Continuous Subcutaneous Insulin Infusion Treatment Research Articles

Treatment of Severe Hyperglycemia in Extremely Preterm Infants Using Continuous Subcutaneous Insulin Therapy.

Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of iv insulin treatment. The aim of our study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants. Clinical data from 15 extemely premature infants (< 28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia at the NICU were included. Blood glucose levels during CSII as well as the nutritional intake and insulin intake were sampled. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy. Normoglycemia rates were best in the iv insulin-cohort (50.3%; 15.6%). Hypoglycemia was very rare in both groups (0.4%; 0.0%). CSII therapy might require higher insulin doses compared to continuous iv therapy. Subcutaneous Insulin therapy in extremely preterm infants is feasible, regarding the prevention of hypoglycemia. However, dose control needs to be improved. The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII.

Hand grip strength is inversely associated with total daily insulin dose requirement in patients with type 2 diabetes mellitus: a cross-sectional study.

Short-term (2 weeks to 3 months) insulin intensive therapy using continuous subcutaneous insulin infusion (CSII) can improve islet beta cell function and prolong glycemic remission in patients with newly diagnosed type 2 diabetes mellitus (T2DM). However, the total daily insulin dose (TDD, IU/kg/d) required to achieve near-normoglycemic control with CSII still needs to be frequently adjusted based on blood glucose monitoring. Although real-time continuous glucose monitoring (rtCGM), which measures the interstitial fluid glucose concentration continuously without much difficulty, facilitates the adjustment of insulin dosage, its adoption in the T2DM population is strictly limited by insurance coverage and lack of awareness of rtCGM among clinicians. Thus, it is of clinical significance to identify easy-to-use parameters that may allow a more rapid and accurate prediction of TDD requirement. This study aimed to explore the association between hand grip strength (HGS) and TDD requirement in patients with T2DM receiving CSII therapy. A total of 180 eligible patients with T2DM were enrolled in the study and divided into three groups based on their HGS: low (L), medium (M), and high (H). The TDD requirement was calculated on day 7 or 8 of CSII treatment. Anthropometric parameters, including HGS, skeletal muscle mass, skeletal muscle index (SMI) and 6-m gait speed, and laboratory data, were collected on the morning of the second day after admission, within the first 24 h of CSII therapy. These parameters were used to identify significant predictors of TDD requirement using Pearson or Spearman correlation test, and stepwise multiple regression analysis. There were no significant differences in age, duration of T2DM, waist-to-hip ratio (WHR), body mass index (BMI), blood pressure, liver function, estimated glomerular filtration rate, triglyceride, total cholesterol, glycosylated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta cell function (HOMA-β) among the groups. The H group had higher body muscle mass-to-fat ratio (BMFR), skeletal muscle mass-to-fat ratio (SMFR), SMI, 6-m gait speed, and lower TDD requirement than the M and L groups. The HGS negatively correlated with TDD requirement (r = -0.33, p < 0.001) after adjusting for sex, age, BMI, WHR, HbA1c, Ln (HOMA-β), Ln (HOMA-IR), Ln (BMFR), Ln (SMFR), SMI, and 6-m gait speed. Multivariate stepwise regression analysis indicated that HGS was an independent predictor of TDD requirement in patients with T2DM (β = -0.45, p < 0 001). Lower HGS is associated with an increased TDD requirement in T2DM patients. HGS may facilitate the prediction of TDD requirement in T2DM patients receiving CSII therapy.

Monitoring of continuous subcutaneous insulin infusion treatment in Portugal and its implications for diabetes management.

Intensive insulin therapy in the treatment of type 1 diabetes can, in place of multiple daily injections of subcutaneous insulin (MDI), be performed with continuous subcutaneous insulin infusion (CSII) systems. This method allows for better glycemic control and thus reduces the risk of complications of the disease. The aim of this study was to evaluate the results of treatment with CSII in Portugal. A retrospective analysis of the records on the national CSII platform was carried out between January 2010 and August 2021. All the registered patients are followed in certified CSII treatment centers in Portugal. Of the 7135 registered patients, 3807 were excluded due to absence of monitoring data. The reasons for treatment were analyzed and a comparison was made between patients with and without CSII. The statistical significance considered was α < 0.05. A total of 3328 patients were included in the study, 1136 under MDI and 2192 under CSII. The main reasons for CSII use were marked glycemic variability (25%) and HbA1c greater than 7% (23%). Patients under CSII had a lower HbA1c (7.7 ± 1.0% vs. 8.0 ± 1.5%, p < 0.001), as well as a lower frequency of episodes of severe hypoglycemia (1.4 vs. 3.3 per 100 patient-years, p < 0.001), and ketoacidosis (1 vs. 2.4 per 100 patient-years, p < 0.001). The present analysis validates the advantage of using CSII in metabolic control and reduction of acute complications of type 1 diabetes, both severe hypoglycemia and ketoacidosis, in the Portuguese population. CSII therapy is classically associated with an increased risk of ketoacidosis; however, in experienced centers and adequate patient education, the opposite is found.

Diabete hi-tech

Recently, technological innovations have radically changed diabetes care. Insulin pumps and continuous glucose monitoring systems have significantly improved diabetes outcomes in both children and adults with Type 1 diabetes. For this reason, the major international associations recommend the use of technology in the management of Type 1 diabetes. The limitations of glycemic self-monitoring have prompted research to develop alternative techniques, favouring the expansion of continuous blood glucose monitoring systems (CGMs). CGM measures interstitial glucose through tiny sensors inserted in the subcutaneous tissue. Sensors can provide information in real time on the current glucose level and its trend. These data can be uploaded to the cloud and checked any time by doctors, patients and their caregivers. CGM can be combined with multiple daily injections (MDI) therapy or continuous subcutaneous insulin infusion (CSII). With CSII, basal insulin is supplied in the form of a continuous infusion and pre-meal bolus doses are calculated based on the meals’ carbohydrate content. A variety of insulin pumps is available, some of which can communicate with specific CGM devices, helping the patient to make better decisions about insulin dosing. This approach is known as sensor-augmented insulin pump therapy and it is the gold standard for the treatment of Type 1 diabetes in children and young adults, as recommended by the Italian Association of Paediatric Endocrinology and Diabetology. In the most recent systems, basal insulin delivery can be automatically modified through algorithms, based on CGM results, target glucose and the amount of active insulin, even though the patients still have to set the pre-meal insulin bolus manually. This system is defined as a partially hybrid closed-loop system, also known as artificial pancreas. Compared to MDI, CSII is associated with better control of blood glucose - measured by haemoglobin A1c and glycemic variability -, reduction of daily insulin requirement and an improvement of the quality of life. Psychophysical disabilities, language barriers or socio-economic disadvantage should not be considered limitations of CSII treatment as long as the caregiver is able to manage the therapy. Nowadays, MDI is recommended as first line therapy exclusively for those patients who do not want to use insulin pumps due to physical discomfort. The aim of this article is to provide updated information on the management of paediatric diabetes with modern technological devices for glucose monitoring and insulin delivery.

Continuous Subcutaneous Insulin Infusion in Type 1 Diabetes Mellitus Patients: Results from the Spanish National Registry.

Aim: To analyze the clinical effect of continuous subcutaneous insulin infusion (CSII) in type 1 diabetes mellitus (T1D) patients in the Spanish real-world scenario. Methods: All T1D patients on CSII registered in the SPAnish Insulin Pump (SPAIP) registry were included. The primary efficacy outcome was change in HbA1c during follow-up. Secondary efficacy outcomes included: insulin pump indications, diabetes complication rates, insulin and pump use, and continuous glucose monitoring (CGM) glycometrics. Patient data were typed through the web-based SPAIP registry. Results: Data from 2979 T1D patients treated with CSII were analyzed. The median age was 44 years (interquartile range [IQR] 34-52 years), and T1D duration was 27 years (IQR 18-35 years). The median duration of CSII therapy was 6 years (IQR 3-10 years). The main indications for treatment were suboptimal glycemic control (33.8%), hypoglycemia (22.1%), and increased glycemic variability (18.8%). Glycated hemoglobin decreased by 6 mmol/mol (95% CI, -5 to -6 mmol/mol, P < 0.001) [-0.5%, 95% CI, -0.4 to -0.5, P < 0.001] during the follow-up. The percentage of patients with severe hypoglycemia decreased from 14.9% to 0.9% (P < 0.001). We observed an inverse correlation between final HbA1c levels and CGM adherence (R = -0.24, P < 0.001) or percentage of time with active hybrid closed-loop functions (R = -0.25, P < 0.001). Conclusions: CSII treatment was associated with a sustained improvement in glycemic control in the Spanish population. This benefit was greater among patients with higher CGM or active hybrid closed-loop functions adherence. The protocol was publicly registered at ClinicalTrials.gov (NCT04761094).

777-P: Short-Term Continuous Subcutaneous Insulin Infusion Treatment Improves Peripheral Autonomic Neuropathy in Type 2 Diabetes

Background: Short-term continuous subcutaneous insulin infusion treatment (CSII) in patients with newly diagnosed type 2 diabetes (T2DM) can improve β-cell function and insulin sensitivity, which results in long-term remission. However, the effect of CSII on peripheral neuropathy is rarely studied. Methods: 63 T2DM patients (HbA1c&amp;gt;9%) were hospitalized and treated with CSII for 2 weeks. Peripheral autonomic neuropathy was measured by SUDOSCAN, which provides an age adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤60 indicating sudomotor dysfunction. Blood glucose, HbA1c, C-peptide and SUDOSCAN were measured before and after CSII. HOMA-B was used for assessment of β-cell function. Results: The average HbA1c of included patients was 10.5% with median duration of T2DM was 3.5 years. There were 27 (42.9%) patients who had sudomotor dysfunction at baseline. After 2 weeks of CSII, the proportion of sudomotor dysfunction (42.9% vs. 31.7%, P=0.020) was significantly deceased along with significantly improved HbA1c (10.0±1.9 vs. 8.1±1.0, P&amp;lt;0.001) and HOMA-B [22.0 (IQR 12.1-37.0) vs. 56.9 (IQR 42.4-81.8) , P&amp;lt;0.001]. Correlation analysis revealed that higher ESC composite score was correlated with better HOMA-B after CSII (r=0.445, P=0.015) . Conclusion: Peripheral autonomic neuropathy could be improved by CSII in T2DM. The improvement of β-cell function could be responsible for the amelioration of peripheral nerve function. Keywords: Short-term continuous subcutaneous insulin infusion treatment; peripheral autonomic neuropathy; type 2 diabetes; β-cell function Disclosure J.Jin:None. Funding National Key R&amp;D Program of China (2018YFC1314100) ; the Key-Area Research and Development Program ofGuangdong Province (2019B020230001) ; the China Postdoctoral ScienceFoundation (2018M640871)

Comparison of continuous subcutaneous insulin infusion treatment and multiple daily injection treatment on the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

ABSTRACTTo evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima‐media thickness and brachial‐ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile‐onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments.

The effect of short-term intensive insulin therapy on inflammatory cytokines in patients with newly diagnosed type 2 diabetes.

BackgroundDiabetes mellitus was a chronic low‐grade inflammatory disease and had increased circulating inflammatory cytokines and acute phase proteins. We aimed to identify the changes of inflammatory cytokines in newly diagnosed type 2 diabetic patients after short‐term intensive insulin therapy using continuous subcutaneous insulin infusion (CSII).MethodsThirty‐three newly diagnosed type 2 diabetic patients were enrolled between September 2020 to December 2020. Expression of 40 inflammatory cytokines of the patients were tested with RayBiotech antibody array before and after 1 week of intensive insulin therapy of CSII. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out to explore the signaling pathway involved in the therapy.ResultsFive inflammatory cytokines were downregulated significantly after 1 week of CSII therapy. They were interleukin‐6 receptor (IL‐6R), regulated upon activation normal T‐cell expressed and secreted (RANTES), intercellular adhesion molecule‐1 (ICAM‐1), tissue inhibitor of metalloproteinase‐1 (TIMP‐1), and platelet‐derived growth factor type BB (PDGF‐BB) (p < 0.05 and foldchange <0.83). Among patients with baseline glycated hemoglobin (HbA1c) < 10%, three proinflammatory cytokines were decreased significantly after therapy: IL‐6R, RANTES, and ICAM‐1. As for the patients with baseline HbA1c ≥ 10%, eight inflammatory cytokines were inhibited significantly after the treatment, including ICAM‐1, IL‐6R, RANTES, TIMP‐1, TIMP‐2, macrophage inflammatory protein‐1 beta (MIP‐1β), PDGF‐BB, and tumor necrosis factor receptor type II (TNF RII). No matter which subgroup of baseline HbA1c level was considered, the decreased cytokines after CSII therapy were significantly involved in TNF signaling pathway. Nuclear factor‐kappa B (NF‐κB) signaling pathway was mainly enriched in patients with baseline HbA1c ≥ 10%.ConclusionsA panel of 40 inflammatory cytokines, measured by protein microarray, were evaluated for 1 week of CSII treatment in newly diagnosed type 2 diabetic patients. After treatment, many proinflammatory cytokines decreased. In the higher baseline HbA1c subgroup, more proinflammatory cytokines improved. No matter which subgroup of HbA1c level was considered, IL‐6R, RANTES, and ICAM‐1, which were involved in TNF signaling pathway, decreased significantly after CSII therapy. This was the first report showing that the cytokines of IL‐6R, TIMP‐2, PDGF‐BB, and TNF RII decreased after the CSII therapy.

Continuous subcutaneous insulin infusion ameliorates bone structures and mechanical properties in type 2 diabetic rats by regulating bone remodeling.

Continuous subcutaneous insulin infusion (CSII) is an intensive insulin therapy for patients with type 2 diabetes mellitus (T2DM) who have poor glycemic control, but its effect on T2DM-related bone disorder is unclear. This study described the possible mechanisms by which CSII affects bone remodeling, structures, and mechanical properties in T2DM rats. Herein, male rats (6-week-old) were assigned randomly to 4-week and 8-week administration groups, each of which included healthy control, T2DM, CSII, and Placebo groups. Then, metabolic markers, bone formation and resorption markers in serum and protein expressions of osteoclastogenesis regulators in tibias were detected. Meanwhile, microstructures, nanostructures, macro-mechanical properties, nano-mechanical properties, and mineral compositions in femurs were evaluated. 4-week later, CSII treatment restored circulatory metabolites, bone formation and resorption markers, and osteoclastogenesis regulators, improved certain bone microstructures, decreased matrix mineralization, and increased fracture toughness in T2DM rats. For 8-week group, CSII treatment restored bone formation and resorption markers, osteoclastogenesis regulators, and bone microstructures, besides improved bone mineral compositions and nanostructures, enhanced bone mechanical properties such as fracture toughness, maximum load, elastic modulus, indentation modulus and hardness. Collectively, 8-week CSII treatment is more conducive to ameliorating bone structures and mechanical properties in T2DM rats by regulating bone remodeling compared with 4-week CSII treatment, thus improving whole bone quality and providing valuable information for clinical prevention and treatment of T2DM-related bone disorders.

Vascular and Myocardial Function in Young People with Type 1 Diabetes Mellitus: Insulin Pump Therapy Versus Multiple Daily Injections Insulin Regimen.

Multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) are two modalities of treating type 1 diabetes mellitus (T1DM). The benefits of CSII on long-term metabolic control and outcomes compared to those of MDI are still debated. We investigated both vascular function and myocardial performance in T1DM adolescents on MDI or CSII treatment. One hundred twenty-three T1DM subjects (mean age 14.16±2.55 years), 63 on MDI regimen, 60 on CSII, and 57 controls were enrolled. Anthropometric and biochemical characteristics were evaluated. Ultrasound assessments of carotid intima-media thickness (cIMT), flow-mediated dilatation of brachial artery, anteroposterior diameter of the infrarenal abdominal aorta (APAO), and transthoracic echocardiography were performed. T1DM subjects on the CSII regimen showed better glycemic control than those on MDI, expressed as glycated haemoglobin (HbA1c). c-IMT and APAO were higher in MDI than CSII patients (0.61±0.11 mm vs. 0.56±0.07 mm, p=0.04; 13.61±3.29 mm vs. 11.65±1.84 mm, p=0.01, respectively). Left and right Tei index and left E/e' ratio were higher in MDI than CSII subjects (0.82±0.40 vs. 0.52±0.19, p=0.002; 0.86±0.41 vs. 0.64±0.1, p=0.02; 5.89±2.0 vs. 4.73±1.59, p=0.02, respectively). Multiple regression analyses showed that glucose level, HbA1c and diabetes onset were significantly related to vascular and echocardiographic parameters in MDI and CSII patients. CSII regimen in T1DM adolescents improves glycemic control and seems to ameliorate endothelial function and global myocardial performance as compared to MDI therapy.

Real-World Analysis of Therapeutic Outcome in Type 1 Diabetes Mellitus at a Tertiary Care Center.

Insulin replacement in type 1 diabetes mellitus (T1DM) needs intensified treatment, which can either be performed by multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). This retrospective analysis of a real-world scenario aimed to evaluate whether glycaemic and cardiovascular risk factors could be controlled with CSII outclass MDI as suggested by recent evidence. Data from patients with either insulin pump (n=68) or injection (n=224) therapy at an Austrian tertiary care centre were analysed between January 2016 and December 2017. There were no significant differences with regard to the latest glycosylated hemoglobin, cardiovascular risk factor control or diabetes-associated late complications. Hypoglycaemia was less frequent (P<0.001), sensor-augmented therapy was more common (P=0.003) and mean body mass index (BMI) was higher (P=0.002) with CSII treatment. This retrospective analysis of real-world data in T1DM did not demonstrate the superiority of insulin pump treatment with regard to glycaemic control or cardiovascular risk factor control.

Association of Body Fat Percentage with Time in Range Generated by Continuous Glucose Monitoring during Continuous Subcutaneous Insulin Infusion Therapy in Type 2 Diabetes.

Background Obesity is a crucial risk factor associated with type 2 diabetes mellitus (T2DM). Excessive accumulation of body fat may affect the glycemia control in T2DM. This study investigated the relationship between body fat percentage and time in range (TIR) assessed by continuous glucose monitoring (CGM) during short-term continuous subcutaneous insulin infusion (CSII) therapy in T2DM patients. Method A total of 85 T2DM patients were recruited in this cross-sectional study. All participants underwent 72 h CGM period during short-term CSII therapy. TIR was defined as the percentage of time spent within the target glucose range of 3.9-10.0 mmol/L. Body composition was measured using bioelectrical impedance analysis (BIA) and overfat was defined as an amount of body fat of at least 25% of total body mass for men or at least 30% for women. Multiple linear regression models were used to evaluate the independent association of body fat percentage with TIR after adjusting for confounding factors. Results Compared with normal fat T2DM patients, individual with a higher body fat percentage exhibited lower levels of TIR (P = 0.004) and higher 72 h mean blood glucose (72 h MBG) (P = 0.001) during short-term CSII treatment. The prevalence of overfat assessed by body fat percentage decreased with the ascending TIR tertiles (P < 0.05). Multiple linear regression analysis indicated that body fat percentage was significantly associated with TIR independent of age, gender, diabetes duration, HbA1c, and BMI (P = 0.043). Conclusions Body fat percentage was significantly associated with TIR in T2DM during short-term CSII therapy. Reduction of body fat may be an important therapeutic target to improve glycemic control in high body fat T2DM patients, who may benefit less from intensive insulin treatment.

Clinical Outcome and Cost-Effectiveness Analysis of CSII Versus MDI in Children and Adolescent With Type 1 Diabetes Mellitus in a Public Health Care System of China.

ObjectivesTo evaluate the clinical and economic consequences of continuous subcutaneous insulin infusion (CSII) vs. multiple daily injections (MDI) in children and adolescents with type 1 diabetes mellitus (T1DM) from a public health care system in developed areas of developing country, considering changes in glycemic Control, daily insulin requirements, lipid profile, body mass index (BMI), frequency of severe hypoglycemia and Diabetic Ketoacidosis (DKA) and diabetic complications.MethodsThis was a retrospective cohort study of children and adolescents with T1DM. Data were collected at baseline and the end of every year including glycated hemoglobin (HbA1c), insulin dose, lipid profile, blood pressure, and adverse events (severe hypoglycemia and DKA). The Cost-effectiveness analysis was performed using the IQVIA CORE Diabetes Model (CDM) to simulate diabetes progression by utilizing the clinical data obtained from the two groups. The main outcome measures were Life Expectancy, Quality adjusted life years (QALYs), Total Costs and Incremental Costs and Effectiveness Ratio (ICER) of CSII compared with MDI in Chinese pediatric patients with T1DM in Qingdao City (60 years).ResultsMean HbA1c values and daily insulin doses were significantly lower in those receiving CSII therapy throughout follow-up. Mean direct lifetime costs were ¥ 67,137 higher with CSII treatment than with MDI for pediatric patients. Treatment with CSII was associated with an improvement in life expectancy of 0.41 years for pediatric patients compared with MDI based on CORE diabetes model simulation. The corresponding gains in QALYs were 0.42. These data produced corresponding ICER is ¥ 161,815 per QALY for pediatric T1DM patients in Qingdao. Sensitivity analyses suggested that our base-case assumptions were mostly robust.ConclusionsCSII is associated with improved long‐term clinical outcomes compared with MDI. Based on this model analysis, CSII appears to be more cost-effective for the Qingdao TIDM pediatric population and health care system.

Long-term follow-up of efficacy of insulin pump in the treatment of children with type 1 diabetes mellitus

Objective To study the clinical effect of continuous subcutaneous insulin infusion (CSⅡ) versus multiple daily injection (MDI) on blood glucose control in children with type 1 diabetes mellitus (T1DM). Methods A retrospective analysis was performed on the medical data of 91 children with T1DM who were treated with CSⅡ for more than 1 year and 75 children with T1DM who were treated with MDI. The two groups were compared in terms of glycosylated hemoglobin (HbA1C) and the recurrence of diabetic ketoacidosis (DKA) to evaluate the difference in the efficacy during the 3-year follow-up. A survey was conducted for the children in the CSⅡ group and their family members to investigate the degree of satisfaction with insulin pump. Results There was no significant difference in age, sex, and course of diabetes between the CSⅡ and MDI groups at disease onset and in the first year, the second year, and the third year of follow-up (P > 0.05). There was no significant difference in the HbA1C level between the two groups at disease onset (P > 0.05), but in the first year of follow-up, the CSⅡ group had a significantly lower HbA1C level than the MDI group (P=0.04). There was no significant difference in the HbA1C level between the two groups in the second year and the third year of follow-up (P > 0.05). The CSⅡ group had a higher proportion of children with HbA1C 0.05). Within the 3 years of follow-up, 2 children in the CSⅡ group and 8 in the MDI group experienced the recurrence of DKA. In the third year of follow-up, there was no significant difference in blood pressure and blood lipids between the CSⅡ and MDI groups (P > 0.05). Most children and their family members (87%) were satisfied with CSⅡ treatment. Conclusions Children with T1DM treated with CSⅡ have a better control of blood glucose than those treated with MDI, and children and their family members are satisfied with CSⅡ treatment. Therefore, it holds promise for clinical application.

Real-world outcomes of insulin pump compared to multiple daily injection therapy in adult type 1 diabetes mellitus patients in a Mediterranean scenario

To analyze the real-life outcomes of insulin pump therapy, as compared to multiple daily injection (MDI) treatment, in adult type 1 diabetes mellitus (T1DM) patients from a tertiary diabetes care hospital in a Mediterranean scenario. Observational cross-sectional study regarding all T1DM patients on insulin pump therapy compared (1:1) with MDI-treated patients selected through simple random sampling from our database. Primary efficacy outcome was to describe glycated hemoglobin A1c (HbA1c) differences. Ninety patients were analyzed (male 53%). Mean age was 40.0 ± 14.4 years, and T1DM duration was 19.7 ± 11.8 years. Duration of continuous subcutaneous insulin infusion (CSII) therapy was 5.6 ± 3.9 years, and most frequent indication (47%) for CSII treatment was HbA1c ≥ 53 mmol/mol (7%). More patients treated with CSII used interstitial glucose monitoring compared with MDI patients (73% vs. 20%, p < 0.001). Self-monitoring of blood glucose (SMBG) daily frequency was higher among insulin pump–treated patients compared with patients receiving MDI therapy (5.0 ± 2.2 times/day vs. 3.8 ± 3.2 times/day, p = 0.048). Glycated hemoglobin was lower among patients on insulin pump therapy compared with MDI-treated patients (54 ± 10 mmol/mol vs. 60 ± 13 mmol/mol, 7.1 ± 0.9% vs. 7.6 ± 1.2%; p = 0.038). Besides, patients on insulin pump showed less hypoglycemia frequency (6% vs. 11%, p = 0.006) and suffered less from frequent hypoglycemia (20% vs. 42%, p = 0.02). Patients using insulin pump therapy had a better glycemic control relative to the injection therapy cohort in a real-world Mediterranean scenario. Clinical Trials NCT03793283.

Fast-acting insulin aspart: a review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences

Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) with two added excipients, L-arginine and niacinamide, to ensure formulation stability with accelerated initial absorption after subcutaneous administration compared with previously developed rapid-acting insulins. The pharmacokinetic/pharmacodynamic properties of faster aspart have been characterised in clinical pharmacology trials with comparable overall methodology. In subjects with type 1 (T1D) or type 2 (T2D) diabetes, the serum IAsp concentration-time and glucose-lowering effect profiles are left-shifted for faster aspart compared with IAsp. In addition, faster aspart provides earlier onset, doubling of initial exposure, and an up to 2.5-fold increase in initial glucose-lowering effect within 30 min of subcutaneous injection, as well as earlier offset of exposure and effect. Similar results have been shown using continuous subcutaneous insulin infusion (CSII). The improved pharmacological properties of faster aspart versus IAsp are consistent across populations, i.e. in the elderly, children, adolescents and the Japanese. Thus, the faster aspart pharmacological characteristics more closely resemble the mealtime insulin secretion in healthy individuals, giving faster aspart the potential to further improve postprandial glucose control in subjects with diabetes. Indeed, change from baseline in 1-h postprandial glucose increment is in favour of faster aspart versus IAsp when used as basal-bolus or CSII treatment in phase III trials in subjects with T1D or T2D. This review summarises the currently published results from clinical pharmacology trials with faster aspart and discusses the potential clinical benefits of faster aspart compared with previous rapid-acting insulin products.

Increased Preoperative Glucose Variability Is Associated with Adverse Perioperative Outcomes Following Orthopedic Surgery in Patients with Type 2 Diabetes Mellitus

The association between glucose variability (GV) and adverse perioperative outcomes in type 2 diabetes mellitus (T2DM) patients undergoing orthopedic surgery was investigated. A retrospective cohort study was performed by analyzing data on T2DM patients receiving continuous blood glucose (BG) monitoring and continuous subcutaneous insulin infusion treatment due to poorly controlled preoperative BG prior to orthopedic surgery. GV was assessed with coefficient of variation (CV). Postoperative and perioperative CV, hypoglycemia cases, and other perioperative outcomes (diabetes preparation time [DPT], length of stay [LOS], and perioperative and infective complication cases) were analyzed. Results showed that a total of 168 patients were grouped into preoperative CV tertiles: 1st (n=56): 0-0.2921, 2nd (n=58): 0.2922-0.3779, and 3rd (n=54): 0.3780-0.5750. Fasting blood glucose (FBG), perioperative CV, rate of hypoglycemia cases (OR: 5.53, 95%CI: 2.43-12.59) (all P<0.001) and DPT (P=0.024) were higher in the 3rd than in the 1st tertile. After adjustments of covariates, regression analysis indicated that the 3rd tertile was associated with increased perioperative CV (adjusted coefficient=0.515, P<0.001), DPT (adjusted coefficient =0.169, P=0.073), rate of hypoglycemia cases (OR: 6.72, 95%CI: 2.69-16.82, P<0.001) and perioperative complication cases (OR: 2.50, 95%CI: 0.90-7.01, P=0.080). In conclusion, preoperative GV is associated with increased perioperative GV and adverse perioperative outcomes including longer DPT and higher rates of hypoglycemia and perioperative complications.

Hypoglycemia during Short-Term Intensive Insulin Therapy and Its Association with Long-Term Glycemic Remission in Patients with Newly Diagnosed Type 2 Diabetes.

Background Short-term intensive insulin therapy induces long-term glycemic remission in half of patients with newly diagnosed type 2 diabetes. The concomitant hypoglycemia needs further analysis. Methods We collected data from three randomized trials conducted with the same inclusion and exclusion criteria at our institution from 2002 to 2015. Continuous subcutaneous insulin infusion (CSII) was provided to achieve the glycemic goals within a week and then maintained for 14 days. Hypoglycemia episodes during short-term treatment and the one-year drug-free glycemic remission were observed. Results A total of 244 patients were included. The per day episode of mild hypoglycemia (3.0-3.9 mmol/L) was higher in the remission group than in the nonremission group (0.26 ± 0.20 vs. 0.18 ± 0.21, P = 0.005). However, a moderate hypoglycemia episode (<3.0 mmol/L) per day was insignificantly lower in the remission group (0.02 ± 0.04 vs. 0.03 ± 0.04, P = 0.005). However, a moderate hypoglycemia episode (<3.0 mmol/L) per day was insignificantly lower in the remission group (0.02 ± 0.04 vs. 0.03 ± 0.04, P = 0.005). However, a moderate hypoglycemia episode (<3.0 mmol/L) per day was insignificantly lower in the remission group (0.02 ± 0.04 vs. 0.03 ± 0.04, P = 0.005). However, a moderate hypoglycemia episode (<3.0 mmol/L) per day was insignificantly lower in the remission group (0.02 ± 0.04 vs. 0.03 ± 0.04, Conclusions Mild hypoglycemic episodes during the continuing insulin dose reduction period indicate a long-term drug-free euglycemic remission in patients with newly diagnosed type 2 diabetes. However, the insulin dosage should be reduced even more quickly in the future treatment to decrease the potential harms.

Evaluation of Glycaemic Control, Glucose Variability and Hypoglycaemia on Long-Term Continuous Subcutaneous Infusion vs. Multiple Daily Injections: Observational Study in Pregnancies With Pre-Existing Type 1 Diabetes.

IntroductionWe evaluated the effectiveness of long-term continuous subcutaneous insulin infusion (CSII) compared with multiple daily insulin (MDI) injections for glycaemic control and variability, hypoglycaemic episodes and maternal/neonatal outcomes in pregnant women with pre-existing type 1 diabetes (pT1D).MethodsOur observational cohort study included 128 consecutive pregnant women with pT1D, who were treated from 1 January 2010 to 31 December 2017. Of 128 participants, 48 were on CSII and 80 were on MDI. Glycaemic control was determined by glycated haemoglobin (HbA1c) (captured in preconception and each trimester of pregnancy). Glucose variability (GV) was expressed as the coefficient of variation (CV) [calculated from self-monitoring of blood glucose (SMBG) values], and hypoglycaemia was defined as glucose values < 3.9 mmol/l. The data on maternal and neonatal outcomes were collected from obstetrical records.ResultsDuration of the treatment was 8.8 ± 5.3 years in the CSII and 12.6 ± 8.0 years in the MDI group. The CSII lowered HbA1c in preconception (7.1 ± 0.1 vs. 7.9 ± 0.2%, p = 0.03) and the first (6.9 ± 0.1 vs. 7.7 ± 0.2%, p = 0.02), second (6.6 ± 0.1 vs. 7.2 ± 0.1%, p = 0.003) and third (6.5 ± 0.1 vs. 6.8 ± 0.1%, p = 0.02) trimesters significantly better than MDI. Significantly lower CV was observed only for fasting glycaemia in the first trimester (17.1 vs 28.4%, p < 0.001) in favour of CSII. Moreover, the CSII group had significantly lower mean hypoglycaemic episodes/week/patient only during the first trimester (2.0 ± 1.7 vs 4.8 ± 1.5, p < 0.01). In early pregnancy, the majority of women on CSII had less hypoglycaemia than on MDI (0–3: 79.1 vs. 29.1%; 4–6: 18.8 vs. 65.8%; ≥ 7: 2.1 vs. 5.1%, p < 0.01, respectively). We found no difference in the incidence of adverse maternal/neonatal outcomes.ConclusionsTreatment with CSII resulted in a favourable reduction of HbA1c in the preconception period and each trimester in pregnancy. Moreover, long-term CSII treatment demonstrated more stable metabolic control with less GV of fasting glycaemia and fewer hypoglyacemic episodes only during early pregnancy.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00780-7) contains supplementary material, which is available to authorized users.

Insulin pumps use in Greece: Efficacy and safety data from 140 patients with type 1 diabetes mellitus

ObjectiveThe aim of this study was to investigate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) regarding glycaemic control and quality of life in patients with type 1 diabetes mellitus (T1DM), who were previously treated with multiple daily injections (MDI). Patients and methods140 patients with T1DM [mean age 33.7 ± 22.1 years; 54 males, 76 females, 10 children; duration of diabetes 19.1 ± 8.4 years; total daily insulin usage while on MDI (IU/day) 57.86 ± 15.32; HbA1c at the beginning of CSII treatment 8.67 ± 1.54%] were included in the study. HbA1c, glucose levels, BMI, severe hypoglycemic and diabetic ketoacidosis (DKA) episodes were recorded and compared to the data prior to CSII introduction. The evaluation of the quality of life was assessed with a self-questionnaire adjusted from the SF-12 and diabetes quality of life (DQoL) questionnaires. ResultsHbA1c was reduced from 8.67 ± 1.54 to 6.85 ± 0.52% (p < 0.001). This reduction was independent of age, gender, body mass index (BMI) and diabetes duration. Daily insulin requirements were lower at the end of the follow-up (36.40 ± 12.20 IU/day) compared with the needs during enrolment (57.86 ± 15.32 IU/day) (p < 0.001). BMI presented no significant alterations. Ten (10) severe hypoglycemic episodes were recorded but the overall rate was decreased by 71.5% (p < 0.001). Only 3 cases of ketoacidosis were recorded. Quality of life parameters were remarkably improved. ConclusionsThis study provided evidence that CSII treatment was superior to MDI for patients with T1DM in Greece. CSII offered a safe, effective alternative to MDI, while improving glycaemic control, side-effects and quality of life.