Multiple Daily Insulin Therapy Research Articles

Short- and Long-Term Effects on Glucose Control of Nonadherence to Insulin Therapy in People With Type 2 Diabetes An In Silico Study.

Strict adherence to multiple daily insulin (MDI) therapy is a cornerstone for the achievement of good glucose control in people with advanced type 2 diabetes (T2D). Here, we aim to in silico assess glucose control in T2D subjects with poor adherence to MDI therapy. We tuned the Padova T2D Simulator, originally describing early-stage T2D physiology, around advanced T2D people. One hundred in silico advanced T2D subjects were generated and equipped with optimal MDI therapy: specifically, basal and bolus insulin amounts and injection times were individualized for each subject by applying titration algorithms that iteratively update insulin dose based on glucose deviation from its target. Then, the effect of nonadhering to MDI therapy was assessed using standard glucose control metrics calculated in two 6-month 3-meal/day in silico scenarios: in Scenario 1, subjects received the optimal basal and prandial insulin bolus at each meal; in Scenario 2, subjects received optimal basal insulin and randomly delayed or skipped the prandial insulin bolus in 3 lunches during working days and 1 dinner during weekends. A statistically significant degradation was found in all glucose control outcome metrics in Scenario 2 versus Scenario 1: e.g., percent time above 180 mg/dL increased by 22.2% and glucose management index by 0.2%. Impaired adherence to MDI therapy in T2D leads to glucose control deteriorations in both short and long terms. Interestingly, short-term hyperglycemia seems being contrasted by residual endogenous insulin secretion, which statistically increased by 3-fold after delayed/skipped insulin boluses compared with optimal ones.

Shining the Spotlight on Multiple Daily Insulin Therapy: Real-World Evidence of the InPen Smart Insulin Pen.

Objective: Connected insulin pens are creating opportunities for the millions of individuals with diabetes using multiple daily injections (MDI) therapy across the globe. Continuous glucose monitoring (CGM) data from connected insulin pens are revealing gaps and opportunities to significantly improve care for this population. In this article, we report real-world findings of the InPen™ smart insulin pen paired with CGM (InPen system), used by persons with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods: A retrospective cohort analysis was conducted with the real-world data collected from the InPen system of individuals (N = 3793 with T1D, N = 552 with T2D, and N = 808 unidentified) who used the system from January 01, 2020, to December 31, 2021. Diabetes management (e.g., missed and mistimed insulin dosing, mismatched food intake, and correction dose delivery) and glycemic outcomes were assessed. Results: In the overall and T1D populations, a dosing frequency of ≥3 doses per day and a missed dose frequency of <20% was associated with improved glycemia. In adults with T2D, missing <20% of doses was the significant factor determining improved glycemia. Conclusion: This analysis, integrating data from a smart insulin pen and CGM, provides insights into the impact of dosing behavior on glycemic outcomes and informs counseling strategies for the diabetes care team, through technologically advanced insulin management for those using MDI therapy.

Study of Pentraxin-3 as an Early Marker of Diabetic Vascular Complications in Children and Adolescents with Type 1 Diabetes Mellitus

Background Vascular complications are the major cause of morbidity and mortality in diabetic patients. These can result from interactions between systemic metabolic abnormalities, such as hyperglycemia, dyslipidemia, genetic and epigenetic modulators, and local tissue responses to toxic metabolites. Aim of the Work To assess the role of PTX3 as an early marker of vascular complications in children and adolescents with type 1 diabetes mellitus and its correlation with metabolic control and its relation to hsCRP level. Patients and Methods Fifty adolescents with type 1 diabetes mellitus and 40 age and sex matched control group, Detailed history taking, full systemic examination were done, Patients also were investigated using HbA1c, lipid profile, ALT, Alb/Cr ratio in urine, PTX3, hsCRP and carotid intima media thickness (CIMT). An informed consent was obtained from patients, controls or their legal guardians before enrollment in the study. Inclusion criteria Patients with type 1 diabetes their age ranging from 5 to 18 years old with at least 5 years disease duration and on regular clinic visits and multiple daily insulin therapy . Exclusion criteria Patients with proven vascular complications and those with any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases, also patients with morbid obesity were excluded. Results PTX3 and hsCRP were significantly higher in patients compared to control group. A significant positive correlation between serum PTX3 and level of HbA1c%, level of Triglycerides (TG), level of Total Cholesterol was observed. Additionally, PTX3 and hsCRP levels were elevated in patients with elevated lipid profile (TG and Cholesterol) and high HbA1c% level in comparison with those with normal lipid profile and those with controlled HbA1c% level (p &amp;lt; 0.001). No significant difference was found between patients and control groups as regard CIMT. Conclusion . The increased levels of PTX3 and hsCRP in patients with uncontrolled diabetes even before development of both microvascular and macrovascular complications add a promising tool for their follow up and applying early protective measures.

996-P: Prevalence of Functional Hyperandrogenism in Young Women with Type 1 Diabetes: A Preliminary Analysis from a Cross-Sectional Study of a Spanish Cohort

Introduction: Increased prevalence of functional hyperandrogenism/polycystic ovary syndrome (PCOS) has been previously described in type 1 diabetes (T1DM) patients. However, the reported prevalence rates vary depending on different diagnostic criteria. Our study aim was to determine the prevalence of PCOS and hyperandrogenic traits in premeopausal women with T1DM. Methods: A cross-sectional study was conducted at a diabetes outpatient clinic in a tertiary Hospital from Madrid, Spain. We recruited consecutive premenopausal woman with T1DM, and menarche at least 2 years before the study. For this preliminary report, we included 40 patients. History data collection, physical exam, a complete hormonal analysis in follicular phase (including d4-androstenedione, DHEA-S, total testosterone, SHBG, 17-OH-progesterone, FSH, LH, prolactin, and TSH), and ovarian ultrasound were performed. Results: Mean age of patients was of 28 ± 8 yr; mean duration of T1DM was of 13 ± 8 yr-old. Twenty-seven patients were on multiple daily insulin therapy, while 13 of them were on continuous subcutaneous insulin infusion. Mean BMI was of 23.8 ± 3.7 Kg/m2. Mean daily insulin dose was 0.64 ± 0.2 U/kg and mean A1C was 7.5 ± 1.8%. PCOS was diagnosed in 7 patients resulting in a 18% (95% CI: 8; 32) prevalence of PCOS according to NIH-Rotterdam, and in 6 patients resulting in a 15% (95% CI: 7; 29) prevalence of PCOS according to AES-PCOS criteria. Three patients [7% (95% CI: 3; 20)] had isolated polycystic ovarian morphology (PCOM), and 7 patients [18% (95% CI: 8; 32)] presented with oligo-amenorrhea (ovulatory dysfunction-WHO class 2). Conclusion: Our preliminary data show a significant increase in prevalence of PCOS in premenopausal women with T1DM with respect to the general population. Disclosure A. Bayona: None. L. Nattero-chávez: None. E. Fernández durán: None. B. Dorado avendaño: None. H. F. Escobar-morreale: Consultant; Self; InsudPharma. M. Luque-ramírez: None.

Effect of Injection Site Cooling and Warming on Insulin Glargine Pharmacokinetics and Pharmacodynamics.

In type 1 diabetes (T1D), closed-loop systems provide excellent overnight fasting blood glucose control by adjusting the insulin infusion rate based on corresponding changes in sensor glucose levels. In patients on multiple daily insulin (MDI) injections, such control in overnight glucose levels has not been possible due to the inability to alter the absorption rate of long-acting insulin after injection. In this study, we tested the hypothesis that increases/decreases of fasting glucose levels could be achieved by cooling/warming the skin around the injection site, which would result in lower/higher Glargine absorption rates from its subcutaneous depot. Fourteen subjects with T1D (4 females; age 39.6 ± 16.7 years, HbA1c 7.8 ± 1.1%, BMI 25.4 ± 2.8 kg/m2) on MDI therapy underwent fasting pharmacokinetic and pharmacodynamic studies that started at ~8 am and lasted 240 min on 3 separate days in random order: a control day without warming or cooling of the injection site and two experimental days, one day with injection site warming and the other with cooling. Cooling the skin around the glargine injection site reduced insulin concentrations by >40% (P < .01 versus the warming study, P = .21 versus the control study), accompanied by a 55 mg/dL increase in serum glucose (P < .01 versus the control study). Conversely, skin warming prevented the fall in serum insulin (P = .2 versus the control study; P < .01 versus the cooling study), resulting in a 40 mg/dL reduction in serum glucose (P < .001 versus the cooling study, P = .11 versus the control study). This proof of concept study has shown that cooling and warming the skin around the injection site provides a means to decrease and increase the rate of absorption and action of insulin glargine from its subcutaneous depot.

Efficacy of real-time continuous glucose monitoring on glycaemic control and glucose variability in type 1 diabetic patients treated with either insulin pumps or multiple insulin injection therapy: a randomized controlled crossover trial.

The aim of this study was to determine the efficacy of real-time continuous glucose monitoring in T1D patients treated with insulin pump therapy or multiple daily insulin therapy. Twenty adult patients (ten insulin pump therapy and ten multiple daily insulin) with poor glycaemic control (HbA1c > 8.0%) were randomized into two groups for 6 months: the continuous glucose monitoring arm (using real-time continuous glucose monitoring) and the SMBG arm. After 2 months of wash-out, the participants crossed over. The primary outcome was HbA1c reduction. The secondary outcomes were hypoglycaemia and hyperglycaemia risk assessment (area under the curve < 70 mg/dL/day and AUC > 200 mg/dL/day, respectively) and glucose variability. Fourteen patients (eight multiple daily insulin, six insulin pump therapy) used continuous glucose monitoring appropriately (at least 40% of the time). In these patients, the improvement in glycaemic control was more evident during the real-time continuous glucose monitoring period (7.76% ± 0.4 vs 8.54% ± 0.4, p < 0.05) than during the self-monitoring of blood glucose period (8.42% ± 0.4 vs 8.56% ± 0.5, p = 0.2). Better results with continuous glucose monitoring were observed in patients using multiple daily insulin with greater improvement in both glycaemic control (7.71% ± 0.2 vs 8.58% ± 0.2, p < 0.05) and glucose variability and with a marked reduction in the risk of both hypoglycaemia and hyperglycaemia. Appropriate use of real-time continuous glucose monitoring improved glycometabolic control in T1D patients. The effects of continuous glucose monitoring were more evident in patients under multiple daily insulin treatment, compared with insulin pump therapy. Glucose variability, in addition to glycaemic control, was improved in compliant diabetic patients.

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis

We compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus. The electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for randomised controlled trials up to March 2007. A systematic review and meta-analysis were performed. Overall, 22 studies were included (17 on type 1 diabetes mellitus, two on type 2 diabetes mellitus, three on children). With regard to adults with type 1 diabetes mellitus, our meta-analysis found a between-treatment difference of -0.4% HbA(1c) (six studies) in favour of CSII therapy. Available median rates of mild or overall hypoglycaemic events were comparable between the different interventions (1.9 [0.9-3.1] [CSII] vs 1.7 [1.1-3.3] [MDI] events per patient per week). Total daily insulin requirements were lower with CSII than with MDI therapy. In patients with type 2 diabetes mellitus, CSII and MDI treatment showed no statistically significant difference for HbA(1c). The incidence of mild hypoglycaemic events was comparable between the treatment groups. In adolescents with type 1 diabetes mellitus, glycated haemoglobin and insulin requirements were significantly lower in the CSII groups; no data were available on hypoglycaemic events. The only study performed in younger children did not provide enough data for conclusive inferences. No overall conclusions were possible for severe hypoglycaemia and adverse events for any of the different patient groups due to rareness of such events, different definitions and insufficient reporting. CSII therapy in adults and adolescents with type 1 diabetes mellitus resulted in a greater reduction of glycated haemoglobin, in adult patients without a higher rate of hypoglycaemia. No beneficial effect of CSII therapy could be detected for patients with type 2 diabetes mellitus.

Flexible Insulin Therapy With Glargine Insulin Improved Glycemic Control and Reduced Severe Hypoglycemia Among Preschool-Aged Children With Type 1 Diabetes Mellitus

Insulin replacement regimens now stress the importance of administering throughout the day insulin doses that are based on flexible food choices and focusing on improved metabolic control. A flexible multiple daily insulin (FMDI) regimen (premeal lispro plus bedtime glargine) results in lower hemoglobin A1c (HbA1c) levels and fewer hypoglycemic episodes than does a multiple daily insulin (MDI) regimen among school-aged children and adolescents with type 1 diabetes mellitus (DM). The purpose of this study was to determine the feasibility of FMDI therapy for a group of preschool-aged children with type 1 DM who were transitioned from MDI therapy (premeal lispro plus ultralente insulin twice per day), by comparing BMI, total daily insulin requirements, HbA1c levels, and episodes of severe hypoglycemia. Data were collected over a 2-year period, during quarterly DM clinic visits, from 35 patients (17 female patients and 18 male patients, 4.8 +/- 1.0 years of age) who had received MDI insulin therapy for > or =1 year before being transitioned to a FMDI regimen. Although there was no significant change in BMI with FMDI therapy (17.1 +/- 1.8 kg/m2 vs 17.0 +/- 1.7 kg/m2), 43% of patients (6 female subjects and 9 male subjects) were overweight (BMI of >85th percentile for age) both before and after treatment. The total daily insulin requirement (0.67 +/- 0.13 U/kg per day vs 0.78 +/- 0.14 U/kg per day) and bolus/basal insulin ratio (1.1 +/- 0.4 vs 1.9 +/- 0.6) were significantly increased and overall glycemic control was improved after transition to FMDI therapy (HbA1c levels: 8.8 +/- 0.9% vs 8.3 +/- 0.8%). However, HbA1c levels improved only among normal-weight subjects (9.0 +/- 1.0% vs 8.3 +/- 1.0%) and not among overweight subjects (8.7 +/- 0.7% vs 8.4 +/- 0.6%) after FMDI therapy. The overall rate of severe hypoglycemia was significantly decreased with the FMDI regimen (25.5 events per 100 patient-years vs 10.6 events per 100 patient-years) but again only for normal-weight children (29.7 events per 100 patient-years vs 7.4 events per 100 patient-years). The use of FMDI therapy with glargine among preschool-aged children with type 1 DM was associated with improved overall glycemic control and decreased frequency of severe hypoglycemia. Although our study did not have a control group, these findings suggest that FMDI regimens may be a feasible therapeutic alternative to MDI treatment for preschool-aged children with type 1 DM. However, excess body weight status appeared to preclude a desirable therapeutic response in this group of patients.

Implantable Insulin Pump vs Multiple-Dose Insulin for Non—Insulin-Dependent Diabetes Mellitus

To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life.Randomized clinical trial.Seven Veterans Affairs medical centers.One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above.Intensive therapy (IIP or MDI) for 1 year.Hemoglobin A1c and blood glucose levels.Blood glucose levels declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump.Intensive insulin therapy with IIP and MDI is effective in controlling non-insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.