Changes In Insulin Requirements Research Articles

Changes in Basal and Bolus Insulin Requirements with Tirzepatide as an Adjunctive Therapy in Adults with Type 1 Diabetes Using Tandem Control-IQ.

This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8months of tirzepatide treatment. In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64% female and mean body mass index of 39.6kg/m2). Data were compared from baseline and over 8months. Within 2months of tirzepatide treatment, there were significant reductions in total daily insulin [median (IQR) 73.9 (47.6-95.8) to 51.7 (46.7-66.8) units/day, p < 0.001], basal insulin [47 (28.2-51.8) to 32.4 (25.5-46.3) units/day, p < 0.001], and bolus insulin [31.4 (19.9-38.3) to 17.9 (14.9-22.2) units/day, p < 0.001] requirements. Insulin dose reduction from 2 to 8months was modest. The frequency of user-initiated boluses did not differ throughout the study. Despite reductions in total insulin requirement, time in range (70-180mg/dl) increased by 7%, A1c reduced by 0.5%, weight reduced by 9%, without increase in time below 70mg/dl. This pilot study provides clinical guidance on insulin titration for adults with T1D who may initiate tirzepatide therapy. Based on the findings of this study, we recommend reducing 25% of total daily insulin dose at tirzepatide initiation in adults with T1D using AID with baseline A1c of less than 7.5%. Higher doses of tirzepatide were associated with greater weight loss, however, the reduction in insulin requirement was minimal.

Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda=0.34, F(6,14)=4.52, p=0.009), basal insulin (Wilks' Lambda=0.41, F(6,14)=3.30, p=0.031) and bolus insulin (Wilks' Lambda=0.43, F(6,14)=3.02, p=0.041). Total insulin/kg requirements increased by 5.5% from 13-20weeks to 20-26weeks, 19% from 20-26weeks to 26-33weeks, and 17.4% from 26 to 33weeks to delivery (p for trend=0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p<0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

Model predictive control to account for prolonged changes in insulin requirements following exercise in type 1 diabetes

Automated insulin delivery systems are becoming increasingly available in the treatment of type 1 diabetes. They can improve glycemic outcomes while reducing patient burden, but good glycemic control during and after exercise remains challenging. Exercise causes substantial and prolonged changes in insulin sensitivity that consequently affect insulin requirements, and can lead to late-onset hypoglycemia if not accounted for.Here, we present a model predictive control algorithm that adjusts insulin delivery during the recovery period to improve glycemic outcomes after aerobic exercise. The algorithm continuously estimates insulin sensitivity from glucose measurements via an unscented Kalman filter. It integrates the estimate by continuously updating the target insulin input as well as the process model to account for changing insulin demands. The proposed approach is generic and transferable to other control formulations.We evaluate our new control strategy in-silico using a validated diabetes patient model with aerobic exercise. We consider a virtual patient population in full-day simulations including a wide variety of exercise scenarios covering moderate to high intensities and different timing and duration of the exercise. We demonstrate improved glycemic outcomes over night following a day with exercise for all scenarios and show robustness of our approach to common disturbances.

The acute effects of a DASH diet and whole food, plant-based diet on insulin requirements and related cardiometabolic markers in individuals with insulin-treated type 2 diabetes

AimsThere is limited research regarding insulin dosing changes following adoption of plant-based diets. We conducted a nonrandomized crossover trial utilizing two plant-based diets (Dietary Approaches to Stop Hypertension, or DASH, and Whole Food, Plant-Based, or WFPB) to assess acute changes in insulin requirements and associated markers among individuals with insulin-treated type 2 diabetes. MethodsParticipants (n = 15) enrolled in a 4-week trial with sequential, one-week phases: Baseline, DASH 1, WFPB, and DASH 2. Each diet was ad libitum and meals were provided. ResultsCompared to baseline, daily insulin usage was 24%, 39%, and 30% lower after DASH 1, WFPB, and DASH 2 weeks respectively (all p < 0.01). Insulin resistance (HOMA-IR) was 49% lower (p < 0.01) and the insulin sensitivity index was 38% higher (p < 0.01) at the end of the WFPB week before regressing toward baseline during DASH 2. Total, LDL, and HDL cholesterol, leptin, urinary glucose, and hsCRP decreased to a nadir at the end of the WFPB week before increasing during DASH 2. ConclusionsAdopting a DASH or WFPB diet can result in significant, rapid changes in insulin requirements, insulin sensitivity, and related markers among individuals with insulin-treated type 2 diabetes, with larger dietary changes producing larger benefits.

Comparison of A1c Reduction, Weight Loss, and Changes in Insulin Requirements With Addition of GLP-1 Agonists vs SGLT-2 Inhibitors in Patients Using Multiple Daily Insulin Injections

Objective: To determine whether Glucagon-Like Peptide 1 (GLP-1) agonists or Sodium Glucose Transporter 2 (SGLT-2) inhibitors result in greater A1c reduction, weight loss, and reduction of insulin requirements in veterans using multiple daily doses of insulin. Methods: This retrospective, single-site, cohort study included patients of VA Eastern Kansas Health Care System with a diagnosis of Type II Diabetes utilizing multiple daily dose insulin and an SGLT-2 inhibitor or GLP-1 agonist. SAS Enterprise Guide was utilized to complete a multivariate analysis of variance to evaluate all outcomes. Key Findings: 150 patients met selection criteria. The GLP-1 group averaged a .65% reduction in A1c compared to a 1.05% reduction in the SGLT-2 group (P = .1397). The Basal insulin dose was reduced by 5.5 units in the GLP-1 group vs 2.45 units in the SGLT-2 group (P = .3132), and 7.12 units vs 8.14 units respectively for short-acting insulin (P = .8170). The resulting weight reduction was 4.1 Kg in the GLP-1 group compared to 3.6 Kg in the SGLT-2 group (P = .6993). Conclusion: The results suggest there is not a statistically significant difference in changes to A1c, insulin requirements, or weight after 1 year of treatment with an SGLT-2 vs GLP-1 in patients using multiple daily insulin injections.

Clinical Features and Changes in Insulin Requirements in People with Type 2 Diabetes Requiring Insulin When Hospitalised with SARS-CoV-2 Infection

Background Uncontrolled hyperglycaemia before and during hospitalisation is a risk factor for adverse outcomes in people with diabetes and SARS-CoV-2 infection. Insulin often at high doses is frequently required to manage hyperglycaemia associated with SARS-CoV-2 infection during hospitalisation. However, there is limited information on the clinical features and sequelae of people with type 2 diabetes (T2DM) not previously on insulin that require insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Aims To describe the clinical features and insulin treatment sequelae of 113 people with T2DM that required insulin as a new treatment when hospitalised with SARS-CoV-2 infection. Methods A single-centre study of 113 people with T2DM who were not on insulin before their admission for SARS-CoV-2 infection. The primary aim of our study was to identify clinical and biochemical features that were associated with the need for insulin as a new treatment in people with known T2DM not on insulin treatment at the time of hospitalisation for SARS-CoV-2 infection. We also describe changes in insulin requirements at time of discharge from hospital and 6 weeks later during the first wave of SARS-CoV-2 infection (April–March 2020) in the UK. Clinical, biochemical, and anthropometric data were collected from electronic health records. Results We observed that of 113 people with T2DM, 35% (n = 39) needed insulin as a new treatment during their hospitalisation for SARS-CoV-2 infection. People requiring insulin were younger, had a higher preadmission HbA1c, were more frequently on oral medication for diabetes before the admission, and were more likely to be obese (body mass index ≥30 kg/m2), with p ≤ 0.001 for all. In multivariable logistic regression analyses, we observed that younger age and higher HbA1c before admission were independently associated with needing insulin, with one-year increase in age associated with decreased odds of needing insulin initiation (OR 0.91, 95% CI 0.83–0.99), and increasing preadmission HbA1c by 1 mmol/mol associated with an increased odds of insulin initiation (OR 1.05, 95% CI 1.002–1.11) (p < 0.05 for both). Of the 39 people with T2DM who required insulin as a new treatment, 28% remained on insulin at the time of discharge with their insulin dose falling from 1.26 U/kg within the first 7 days of admission to 0.39 U/kg at discharge. At 6 weeks after discharge, 24% of people remained on insulin. Conclusion More than one-third of people with T2DM not previously treated with insulin required new insulin treatment when hospitalised with SARS-CoV-2 infection, and of this group, 24% remained on insulin at 6 weeks after discharge. This study highlights the important variations of insulin requirements in people with T2DM new to insulin and the importance of a dedicated team for patient education and close follow-up.

Dynamic changes in insulin requirements with post-operative time using bedside artificial pancreas to maintain normoglycemia without hypoglycemia after cardiac surgery.

It is difficult to manage postoperative blood glucose levels without hyperglycemia and hypoglycemia in cardiac surgery patients even if continuous intravenous insulin infusion is used. Therefore, the insulin requirements for maintaining normoglycemia may be difficult to evaluate and need to be elucidated. In this single-center retrospective study, 30 adult patients (age 71.5 ± 9.0years old, men 67%, BMI 22.0 ± 3.1kg/m2, diabetes 33%) who underwent cardiac surgery and used bedside artificial pancreas (STG-55) as a perioperative glycemic control were included. We investigated the insulin and glucose requirements to maintain normoglycemia until the day after surgery. The bedside artificial pancreas achieved intensive glycemic control without hypoglycemia under fasting conditions for 15h after surgery (mean blood glucose level was 103.3 ± 3.1mg/dL and percentage of time in range (70-140mg/dL) was 99.4 ± 2.0%). The total insulin requirement for maintaining normoglycemia differed among surgical procedures, including the use of cardiopulmonary bypass during surgery, while it was not affected by age, body mass index, or the capacity of insulin secretion. Moreover, the mean insulin requirement and the standard deviationof the insulin requirements were variable and high, especially during the first several hours after surgery. Treatment using the bedside artificial pancreas enabled intensive postoperative glycemic control without hypoglycemia. Furthermore, the insulin requirements for maintaining normoglycemia after cardiac surgery vary based on surgical strategies and change dynamically with postoperative time, even in the short term.

Examination of the Igls Criteria for Defining Functional Outcomes of β-cell Replacement Therapy: IPITA Symposium Report.

The Igls criteria were developed to provide a consensus definition for outcomes of β-cell replacement therapy in the treatment of diabetes during a January 2017 workshop sponsored by the International Pancreas & Islet Transplant Association (IPITA) and the European Pancreas & Islet Transplant Association. In July 2019, a symposium at the 17th IPITA World Congress was held to examine the Igls criteria after 2 years in clinical practice, including validation against continuous glucose monitoring (CGM)-derived glucose targets, and to propose future refinements that would allow for comparison of outcomes with artificial pancreas system approaches. Utilization of the criteria in various clinical and research settings was illustrated by population as well as individual outcome data of 4 islet and/or pancreas transplant centers. Validation against CGM metrics was conducted in 55 islet transplant recipients followed-up to 10 years from a fifth center. The Igls criteria provided meaningful clinical assessment on an individual patient and treatment group level, allowing for comparison both within and between different β-cell replacement modalities. Important limitations include the need to account for changes in insulin requirements and C-peptide levels relative to baseline. In islet transplant recipients, CGM glucose time in range improved with each category of increasing β-cell graft function. Future Igls 2.0 criteria should consider absolute rather than relative levels of insulin use and C-peptide as qualifiers with treatment success based on glucose assessment using CGM metrics on par with assessment of glycated hemoglobin and severe hypoglycemia events.

585-P: Effect of Hydroxychloroquine on HbA1c and Lipid Parameters in T2DM Subjects with Diabetic Neuropathy Who Are on Statins

Aim: We decided to explore the effects of HCQ in combination with rosuvastatin on Lipid profile and HbA1c of patients with DKD. Method: This is a real world study. T2DM (N=67, Age 52± 09), HbA1c ≥ 7%, with clinical evidence of DKD) were selected and alternatively divided into two groups with one group taking HCQ 400 mg in addition to their regular medications and other group without HCQ. Both groups were followed for next 3 months and changes in their serum creatinine(S.Cr), eGFR, Urine ACR, HbA1C,FPG, PPG, LDL, HDL, TG were noted. All patients were on DPP-4i and metformin along with short acting insulin with dosage modified according to daily insulin need and changes in insulin requirement with changing renal function for at least 3months prior to the study. Results: TG levels were reduced by 25.01% and 10.69% in the HCQ and Non - HCQ Gr respectively, LDL-cholesterol levels were reduced in HCQ while it increase in the Non HCQ. TC declined more with HCQ and significant increase in HDL. SCr. was decline in HCQ Gr, while it increased in Non-HCQ. Similarly, eGFR was rising in the HCQ and decreased in the Non-HCQ. Also, Urinary ACR decreased with HCQ, but continued to increase in Non-HCQ. Conclusion: Therefore, we concluded that HCQ can be an option in patients of early stages of DKD in such patients and it may be combined with rosuvastatin for better lowering of lipid levels and better control of HbA1c. Disclosure A. Baidya: None. S. Guha: None. S. Kumar: None. A. Shankar: None.

382-P: Insulin Requirements after Hospital Discharge in Patients with Type 2 Diabetes

Changes in insulin requirements after hospital discharge in insulin-treated patients with type 2 diabetes (T2D) are not known. We conducted a pooled analysis of 4 randomized clinical trials with 3-month follow-up data to determine changes in insulin requirement after discharge. These studies followed a discharge algorithm based on admission HbA1c to guide outpatient insulin therapy. A total of 255 insulin-treated patients (age: 55.6 year, BMI 34.6 kg/m2, duration DM: 11.2±8 year) were discharged on glargine + oral antidiabetic (OAD) agents (75%), glargine + exenatide (4%), or basal bolus (21%). Patients with HbA1c &amp;lt;7% (11.4%) were discharged on the same outpatient therapy. Those with an HbA1c between 7% and 9% (37.2%) were discharged on glargine at 50% of hospital TDD + their outpatient OAD agents. Those with an HbA1c &amp;gt;9% (51.4%) were discharged on glargine at 80% of hospital TDD in combination to OAD or with basal bolus regimen. Treatment was adjusted to achieve a target HbA1c level &amp;lt;7%. The primary outcome was change in insulin total daily dose (TDD) at 3 months after discharge. Changes in HbA1c, hypoglycemia, insulin TDD, and change in insulin requirements at 3 months of follow-up are shown in Table. In summary, insulin TDD requirements vary greatly after hospital discharge in patients with T2D. Most patients required frequent insulin adjustments to maintain glycemic control and to avoid hypoglycemia after hospital discharge. Disclosure M. Fayfman: None. D. LeRoith: Advisory Panel; Self; AstraZeneca, MannKind Corporation. F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. I. Anzola: None. M.A. Urrutia: None. H. Wang: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck 0026 Co., Inc., Novo Nordisk Inc., Sanofi US.

Temporary Reductions in Insulin Requirements Are Associated with Hypoglycemia in Type 2 Diabetes.

Background: In patients with type 2 diabetes, insulin therapy necessitates regular and frequent dosage titration to overcome variations in insulin requirements. The goal of this study was to evaluate changes in insulin requirements, using data from a technology-based insulin-titration service. Methods: To keep glycemia stable, the service adjusts and records insulin dosage at least weekly. Therefore, insulin dosage closely tracks insulin requirement. Events of considerable and persistent decrease in insulin requirements were identified by reductions in total daily dose (TDD) of insulin ≥25%. Periods ended when a persistent increase in TDD of insulin has started. The average frequency of hypoglycemia was expressed as any glucose reading <54 mg/dL (both inside or outside periods of decrease in insulin dosage) divided by the total number of months for each patient. Results: Patients (n = 246) were followed for 2.8 ± 0.9 years. Reductions of TDD of insulin were experienced by 70.3% of the patients, occurred 0.8 ± 0.5 times per year, lasted 10.0 ± 7.7 weeks, and insulin requirements declined by 39.9% ± 12.6%. The frequency of hypoglycemia (<54 mg/dL) was low, at 0.5 ± 0.6 per month, and the difference in frequencies in biphasic/premixed and basal-bolus insulin regimens was not statistically significant. Hypoglycemia was 6.5 times more prevalent during reductions in TDD of insulin. Conclusions: Sizeable changes in insulin requirements occur over time, which demand persistent and frequent titration to preserve treatment safety.

Changes in insulin requirements during pregnancy in Japanese women with type 1 diabetes.

We investigated the changes in insulin requirements, and other relevant factors, in pregnant Japanese women with type 1 diabetes. This retrospective observational study was conducted on 77 singleton pregnant women with type 1 diabetes, treated with multiple daily injections of insulin. We examined changes in daily insulin dose during pregnancy and defined the increased insulin doses as the ratio of maximum dose to the pre-pregnancy dose. The relationship between the increased insulin doses and maternal features or pregnancy outcomes was investigated. The insulin dose gradually increased during pregnancy, reaching a maximum dose that was 1.6 times of that prior to pregnancy, at 35weeks of gestation. A negative significant correlation was observed between the insulin dose increases and duration of diabetes (p=0.008). Greater increases in insulin doses were noted in women with multiparity, compared to nulliparity (p=0.047). Multiple regression analyses revealed that shorter duration of diabetes was independently associated with the increases in insulin dose during pregnancy. Women with a longer duration of diabetes required smaller increases in insulin dose during pregnancy, suggesting that long diabetic duration may decrease placental function. Further investigations are needed to clarify the mechanisms that the duration of diabetes influences on insulin requirement during pregnancy.

Parity Increases Insulin Requirements in Pregnant Women With Type 1 Diabetes.

Tight glycemic control throughout pregnancy in women with type 1 diabetes is crucial, and knowledge about which factors that affect insulin sensitivity could improve the outcome for both mother and offspring. To evaluate insulin requirements in women with type 1 diabetes during pregnancy and test whether parity affects insulin requirements. Observational cohort study consisting of women with type 1 diabetes who gave birth at Aarhus University Hospital, Denmark, from 2004 to 2014. Daily insulin requirement (the hypothesis that parity could affect insulin resistance was formulated before data collection). A total of 380 women with a total of 536 pregnancies were included in the study. Mean age was 31.1 years, and prepregnancy hemoglobin A1c was 60 mmol/mol. Parity was as follows: P0, 43%; P1, 40%; P2, 14%; and P3+4, 3%. Insulin requirements from weeks 11 to 16 decreased significantly by 4% (P = 0.0004) and rose from week 19 to delivery with a peak of 70% (P < 0.0005) at weeks 33 to 36. Overall, insulin requirements increased significantly with parity. The unadjusted differences between P0 and P1, P2, and P3+4 were 9% (P < 0.0005), 12% (P < 0.0005), and 23% (P < 0.0011), respectively. After adjustment for confounders, differences were 13% (P < 0.0005), 20% (P < 0.0005), and 36% (P < 0.0005). We also observed an adjusted difference between P1 and P3+4 of 20% (P < 0.0012). The data show changes in insulin requirements from week to week in pregnancy and indicate that insulin requirements increase with parity. This suggests that the patient's parity probably should be considered in choosing insulin dosages for pregnant women with type 1 diabetes.

Enhancing automatic closed-loop glucose control in type 1 diabetes with an adaptive meal bolus calculator – in silico evaluation under intra-day variability

Background and ObjectiveCurrent prototypes of closed-loop systems for glucose control in type 1 diabetes mellitus, also referred to as artificial pancreas systems, require a pre-meal insulin bolus to compensate for delays in subcutaneous insulin absorption in order to avoid initial post-prandial hyperglycemia. Computing such a meal bolus is a challenging task due to the high intra-subject variability of insulin requirements. Most closed-loop systems compute this pre-meal insulin dose by a standard bolus calculation, as is commonly found in insulin pumps. However, the performance of these calculators is limited due to a lack of adaptiveness in front of dynamic changes in insulin requirements. Despite some initial attempts to include adaptation within these calculators, challenges remain. MethodsIn this paper we present a new technique to automatically adapt the meal-priming bolus within an artificial pancreas. The technique consists of using a novel adaptive bolus calculator based on Case-Based Reasoning and Run-To-Run control, within a closed-loop controller. Coordination between the adaptive bolus calculator and the controller was required to achieve the desired performance. For testing purposes, the clinically validated Imperial College Artificial Pancreas controller was employed. The proposed system was evaluated against itself but without bolus adaptation. The UVa-Padova T1DM v3.2 system was used to carry out a three-month in silico study on 11 adult and 11 adolescent virtual subjects taking into account inter-and intra-subject variability of insulin requirements and uncertainty on carbohydrate intake. ResultsOverall, the closed-loop controller enhanced by an adaptive bolus calculator improves glycemic control when compared to its non-adaptive counterpart. In particular, the following statistically significant improvements were found (non-adaptive vs. adaptive). Adults: mean glucose 142.2 ± 9.4vs. 131.8 ± 4.2mg/dl; percentage time in target [70, 180]mg/dl, 82.0 ± 7.0vs. 89.5 ± 4.2; percentage time above target 17.7 ± 7.0vs. 10.2 ± 4.1. Adolescents: mean glucose 158.2 ± 21.4vs. 140.5 ± 13.0mg/dl; percentage time in target, 65.9 ± 12.9vs. 77.5 ± 12.2; percentage time above target, 31.7 ± 13.1vs. 19.8 ± 10.2. Note that no increase in percentage time in hypoglycemia was observed. ConclusionUsing an adaptive meal bolus calculator within a closed-loop control system has the potential to improve glycemic control in type 1 diabetes when compared to its non-adaptive counterpart.

Assessment of changes in insulin requirement in patients of type 2 diabetes mellitus on maintenance hemodialysis.

Background:Hemodialysis improves insulin sensitivity. Currently, there is no recommendation for the adjustment of insulin dose on dialysis day and nondialysis day in diabetic patients. This study was undertaken to determine the variations in insulin requirement based on blood glucose levels on dialysis days and nondialysis days in type 2 diabetic patients with chronic kidney disease on maintenance hemodialysis.Methodology:Twenty-eight diabetic patients on hemodialysis were recruited into the study after obtaining written informed consent and approval from Azeezia Ethics Committee. Capillary blood glucose levels, just before dialysis and 2 h after dialysis, were checked and compared with fasting and postprandial glucose levels on–off dialysis days.Results:Mean age of the patients was 59.5 (±2.3) years. The average duration of dialysis was 20.2 months. There was significant (35.8%) decrease in blood glucose levels 2 h after dialysis in comparison to predialysis levels (from mean level of 258–165 mg/dl). The decrease in the blood glucose levels from predialysis level to 2 h postdialysis level was statistically significant (P < 0.001). Both sets of data showed “strong” positive correlation with r = 0.657 and 0.849. The blood glucose levels on the day of dialysis were significantly lower than the off-day values.Conclusions:Diabetic patients with end-stage renal disease on hemodialysis have lower capillary blood glucose levels postdialysis. This has to be addressed clinically to prevent hypoglycemic episodes by reducing exogenous insulin administration on the day of dialysis.

Insulin degludec and insulin degludec/insulin aspart in Ramadan: A single center experience.

This study aimed to document the utility and safety of insulin degludec (IDeg) and insulin degludec aspart (IDegAsp) in persons with type 2 diabetes, observing the Ramadan fast. An observational study was conducted at a single center, in the real world setting, on six persons who either switched to IDeg or IDegAsp a month before Ramadan or changed time of administration of IDegAsp at the onset of Ramadan, to keep the fast in a safe manner. Subjects were kept under regular monitoring and surveillance before, during, and after Ramadan, and counseled in an opposite manner. Four persons, who shifted from premixed insulin to IDegAsp, experienced a 12–18% dose reduction after 14 days. At the onset of Ramadan, the Suhur dose was reduced by 30%, and this remained unchanged during the fasting month. The Iftar dose had to be increased by 4 units. One person who shifted from neutral protamine hagedorn to IDeg demonstrated a 25% dose reduction at 20 days, without any further change in insulin requirement during Ramadan. One person who changed time of injection of IDegAsp from morning to night reported no change in dosage. No episode of major hypoglycemia was reported. IDeg and IDegAsp are effective, safe, and well-tolerated means of achieving glycemic control in persons with type 2 diabetes who wish to fast.

Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study.

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.

Method for automatic adjustment of an insulin bolus calculator: In silico robustness evaluation under intra-day variability

Background and objectiveInsulin bolus calculators are simple decision support software tools incorporated in most commercially available insulin pumps and some capillary blood glucose meters. Although their clinical benefit has been demonstrated, their utilisation has not been widespread and their performance remains suboptimal, mainly because of their lack of flexibility and adaptability. One of the difficulties that people with diabetes, clinicians and carers face when using bolus calculators is having to set parameters and adjust them on a regular basis according to changes in insulin requirements. In this work, we propose a novel method that aims to automatically adjust the parameters of a bolus calculator. Periodic usage of a continuous glucose monitoring device is required for this purpose. MethodsTo test the proposed method, an in silico evaluation under real-life conditions was carried out using the FDA-accepted Type 1 diabetes mellitus (T1DM) UVa/Padova simulator. Since the T1DM simulator does not incorporate intra-subject variability and uncertainty, a set of modifications were introduced to emulate them. Ten adult and ten adolescent virtual subjects were assessed over a 3-month scenario with realistic meal variability. The glycaemic metrics: mean blood glucose; percentage time in target; percentage time in hypoglycaemia; risk index, low blood glucose index; and blood glucose standard deviation, were employed for evaluation purposes. A t-test statistical analysis was carried out to evaluate the benefit of the presented algorithm against a bolus calculator without automatic adjustment. ResultsThe proposed method statistically improved (p<0.05) all glycemic metrics evaluating hypoglycaemia on both virtual cohorts: percentage time in hypoglycaemia (i.e. BG<70mg/dl) (adults: 2.7±4.0 vs. 0.4±0.7, p=0.03; adolescents: 7.1±7.4 vs. 1.3±2.4, p=0.02) and low blood glucose index (LBGI) (adults: 1.1±1.3 vs. 0.3±0.2, p=0.002; adolescents: 2.0±2.19 vs. 0.7±1.4, p=0.05). A statistically significant improvement was also observed on the blood glucose standard deviation (BG SDmg/dL) (adults: 33.5±13.7 vs. 29.2±8.3, p=0.01; adolescents: 63.7±22.7 vs. 44.9±23.9, p=0.01). Apart from a small increase in mean blood glucose on the adult cohort (129.9±11.9 vs. 133.9±11.6, p=0.03), the rest of the evaluated metrics, despite showing an improvement trend, did not experience a statistically significant change. ConclusionsA novel method for automatically adjusting the parameters of a bolus calculator has the potential to improve glycemic control in T1DM diabetes management.

Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin Infusion (CSII) Until Optimization of Glycemic Control.

The aim was to evaluate changes in insulin requirements from onset of continuous subcutaneous insulin infusion (CSII) until glucose optimization in type 1 diabetes and to determine patient characteristics to be considered when CSII is implemented. We retrospectively analyzed 74 type 1 diabetic patients over a follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c levels at the end of follow-up were excluded. We compared total daily doses (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI), diabetes duration, and indication for CSII. At follow-up, HbA1c decreased by 0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate was 60% of total basal rate. Insulin requirements were higher in males and in obese patients. Female patients and patients with longer diabetes duration showed a higher percentage of basal insulin. The number of basal segments was 4.9 ± 2.9. Basal requirements were higher in the second half of the nocturnal period. The dawn phenomenon was more relevant in men. Improvements in glycemic control were more marked in younger patients, in patients with higher HbA1c, in patients using more basal segments, and in patients initiating CSII for glucose control before pregnancy. Sex, diabetes duration, and BMI should be considered when initiating CSII. Our findings may help clinicians in clinical decision making regarding CSII therapy.

Role of microRNAs in islet beta-cell compensation and failure during diabetes.

Pancreatic beta-cell function and mass are markedly adaptive to compensate for the changes in insulin requirement observed during several situations such as pregnancy, obesity, glucocorticoids excess, or administration. This requires a beta-cell compensation which is achieved through a gain of beta-cell mass and function. Elucidating the physiological mechanisms that promote functional beta-cell mass expansion and that protect cells against death, is a key therapeutic target for diabetes. In this respect, several recent studies have emphasized the instrumental role of microRNAs in the control of beta-cell function. MicroRNAs are negative regulators of gene expression, and are pivotal for the control of beta-cell proliferation, function, and survival. On the one hand, changes in specific microRNA levels have been associated with beta-cell compensation and are triggered by hormones or bioactive peptides that promote beta-cell survival and function. Conversely, modifications in the expression of other specific microRNAs contribute to beta-cell dysfunction and death elicited by diabetogenic factors including, cytokines, chronic hyperlipidemia, hyperglycemia, and oxidized LDL. This review underlines the importance of targeting the microRNA network for future innovative therapies aiming at preventing the beta-cell decline in diabetes.