 1.4% (p = 0.01). The greatest response was seen in children with an A1c > 12.0%, who dropped their hemoglobin A1c by 3.5 +/- 1.9%. Compared with responders, non-responders had significantly less contact with the diabetes team in the form of clinic visits and telephone conversations both before and after initiation of glargine therapy. Sixty-two per cent of patients received insulin glargine at lunchtime, when injections could be supervised at school. Three episodes of severe hypoglycemia occurred after initiation of insulin glargine therapy. CONCLUSIONS Insulin glargine substantially improved glycemic control in children and adolescents with poorly controlled type 1 diabetes. This response was most remarkable in those with a baseline hemoglobin A1c level > 12.0%, and may have been related to increased supervision of injections.
Collapse
Affiliation(s)
- Anne Jackson
- Department of Pediatrics, University of Minnesota, 516 Delaware St. SE, Mpls, MN 55455, USA
| | | | | | | | | | | | | |
Collapse
|
|
38
|
Lam S. Insulin glargine: a new once-daily basal insulin for the management of type 1 and type 2 diabetes mellitus. HEART DISEASE (HAGERSTOWN, MD.) 2003; 5:231-40. [PMID: 12783637 DOI: 10.1097/01.hdx.0000074514.20750.57] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Optimal glucose control is the primary goal for treating diabetes mellitus and preventing long-term complications of diabetes, such as coronary heart disease, nephropathy, neuropathy and retinopathy. Insulin glargine is a novel, long-acting human insulin analog that is indicated in type 1 diabetic patients aged >or=6, or in type 2 diabetic patients who require basal insulin for glycemic control. Insulin glargine is a recombinant insulin with a modified structure that allows it to dissolve in an acidic solution, but to precipitate in the physiological subcutaneous tissue forming a depot effect. In contrast to Neutral Protamine Hagedorn (NPH) insulin, insulin glargine has a slower onset, a longer duration of action, and no peak in metabolic activity. Once-daily subcutaneous administration of insulin glargine at bedtime has comparable efficacy to that of NPH insulin once or twice daily when used in combination with bolus insulin in type 1 diabetic patients, or in conjunction with oral antidiabetic drugs in type 2 diabetic patients. Overall, insulin glargine has similar adverse effects when compared with NPH insulin. Insulin glargine has been associated with less nocturnal hypoglycemia and improved treatment satisfaction in several clinical trials with durations of < 52 weeks. Pharmacoeconomic analysis comparing insulin glargine with other intermediate- or long-acting insulin preparations used as basal insulin therapy has not been performed. In summary, insulin glargine offers a promising alternative as a once-daily basal insulin therapy in patients with type 1 and type 2 diabetes.
Collapse
Affiliation(s)
- Sum Lam
- Geriatric Research, Education & Clinical Center (GRECC), Veterans Affairs Medical Center, Durham, NC, USA.
| |
Collapse
|
|
39
|
Hathout EH, Fujishige L, Geach J, Ischandar M, Maruo S, Mace JW. Effect of therapy with insulin glargine (lantus) on glycemic control in toddlers, children, and adolescents with diabetes. Diabetes Technol Ther 2003; 5:801-6. [PMID: 14633345 DOI: 10.1089/152091503322527003] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
To determine the effect of insulin glargine on glycemic control in pediatric type 1 and 2 diabetes, a retrospective repeated-measure analysis of variance was performed of hemoglobin A1C (HbA1C), frequency of hypoglycemia and hyperglycemia, mean blood glucose, body mass index (BMI), and daily weight-adjusted insulin dosage before and after institution of glargine therapy in 72 children and adolescents with diabetes. At glargine start, age range was 1.2-19.6 years, mean age was 12.5 +/- 4.6 years, BMI was 22.48 +/- 6.3 kg/m(2), and mean HbA1C was 9.7 +/- 1.9%. Mean duration of diabetes was 3.58 years, and mean baseline insulin dose was 0.93 U/kg/day. Gender breakdown was 60% female, and the majority (83%) had type 1 diabetes. Average HbA1C decreased from 9.5% pre-glargine to 8.6% post-glargine (p < 0.001). HbA1C decrease was significant in both types of diabetes without a concomitant increase in frequency of hypoglycemia, BMI, or weight-adjusted insulin dose. Hypoglycemia decreased significantly in type 1 diabetes. Thus, glargine therapy may decrease HbA1C and frequency of hypoglycemia in toddlers, children, and adolescents with diabetes, without an increase in BMI or insulin requirements.
Collapse
Affiliation(s)
- Eba H Hathout
- Pediatric Diabetes Center, Loma Linda University, Loma Linda, California 92354, USA.
| | | | | | | | | | | |
Collapse
|
|
40
|
Abstract
Insulin glargine is an innovative, long-acting human insulin analogue, whose prolonged mean activity profile has no pronounced peak. Accordingly, it mimics more closely the natural physiological profile of basal endogenous insulin secretion than do traditional extended-acting insulins such as NPH insulin. As would be expected for a more satisfactory basal insulin, clinical trials comparing insulin glargine with NPH insulin show less nocturnal hypoglycaemia, improved pre-breakfast blood glucose levels, or both. Furthermore, no substantive safety concerns have emerged for insulin glargine. Thus, insulin glargine represents the first major advance in the provision of basal insulin injection therapy for people with type 1 and type 2 diabetes for over 50 years.
Collapse
Affiliation(s)
- Philip D Home
- Department of Diabetes and Metabolism, University of Newcastle upon Tyne, UK.
| | | |
Collapse
|
|
41
|
Abstract
Hypoglycemia is an inevitable consequence of the treatment of type 1 diabetes in childhood. Nocturnal hypoglycemia is often considered as merely the submerged part of this serious complication yet there are reasons to believe that hypoglycemia occurring during sleep may be different in physiological terms. Glucose homeostasis during fasting, delayed effects of exercise and alterations in sleep physiology, itself, may not only affect the risk of nocturnal hypoglycemia but may influence the ability to correct glucose concentration as it falls, leading to episodes of hypoglycemia which are both profound and prolonged. The etiology and potential repercussions are incompletely understood and the most appropriate defense remains unclear. A greater understanding of this enigmatic phenomenon is essential before appropriate methods for hypoglycemia avoidance can be developed.
Collapse
Affiliation(s)
- Krystyna A Matyka
- Division of Medicine, Division of Medical Sciences, University of Birmingham, Birmingham Heartlands Hospital, Birmingham, UK.
| |
Collapse
|